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In spite of their important roles in many ecosystems, data regarding population structure and biogeographic patterns of leeches are scarce. To begin to address this knowledge gap, we herein perform a phylogeographic analysis of the North American medicinal leech, Macrobdella decora (Say, 1824). A total of 224 M. decora specimens were collected from 35 localities across large swaths of USA and Canada and covering most of the known range of the species. Using four loci (mitochondrial cytochrome c oxidase subunit I [COI] and NADH dehydrogenase I [ND1], as well as nuclear 18S rRNA [18S] and 28S rRNA [28S]), we construct phylogenetic trees using several optimality criteria and superimpose geographic patterns onto the trees in order to tease out any potential structure among the populations. Rather surprisingly, given the large geographic range of the species and abundance of potential geographic barriers to gene flow, the analyses showed a conspicuous lack of structure among the different populations of M. decora. However, an AMOVA did show statistically significant differences between the genetic variation within populations and between populations (COI: FST = 0.65412, p < .00001; ND1: FST = 0.69245, p < .00001), which was largely driven by only 6 out of the 35 populations, and indicated a potential barrier for dispersal across the Appalachian Mountains. Finally, a Mantel test showed a weak, but significant, correlation between geographic distance and genetic distance (COI: r = 0.209, p = .027; ND1: r = 0.1289, p = .030); however, this correlation was primarily driven by a single locality. The overall weak structure suggests that M. decora is panmictic throughout its range, and we discuss this in light of previous population level studies in both bloodfeeding and non‐bloodfeeding species, concluding that the lack of structure in M. decora might be due to its high capacity for dispersal via hosts. [ABSTRACT FROM AUTHOR]

The hypervariable region (HVR) in the control region of the mitochondrial DNA has frequently been used for population genetics and phylogeographic studies because of its highly variable nature. Although the HVR is beneficial for evaluating recent evolutionary history, including population demography, recent studies have implied the incidence of homoplasy in this region. To assess the accuracy of relying solely on the HVR for population genetics studies, molecular evolutionary analysis of the HVR, NADH-dehydrogenase subunit 2 (ND2), and cytochrome b genes were performed using 120 individuals of marbled flounder Pseudopleuronectes yokohamae. The HVR exhibited the highest genetic variability among the three regions, with sites showing high site-specific substitution rates. Considering the reticulate haplotype network structure and evolutionary linkages between regions, homoplastic mutations were indicated in the HVR in addition to ND2, underestimating genetic diversity. We found that homoplasy was less likely to affect coalescent-based demographic inferences in the population; however, there is still a potential risk of misinterpretation of population demography when solely using the HVR owing to its hypervariable nature. Collectively, we suggest analyzing other regions in addition to the HVR in fish population genetic research to improve accuracy and eliminate biases caused by homoplasy. [ABSTRACT FROM AUTHOR]

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Background: Opisthorchis-like eggs are a public health problem in northern and northeastern Thailand. However, the genetic epidemiology and structure of these parasites in northern Thailand are unknown. Thus, this study investigated their population genetic structure using cytochrome c oxidase subunit 1 (cox1) and NADH dehydrogenase subunit 1 (nad1) nucleotide sequences. Methodology/Principal findings: A study was conducted in the hill tribe regions of Chiang Mai Province, northern Thailand. Internal transcribed spacer 2 polymerase chain reaction and restriction fragment length polymorphism were used to distinguish 205 positive feces samples for Opisthorchis-like eggs. The results showed that the prevalence of O. viverrini and Haplorchis taichui was 10.5% and 38.2%, respectively, and the co-infection rate was 37.2%. To determine the genetic structure of O. viverrini and H. taichui using cox1 and nad1 genes, genetic analysis was performed using 30 randomly chosen fecal samples for Opisthorchis-like eggs. Pairwise FST analysis indicated that O. viverrini and H. taichui displayed nonsignificant genetic differentiation within Chiang Mai Province and between interpopulations from different geographic areas. Moreover, within the intrapopulation in Chiang Mai Province,cox1 presented higher gene flow than nad1 in O. viverrini, while nad1 demonstrated higher gene flow than cox1 in H. taichui. The neutrality tests based on Fu's Fs indicated population expansion and selective sweep from bottleneck or hitchhiking in O. viverrini and H. taichui populations, supported by haplotype network patterns. Phylogenetic tree analysis based on cox1 and nad1 revealed the monophyly of O. viverrini and H. taichui and genetic relationships with other isolates collected from Thailand, Lao People's Democratic Republic (PDR), and Vietnam. Conclusions/Significance: This study investigated the molecular discrimination and genetic structure of Opisthorchis-like eggs in northern Thailand. The genetic information derived from this study could be associated with the background, molecular epidemiology, and disease severity of these parasites. Author summary: Opisthorchis-like egg infections are highly prevalent in northern and northeastern Thailand; however, their genetic epidemiology and structure in northern Thailand are unknown. Thus, this study examined the genetic structure of Opisthorchis-like eggs in the hill tribe population of Chiang Mai Province, northern Thailand, using mitochondrial genes [cytochrome c oxidase subunit 1 (cox1) and NADH dehydrogenase subunit 1 (nad1)]. A total of 205 positive feces samples for Opisthorchis-like eggs were collected and examined using internal transcribed spacer 2 polymerase chain reaction and restriction fragment length polymorphism assays. Thirty fecal samples of O. viverrini and Haplorchis taichui were randomly selected for investigating population genetic structure using cox1 and nad1. Pairwise FST analysis demonstrated nonsignificant genetic differentiation within the intrapopulation of Chiang Mai Province and interpopulations from different geographic areas. Gene flow estimation showed that cox1 had higher gene flow than nad1 in O. viverrini, whereas both genes showed low gene flow in H. taichui. Moreover, neutrality tests and haplotype networks revealed a population expansion from the bottleneck or selective sweep. Additionally, the phylogenetic trees of O. viverrini and H. taichui revealed monophyletic groups and were genetically similar to isolates in other regions in Thailand, Lao PDR, Cambodia and Vietnam. [ABSTRACT FROM AUTHOR]

Simple Summary: More than 350 species (32 species groups) of Cyrtodactylus Gray, 1827, are reported currently, with a wide distribution from Himalaya, South Asia, Southeast Asia, to Melanesia. Cyrtodactylus tibetanus group, as the earliest Cyrtodactylus diverging clade, are endemic to the Yarlung–Tsangpo River Basin of Tibetan Plateau, only containing two species: C. tibetanus and C. zhaoermii. However, two newly collected Cyrtodactylus specimens from the eastern region of Lang County, Linzhi City, Xizang Autonomous Region, China, were found to be an unnamed taxon of this group based upon the molecular phylogeny, which was conducted using a concatenation data matrix (the partial 16S ribosomal RNA gene (16S), the partial cytochrome c oxidase subunit 1 gene (CO1), and the partial NADH dehydrogenase subunit 2 gene (ND2)) and morphological comparisons, as the new species could be easily identified from other C. tibetanus group species through the absence of the tubercles on dorsum, tail segments, and the tubercles on tails. The new species is currently only known from the type locality with its extremely small populations, with great demand for future investigations to figure out its distribution range, population status, natural history, and mechanisms so that this new species can coexist with Altiphylax medogense. A new Cyrtodactylus species, C. laevissp. nov., from the dry-hot valleys near the Yarlung Zangbo River in Re Village, Jindong Countryside, Lang County, Linzhi City, Xizang Autonomous Region, China, is described herein based upon the integrative taxonomic results combining molecular phylogenetic systematics and morphological characteristic comparisons. Our molecular phylogeny was inferred by combining three mitochondrial gene fragments (16S/CO1/ND2), and it indicated a distinct differentiation between the new species and C. tibetanus species complex, with obvious genetic distances (16S 9.9–11.8%/CO1 16.5–18.2%/ND2 16.6–18.5%) detected, supporting its validity. Morphologically, the new species can be easily distinguished from its congers by the following characters: (1) medium size (SVL 48.58–50.92 mm), (2) tubercles on dorsum sparse, (3) tail segments absent and tubercles on tails absent, (4) supralabials 10–12 and infralabials 8–10, (5) interorbital scales between anterior corners of the eyes 28–32, (6) scale rows at midbody 96–98, (7) ventral scales between mental and cloacal slit 145–153, (8) ventral scale rows 41–45, and (9) 4 to 5 white–yellow transverse bands with brown dots and black merges between the nape and sacrum. The description of C. laevis sp. nov. increased the total species number of C. tibetanus group to three, and the total Cyrtodactylus species number in Xizang to six and in China to eleven. The new species is currently only known from the type locality with its extremely small populations and needs future surveys to reveal its distribution range, population status, natural history, and mechanisms so that the new species can coexist with Altiphylax medogense. [ABSTRACT FROM AUTHOR]

Sertoli cell (SC) proliferation plays an important role in sperm production and quality; however, the regulatory mechanism of SC proliferation is not well understood. This study investigated the role of adenosine monophosphate-activated protein kinase (AMPK) in the regulation of immature boar SC activity. Cell counting kit-8, Seahorse XFe96, mitochondrial respiratory enzyme-related assay kits, and transmission electron microscopy were used to detect SC proliferative viability, oxygen consumption rate (OCR), mitochondrial respiratory enzyme activity, and the ultrastructure of primary cultured SCs in vitro from the testes of 21-day-old boars. A dual luciferase reporter assay was performed to determine the miRNA-mRNA target interaction. Western blotting was used to analyze cell proliferation-related protein expression of p38, p21, proliferating cell nuclear antigen (PCNA), Cyclin-dependent kinase 4 (CDK4), Cyclin D3, and phosphorylated retinoblastoma protein (Rb). Each experiment had a completely randomized design, with three replicates in each experiment. The results showed that the AMPK inhibitor (Compound C, 20 μM-24 h) increased cell proliferation viability, ATP production, and maximal respiration of SCs by 0.64-, 0.12-, and 0.08-fold (p < 0.05), respectively; increased the SC protein expression of PCNA, CDK4, Cyclin D3, and p-Rb by 0.13-, 0.09-, 0.88-, and 0.12-fold (p < 0.05), respectively; and decreased the SC protein expression of p38 and p21 by 0.36- and 0.27-fold (p < 0.05), respectively. The AMPK agonist AICAR (2 mM-6 h) significantly inhibited SC ultrastructure, OCR, mitochondrial respiratory enzyme activity, and cell proliferation-related protein levels. AMPK was validated to be a target gene of miR-1285 based on the result in which the miR-1285 mimic inhibited the luciferase activity of wild-type AMPK by 0.54-fold (p < 0.001). MiR-1285 mimic promoted the OCR of SCs, with 0.45-, 0.15-, 0.21-, and 0.30-fold (p < 0.01) increases in ATP production, basal and maximal respiration, and spare capacity, respectively. MiR-1285 mimic increased the mitochondrial respiratory enzyme activity of SCs, with 0.63-, 0.70-, and 0.97-fold (p < 0.01) increases in NADH-Q oxidoreductase, cytochrome c oxidase, and ATP synthase, respectively. Moreover, the miR-1285 mimic increased the protein expression of PCNA, CDK4, Cyclin D3, and p-Rb by 0.24-, 0.30-, 0.22-, and 0.13-fold (p < 0.05), respectively, and reduced the protein expression of p38 and p21 by 0.58- and 0.66-fold (p < 0.001). MiR-1285 inhibitor showed opposite effects on the above indicators and induced numerous autophagosomes and large lipid droplets in SCs. A high dose of estradiol (10 μM-6 h, showed a promotion of AMPK activation in a previous study) significantly inhibited SC ultrastructure, mitochondrial function, and proliferation-related pathways, while these adverse effects were weakened by Compound C treatment or miR-1285 mimic transfection. Our findings suggest that the activation and inhibition of AMPK induced by specific drugs or synthesized targeted miRNA fragments could regulate immature boar SC proliferative activity by influencing the CDK4/Cyclin D3 pathway and mitochondrial function; this helps to provide a basis for the prevention and treatment of male sterility in clinical practice. • Compound C increases immature boar SC proliferative activity. • MiR-1285 mimic can target and inhibit AMPK. • AMPK inhibition increases SC mitochondrial function and CDK4/Cyclin D3 pathway. • AMPK activation damages SC ultrastructure. • AMPK inhibition reduces adverse effects of estradiol on SCs. [ABSTRACT FROM AUTHOR]

Background: Bartonellosis, caused by bacteria of the genus Bartonella, is a zoonotic disease with several mammalian reservoir hosts. In Somalia, a country heavily reliant on livestock, zoonotic diseases pose significant public health and economic challenges. To the best of our knowledge, no study has been performed aiming to verify the occurrence of Bartonella spp. in Somalia. This study investigated the occurrence and molecular characterization of Bartonella in dromedary (Camelus dromedarius, Linnaeus, 1758), cattle, sheep, and goats from Somalia. Materials and Methods: 530 blood samples were collected from various animals (155 dromedary, 199 goat, 131 cattle, and 45 sheep) in Benadir and Lower Shabelle regions. DNA was extracted for molecular analysis, and a qPCR assay targeting the NADH dehydrogenase gamma subunit (nuoG) gene was used for Bartonella screening. Positive samples were also subjected to PCR assays targeting seven molecular markers including: nuoG, citrate synthase gene (gltA), RNA polymerase beta‐subunit gene (rpoB), riboflavin synthase gene (ribC), 60 kDa heat‐shock protein gene (groEL), cell division protein gene (ftsZ), and pap31 and qPCR targeting the 16‐23S rRNA internal transcribed spacer (ITS) followed by Sanger sequencing, BLASTn and phylogenetic analysis. Results: Out of 530 tested animals, 5.1% were positive for Bartonella spp. by the nuoG qPCR assay. Goats showed the highest Bartonella occurrence (17/199, 8.5%), followed by sheep (6/44, 6.8%), cattle (4/131, 3.1%), and dromedary (1/155, 1.9%). Goats, sheep, and cattle had higher odds of infection compared to dromedary. Among nuoG qPCR‐positive samples, 11.1%, 14.8%, 11.1%, and 25.9% were positive in PCR assays based on nuoG, gltA, and pap31 genes, and in the qPCR based on the ITS region, respectively. On the other hand, nuoG qPCR‐positive samples were negative in the PCR assays targeting the ribC, rpoB, ftsZ, and groEL genes. While Bartonella bovis sequences were detected in cattle (nuoG and ITS) and goats (gltA), Bartonella henselae ITS sequences were detected in dromedary, goat, and sheep. Phylogenetic analysis placed gltA Bartonella sequence from a goat in the same clade of B. bovis. Conclusion: The present study showed, for the first time, molecular evidence of Bartonella spp. in dromedary and ruminants from Somalia and B. henselae in sheep and goats globally. These findings contribute valuable insights into Bartonella spp. occurrence in Somali livestock, highlighting the need for comprehensive surveillance and control measures under the One Health approach. [ABSTRACT FROM AUTHOR]

Abstract—Using the next-generation sequencing (NGS) technology, the nucleotide polymorphism in a fragment of the ND4 gene encoding NADH dehydrogenase subunit 4 was studied in 14 samples from three populations of the bird cherry-oat aphid (Rhopalosiphum padi L.) and the range of nucleotide polymorphism was determined. The insects were collected in 2021 and 2022 in the Northwest of Russia (in the vicinity of St. Petersburg) and in the northern Caucasus (Krasnodar Territory and Dagestan). Mitochondrial DNA haplotypes were identified, which have 97.95–99.80% sequence identity with the reference GenBank accession number KT447631.1. The level of intraspecific polymorphism of a 438 bp ND4 gene fragment in Rh. padi varied from 0.2 to 4.3%. In 2-year experiments, 33 polymorphic sites (17 transitions and 16 transversions) were found in the ND4 sequences, which made it possible to identify 30 mitochondrial DNA haplotypes. The Rh. padi populations collected simultaneously on different host plants or at different times on bird cherry (spring) and cereals (summer) differed in the proportion of the main haplotype, as well as in the composition of unique minor haplotypes. Analysis of the ratio of mitochondrial DNA haplotypes suggests the important role of the host plant genotype in the formation of the structure of Rh. padi populations. [ABSTRACT FROM AUTHOR]

Inhibition of mitochondrial complex I (NADH dehydrogenase) is the primary mechanism of the antidiabetic drug metformin and various unrelated natural toxins. Complex I inhibition can also be induced by antidiabetic PPAR agonists, and it is elicited by methionine restriction, a nutritional intervention causing resistance to diabetes and obesity. Still, a comprehensible explanation to why complex I inhibition exerts antidiabetic properties and engenders metabolic inefficiency is missing. To evaluate this issue, we have systematically reanalyzed published transcriptomic datasets from MPP-treated neurons, metformin-treated hepatocytes, and methionine-restricted rats. We found that pathways leading to NADPH formation were widely induced, together with anabolic fatty acid biosynthesis, the latter appearing highly paradoxical in a state of mitochondrial impairment. However, concomitant induction of catabolic fatty acid oxidation indicated that complex I inhibition created a "futile" cycle of fatty acid synthesis and degradation, which was anatomically distributed between adipose tissue and liver in vivo. Cofactor balance analysis unveiled that such cycling would indeed be energetically futile (-3 ATP per acetyl-CoA), though it would not be redox-futile, as it would convert NADPH into respirable FADH2 without any net production of NADH. We conclude that inhibition of NADH dehydrogenase leads to a metabolic shift from glycolysis and the citric acid cycle (both generating NADH) towards the pentose phosphate pathway, whose product NADPH is translated 1:1 into FADH2 by fatty acid cycling. The diabetes-resistant phenotype following hepatic and intestinal complex I inhibition is attributed to FGF21- and GDF15-dependent fat hunger signaling, which remodels adipose tissue into a glucose-metabolizing organ. [ABSTRACT FROM AUTHOR]

There are some natural products from plants that can prevent and treat disease. Metformin, a derivative of galegine, is the basic drug to treat diabetes. Moreover, this molecule has anticancer properties that inhibit cancer cell growth and proliferation. In this study, the main interactions of galegine and metformin with various cancer‐involved proteins, including mitochondrial alpha‐glycerophosphate dehydrogenase, yeast NADH dehydrogenase, and transforming growth factor‐β1, were surveyed by molecular docking and molecular dynamics simulations. The results showed that each of the proteins makes complexes with the ligands via favorable non‐bonded interactions, especially hydrogen bond interactions. There is greater stability for complexes containing galegine based on the root mean square deviation results. The higher structure compactness is also found in galegine receptors than in metformin receptors. Calculation of ΔGbinding, using the MM/PBSA methodology, shows that the binding energy values for metformin and galegine in interaction with each of the receptors are almost the same, and galegine has similar binding properties with metformin in interaction with the studied protein receptors. Therefore, galegine, a natural ingredient with better binding properties to cancer‐involved proteins than metformin (with various side effects), can be applied as a new drug for cancer treatment. [ABSTRACT FROM AUTHOR]

Oxidative phosphorylation is becoming increasingly important in the induction and development of endometriosis. Recently, it has been reported that ring finger protein 43 (RNF43) is involved in the process of oxidative phosphorylation, but the mechanism remains unclear. Our investigation is to delve into the roles of RNF43 in endometriosis and elucidate the related mechanisms. We found RNF43 was downregulated in ectopic endometrial tissue and primary ectopic endometrial stromal cells (ECESCs). Knockdown of RNF43 enhanced cell viability and migration by activating oxidative phosphorylation in eutopic endometrial stromal cells (EUESCs), while overexpression of RNF43 led to the opposite results. Moreover, RNF43 reinforced the ubiquitination and degradation of NADH dehydrogenase Fe‐S protein 1 (NDUFS1) by interacting with it. Likewise to RNF43 overexpression, NDUFS1 silencing inhibited cell viability, migration, and oxidative phosphorylation in ECESCs. NDUFS1 was a downstream target of RNF43, mediating its biological role in endometriosis. Interestingly, the expression and stability of RNF43 mRNA were regulated by the Methyltransferase‐like 3 (METTL3)/IGF2BP2 m6A modification axis. The results of rat experiments showed decreased RNF43 expression and increased NDUFS1 expression in endometriosis rats, which was enhanced by METTL3 inhibition. Those observations indicated that m6A methylation‐mediated RNF43 negatively affects viability and migration of endometrial stromal cells through regulating oxidative phosphorylation via NDUFS1. The discovery of METTL3/RNF43/NDUFS1 axis suggested promising therapeutic targets for endometriosis. [ABSTRACT FROM AUTHOR]

The prohibitins Phb1 and Phb2 assemble at the mitochondrial inner membrane to form a multi-dimeric complex. These scaffold proteins are highly conserved in eukaryotic cells, from yeast to mammals, and have been implicated in a variety of mitochondrial functions including aging, proliferation, and degenerative and metabolic diseases. In mammals, PHB2 regulates PINK1-PRKN mediated mitophagy by interacting with lipidated MAP1LC3B/LC3B. Despite their high conservation, prohibitins have not been linked to mitophagy in budding yeasts. In this study, we demonstrate that both Phb1 and Phb2 are required to sustain mitophagy in Saccharomyces cerevisiae. Prohibitin-dependent mitophagy requires formation of the Phb1-Phb2 complex and a conserved AIM/LIR-like motif identified in both yeast prohibitins. Furthermore, both Phb1 and Phb2 interact and exhibit mitochondrial colocalization with Atg8. Interestingly, we detected a basal C terminus processing of the mitophagy receptor Atg32 that depends on the presence of the i-AAA Yme1. In the absence of prohibitins this processing is highly enhanced but reverted by the inactivation of the rhomboid protease Pcp1. Together our results revealed a novel role of yeast prohibitins in mitophagy through its interaction with Atg8 and regulating an Atg32 proteolytic event. Abbreviation: AIM/LIR: Atg8-family interacting motif/LC3-interacting region; ANOVA: analysis of variance; ATG/Atg: autophagy related; C terminus/C-terminal: carboxyl terminus/carboxyl-terminal; GFP: green fluorescent protein; HA: human influenza hemagglutinin; Idh1: isocitrate dehydrogenase 1; MAP1C3B/LC3B: microtubule associated protein 1 light chain 3 beta; mCh: mCherry; MIM: mitochondrial inner membrane; MOM: mitochondrial outer membrane; N starvation: nitrogen starvation; N terminus: amino terminus; PARL: presenilin associated rhomboid like; Pcp1: processing of cytochrome c peroxidase 1; PCR: polymerase chain reaction; PGAM5: PGAM family member 5 mitochondrial serine/threonine protein phosphatase; PHBs/Phb: prohibitins; PINK1: PTEN induced kinase 1; PMSF: phenylmethylsulfonyl fluoride; PRKN: parkin RBR E3 ubiquitin protein ligase; SD: synthetic defined medium; SDS: sodium dodecyl sulfate; SMD-N: synthetic defined medium lacking nitrogen; WB: western blot; WT: wild type; Yme1: yeast mitochondrial escape 1; YPD: yeast extract-peptone-dextrose medium; YPLac: yeast extract-peptone-lactate medium. [ABSTRACT FROM AUTHOR]

Thioredoxins (TRXs) are central to redox regulation, modulating enzyme activities to adapt metabolism to environmental changes. Previous research emphasized mitochondrial and microsomal TRX o1 and h2 influence on mitochondrial metabolism, including photorespiration and the tricarboxylic acid (TCA) cycle. Our study aimed to compare TRX‐based regulation circuits towards environmental cues mainly affecting photorespiration. Metabolite snapshots, phenotypes and CO2 assimilation were compared among single and multiple TRX mutants in the wild‐type and the glycine decarboxylase T‐protein knockdown (gldt1) background. Our analyses provided evidence for additive negative effects of combined TRX o1 and h2 deficiency on growth and photosynthesis. Especially metabolite accumulation patterns suggest a shared regulation mechanism mainly on mitochondrial dihydrolipoamide dehydrogenase (mtLPD1)‐dependent pathways. Quantification of pyridine nucleotides, in conjunction with 13C‐labelling approaches, and biochemical analysis of recombinant mtLPD1 supported this. It also revealed mtLPD1 inhibition by NADH, pointing at an additional measure to fine‐tune it's activity. Collectively, we propose that lack of TRX o1 and h2 perturbs the mitochondrial redox state, which impacts on other pathways through shifts in the NADH/NAD+ ratio via mtLPD1. This regulation module might represent a node for simultaneous adjustments of photorespiration, the TCA cycle and branched chain amino acid degradation under fluctuating environmental conditions. Summary statement: Thioredoxins o1 and h2 concertedly adapt the performance of mtLPD1‐dependent pathways towards short‐ and long‐term environmental changes. Simultaneous adjustments of mitochondrial pathway fluxes are achieved through fine tuning of mtLPD1 activity via redox regulation and subcellular NADH/NAD+ ratios. [ABSTRACT FROM AUTHOR]

In Brazil, the Whitespotted Eagle Ray Aetobatus narinari is considered data-deficient due to the scarcity of basic information on its biology, ecology, and vulnerability to capture. Despite this, the species is caught by artisanal fishing along most of the coast, especially in the northeast of Brazil. This study analyzed mitochondrial DNA data in specimens of A. narinari caught by artisanal fishing in the northeast coast of Brazil to understand their population structure. For this, 42 individuals were sequenced at three mitochondrial genes: cytochrome oxidase 1 (COI), cytochrome b (Cytb), and NADH dehydrogenase subunit 4 (ND4). Concatenated COI-Cytb-ND4 sequences yielded 14 haplotypes, with moderate haplotype diversity (h = 0.646), low nucleotide diversity (π = 0.00087), and low fixation index ΦST values, indicating no population structure. Our results suggest that there is only one population of A. narinari in the study area. Genetic studies can contribute to improving management plans in these areas, avoiding the overexploitation of this and other species. [ABSTRACT FROM AUTHOR]

As ecosystem disruptors and intermediate hosts for various parasites, freshwater snails have significant socioeconomic impacts on human health, livestock production, and aquaculture. Although traditional molluscicides have been widely used to mitigate these effects, their environmental impact has encouraged research into alternative, biologically based strategies to create safer, more effective molluscicides and diminish the susceptibility of snails to parasites. This review focuses on alterations in glucose metabolism in snails under the multifaceted stressors of parasitic infections, drug exposure, and environmental changes and proposes a novel approach for snail management. Key enzymes within the glycolytic pathway, such as hexokinase and pyruvate kinase; tricarboxylic acid (TCA) cycle; and electron transport chains, such as succinate dehydrogenase and cytochrome c oxidase, are innovative targets for molluscicide development. These targets can affect both snails and parasites and provide an important direction for parasitic disease prevention research. For the first time, this review summarises the reverse TCA cycle and alternative oxidase pathway, which are unique metabolic bypasses in invertebrates that have emerged as suitable targets for the formulation of low-toxicity molluscicides. Additionally, it highlights the importance of other metabolic pathways, including lactate, alanine, glycogenolysis, and pentose phosphate pathways, in snail energy supply, antioxidant stress responses, and drug evasion mechanisms. By analysing the alterations in key metabolic enzymes and their products in stressed snails, this review deepens our understanding of glucose metabolic alterations in snails and provides valuable insights for identifying new pharmacological targets. [ABSTRACT FROM AUTHOR]

This study presents the first molecular phylogenetic analysis of the Clinocerinae, challenging the traditionally accepted monophyly of this subfamily. DNA was extracted from fresh and museum specimens representing all biogeographical regions. Maximum likelihood (ML) and Bayesian inference (BI) phylogenetic analyses were performed based on sequences from two mitochondrial genes, cytochrome c oxidase subunit I (COI) and cytochrome β, and three nuclear genes, carbomoylphosphate synthase domain of rudimentary, elongation factor‐1α and isocitrate dehydrogenase. Through molecular data and morphological examination, our results reveal a division within Clinocerinae, distinguishing 'typical' or Clinocerinae (s.s.) from several genera, specifically Afroclinocera Sinclair, Asymphyloptera Collin and Proagomyia Collin, possibly lending support for a reclassification of these genera outside Clinocerinae. Bergenstammia Mik is proposed as a junior synonym of Phaeobalia Mik, syn. n., and the following new combinations are recognized: Phaeobalia albanica (Wagner) comb. n., Phaeobalia aurinae (Pusch & Wagner) comb. n., Phaeobalia carniolica (Horvat) comb. n., Phaeobalia frigida (Vaillant) comb. n., Phaeobalia glacialis (Palaczyk & Słowińska) comb. n., Phaeobalia multiseta (Strobl) comb. n., Phaeobalia nudimana (Vaillant) comb. n., Phaeobalia nudipes (Loew) comb. n., Phaeobalia pulla (Vaillant & Wagner) comb. n., Phaeobalia pyrenaica (Vaillant & Vinçon) comb. n., Phaeobalia slovaca (Wagner) comb. n. and Phaeobalia thomasi (Vaillant & Vinçon) comb. n. Re‐evaluation of the genus Roederiodes resulted in the following new combinations: Clinocerella macedonicus (Wagner & Horvat) comb. n. and Clinocerella montenegrinus (Wagner & Horvat) comb. n. The origins of Clinocerinae (s.s.) are traced back to the Holarctic region, Laurasian origin, with a likely complex history of dispersal events into the Southern Hemisphere. Based on current knowledge, the greatest generic and species richness is confined to the Palaearctic Region. These findings provide valuable insights into the evolutionary relationships and distribution patterns of Clinocerinae (s.s.), challenging existing taxonomic classifications and shedding light on their historical biogeography. [ABSTRACT FROM AUTHOR]

Abstract Microbial fuel cells (MFCs), which use bacterial electron transport mechanisms to generate energy, have become a viable technology for renewable energy production. This review investigates the evolutionary and functional connections between bacterial energy transduction mechanisms and mitochondrial electron transport chains, building on the endosymbiont theory of eukaryotic cell evolution. The conserved features and similarities between prokaryotic and eukaryotic electron transport pathways were elucidated, highlighting their common origins and roles in cellular bioenergetics. This discussion explores the essential mechanisms governing the movement of electrons and ions across biological membranes, crucial for generating energy and maintaining electrochemical gradients in bacteria and mitochondria. Capitalizing on these insights, we explore the applications of electrogenic bacteria in MFCs for renewable electricity generation. Optimal conditions for enhancing bacterial electron transfer to electrode surfaces are identified, paving the way for improved MFC performance. Potential large-scale implementations of MFCs in wastewater treatment, biosensing, and bioremediation of contaminated environments are discussed, underscoring their versatility and environmental benefits. The importance of investigating bioenergetic mechanisms at both the cellular and molecular scales of fully harnessing the capabilities of microbial energy conversion systems is highlighted in this review. By bridging the gap between fundamental cellular processes and sustainable technologies, we aim to advance renewable energy solutions that harness the remarkable capabilities of electrogenic microorganisms.

Bivalves are an extraordinary class of animals in which species with a doubly uniparental inheritance (DUI) of mitochondrial DNA have been described. DUI is characterized as a mitochondrial homoplasmy of females and heteroplasmy of male individuals where F-type mitogenomes are passed to the progeny with mother egg cells and divergent M-type mitogenomes are inherited with fathers sperm cells. However, in most cases only male individuals retain divergent mitogenome inherited with spermatozoa. Additionally, in many of bivalves, unique mitochondrial features, like additional genes, gene duplication, gene extensions, mitochondrial introns, and recombination, were observed. In this study, we sequenced and assembled male-type mitogenomes of three Donax species. Comparative analysis of mitochondrial sequences revealed a lack of all seven NADH dehydrogenase subunits as well as the presence of three long additional open reading frames lacking identifiable homology to any of the existing genes. [ABSTRACT FROM AUTHOR]

The orchid genus Dipodium R.Br. (Epidendroideae) comprises leafy autotrophic and leafless mycoheterotrophic species, with the latter confined to sect. Dipodium. This study examined plastome degeneration in Dipodium in a phylogenomic and temporal context. Whole plastomes were reconstructed and annotated for 24 Dipodium samples representing 14 species and two putatively new species, encompassing over 80% of species diversity in sect. Dipodium. Phylogenomic analysis based on 68 plastid loci including a broad outgroup sampling across Orchidaceae found that sect. Leopardanthus is the sister lineage to sect. Dipodium. Dipodium ensifolium, the only leafy autotrophic species in sect. Dipodium, was found to be a sister to all leafless, mycoheterotrophic species, supporting a single evolutionary origin of mycoheterotrophy in the genus. Divergence-time estimations found that Dipodium arose ca. 33.3 Ma near the lower boundary of the Oligocene and that crown diversification commenced in the late Miocene, ca. 11.3 Ma. Mycoheterotrophy in the genus was estimated to have evolved in the late Miocene, ca. 7.3 Ma, in sect. Dipodium. The comparative assessment of plastome structure and gene degradation in Dipodium revealed that plastid ndh genes were pseudogenised or physically lost in all Dipodium species, including in leafy autotrophic species of both Dipodium sections. Levels of plastid ndh gene degradation were found to vary among species as well as within species, providing evidence of relaxed selection for retention of the NADH dehydrogenase complex within the genus. Dipodium exhibits an early stage of plastid genome degradation, as all species were found to have retained a full set of functional photosynthesis-related genes and housekeeping genes. This study provides important insights into plastid genome degradation along the transition from autotrophy to mycoheterotrophy in a phylogenomic and temporal context. [ABSTRACT FROM AUTHOR]

Background: Although, oocytes from prepubertal donors are known to be less developmentally competent than those from adult donors it does not restrain their ability to produce full-term pregnancies. The transcriptomic profile of embryos could be used as a predictor for embryo's individual developmental competence. The aim of the study was to compare transcriptomic profile of blastocysts derived from prepubertal and pubertal heifers oocytes. Bovine cumulus-oocyte complexes (COCs) were obtained by ovum pick- up method from prepubertal and pubertal heifers. After in vitro maturation COCs were fertilized and cultured to the blastocyst stage. Total RNA was isolated from both groups of blastocysts and RNA-seq was performed. Gene ontology analysis was performed by DAVID (Database for Annotation, Visualization and Integrated Discovery). Results: A higher average blastocyst rate was obtained in the pubertal than in the pre-pubertal group. There were no differences in the quality of blastocysts between the examined groups. We identified 436 differentially expressed genes (DEGs) between blastocysts derived from researched groups, of which 247 DEGs were downregulated in blastocysts derived from pubertal compared to prepubertal heifers oocytes, and 189 DEGs were upregulated. The genes involved in mitochondrial function, including oxidative phosphorylation (OXPHOS) were found to be different in studied groups using Kyoto Encyclopedia of Genes (KEGG) pathway analysis and 8 of those DEGs were upregulated and 1 was downregulated in blastocysts derived from pubertal compared to prepubertal heifers oocytes. DEGs associated with mitochondrial function were found: ATP synthases (ATP5MF-ATP synthase membrane subunit f, ATP5PD- ATP synthase peripheral stalk subunit d, ATP12A- ATPase H+/K + transporting non-gastric alpha2 subunit), NADH dehydrogenases (NDUFS3- NADH: ubiquinone oxidoreductase subunit core subunit S3, NDUFA13- NADH: ubiquinone oxidoreductase subunit A13, NDUFA3- NADH: ubiquinone oxidoreductase subunit A3), cytochrome c oxidase (COX17), cytochrome c somatic (CYCS) and ubiquinol cytochrome c reductase core protein 1 (UQCRC1). We found lower number of apoptotic cells in blastocysts derived from oocytes collected from prepubertal than those obtained from pubertal donors. Conclusions: Despite decreased expression of genes associated with OXPHOS pathway in blastocysts from prepubertal heifers oocytes, the increased level of ATP12A together with the lower number of apoptotic cells in these blastocysts might support their survival after transfer. [ABSTRACT FROM AUTHOR]

Paris polyphylla var. yunnanensis, a well-known Chinese medicinal herb, shows a unique physiological trait characterized by the cyclic opening and closing of its anthers after pollen maturation. The aim of this study was to explore the implications of this phenomenon on breeding. RNA sequencing coupled with methylation sequencing was used to scrutinize and compare gene expression profiles and methylation alterations in pollen and seeds during anther opening and closing, along with cold exposure. Genes enriched within Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were examined to identify gene clusters susceptible to temperature-related methylation changes in both pollen and seeds. Four pollen treatment models, namely, normal control, "pollen protected from low temperatures," "pollen from just-opened anther," and "pollen from close-blocked anther," were used to produce corresponding seeds via artificial pollination. Subsequently, qRT-PCR was used to validate modifications in the expression patterns of marker genes in pollinated seeds under diverse treatment scenarios. Genes exhibiting significant differences in expression between anthers and normal tissues, along with gene regions linked to methylation variations attributed to low-temperature-treated pollen and seeds, were identified through transcriptomic analysis. Convergence was observed in three signaling pathways: oxidative phosphorylation (ko00190), plant hormone signal transduction (Ko04075), and zeatin biosynthesis (ko00908). Notably, gene clusters prone to temperature-induced methylation changes, such as NADH-ubiquinone oxidoreductase chain 5, plasma membrane ATPase 4, cytochrome c oxidase subunit 2, cis-zeatin O-glucosyltransferase, ABSCISIC ACID-INSENSITIVE 5-like protein 4, and indole-3-acetic acid-amido synthetase (IAAS), were identified. Evaluation using various pollen pollination models revealed altered expression patterns of five dormancy-regulating marker genes: IAAS, sucrose synthase (SUS), gibberellin 2-oxidase (GA2ox), ABA INSENSITIVE 2 (ABI2), and auxin-repressed protein (ARP), in seeds pollinated with pollen from close-blocked anthers, cold-protected pollen, and pollen from freshly opened anthers. The close-blocked anther treatment led to significantly upregulated expression of IAAS, SUS, GA2ox, and ABI2, whereas ARP expression decreased markedly, indicating a propensity toward prolonged seed dormancy. Conversely, in the low-temperature-protected anther model, SUS, ARP, GA2ox, and IAAS exhibited reduced expression levels, whereas the expression of ABI2 was upregulated, overall facilitating seed germination. [ABSTRACT FROM AUTHOR]

The effects of microalgae Chlorella pyrenoidosa on the hybrid groupers' (Epinephelus lanceolatus♂ × E. fuscoguttatus♀) growth, gut microbiome, and transcriptome were examined in this study. Feeding trials with a duration of 15 days (15d) and 60 days (60d) were conducted on three experimental groups (n = 3) as follows: (T1) grouper fed with basal diet and reared in filtered seawater (control treatment); (T2) grouper fed with basal diet and reared in C. pyrenoidosa monoculture water (CMW); and (T3) grouper fed with basal diet partially replaced with 15% of dried C. pyrenoidosa (CRM) and reared in filtered seawater. The findings revealed that groupers reared 15d in T2 treatment (T2-15d) had a higher fat content, with an apparent shift of microbial composition and functional pathways in the gut. Groupers reared 60d in T2 treatment (T2-60d) displayed an increased NADH dehydrogenase and cytochrome c oxidases gene expression, indicating more robust oxidative phosphorylation activity and ATP production crucial for metabolic homeostasis. The reduction in the total amino acid content was also detected in groupers raised in T2-60d. Gastritis, enteritis, and lipid malabsorption syndrome were observed in groupers raised 60d in T3 treatment (T3-60d), with the condition likely due to a higher intake of omega-6 to omega-3 fatty acids ratio in groupers raised 15 days in T3 (T3-15d) and T3-60d. All signs of intestinal inflammation may arise from the inclusion of dried C. pyrenoidosa. Overall, outcomes from this study revealed that introducing live C. pyrenoidosa to the culture water is advantageous for digestion and enhances the energy metabolism of juvenile groupers. [ABSTRACT FROM AUTHOR]

Plants grown without soil are believed to be less affected by soilborne diseases. However, in a commercial greenhouse in Ethiopia's Rift valley, Lavender plants grown in hydroponic showed signs of severe stunting and galled roots. To identify the cause of the problem, root samples were taken. From these samples, single egg masses were obtained and used as inoculum for tomato cv. Moneymaker seedlings. The resulting seedlings were grown to produce a pure culture. DNA was extracted from second-stage juveniles (J2) from sixteen isolates derived from pure cultures and amplified the 28S rRNA and NADH dehydrogenase subunit 5 (Nad5) region of the mtDNA. The 28S rRNA and Nad5 were sequenced for two and five randomly selected isolates. A BLAST search of 28S rRNA sequences at NCBI showed a 98.34% sequence homology with known sequences of Meloidogyne javanica isolates. Moreover, Nad5 gene analysis, female perennial pattern, and the phylogenetic trees further confirmed the correct identification of this species. This is the first report of a nematode infecting plants growing in a hydroponic greenhouse in Ethiopia. Therefore, isolating any potential contaminants of the potting media for future lavender production are important. [ABSTRACT FROM AUTHOR]

Background Age is the greatest risk factor for lower urinary tract symptoms attributed to benign prostatic hyperplasia (LUTS/BPH). Although LUTS/BPH can be managed with pharmacotherapy, treatment failure has been putatively attributed to numerous pathological features of BPH (eg, prostatic fibrosis, inflammation). Mitochondrial dysfunction is a hallmark of aging; however, its impact on the pathological features of BPH remains unknown. Methods Publicly available gene array data were analyzed. Immunohistochemistry examined mitochondrial proteins in the human prostate. The effect of complex I inhibition (rotenone) on a prostatic cell line was examined using quantitative polymerase chain reaction, immunocytochemistry, and Seahorse assays. Oleic acid (OA) was tested as a bypass of complex I inhibition. Aged mice were treated with OA to examine its effects on urinary dysfunction. Voiding was assessed longitudinally, and a critical complex I protein measured. Results Mitochondrial function and fibrosis genes were altered in BPH. Essential mitochondrial proteins (ie, voltage-dependent anion channels 1 and 2, PTEN-induced kinase 1, and NADH dehydrogenase [ubiquinone] iron–sulfur protein 3, mitochondrial [NDUFS3]) were significantly (p  < .05) decreased in BPH. Complex I inhibition in cultured cells resulted in decreased respiration, altered NDUFS3 expression, increased collagen deposition, and gene expression. OA ameliorated these effects. OA-treated aged mice had significantly (p  < .05) improved voiding function and higher prostatic NDUFS3 expression. Conclusions Complex I dysfunction is a potential contributor to fibrosis and lower urinary tract dysfunction in aged mice. OA partially bypasses complex I inhibition and therefore should be further investigated as a mitochondrial modulator for treatment of LUTS/BPH. Hypotheses generated in this investigation offer a heretofore unexplored cellular target of interest for the management of LUTS/BPH. [ABSTRACT FROM AUTHOR]

OMT-28 is a metabolically robust small molecule developed to mimic the structure and function of omega-3 epoxyeicosanoids. However, it remained unknown to what extent OMT-28 also shares the cardioprotective and antiinflammatory properties of its natural counterparts. To address this question, we analyzed the ability of OMT-28 to ameliorate hypoxia/reoxygenation (HR)-injury and lipopolysaccharide (LPS)-induced endotoxemia in cultured cardiomyocytes. Moreover, we investigated the potential of OMT-28 to limit functional damage and inflammasome activation in isolated perfused mouse hearts subjected to ischemia/reperfusion (IR) injury. In the HR model, OMT-28 (1 μM) treatment largely preserved cell viability (about 75 versus 40% with the vehicle) and mitochondrial function as indicated by the maintenance of NAD+/NADH-, ADP/ATP-, and respiratory control ratios. Moreover, OMT-28 blocked the HR-induced production of mitochondrial reactive oxygen species. Pharmacological inhibition experiments suggested that Gai, PI3K, PPARa, and Sirt1 are essential components of the OMT-28-mediated pro-survival pathway. Counteracting inflammatory injury of cardiomyocytes, OMT-28 (1 mM) reduced LPS-induced increases in TNFa protein (by about 85% versus vehicle) and NF-kB DNA binding (by about 70% versus vehicle). In the ex vivo model, OMT-28 improved post-IR myocardial function recovery to reach about 40% of the baseline value compared to less than 20% with the vehicle. Furthermore, OMT-28 (1 μM) limited IR-induced NLRP3 inflammasome activation similarly to a direct NLRP3 inhibitor (MCC950). Overall, this study demonstrates that OMT-28 possesses potent cardio-protective and anti-inflammatory properties supporting the hypothesis that extending the bioavailability of omega-3 epoxyeicosanoids may improve their prospects as therapeutic agents. [ABSTRACT FROM AUTHOR]

Microbial fuel cells (MFCs), which use bacterial electron transport mechanisms to generate energy, have become a viable technology for renewable energy production. This review investigates the evolutionary and functional connections between bacterial energy transduction mechanisms and mitochondrial electron transport chains, building on the endosymbiont theory of eukaryotic cell evolution. The conserved features and similarities between prokaryotic and eukaryotic electron transport pathways were elucidated, highlighting their common origins and roles in cellular bioenergetics. This discussion explores the essential mechanisms governing the movement of electrons and ions across biological membranes, crucial for generating energy and maintaining electrochemical gradients in bacteria and mitochondria. Capitalizing on these insights, we explore the applications of electrogenic bacteria in MFCs for renewable electricity generation. Optimal conditions for enhancing bacterial electron transfer to electrode surfaces are identified, paving the way for improved MFC performance. Potential large-scale implementations of MFCs in wastewater treatment, biosensing, and bioremediation of contaminated environments are discussed, underscoring their versatility and environmental benefits. The importance of investigating bioenergetic mechanisms at both the cellular and molecular scales of fully harnessing the capabilities of microbial energy conversion systems is highlighted in this review. By bridging the gap between fundamental cellular processes and sustainable technologies, we aim to advance renewable energy solutions that harness the remarkable capabilities of electrogenic microorganisms. [ABSTRACT FROM AUTHOR]

Objectives: Alveolar echinococcosis is caused by Echinococcus multilocularis, a parasite of zoonotic significance with a wide range of intermediate and final hosts, and the parasite survives successfully in diversified conditions. Plentiful studies have been done to study the genetic structure of the population of the parasite and the level of intimate kinship using mitochondrial (mt) DNA. The present study was conducted to investigate the population structure, genetic variation, and phylogenetic relationship of various isolates of E. multiocularis submitted to GenBank worldwide. Sequences of mt genes (mt-cytochrome c oxidase (cox1), mt-NADH dehydrogenase (nad1)) of E. multilocularis were analyzed to achieve the set goals. Materials and Methods: A total of 275 and 124 gene sequences of mt-cox1 and mt-nad1 belonging to E. multilocularis, respectively, were retrieved from the National Center for Biotechnology Information GenBank. The retrieved sequences were subjected to alignment with respective reference sequences using MEGA software. The PopArt software was used to establish median-joining networks, while DnaSp was used to calculate neutrality and diversity indices. MrBayes software was used to investigate the phylogenetic association between haplotypes based on Bayesian phylogeny. Results: Approximately 13 and 20 distinctive haplotypes of nad1 and cox1 genes, respectively, were observed in the present study. In both of the mt genes, diversity indices indicated low haplotype (mt-cox1 = 0.140; mt-nad1 = 0.374) and nucleotide (mt-cox1 = 0.00111; mt-nad1 = 0.00287) diversities. The values of Tajima's D and Fu Fs for a population of both of the genes under study were found to be negative. Conclusion: This study is a maiden attempt to provide insights into the population structure and genetic variation of E. multilocularis on a global scale. However, it is suggested that to better understand the population structure and genetic diversity of E. multilocularis, more geographical locations and amplifications of full-length gene sequences should be considered, which could be helpful in widening the insights into the genetic diversity of E. multilocularis. [ABSTRACT FROM AUTHOR]

Background: Staphylococcus aureus is a common pathogenic microorganism in humans and animals. Type II NADH oxidoreductase (NDH-2) is the only NADH:quinone oxidoreductase present in this organism and represents a promising target for the development of anti-staphylococcal drugs. Recently, myricetin, a natural flavonoid from vegetables and fruits, was found to be a potential inhibitor of NDH-2 of S. aureus. The objective of this study was to evaluate the inhibitory properties of myricetin against NDH-2 and its impact on the growth and expression of virulence factors in S. aureus. Results: A screening method was established to identify effective inhibitors of NDH-2, based on heterologously expressed S. aureus NDH-2. Myricetin was found to be an effective inhibitor of NDH-2 with a half maximal inhibitory concentration (IC50) of 2 μM. In silico predictions and enzyme inhibition kinetics further characterized myricetin as a competitive inhibitor of NDH-2 with respect to the substrate menadione (MK). The minimum inhibitory concentrations (MICs) of myricetin against S. aureus strains ranged from 64 to 128 μg/mL. Time–kill assays showed that myricetin was a bactericidal agent against S. aureus. In line with being a competitive inhibitor of the NDH-2 substrate MK, the anti-staphylococcal activity of myricetin was antagonized by MK-4. In addition, myricetin was found to inhibit the gene expression of enterotoxin SeA and reduce the hemolytic activity induced by S. aureus culture on rabbit erythrocytes in a dose-dependent manner. Conclusions: Myricetin was newly discovered to be a competitive inhibitor of S. aureus NDH-2 in relation to the substrate MK. This discovery offers a fresh perspective on the anti-staphylococcal activity of myricetin. [ABSTRACT FROM AUTHOR]

The Kerinci duck (Anas platyrhynchos), hailing from Jambi Province, represents one of the local duck breeds of Indonesia. This study aimed to ascertain the matrilineal origin of Kerinci ducks through analysis of the mitochondrial NADH Dehydrogenase subunit 2 (MT-ND2) gene. In this pursuit, forward sequences of the MT-ND2 gene (490 bp) were extracted from unsexed Kerinci ducks, totalling forty-eight (48) sequences, procured from blood samples. The findings demonstrated the identification of fifteen (15) distinct haplotypes within the MTND2 gene, with corresponding haplotype diversity (Hd) and nucleotide diversity (pi) values of 0.74 and 0.003, respectively. The resulting phylogenetic tree unveiled that Kerinci ducks exhibit two matrilineal origins: an Asian and an independent Kerinci lineage. Moreover, most Kerinci ducks were categorised within the H4 group (24 birds) of the Asian lineage. Nevertheless, this study also revealed the existence of an independent Kerinci lineage comprising eight (8) duck haplotypes. In conclusion, the analysis of the MT-ND2 gene underscored the genetic introgression of A. zonorhyncha and A. poecilorhyncha in Kerinci ducks. [ABSTRACT FROM AUTHOR]

Lactococcus lactis, a lactic acid bacterium used in food fermentations and commonly found in the human gut, is known to possess a fermentative metabolism. L. lactis, however, has been demonstrated to transfer metabolically generated electrons to external electron acceptors, a process termed extracellular electron transfer (EET). Here, we investigated an L. lactis mutant with an unusually high capacity for EET that was obtained in an adaptive laboratory evolution (ALE) experiment. First, we investigated how global gene expression had changed, and found that amino acid metabolism and nucleotide metabolism had been affected significantly. One of the most significantly upregulated genes encoded the NADH dehydrogenase NoxB. We found that this upregulation was due to a mutation in the promoter region of NoxB, which abolished carbon catabolite repression. A unique role of NoxB in EET could be attributed and it was directly verified, for the first time, that NoxB could support respiration in L. lactis. NoxB, was shown to be a novel type-II NADH dehydrogenase that is widely distributed among gut microorganisms. This work expands our understanding of EET in Gram-positive electroactive microorganisms and the special significance of a novel type-II NADH dehydrogenase in EET. [ABSTRACT FROM AUTHOR]

Background: Hypertrophic cardiomyopathy (HCM) is a dominantly inherited disease associated with sudden immune cell associations that remain unclear. The aim of this study was to comprehensively screen candidate markers associated with HCM and immune cells and explore potential pathogenic pathways. Methods: First, download the GSE32453 dataset to identify differentially expressed genes (DEGs) and perform Gene Ontology and pathway enrichment analysis using DAVID and GSEA. Next, construct protein-protein interaction (PPI) networks using String and Cytoscape to identify hub genes. Afterward, use CIBERSORT to determine the proportion of immune cells attributed to key genes in HCM and conduct ROC analysis based on the external dataset GSE36961 to evaluate their diagnostic value. Finally, validate the expression of key genes in the hypertrophic cardiomyocyte model through qRT-PCR using data from the HPA database. Results: Comprehensive analysis revealed that there were 254 upregulated genes and 181 downregulated genes in HCM. The enrichment study underscored pathways of inflammatory signaling, including MAPK and PI3K-Akt pathways. Pathways abundant in genes associated with HCM encompassed myocardial contraction and NADH dehydrogenase activity. Additionally, the analysis of immune infiltration revealed a notable increase in macrophages, NK cells, and monocytes in the HCM group, showing statistically significant variances in CD4 memory resting T cell infiltration when compared to the healthy control group. Within the validation dataset GSE36961, the Area Under the Curve (AUC) scores for eight crucial genes (FOS, CD86, CD68, BDNF, PIK3R1, PLEK, RAC2, CCL2) each exceeded 0.8. The HPA database revealed the positioning traits and paths of these eight crucial genes in smooth muscle cells, myocardial cells, and fibroblasts. The outcomes of the qRT-PCR were aligned with the sequencing findings. Conclusion: Bioinformatics analysis unveiled pivotal genes, pathways, and immune involvement, illuminating the molecular underpinnings of HCM. These findings suggest promising therapeutic targets for clinical applications. [ABSTRACT FROM AUTHOR]

With aging, men develop testosterone-deficiency syndrome (TDS). The development is closely associated with age-related mitochondrial dysfunction of Leydig cell and oxidative stress-induced reactive oxygen species (ROS). Testosterone-replacement therapy (TRT) is used to improve the symptoms of TDS. However, due to its various side effects, research on functional ingredients derived from natural products that do not have side effects is urgently needed. In this study, using the mitochondrial dysfunction TM3 (mouse Leydig) cells, in which testosterone biosynthesis is reduced by H2O2, we evaluated the effects of elderberry extract and monosaccharide-amino acid (fructose–leucine; FL) on mRNA and protein levels related to steroidogenesis-related enzymes steroidogenic acute regulatory protein (StAR), cytochrome P450 11A1(CYP11A1, cytochrome P450 17A1(CYP17A1), cytochrome P450 19A1(CYP19A1, aromatase), 3β-hydroxysteroid dehydrogenase (3β-HSD), and 17β-hydroxysteroid dehydrogenase(17β-HSD). We analyzed elderberry extract and extract-derived FL for changes in ROS scavenging activity and testosterone secretion. Elderberry extract and FL significantly reduced H2O2-induced intracellular ROS levels, improved testosterone secretion, and increased the mRNA and protein expression levels of steroidogenesis-related enzymes (StAR, 3b-HSD, 17b-HSD, CYP11A1, CYp17A1). However, the conversion of testosterone to estradiol was inhibited by elderberry extract and extract-derived FL, which reduced the mRNA and protein expression of CYP19A1. In conclusion, elderberry extract and FL are predicted to have value as novel functional ingredients that may contribute to the prevention of TDS by ameliorating reduced steroidogenesis. [ABSTRACT FROM AUTHOR]

Pancreatic cancer, most frequently as ductal adenocarcinoma (PDAC), is the third leading cause of cancer death. Clear-cell primary adenocarcinoma of the pancreas (CCCP) is a rare, aggressive, still poorly characterized subtype of PDAC. We report here a case of a 65-year-old male presenting with pancreatic neoplasia. A histochemical examination of the tumor showed large cells with clear and abundant intracytoplasmic vacuoles. The clear-cell foamy appearance was not related to the hyperproduction of mucins. Ultrastructural characterization with transmission electron microscopy revealed the massive presence of mitochondria in the clear-cell cytoplasm. The mitochondria showed disordered cristae and various degrees of loss of structural integrity. Immunohistochemistry staining for NADH dehydrogenase [ubiquinone] 1 alpha subcomplex, 4-like 2 (NDUFA4L2) proved specifically negative for the clear-cell tumor. Our ultrastructural and molecular data indicate that the clear-cell nature in CCCP is linked to the accumulation of disrupted mitochondria. We propose that this may impact on the origin and progression of this PDAC subtype. [ABSTRACT FROM AUTHOR]

The mechanisms that underlie the regulation of enzymatic reactions by biomolecular condensates and how they scale with compartment size remain poorly understood. Here we use intrinsically disordered domains as building blocks to generate programmable enzymatic condensates of NADH-oxidase (NOX) with different sizes spanning from nanometers to microns. These disordered domains, derived from three distinct RNA-binding proteins, each possessing different net charge, result in the formation of condensates characterized by a comparable high local concentration of the enzyme yet within distinct environments. We show that only condensates with the highest recruitment of substrate and cofactor exhibit an increase in enzymatic activity. Notably, we observe an enhancement in enzymatic rate across a wide range of condensate sizes, from nanometers to microns, indicating that emergent properties of condensates can arise within assemblies as small as nanometers. Furthermore, we show a larger rate enhancement in smaller condensates. Our findings demonstrate the ability of condensates to modulate enzymatic reactions by creating distinct effective solvent environments compared to the surrounding solution, with implications for the design of protein-based heterogeneous biocatalysts. Here, the authors show that biomolecular condensates can enhance enzymatic rates by creating distinct solvent environments compared to the surrounding solution, and this emergent property can manifest within assemblies as small as nanometers. [ABSTRACT FROM AUTHOR]

Histidine triad nucleotide‐binding protein 2 (HINT2) is an enzyme found in mitochondria that functions as a nucleotide hydrolase and transferase. Prior studies have demonstrated that HINT2 plays a crucial role in ischemic heart disease, but its importance in cardiac remodelling remains unknown. Therefore, the current study intends to determine the role of HINT2 in cardiac remodelling. HINT2 expression levels were found to be lower in failing hearts and hypertrophy cardiomyocytes. The mice that overexpressed HINT2 exhibited reduced myocyte hypertrophy and cardiac dysfunction in response to stress. In contrast, the deficiency of HINT2 in the heart of mice resulted in a worsening hypertrophic phenotype. Further analysis indicated that upregulated genes were predominantly associated with the oxidative phosphorylation and mitochondrial complex I pathways in HINT2‐overexpressed mice after aortic banding (AB) treatment. This suggests that HINT2 increases the expression of NADH dehydrogenase (ubiquinone) flavoprotein (NDUF) genes. In cellular studies, rotenone was used to disrupt mitochondrial complex I, and the protective effect of HINT2 overexpression was nullified. Lastly, we predicted that thyroid hormone receptor beta might regulate HINT2 transcriptional activity. To conclusion, the current study showcased that HINT2 alleviates pressure overload‐induced cardiac remodelling by influencing the activity and assembly of mitochondrial complex I. Thus, targeting HINT2 could be a novel therapeutic strategy for reducing cardiac remodelling. [ABSTRACT FROM AUTHOR]

Cerebrovascular disease accounts for major neurologic disabilities in patients with type 2 diabetes mellitus (DM). A potential association of mitochondrial DNA (mtDNA) and inflammation with cerebral vessel remodeling in patients with type 2 DM was evaluated. A cohort of 150 patients and 30 healthy controls were assessed concerning urinary albumin/creatinine ratio (UACR), synaptopodin, podocalyxin, kidney injury molecule-1 (KIM-1), N-acetyl-β-(D)-glucosaminidase (NAG), interleukins IL-17A, IL-18, IL-10, tumor necrosis factor-alpha (TNFα), intercellular adhesion molecule-1 (ICAM-1). MtDNA-CN and nuclear DNA (nDNA) were quantified in peripheral blood and urine by qRT-PCR. Cytochrome b (CYTB) gene, subunit 2 of NADH dehydrogenase (ND2), and beta 2 microglobulin nuclear gene (B2M) were assessed by TaqMan assays. mtDNA-CN was defined as the ratio of the number of mtDNA/nDNA copies, through analysis of the CYTB/B2M and ND2/B2M ratio; cerebral Doppler ultrasound: intima-media thickness (IMT)—the common carotid arteries (CCAs), the pulsatility index (PI) and resistivity index (RI)- the internal carotid arteries (ICAs) and middle cerebral arteries (MCAs), the breath-holding index (BHI). The results showed direct correlations of CCAs-IMT, PI-ICAs, PI-MCAs, RI-ICAs, RI-MCAs with urinary mtDNA, IL-17A, IL-18, TNFα, ICAM-1, UACR, synaptopodin, podocalyxin, KIM-1, NAG, and indirect correlations with serum mtDNA, IL-10. BHI correlated directly with serum IL-10, and serum mtDNA, and negatively with serum IL-17A, serum ICAM-1, and NAG. In neurologically asymptomatic patients with type 2 DM cerebrovascular remodeling and impaired cerebrovascular reactivity may be associated with mtDNA variations and inflammation from the early stages of diabetic kidney disease. [ABSTRACT FROM AUTHOR]

Background and Aim: In Kazakhstan, the study of Echinococcus infection among farm animals is crucial to monitor the invasion among livestock and map the data obtained. Unfortunately, there are only partial data on the study of Echinococcus among cattle's in Kazakhstan, which makes it difficult to conduct a comparative analysis of the epidemiological situation among livestock animals. The present study aimed to molecularly identify the species and haplotypes of the E. granulosus complex infecting cattle in Kazakhstan and investigate their genetic variation relative to mitochondrial (mt) targets. Materials and Methods: Individual cyst isolates (n = 700) were collected from infected cattle lungs and livers after slaughter from the slaughterhouse. Total DNA was extracted from the germinal layers of the cyst from each isolate. This DNA sequenced partial mt genes of cytochrome c oxidase 1 (450 bp) and NADH dehydrogenase 1 (1200 bp). Results: We determined that all the sequences were detected as E. granulosus s.s., of which 69 (94.5%) samples belonged to G1, and only 4 (5.4%) samples belonged to the G3 genotype. After bioinformatic analysis, 38 haplotypes were identified. Conclusion: Our findings revealed that the G1 genotype of E. granulosus s.s. is the predominant cattle genotype in Kazakhstan. However, only one region showed the presence of two genotypes G1 and G3, in the sequence, which suggests that further research is needed to investigate the epidemiology of Echinococcus infection in cattle in Kazakhstan. [ABSTRACT FROM AUTHOR]

Hydatid cyst disease, caused by Echinococcus granulosus sensu lato (s.l.), is linked to endemic areas in the Levant region, such as Jordan. There is a scarcity of epidemiological data about this disease. Our goal was to pinpoint the particular genotypes accountable for sheep and goat infection in unexplored regions of Southern Jordan. Partial sequences of cytochrome C oxidase (Cox1, 450 bp) and NADH dehydrogenase subunit 2 (Nad2, 820 bp) of the E. granulosus from Jordan were analysed and compared with E. granulosus s.l. reference genomes, to infer the phylogeny of the species. This analysis demonstrated a significant degree of intraspecific similarity and identified the presence of E. granulosus sensu stricto (G1, G3). The G1 genotype was the most prevalent (Cox1, n = 17/17); (Nad2, n = 13/18). The study examined partial Cox1 sequences from different countries (Jordan, Lebanon, Iran, India) and regions (South America) to analyze the genetic architecture and phylogeography of the G1 genotype at regional and global levels. One primary haplotype (Hap_1) was present in the research locations. We hypothesized that a certain branch of G1, known as Hap_1, was prevalent among regions that were not geographically connected. Future research on the biology and distribution of E. granulosus s.s. will be enhanced by this information. [ABSTRACT FROM AUTHOR]

Avilamycins, which possess potent inhibitory activity against Gram-positive bacteria, are a group of oligosaccharide antibiotics produced by Streptomyces viridochromogenes. Among these structurally related oligosaccharide antibiotics, avilamycin A serves as the main bioactive component in veterinary drugs and animal feed additives, which differs from avilamycin C only in the redox state of the two-carbon branched-chain of the terminal octose moiety. However, the mechanisms underlying assembly and modification of the oligosaccharide chain to diversify individual avilamycins remain poorly understood. Here, we report that AviZ1, an aldo-keto reductase in the avilamycin pathway, can catalyze the redox conversion between avilamycins A and C. Remarkably, the ratio of these two components produced by AviZ1 depends on the utilization of specific redox cofactors, namely NADH/NAD+ or NADPH/NADP+. These findings are inspired by gene disruption and complementation experiments and are further supported by in vitro enzymatic activity assays, kinetic analyses, and cofactor affinity studies on AviZ1-catalyzed redox reactions. Additionally, the results from sequence analysis, structure prediction, and site-directed mutagenesis of AviZ1 validate it as an NADH/NAD+-favored aldo-keto reductase that primarily oxidizes avilamycin C to form avilamycin A by utilizing abundant NAD+ in vivo. Building upon the biological function and catalytic activity of AviZ1, overexpressing AviZ1 in S. viridochromogenes is thus effective to improve the yield and proportion of avilamycin A in the fermentation profile of avilamycins. This study represents, to our knowledge, the first characterization of biochemical reactions involved in avilamycin biosynthesis and contributes to the construction of high-performance strains with industrial value. IMPORTANCE Avilamycins are a group of oligosaccharide antibiotics produced by Streptomyces viridochromogenes, which can be used as veterinary drugs and animal feed additives. Avilamycin A is the most bioactive component, differing from avilamycin C only in the redox state of the two-carbon branched-chain of the terminal octose moiety. Currently, the biosynthetic pathway of avilamycins is not clear. Here, we report that AviZ1, an aldo-keto reductase in the avilamycin pathway, can catalyze the redox conversion between avilamycins A and C. More importantly, AviZ1 exhibits a unique NADH/NAD+ preference, allowing it to efficiently catalyze the oxidation of avilamycin C to form avilamycin A using abundant NAD+ in cells. Thus, overexpressing AviZ1 in S. viridochromogenes is effective to improve the yield and proportion of avilamycin A in the fermentation profile of avilamycins. This study serves as an enzymological guide for rational strain design, and the resulting high-performance strains have significant industrial value. [ABSTRACT FROM AUTHOR]

Multifunctional enzyme, type‐1 (MFE1) catalyzes the second and third step of the β‐oxidation cycle, being, respectively, the 2E‐enoyl‐CoA hydratase (ECH) reaction (N‐terminal part, crotonase fold) and the NAD+‐dependent, 3S‐hydroxyacyl‐CoA dehydrogenase (HAD) reaction (C‐terminal part, HAD fold). Structural enzymological properties of rat MFE1 (RnMFE1) as well as of two of its variants, namely the E123A variant (a glutamate of the ECH active site is mutated into alanine) and the BCDE variant (without domain A of the ECH part), were studied, using as substrate 3S‐hydroxybutanoyl‐CoA. Protein crystallographic binding studies show the hydrogen bond interactions of 3S‐hydroxybutanoyl‐CoA as well as of its 3‐keto, oxidized form, acetoacetyl‐CoA, with the catalytic glutamates in the ECH active site. Pre‐steady state binding experiments with NAD+ and NADH show that the kon and koff rate constants of the HAD active site of monomeric RnMFE1 and the homologous human, dimeric 3S‐hydroxyacyl‐CoA dehydrogenase (HsHAD) for NAD+ and NADH are very similar, being the same as those observed for the E123A and BCDE variants. However, steady state and pre‐steady state kinetic data concerning the HAD‐catalyzed dehydrogenation reaction of the substrate 3S‐hydroxybutanoyl‐CoA show that, respectively, the kcat and kchem rate constants for conversion into acetoacetyl‐CoA by RnMFE1 (and its two variants) are about 10 fold lower as when catalyzed by HsHAD. The dynamical properties of dehydrogenases are known to be important for their catalytic efficiency, and it is discussed that the greater complexity of the RnMFE1 fold correlates with the observation that RnMFE1 is a slower dehydrogenase than HsHAD. [ABSTRACT FROM AUTHOR]

The southeastern United States is a hotspot of biodiversity, but aquatic habitats are fragmented by anthropogenic activities such as hydrologic alteration. Small-stream-inhabiting fish can suffer population declines, loss of genetic diversity, and migration impediment from riverine impoundment. The Trispot Darter (Etheostoma trisella) is a small, freshwater fish endemic to the southeastern United States. E. trisella was previously believed to be extinct and has now been listed as threatened under the U.S. Endangered Species Act, due to destruction of its limited habitat and a restricted range. We used mitochondrial DNA (NADH dehydrogenase subunit 2 gene), seven microsatellite loci, and 9732 single nucleotide polymorphisms (SNPs) to evaluate population structure and diversity in E. trisella. Mitochondrial data provided evidence of historical connectivity between populations, with haplotype sharing across populations and weak support for population structure. Microsatellite and SNP data, however, indicate that populations have more recently become isolated. Furthermore, we detect three distinct management units (i.e., genetic groups) which reflect isolated geographic localities (i.e., Little Canoe Creek, Ballplay Creek, and a system including the Conasauga and Coosawattee rivers). We also detected a recent bottleneck event in the Ballplay Creek population as well as a low effective population size. Tests of isolation by distance further suggest that populations are structured by riverine isolation rather than geographic distance. A better understanding about the distribution, abundance, and habitat occupancy of all E. trisella populations will be important for informing future decisions for conservation of the species. [ABSTRACT FROM AUTHOR]

Complex I is a key proton-pumping enzyme in bacterial and mitochondrial respiratory electron transport chains. Using quantum chemistry and electrostatic calculations, we have examined the pKa of the reduced quinone QH-/QH2 in the catalytic cavity of complex I. We find that pKa (QH-/QH2) is very high, above 20. This means that the energy of a single protonation reaction of the doubly reduced quinone (i.e. the reduced semiquinone QH-) is sufficient to drive four protons across the membrane with a potential of 180 mV. Based on these calculations, we propose a possible scheme of redox-linked proton pumping by complex I. The model explains how the energy of the protonation reaction can be divided equally among four pumping units of the pump, and how a single proton can drive translocation of four additional protons in multiple pumping blocks.

Skeletal muscle is a major regulator of glycemic control at rest, and glucose utilization increases drastically during exercise. Sustaining a high glucose utilization via glycolysis requires efficient replenishment of NAD+ in the cytosol. Apoptosis-inducing mitochondrion-associated factor 2 (AIFM2) was previously shown to be a NADH oxidoreductase domain-containing flavoprotein that promotes glycolysis for diet and cold-induced thermogenesis. Here, we find that AIFM2 is selectively and highly induced in glycolytic extensor digitorum longus (EDL) muscle during exercise. Overexpression (OE) of AIFM2 in myotubes is sufficient to elevate the NAD+-to-NADH ratio, increasing the glycolytic rate. Thus, OE of AIFM2 in skeletal muscle greatly increases exercise capacity, with increased glucose utilization. Conversely, muscle-specific Aifm2 depletion via in vivo transfection of hairpins against Aifm2 or tamoxifen-inducible haploinsufficiency of Aifm2 in muscles decreases exercise capacity and glucose utilization in mice. Moreover, muscle-specific introduction of NDE1, Saccharomyces cerevisiae external NADH dehydrogenase (NDE), ameliorates impairment in glucose utilization and exercise intolerance of the muscle-specific Aifm2 haploinsufficient mice. Together, we show a novel role for AIFM2 as a critical metabolic regulator for efficient utilization of glucose in glycolytic EDL muscles.

Simple Summary: In this study, a new species of the genus Pseudocalotes is described from Yingjiang County, Dehong Dai, and Jingpo Autonomous Prefecture, Yunnan Province, China, based on four female specimens. Phylogenetic analyses based on NADH dehydrogenase subunit 2 (ND2) and NADH dehydrogenase subunit 4 (ND4) indicated that the new taxon is different from its congeners. Morphologically, the new species can be diagnosed from the other species by a combination of 18 characters. The recognition of this new species brings the number of described Pseudocalotes species to 22. In this study, a new species of the genus Pseudocalotes is described from Yingjiang County, Dehong Dai and Jingpo Autonomous Prefecture, Yunnan Province, China, based on four female specimens. It can be distinguished from its congeners by the following combination of characters: (1) interoculabials 3 or 4; (2) canthals 5–7; (3) cicrcumorbitals 8–11; (4) 1 scale between rostral and nasal; (5) interparietal 1; (6) superciliaries 4–6; (7) supralabials 6–7, the 1st in contact with the nasal; (8) infralabials 6–8; (9) transverse gular fold and antehumeral fold present; (10) 2–3 enlarged scales between eye and ear; (11) nuchal crest single, consists of 3–5 erected spines; (12) dorsal crest row single, discontinuous and low, located between two keeled, parallel and enlarged scale rows; (13) enlarged postrictals absent; (14) scales around midbody 53–62, dorsal body scales heterogenous in size and shape; (15) midventrals smaller than dorsals; (16) subdigital scales on the 4th finger 20–26, and on the 4th toe 24–29; (17) dorsal background coloration light taupe with four irregular brown patches along the middle of dorsal; (18) inner lips wathet, tongue aurantiacus, throat bluish black. The population from Yingjiang County was nested within a highly supported lineage, formed a sister taxon with P. kakhienensis (SH 97/UFB 100) and according to the p-distance, the new species differed from its congeners by 14.5% to 35.2% for NADH dehydrogenase subunit 2 (ND2) and 15.5% to 25.0% for NADH dehydrogenase subunit 4 (ND4). [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa is a common cause of urinary tract infections by strains that are often multidrug resistant, representing a major challenge to the world's health care system. This microorganism has a highly adaptable metabolism that allows it to colonize many environments, including the urinary tract. In this work, we have characterized the metabolic strategies used by stationary phase P. aeruginosa cells cultivated in urine-like media to understand the adaptations used by this microorganism to survive and produce disease. Our proteomics results show that cells rely on the Entner-Duodoroff pathway, pentose phosphate pathway, the Krebs cycle/glyoxylate shunt and the aerobic oxidative phosphorylation to survive in urine-like media and other conditions. A deep characterization of the oxidative phosphorylation showed that the respiratory rate of stationary phase cells is increased 3-4 times compared to cells in the logarithmic phase of growth, indicating that the aerobic metabolism plays critical roles in the stationary phase of cells grown in urine like media. Moreover, the data show that respiratory complex III, succinate dehydrogenase and the NADH dehydrogenase NQR have important functions and could be used as targets to develop new antibiotics against this bacterium. [ABSTRACT FROM AUTHOR]

Gastrointestinal cancer, one of the most common cancers, continues to be a major cause of mortality and morbidity globally. Accumulating evidence has shown that alterations in mitochondrial energy metabolism are involved in developing various clinical diseases. NADH dehydrogenase 1 alpha subcomplex 4 (NDUFA4), encoded by the NDUFA4 gene located on human chromosome 7p21.3, is a component of mitochondrial respiratory chain complex IV and integral to mitochondrial energy metabolism. Recent researchers have disclosed that NDUFA4 is implicated in the pathogenesis of various diseases, including gastrointestinal cancer. Aberrant expression of NDUFA4 leads to the alteration in mitochondrial energy metabolism, thereby regulating the growth and metastasis of cancer cells, indicating that it might be a new promising target for cancer intervention. This article comprehensively reviews the structure, regulatory mechanism, and biological function of NDUFA4. Of note, the expression and roles of NDUFA4 in gastrointestinal cancer including colorectal cancer, liver cancer, gastric cancer, and so on were discussed. Finally, the existing problems of NDUFA4-based intervention on gastrointestinal cancer are discussed to provide help to strengthen the understanding of the carcinogenesis of gastrointestinal cancer, as well as the development of new strategies for clinical intervention. [ABSTRACT FROM AUTHOR]

Invasive species offer insights into rapid adaptation to novel environments. The iconic cane toad (Rhinella marina) is an excellent model for studying rapid adaptation during invasion. Previous research using the mitochondrial NADH dehydrogenase 3 (ND3) gene in Hawai'ian and Australian invasive populations found a single haplotype, indicating an extreme genetic bottleneck following introduction. Nuclear genetic diversity also exhibited reductions across the genome in these two populations. Here, we investigated the mitochondrial genomics of cane toads across this invasion trajectory. We created the first reference mitochondrial genome for this species using long‐read sequence data. We combined whole‐genome resequencing data of 15 toads with published transcriptomic data of 125 individuals to construct nearly complete mitochondrial genomes from the native (French Guiana) and introduced (Hawai'i and Australia) ranges for population genomic analyses. In agreement with previous investigations of these populations, we identified genetic bottlenecks in both Hawai'ian and Australian introduced populations, alongside evidence of population expansion in the invasive ranges. Although mitochondrial genetic diversity in introduced populations was reduced, our results revealed that it had been underestimated: we identified 45 mitochondrial haplotypes in Hawai'ian and Australian samples, none of which were found in the native range. Additionally, we identified two distinct groups of haplotypes from the native range, separated by a minimum of 110 base pairs (0.6%). These findings enhance our understanding of how invasion has shaped the genetic landscape of this species. [ABSTRACT FROM AUTHOR]

Abnormal mitochondrial function has been implicated in the progression of systemic lupus erythematosus (SLE), the prototypical autoimmune disease, yet the underlying cause remains unclear. In this study, mitochondrial-encoded NADH dehydrogenase 6 gene (MT-ND6) was identified as having increased m6A methylation and decreased expression in peripheral blood mononuclear cells of SLE patients by MeRIP-seq analysis. MT-ND6 expression was negatively correlated with SLE disease activity index score and 24-h urine protein level, and lower in patients with positive anti-Sm or anti-dsDNA antibodies. With the reduction of MT-ND6 levels, CD4+ T cells in SLE patients exhibited mitochondrial dysfunction, as evidenced by increased levels of reactive oxygen species (ROS) and mitochondrial ROS and insufficient ATP production. Accordingly, in vitro MT-ND6 silencing induced abnormalities in the above mitochondrial indicators in CD4+ T cells, and promoted the development of both transcription and inflammatory factors in these cells. In contrast, treatment with targeted mitochondrial antioxidants largely counteracted the silencing effect of MT-MD6. Thus, reduced MT-ND6 in SLE patients may lead to mitochondrial dysfunction through ROS overproduction, thereby promoting inflammatory CD4+ T cells. Representative schematic overview of the effect of the reduction of the MT-ND6 gene on the mitochondria and the cell function of CD4+ T cells. [Display omitted] • The MT-ND6 gene was decreased in SLE patients. • MT-ND6 expression was related to disease activity, renal involvement and antibody production. • MT-ND6 silencing in CD4+ T cells impaired mitochondrial function. • Silencing of MT-ND6 promotes inflammatory CD4+ T cells. • For the functioning of MT-ND6, MtROS was an important intermediary. [ABSTRACT FROM AUTHOR]

Background: Cystic echinococcosis (CE), which is triggered by the parasite Echinococcus granulosus, is a global zoonotic disease that is common in rural regions in which there are frequent encounters between dogs and other domestic animals. The disease can have devastating consequences, impacting the health of people and animals and leading to huge financial losses, especially in the agricultural industry. In the Kingdom of Saudi Arabia (KSA) and Egypt, despite the high incidence of disease, few investigations have been conducted into the genetic variation in species of the genus Echinococcus. Aim: This study sought to compare the genetic features of the hydatid cysts carried in sheep in KSA with those found in Egypt. Methods: DNA from the protoscolices was used in a PCR targeting the mitochondrial NADH dehydrogenase 1 (NAD1), cytochrome c oxidase subunit 1 (COX1), and nuclear actin II (ACT II) genes, and the resulting amplification products of 30 KSA and Egyptian isolates were sequenced and compared. Results: Among the sheep in KSA, the overall prevalence of CE was 0.51%. Of the sheep cyst DNA samples, 95%, 100%, and 52% were positive for the Cox1, nad1, and act II genes, respectively. Targeting all three genes, all KSA samples belonged to the E. granulosus genotype (G1), whereas all Egyptian isolates belonged to E. granulosus (G1) and E. canadensis (G6). Conclusion: We conclude that isolates of E. granulosus from the two countries shared a common origin in Arabic North Africa, with sheep and camels as common hosts. [ABSTRACT FROM AUTHOR]