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Since the development of generalized gradient approximations in the 1990s, approximations based on density functional theory have dominated electronic structure theory calculations. Modern approximations can yield energy differences that are precise enough to be predictive in many instances, as validated by large- and small-scale benchmarking efforts. However, assessing the quality of densities has been the subject of far less attention, in part because reliable error measures are difficult to define. To this end, this work introduces the mean-field error, which directly assesses the quality of densities from approximations. The mean-field error is contextualized within existing frameworks of density functional error analysis and understanding and shown to be part of the density-driven error. It is demonstrated in several illustrative examples. Its potential use in future benchmarking protocols is discussed, and some conclusions are drawn. [ABSTRACT FROM AUTHOR]

There is an ever increasing use of local density dependent potentials in the mesoscale modeling of complex fluids. Questions remain, though, about the dependence of the thermodynamic and structural properties of such systems on the cutoff distance used to calculate these local densities. These questions are particularly acute when it comes to the stability and structure of the vapor/liquid interface. In this article, we consider local density dependent potentials derived from an underlying van der Waals equation of state. We use simulation and density functional theory to examine how the bulk thermodynamic and interfacial properties vary with the cutoff distance, rc, used to calculate the local densities. We show quantitatively how the simulation results for bulk thermodynamic properties and vapor–liquid equilibrium approach the van der Waals limit as rc increases and demonstrate a scaling law for the radial distribution function in the large rc limit. We show that the vapor–liquid interface is stable with a well-defined surface tension and that the interfacial density profile is oscillatory, except for temperatures close to critical. Finally, we show that in the large rc limit, the interfacial tension is proportional to rc and, therefore, unlike the bulk thermodynamic properties, does not approach a constant value as rc increases. We believe that these results give new insights into the properties of local density dependent potentials, in particular their unusual interfacial behavior, which is relevant for modeling complex fluids in soft matter. [ABSTRACT FROM AUTHOR]

The mechanism of gate threshold voltage (VT) shifts observed in high κ/metal gate stacks is investigated by a density functional theory. This finds that VT depends on the band alignments and the chemical trends between the component oxide layers, such as HfO2, SrO, La2O3, Al2O3, and SiO2. Based on the electron counting rule, we have built three insulating SiO2/SrO, SiO2/La2O3, and SiO2/Al2O3 interfaces, all of which feature a clean bandgap. Two methods have been adopted to derive the band alignments between these four oxides, which are consistent with each other. The results show staggered, "staircase" band alignments and enable La2O3 and Al2O3 layers to shift the metal electrode Fermi level in opposite directions and to approach the Si conduction band and valence band edge positions, respectively. This analysis updates previous empirical models of this effect based on metal oxide ion densities or electronegativity scales and confirms that the oxide layer scheme is suitable for controlling the effective metal work functions in metal–oxide–semiconductor field-effect transistors. [ABSTRACT FROM AUTHOR]

Objective To explore the functional improvement effect of acupuncture and moxibustion therapy of traditional Chinese medicine (mainly acupuncture on the three yang meridians of the hand, moxibustion on the governor vessel, and moxibustion through drugs) on cervical spondylosis of wind cold blocking collateral type. Methods 120 patients with wind cold obstruction type cervical spondylosis admitted to our hospital from July 2021 to July 2023 were randomly divided into two groups, with 60 cases in each group, using a random number table method. The control group was treated with conventional cervical traction, while the observation group was treated with traditional Chinese medicine acupuncture and moxibustion on the basis of the control group (mainly acupuncture at the hand Sanyang meridian+moxibustion at the governor's meridian+moxibustion through drugs). Compare the TCM syndrome scores, NDI, HO-1, LpPLA2, clinical efficacy, adverse reactions, hospitalization costs, and duration between two groups. Results After 4 weeks of treatment, the effective rate of disease in the observation group with wind cold obstructing cervical spondylosis (96.67%) was higher than that in the control group (83.33%), while the traditional Chinese medicine syndrome score, NDI score, HO-1, LpPLA2 in the observation group were lower than those in the control group (P < 0.05). No adverse reactions were observed in both groups. Conclusion Traditional Chinese medicine acupuncture and moxibustion therapy (mainly acupuncture of the three yang meridians of the hand, governor vessel moxibustion, and herbal penetration moxibustion) has significant clinical effect in the application of cervical spondylosis of wind cold blocking collateral type, which can effectively improve clinical symptoms and biochemical indicators, promote the rehabilitation of cervical function, and has high safety. [ABSTRACT FROM AUTHOR]

SUMMARY: Photoperiod employs complicated networks to regulate various developmental processes in plants, including flowering transition. However, the specific mechanisms by which photoperiod affects epigenetic modifications and gene expression variations in plants remain elusive. In this study, we conducted a comprehensive analysis of DNA methylation, small RNA (sRNA) accumulation, and gene expressions under different daylengths in facultative long‐day (LD) grass Brachypodium distachyon and short‐day (SD) grass rice. Our results showed that while overall DNA methylation levels were minimally affected by different photoperiods, CHH methylation levels were repressed under their favorable light conditions, particularly in rice. We identified numerous differentially methylated regions (DMRs) that were influenced by photoperiod in both plant species. Apart from differential sRNA clusters, we observed alterations in the expression of key components of the RNA‐directed DNA methylation pathway, DNA methyltransferases, and demethylases, which may contribute to the identified photoperiod‐influenced CHH DMRs. Furthermore, we identified many differentially expressed genes in response to different daylengths, some of which were associated with the DMRs. Notably, we discovered a photoperiod‐responsive gene MYB11 in the transcriptome of B. distachyon, and further demonstrated its role as a flowering inhibitor by repressing FT1 transcription. Together, our comparative and functional analysis sheds light on the effects of daylength on DNA methylation, sRNA accumulation, and gene expression variations in LD and SD plants, thereby facilitating better designing breeding programs aimed at developing high‐yield crops that can adapt to local growing seasons. Significance Statement: Our comprehensive analysis of DNA methylation, small RNA accumulation, and gene expressions combined with functional analysis of long‐day (LD) photoperiod‐induced MYB11 in Brachypodium distachyon offers insights into the impact of daylength on epigenetic modifications, and gene expression variations in LD and short‐day plants. Our research fosters the potential for more calculated scheming of breeding programs that strive to produce high‐yielding crops capable of adapting to their respective local growing seasons. [ABSTRACT FROM AUTHOR]

A typical polyanionic based material Na3V2(PO4)2O2F (Na3VPO2F) attracts much interest as a cathode for large‐scale sodium‐ion batteries in consideration of its stable structure and remarkable energy density. Nevertheless, the large coulombic attraction and repulsion suffered by the mobile Na+ from structural anions and surrounding Na+, respectively, result in a torpid reaction kinetics and inferior rate capability. Herein, Br−‐doped and Na+ vacancy preinstalled Na3−yVPO2−xBrxF is prepared to dilute the charges on and inside the Na+ transportation tunnel. In virtue of density functional theory analysis, Na3−yVPO2−xBrxF reveals a reduction in the bandgap and an increase in electronic conductivity. Meanwhile, the almost electrostatically shielded tunnel in Na3−yVPO2−xBrxF alleviates the coulombic hindrance imposed on Na+ during its (de)intercalation, which demonstrates a Na+ diffusivity about five times higher than that of Na3VPO2F. Consequently, the Na3−yVPO2−xBrxF cathode shows a superior rate capacity of 77.7 mAh g−1 under 50 C and great cycling property corresponding to a high capacity retention of 94.4% over 800 cycles at 10 C. The assembled Na3−yVPO2−xBrxF//hard‐carbon sodium‐ion full‐cell presents excellent specific energy/power (226 Wh kg−1@15424.2 W kg−1) as well as outstanding long‐term cyclic stability over 1000 cycles at 5 C. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a chronic disease that impairs metabolism, and its prevalence has reached an epidemic proportion globally. Most people affected are with type 2 diabetes mellitus (T2DM), which is caused by a decline in the numbers or functioning of pancreatic endocrine islet cells, specifically the β-cells that release insulin in sufficient quantity to overcome any insulin resistance of the metabolic tissues. Genetic and epigenetic factors have been implicated as the main contributors to the T2DM. Epigenetic modifiers, histone deacetylases (HDACs), are enzymes that remove acetyl groups from histones and play an important role in a variety of molecular processes, including pancreatic cell destiny, insulin release, insulin production, insulin signalling, and glucose metabolism. HDACs also govern other regulatory processes related to diabetes, such as oxidative stress, inflammation, apoptosis, and fibrosis, revealed by network and functional analysis. This review explains the current understanding of the function of HDACs in diabetic pathophysiology, the inhibitory role of various HDAC inhibitors (HDACi), and their functional importance as biomarkers and possible therapeutic targets for T2DM. While their role in T2DM is still emerging, a better understanding of the role of HDACi may be relevant in improving insulin sensitivity, protecting β-cells and reducing T2DM-associated complications, among others. [ABSTRACT FROM AUTHOR]

This study utilized Bayesian inference in a genome‐wide association study (GWAS) to identify genetic markers associated with traits relevant to the adaptation of Hereford and Braford cattle breeds. We focused on eye pigmentation (EP), weaning hair coat (WHC), yearling hair coat (YHC), and breeding standard (BS). Our dataset comprised 126,290 animals in the pedigree. Out of these, 233 sires were genotyped using high‐density (HD) chips, and 3750 animals with medium‐density (50 K) single‐nucleotide polymorphism (SNP) chips. Employing the Bayes B method with a prior probability of π = 0.99, we identified and tagged single nucleotide polymorphisms (Tag SNPs), ranging from 18 to 117 SNPs depending on the trait. These Tag SNPs facilitated the construction of reduced SNP panels. We then evaluated the predictive accuracy of these panels in comparison to traditional medium‐density SNP chips. The accuracy of genomic predictions using these reduced panels varied significantly depending on the clustering method, ranging from 0.13 to 0.65. Additionally, we conducted functional enrichment analysis that found genes associated with the most informative SNP markers in the current study, thereby providing biological insights into the genomic basis of these traits. [ABSTRACT FROM AUTHOR]

Summary Shifts in pollinator occurrence and their pollen transport effectiveness drive the evolution of mating systems in flowering plants. Understanding the genomic basis of these changes is essential for predicting the persistence of a species under environmental changes. We investigated the genomic changes in Brassica rapa over nine generations of pollination by hoverflies associated with rapid morphological evolution toward the selfing syndrome. We combined a genotyping‐by‐sequencing (GBS) approach with a genome‐wide association study (GWAS) to identify candidate genes, and assessed their functional role in the observed morphological changes by studying mutations of orthologous genes in the model plant Arabidopsis thaliana. We found 31 candidate genes involved in a wide range of functions from DNA/RNA binding to transport. Our functional assessment of orthologous genes in A. thaliana revealed that two of the identified genes in B. rapa are involved in regulating the size of floral organs. We found a protein kinase superfamily protein involved in petal width, an important trait in plant attractiveness to pollinators. Moreover, we found a histone lysine methyltransferase (HKMT) associated with stamen length. Altogether, our study shows that hoverfly pollination leads to rapid evolution toward the selfing syndrome mediated by polygenic changes. [ABSTRACT FROM AUTHOR]

Heat stress significantly disturbs the production, reproduction, and systems biology of dairy cattle. A complex interaction among biological systems helps to combat and overcome heat stress. Indicine cattle breed Tharparkar has been well known for its thermal adaptability. Therefore, present investigation considered RNA-seq technology to explore the functional transcriptomics of Tharparkar cattle with the help of samples collected in spring and summer season. Among differentially expressed genes, about 3280 genes were highly dysregulated, in which 1207 gene were upregulated and 2073 genes were downregulated (|log2fold change|≥ 1 and p ≤ 0.05). Upregulated genes were related to insulin activation, interferons, and potassium ion transport. In contrast, downregulated genes were related to RNA processing, translation, and ubiquitination. Functional annotation revealed that the pathways associated with nervous system (NPFFR1, ROBO3) and metal ion transport (KCNG2, ATP1A2) were highly activated while mRNA processing and translation (EIF4A, EIF4B) and protein processing pathway (VPS4B, PEX13) were highly downregulated. Protein–protein interactions identified hub genes such as ATP13A3, IFNGR2, UBXN7, EIF4A2, SLC12A8 found to play an important role in immune, ubiquitination, translation and transport function. Co-expression network includes LYZ, PNRC1, SQSTM1, EIF4AB and DDX17 genes which are involved in lysosomal activity, tumor inhibition, ubiquitination, and translation initiation. Chemokine signaling pathway associated with immune response was highly upregulated in cluster analysis. The findings of this study provide insights into transcriptome expression and regulation which may better explain complex thermal resilience mechanism of Tharparkar cattle in heat stress under natural conditions. [ABSTRACT FROM AUTHOR]

Lynch syndrome is caused by inactivating variants in DNA mismatch repair genes, namely MLH1, MSH2, MSH6 and PMS2. We have investigated five MLH1 and one MSH2 variants that we have identified in Turkish and Tunisian colorectal cancer patients. These variants comprised two small deletions causing frameshifts resulting in premature stops which could be classified pathogenic (MLH1 p.(His727Profs*57) and MSH2 p.(Thr788Asnfs*11)), but also two missense variants (MLH1 p.(Asn338Ser) and p.(Gly181Ser)) and two small, in-frame deletion variants (p.(Val647-Leu650del) and p.(Lys678_Cys680del)). For such small coding genetic variants, it is unclear if they are inactivating or not. We here provide clinical description of the variant carriers and their families, and we performed biochemical laboratory testing on the variant proteins to test if their stability or their MMR activity are compromised. Subsequently, we compared the results to in-silico predictions on structure and conservation. We demonstrate that neither missense alteration affected function, while both deletion variants caused a dramatic instability of the MLH1 protein, resulting in MMR deficiency. These results were consistent with the structural analyses that were performed. The study shows that knowledge of protein function may provide molecular explanations of results obtained with functional biochemical testing and can thereby, in conjunction with clinical information, elevate the evidential value and facilitate clinical management in affected families. [ABSTRACT FROM AUTHOR]

Background: The auxin/indole-3-acetic acid (Aux/IAA) gene family is a crucial element of the auxin signaling pathway, significantly influencing plant growth and development. Hence, we conducted a comprehensive investigation of Aux/IAAs gene family using the Sp75 and Monoe-Viroflay genomes in spinach. Results: A total of 24 definitive Aux/IAA genes were identified, exhibiting diverse attributes in terms of amino acid length, molecular weight, and isoelectric points. This diversity underscores potential specific roles within the family, such as growth regulation and stress response. Structural analysis revealed significant variations in gene length and molecular weight. These variations indicate distinct roles within the Aux/IAA gene family. Chromosomal distribution analysis exhibited a dispersed pattern, with chromosomes 4 and 1 hosting the highest and lowest numbers of Aux/IAA genes, respectively. Phylogenetic analysis grouped the identified genes into distinct clades, revealing potential evolutionary relationships. Notably, the phylogenetic tree highlighted specific gene clusters suggesting shared genetic ancestry and potential functional synergies within spinach. Expression analysis under NAA treatment unveiled gene-specific and time-dependent responses, with certain genes exhibiting distinct temporal expression patterns. Specifically, SpoIAA5 displayed a substantial increase at 2 h post-NAA treatment, while SpoIAA7 and SpoIAA9 demonstrated continuous rises, peaking at the 4-hour time point. Conclusions: These observations indicate a complex interplay of gene-specific and temporal regulation in response to auxin. Moreover, the comparison with other plant species emphasized both shared characteristics and unique features in Aux/IAA gene numbers, providing insights into the evolutionary dynamics of this gene family. This comprehensive characterization of Aux/IAA genes in spinach not only establishes the foundation for understanding their specific functions in spinach development but also provides a valuable resource for experimental validation and further exploration of their roles in the intricate network of auxin signaling pathways. [ABSTRACT FROM AUTHOR]

Key message: Lastly, the bZIP gene family encompasses genes that have been reported to play a role in flower development, such as bZIP14 (FD). Notably, bZIP14 is essential for Flowering Locus T (FT) initiation of floral development in Arabidopsis (Abe et al. 2005). Cotton (Gossypium hirsutum L.) is the world's most extensively cultivated fiber crop. However, its reproductive development is poorly characterized at the molecular level. Thus, this study presents a detailed transcriptomic analysis of G. hirsutum at three different reproductive stages. We provide evidence that more than 64,000 genes are active in G. hirsutum during flower development, among which 94.33% have been assigned to functional terms and specific pathways. Gene set enrichment analysis (GSEA) revealed that the biological process categories of floral organ development, pollen exine formation, and stamen development were enriched among the genes expressed during the floral development of G. hirsutum. Furthermore, we identified putative Arabidopsis homologs involved in the G. hirsutum gene regulatory network (GRN) of pollen and flower development, including transcription factors such as WUSCHEL (WUS), INNER NO OUTER (INO), AGAMOUS-LIKE 66 (AGL66), SPOROCYTELESS/NOZZLE (SPL/NZZ), DYSFUNCTIONAL TAPETUM 1 (DYT1), ABORTED MICROSPORES (AMS), and ASH1-RELATED 3 (ASHR3), which are known crucial genes for plant reproductive success. The cotton MADS-box protein–protein interaction pattern resembles the previously described patterns for AGAMOUS (AG), SEEDSTICK (STK), SHATTERPROOF (SHP), and SEPALLATA3 (SEP3) homolog proteins from Arabidopsis. In addition to serving as a resource for comparative flower development studies, this work highlights the changes in gene expression profiles and molecular networks underlying stages that are valuable for cotton breeding improvement. [ABSTRACT FROM AUTHOR]

Glycerol-3-phosphoacyltransferase (GPAT) is an important rate-limiting enzyme in the biosynthesis of triacylglycerol (TAG), which is of great significance for plant growth, development, and response to abiotic stress. Although the characteristics of GPAT have been studied in many model plants, little is known about its expression profile and function in barley, especially under abiotic stress. In this study, 22 GPAT genes were identified in the barley genome and divided into three groups (I, II, III), with the latter Group III subdivided further into three subgroups based on the phylogenetic analysis. The analyses of conserved motifs, gene structures, and the three-dimensional structure of HvGPAT proteins also support this classification. Through evolutionary analysis, we determined that HvGPATs in Group I were the earliest to diverge during 268.65 MYA, and the differentiation of other HvGPATs emerged during 86.83–169.84 MYA. The tissue expression profile showed that 22 HvGPAT genes were almost not expressed in INF1 (inflorescence 1). Many functional elements related to stress responses and hormones in cis-element analysis, as well as qRT-PCR results, confirm that these HvGPAT genes were involved in abiotic stress responses. The expression level of HvGPAT18 was significantly increased under abiotic stress and its subcellular localization indicated its function in the endoplasmic reticulum. Various physiological traits under abiotic stress were evaluated using transgenic Arabidopsis to gain further insight into the role of HvGPAT18, and it was found that transgenic seedlings have stronger resistance under abiotic stress than to the wild-type (WT) plants. Overall, our results provide new insights into the evolution and function of the barley GPAT gene family and enable us to explore the molecular mechanism of functional diversity behind the evolutionary history of these genes. [ABSTRACT FROM AUTHOR]

Simple Summary: Oligoadenylate synthetase (OAS) is a conserved antiviral protein found in several animal species. Among birds, only the ostrich has two genes, OAS1 and OASL, which show oligoadenylate synthetic activity and inhibition of flavivirus-specific genome replication, respectively. However, it remains unclear whether OAS duplication with the separated function is unique to the ostrich. Therefore, we examined the OASs of the emu, which are closely related to the ostrich. We sequenced and cloned emu OAS genes and analyzed their functions. The results showed that the two emu OAS genes had amino acid sequence homologies of 80% for OAS1 and 78% for OASL compared to those of ostriches. The amino acid sequences related to the enzymatic function were almost identical to those of ostriches. Emu OAS1 only showed OAS activity, whereas emu OASL only inhibited flaviviral replication. These results indicate that emus have characteristics similar to ostrich in terms of OAS genes. This study provides insights into the evolution of viral defense by OAS protein family in Palaeognathae. 2′-5′-oligoadenylate synthetase (OAS) is one of the proteins that act as a defense mechanism against foreign RNA in cells. OAS has two functions: an antiviral effect against a wide range of virus species via the OAS/RNase L pathway with synthesized oligoadenylates and inhibition of viral replication specific to viruses of the genus Flavivirus, which is independent of enzymatic activity. Several birds have been reported to possess only one type of OAS family member, OASL, which has both enzymatic activity and inhibitory effects on flaviviral replication. However, the ostrich has two types of OASs, OAS1 and OASL, which show different functions—enzymatic and anti-flaviviral activities, respectively. In this study, emu OASs were cloned to investigate their sequence and function and elucidate the role of OASs in emus. The cloning results showed that emus had OAS1 and OASL, suggesting that emu OASs were more closely related to ostrich than to other birds. Functional investigations showed that emu OAS1 and OASL had enzymatic and anti-flaviviral activities, respectively, similar to those of the ostrich. Emus and ostriches are evolutionarily different from most birds and may be more closely related to mammalian OAS diversity. [ABSTRACT FROM AUTHOR]

Through the shikimate pathway, a massive metabolic flux connects the central carbon metabolism with the synthesis of chorismate, the common precursor of the aromatic amino acids phenylalanine, tyrosine, and tryptophan, as well as other compounds, including salicylate or folate. The alternative metabolic channeling of chorismate involves a key branch-point, finely regulated by aromatic amino acid levels. Chorismate mutase catalyzes the conversion of chorismate to prephenate, a precursor of phenylalanine and tyrosine and thus a vast repertoire of fundamental derived compounds, such as flavonoids or lignin. The regulation of this enzyme has been addressed in several plant species, but no study has included conifers or other gymnosperms, despite the importance of the phenolic metabolism for these plants in processes such as lignification and wood formation. Here, we show that maritime pine (Pinus pinaster Aiton) has two genes that encode for chorismate mutase, PpCM1 and PpCM2. Our investigations reveal that these genes encode plastidial isoenzymes displaying activities enhanced by tryptophan and repressed by phenylalanine and tyrosine. Using phylogenetic studies, we have provided new insights into the possible evolutionary origin of the cytosolic chorismate mutases in angiosperms involved in the synthesis of phenylalanine outside the plastid. Studies based on different platforms of gene expression and co-expression analysis have allowed us to propose that PpCM2 plays a central role in the phenylalanine synthesis pathway associated with lignification. [ABSTRACT FROM AUTHOR]

Aim: The current study aimed at examining the ability of the Weiss Functional Impairment Rating Scale‐Parent Report (WFIRS‐P) to discriminate between children with ADHD and controls in functional impairment and identifying optimal cutoff scores for the WFIRS‐P subscales and total scale. Methods: Parents of 51 children with ADHD (90.2% male; grades 1–6) and 51 gender/grade matched controls (90.2% male; grades 1–6) completed the WFIRS‐P. Receiver operating characteristic (ROC) curve analysis was used to examine the ability of the WFIRS‐P to differentiate children with ADHD from controls and to determine optimal cutoff scores of the WFIRS‐P. Results: Area under the curve (AUC) was 0.98 for the WFIRS‐P total scale, indicating excellent ability to differentiate children with ADHD from controls. The score of 0.45 with 0.88 for sensitivity and 0.96 for specificity was determined as the optimal cutoff score for the total scale of the WFIRS‐P. AUC was 0.73 to 0.97 for the WFIRS‐P subscales, suggesting good to excellent ability for discriminating between children with ADHD and controls. Among the subscales, the family subscale score of 0.42 with 0.92 for sensitivity and 0.96 for specificity showed the highest discriminating power. The self‐concept and life skills subscales had low sensitivity, suggesting Iranian mothers do not identify problems with self‐concept or difficulty with life skills as particularly problematic in ADHD. Conclusions: The WFIRS‐P is a sensitive and specific measure of the functional impairment associated with ADHD in Iranian children. Our sample was predominantly male, limiting the generalizability of results to females. [ABSTRACT FROM AUTHOR]

Objective: To characterize the scalp microbial composition, function, and connection to dandruff severity using a metagenomics approach and to understand the impact of a Piroctone Olamine containing anti‐dandruff shampoo on the scalp microbiome. Methods: Shotgun metagenomics was used to characterize the composition of the scalp microbiomes from 94 subjects with and without clinically defined dandruff. Furthermore, the microbiome of the scalps of 100 dandruff sufferers before and after 3 weeks of treatment with either control or anti‐dandruff shampoo containing 0.5% Piroctone Olamine (PO) was characterized and compared to identify microorganisms associated with the dandruff condition and the associated pathways and processes that may contribute to PO's effect on scalp microbiome. Results: A higher relative abundance of Malassezia restricta and Staphylococcus capitis and a lower abundance of Cutibacterium acnes were associated with the dandruff scalps relative to the no‐dandruff scalps. A 3‐week PO shampoo treatment reduced the relative abundance of Malassezia species and Staphylococcus capitis and increased the relative abundance of Cutibacterium acnes. This change to the scalp microbiome composition is consistent with a return to a healthy no‐dandruff microbiome and improved clinical signs and symptoms as measured by adherent scalp flaking score (ASFS) compared with the control shampoo. Functional genomics analysis showed that the PO shampoo treatment reduced oxidative stress‐associated genes and decreased the abundance of protease, urease, and lipase genes. These changes correlated positively to improvements in dandruff severity. PO treatment favourably shifted scalp microbiomes in dandruff subjects toward the no‐dandruff state. Conclusion: Our results suggest that part of the aetiology of dandruff can be attributed to dysbiosis of the scalp microbiome. PO treatment can restore a healthier microbiome, reducing oxidative stress and promoting better scalp health. [ABSTRACT FROM AUTHOR]

The male sterile line of soybean is crucial for hybrid seed production, and has allowed significant advancements in soybean germplasm innovation and yield increase in China. In this study, we created two bulks of sterile plants and collected a natural population consisting of 100 elite soybean germplasms. There were significant phenotypic differences between the sterile and natural populations resulting from flowers and pods. The sterile plants exhibited fleshy spherical pods and large black‐green leaves in the maturity stage, while the leaves of the fertile plants fell off. After I2‐KI staining, the pollen of the sterile line turned light brown and yellow, while the pollen of the fertile line turned black. On the basis of the SNP sequencing results, the sterility genes were located on eight chromosomes. Additionally, they were fine‐mapped to 13 regions on six chromosomes using 72 pairs of SSR markers. Five genes involved in auxin response and pollen development were predicted as candidate genes underlying soybean sterility. These candidate genes for soybean sterility will help with gene cloning and functional analysis and accelerate the widespread use of hybrid seed production and yield increase in soybean grown in cool regions. [ABSTRACT FROM AUTHOR]

Many different strains of Streptococcus thermophilus are commonly used as starter cultures, and search for new safe strains with desired industrial and probiotic properties is an important issue. In this article, genomes of two new S. thermophilus strains—Str16t and Str159—were sequenced, and the main genome characteristics were determined. In silico analysis of the sequenced genomes revealed the absence of transmissible antibiotic resistance genes, virulence genes associated with pathogenicity, and integrated plasmids; gene clusters encoding class I and class II bacteriocins were found. In vitro tests showed phosphatase, peptidase, β-galactosidase, and esterase activity of both strains. Both strains were capable of fermenting glucose, lactose, sucrose, and ribose; in addition, Str16t fermented mannose. In conclusion, it was demonstrated that both Str16t and Str159 are promising strains for application as starter and probiotic cultures. [ABSTRACT FROM AUTHOR]

Summary: Branch angle (BA) is a critical morphological trait that significantly influences planting density, light interception and ultimately yield in plants. Despite its importance, the regulatory mechanism governing BA in rapeseed remains poorly understood. In this study, we generated 109 transcriptome data sets for 37 rapeseed accessions with divergent BA phenotypes. Relative to adaxial branch segments, abaxial segments accumulated higher levels of auxin and exhibited lower expression of six TCP1 homologues and one GA20ox3. A co‐expression network analysis identified two modules highly correlated with BA. The modules contained homologues to known BA control genes, such as FUL, YUCCA6, TCP1 and SGR3. Notably, a homoeologous exchange (HE), occurring at the telomeres of A09, was prevalent in large BA accessions, while an A02‐C02 HE was common in small BA accessions. In their corresponding regions, these HEs explained the formation of hub gene hotspots in the two modules. QTL‐seq analysis confirmed that the presence of a large A07‐C06 HE (~8.1 Mb) was also associated with a small BA phenotype, and BnaA07.WRKY40.b within it was predicted as candidate gene. Overexpressing BnaA07.WRKY40.b in rapeseed increased BA by up to 20°, while RNAi‐ and CRISPR‐mediated mutants (BnaA07.WRKY40.b and BnaC06.WRKY40.b) exhibited decreased BA by up to 11.4°. BnaA07.WRKY40.b was exclusively localized to the nucleus and exhibited strong expression correlations with many genes related to gravitropism and plant architecture. Taken together, our study highlights the influence of HEs on rapeseed plant architecture and confirms the role of WRKY40 homologues as novel regulators of BA. [ABSTRACT FROM AUTHOR]

Inspired by recent developments in the theory of Banach and operator algebras of locally compact groups, we construct several new classes of bifunctors (A,B)\mapsto A\otimes _{\alpha } B, where A\otimes _\alpha B is a cross norm completion of A\odot B for each pair of C*-algebras A and B. For the first class of bifunctors considered (A,B)\mapsto A{\otimes _p} B (1\leq p\leq \infty), A{\otimes _p} B is a Banach algebra cross-norm completion of A\odot B constructed in a fashion similar to p-pseudofunctions \text {PF}^*_p(G) of a locally compact group. Taking a cue from the recently introduced symmetrized p-pseudofunctions due to Liao and Yu and later by the second and the third named authors, we also consider {\otimes _{p,q}} for Hölder conjugate p,q\in [1,\infty ] – a Banach *-algebra analogue of the tensor product {\otimes _{p,q}}. By taking enveloping C*-algebras of A{\otimes _{p,q}} B, we arrive at a third bifunctor (A,B)\mapsto A{\otimes _{\mathrm C^*_{p,q}}} B where the resulting algebra A{\otimes _{\mathrm C^*_{p,q}}} B is a C*-algebra. For G_1 and G_2 belonging to a large class of discrete groups, we show that the tensor products \mathrm C^*_{\mathrm r}(G_1){\otimes _{\mathrm C^*_{p,q}}}\mathrm C^*_{\mathrm r}(G_2) coincide with a Brown-Guentner type C*-completion of \mathrm \ell ^1(G_1\times G_2) and conclude that if 2\leq p'

This study intends to introduce kernel mean embedding of probability measures over infinite‐dimensional separable Hilbert spaces induced by functional response statistical models. The embedded function represents the concentration of probability measures in small open neighborhoods, which identifies a pseudo‐likelihood and fosters a rich framework for statistical inference. Utilizing Maximum Mean Discrepancy, we devise new tests in functional response models. The performance of new derived tests is evaluated against competitors in three major problems in functional data analysis including Function‐on‐Scalar regression, functional one‐way ANOVA, and equality of covariance operators. [ABSTRACT FROM AUTHOR]

Reward motivation in individuals with high levels of negative schizotypal traits (NS) has been found to be lower than that in their counterparts. But it is unclear that whether their reward motivation adaptively changes with external effort-reward ratio, and what resting-state functional connectivity (rsFC) is associated with this change. Thirty-five individuals with high levels of NS and 44 individuals with low levels of NS were recruited. A 3T resting-state functional brain scan and a novel reward motivation adaptation behavioural task were administrated in all participants. The behavioural task was manipulated with three conditions (effort > reward condition vs. effort < reward condition vs. effort = reward condition). Under each condition were rated 'wanting' and 'liking' for rewards. The seed-based voxel-wise rsFC analysis was conducted to explore the rsFCs associated with the 'wanting' and 'liking' ratings in individuals with high levels of NS. 'Wanting' and 'liking' ratings of individuals with high levels of NS significantly declined in the effort > reward condition but did not rebound as high as their counterparts in the effort < reward condition. The rsFCs in NS group associated with these ratings were altered. The altered rsFCs in NS group involved regions in the prefrontal lobe, dopaminergic brain regions (ventral tegmental area, substantia nigra), hippocampus, thalamus and cerebellum. Individuals with high levels of NS manifested their reward motivation adaptation impairment as a failure of adjustment adaptively during effort-reward imbalance condition and altered rsFCs in prefrontal, dopaminergic and other brain regions. [ABSTRACT FROM AUTHOR]

This article is concerned with the practical stability performance of nonlinear impulsive stochastic functional differential systems driven by G-Brownian motion (G-ISFDSs). Comparing with traditional Lyapunov stability theory, practical stability can portray qualitative behaviour and quantitative properties of suggested systems. By employing G-Itô formula, Lyapunov–Razumikhin approach and stochastic analysis theory, some novel conditions for pth moment practical exponential stability and quasi-sure global practical uniform exponential stability of G-ISFDSs are established. The obtained results show that impulses may influence dynamic behaviour of the addressed system. Two numerical examples are given to verify the validity of our developed results. [ABSTRACT FROM AUTHOR]

Clock genes are essential for the daily functions of vertebrates and invertebrates and participate in a wide variety of biological functions including biochemical, physiological, and behavioral processes. Circadian clock disorders are detrimental to both humans and fish, and therefore research on the regulation of genes involved in the circadian clock has attracted increasing attention. Period 2 (per2) is an important gene whose expression is closely related to melatonin secretion, in addition to being affected by the photoperiod length. To gain more insights into the potential biological function of per2, we have cloned and expressed per2 in Amur minnow (Phoxinus lagowskii). We also analyzed melatonin content and AANAT2 gene expression under different short or long-term photoperiod conditions. In the present study, the secretion of melatonin in P. lagowskii was highest in the dark phase under short-term experiments. In the pituitary, the expression of the per2 gene was highest during the dark phase in both the 16L: 8D and 8L: 16D groups. The expression of the per2 gene in the brain was also highest during the dark phase in the 12L: 12D group. Though the expression of the per2 gene was not the highest in the dark phase for the other groups, there were no significant differences compared to the highest value. In addition, in the brain and pituitary, AANAT2 expression was highest during the light phase, except in the 8L: 16D group. Our findings suggested that Amper2 may participate in the feedback regulation of melatonin by regulating the expression of AANAT2. Fluorescence in situ hybridization analyses confirmed that per2 mRNA was expressed during the dark phase, especially in 16L: 8D group. Immunohistochemistry analyses confirmed that PER2 protein was expressed higher in 8L: 16D group. The dual luciferase experiment first validated the promotion of Wnt/β-Catenin expression by the per2 gene. Our results provide novel insights into the expression and location of per2, which contributes to a better understanding of the role of clock genes in the circadian rhythm and seasonal responses of high-latitude fish and might provide useful information of practical interest for high-latitude aquaculture. [ABSTRACT FROM AUTHOR]

A global analysis of the functional characteristics of meta-assemblages of estuary-associated fishes was undertaken at the marine ecoregion level. Marine ecoregions were grouped into broad biogeographic regions (bioregions) and functional attributes of the fish assemblages compared based on a numerical fish estuary association score, as well as estuarine use functional groups. Relationships between selected environmental characteristics and fish functional attributes were also examined. A significant relationship between ecoregion environmental variables and estuarine fish functional assemblages was recorded, with the key environmental factors identified being related to habitat (estuarine area and macrophyte vegetation), connectivity (mean annual runoff), and physico-chemical (sea surface temperature and sea surface salinity) variables. [ABSTRACT FROM AUTHOR]

We examined the initial stages of orthographic learning in real time as literate adults learned spellings for spoken pseudowords during fMRI scanning. Participants were required to learn and store orthographic word forms because the pseudoword spellings were not uniquely predictable from sound to letter mappings. With eight learning trials per word form, we observed changes in the brain's response as learning was taking place. Accuracy was evaluated during learning, immediately after scanning, and 1 week later. We found evidence of two distinct learning systems—hippocampal and neocortical—operating during orthographic learning, consistent with the predictions of dual systems theories of learning/memory such as the complementary learning systems framework [McClelland, J. L., McNaughton, B. L., & O'Reilly, R. C. Why there are complementary learning systems in the hippocampus and neocortex: Insights from the successes and failures of connectionist models of learning and memory. Psychological Review, 102, 419–457, 1995]. The bilateral hippocampus and the visual word form area (VWFA) showed significant BOLD response changes over learning, with the former exhibiting a rising pattern and the latter exhibiting a falling pattern. Moreover, greater BOLD signal increase in the hippocampus was associated with better postscan recall. In addition, we identified two distinct bilateral brain networks that mirrored the rising and falling patterns of the hippocampus and VWFA. Functional connectivity analysis revealed that regions within each network were internally synchronized. These novel findings highlight, for the first time, the relevance of multiple learning systems in orthographic learning and provide a paradigm that can be used to address critical gaps in our understanding of the neural bases of orthographic learning in general and orthographic word-form learning specifically. [ABSTRACT FROM AUTHOR]

Parkinson's disease is a progressive neurodegenerative disorder with multifactorial causes, among which genetic risk factors play a part. The RAB GTPases are regulators and substrates of LRRK2, and variants in the LRRK2 gene are important risk factors for Parkinson's disease. We aimed to explore genetic variability in RAB GTPases within cases of familial Parkinson's disease. We did whole-exome sequencing in probands from families in Canada and Tunisia with Parkinson's disease without a genetic cause, who were recruited from the Centre for Applied Neurogenetics (Vancouver, BC, Canada), an international consortium that includes people with Parkinson's disease from 36 sites in 24 countries. 61 RAB GTPases were genetically screened, and candidate variants were genotyped in relatives of the probands to assess disease segregation by linkage analysis. Genotyping was also done to assess variant frequencies in individuals with idiopathic Parkinson's disease and controls, matched for age and sex, who were also from the Centre for Applied Neurogenetics but unrelated to the probands or each other. All participants were aged 18 years or older. The sequencing and genotyping findings were validated by case–control association analyses using bioinformatic data obtained from publicly available clinicogenomic databases (AMP-PD, GP2, and 100 000 Genomes Project) and a private German clinical diagnostic database (University of Tübingen). Clinical and pathological findings were summarised and haplotypes were determined. In-vitro studies were done to investigate protein interactions and enzyme activities. Between June 1, 2010, and May 31, 2017, 130 probands from Canada and Tunisia (47 [36%] female and 83 [64%] male; mean age 72·7 years [SD 11·7; range 38–96]; 109 White European ancestry, 18 north African, two east Asian, and one Hispanic] underwent whole-exome sequencing. 15 variants in RAB GTPase genes were identified, of which the RAB32 variant c.213C>G (Ser71Arg) cosegregated with autosomal dominant Parkinson's disease in three families (nine affected individuals; non-parametric linkage Z score=1·95; p=0·03). 2604 unrelated individuals with Parkinson's disease and 344 matched controls were additionally genotyped, and five more people originating from five countries (Canada, Italy, Poland, Turkey, and Tunisia) were identified with the RAB32 variant. From the database searches, in which 6043 individuals with Parkinson's disease and 62 549 controls were included, another eight individuals were identified with the RAB32 variant from four countries (Canada, Germany, UK, and USA). Overall, the association of RAB32 c.213C>G (Ser71Arg) with Parkinson's disease was significant (odds ratio [OR] 13·17, 95% CI 2·15–87·23; p=0·0055; I 2=99·96%). In the people who had the variant, Parkinson's disease presented at age 54·6 years (SD 12·75, range 31–81, n=16), and two-thirds had a family history of parkinsonism. RAB32 Ser71Arg heterozygotes shared a common haplotype, although penetrance was incomplete. Findings in one individual at autopsy showed sparse neurofibrillary tangle pathology in the midbrain and thalamus, without Lewy body pathology. In functional studies, RAB32 Arg71 activated LRRK2 kinase to a level greater than RAB32 Ser71. RAB32 Ser71Arg is a novel genetic risk factor for Parkinson's disease, with reduced penetrance. The variant was found in individuals with Parkinson's disease from multiple ethnic groups, with the same haplotype. In-vitro assays show that RAB32 Arg71 activates LRRK2 kinase, which indicates that genetically distinct causes of familial parkinsonism share the same mechanism. The discovery of RAB32 Ser71Arg also suggests several genetically inherited causes of Parkinson's disease originated to control intracellular immunity. This shared aetiology should be considered in future translational research, while the global epidemiology of RAB32 Ser71Arg needs to be assessed to inform genetic counselling. National Institutes of Health, the Canada Excellence Research Chairs program, Aligning Science Across Parkinson's, the Michael J Fox Foundation for Parkinson's Research, and the UK Medical Research Council. [ABSTRACT FROM AUTHOR]

This paper develops a new nonparametric estimator of the scalar-on function modal regression that is used to analyse the co-variability between a functional regressor and a scalar output variable. The new estimator inherits the smoothness of the kernel method and the robustness of the quantile regression. We assume that the functional observations are structured as a strong mixing functional time series data and we establish the almost complete consistency (with rate) of the constructed estimator. A discussion highlighting the impact of this new estimator in nonparametric functional data analysis is also given. The usefulness of this new estimator is shown using an artificial data example. [ABSTRACT FROM AUTHOR]

Crispr/CAS9‐enabled homologous recombination to insert a tag in frame with an endogenous gene can circumvent difficulties such as context‐dependent promoter activity that complicate analysis of gene expression and protein accumulation patterns. However, there have been few reports examining whether such gene targeting/gene tagging (GT) can alter expression of the target gene. The enzyme encoded by Δ1‐pyrroline‐5‐carboxylate synthetase 1 (P5CS1) is key for stress‐induced proline synthesis and drought resistance, yet its expression pattern and protein localisation have been difficult to assay. We used GT to insert YFP in frame with the 5′ or 3′ ends of the endogenous P5CS1 and At14a‐Like 1 (AFL1) coding regions. Insertion at the 3′ end of either gene generated homozygous lines with expression of the gene‐YFP fusion indistinguishable from the wild type allele. However, for P5CS1 this occurred only after selfing and advancement to the T5 generation allowed initial homozygous lethality of the insertion to be overcome. Once this was done, the GT‐generated P5CS1‐YFP plants revealed new information about P5CS1 localisation and tissue‐specific expression. In contrast, insertion of YFP at the 5′ end of either gene blocked expression. The results demonstrate that GT can be useful for functional analyses of genes that are problematic to properly express by other means but also show that, in some cases, GT can disrupt expression of the target gene. Summary statement: Gene tagging (GT) of Arabidopsis thaliana P5CS1 and AFL1 shows the potential of GT for functional analysis of stress‐related genes, but also provides examples of how GT can dramatically disrupt expression of the target gene. [ABSTRACT FROM AUTHOR]

This study investigates the impact of casein hydrolysates on the poultry ceca inoculated with Campylobacter focusing on microbial molecular preferences for different protein sources in the presence of Campylobacter jejuni. Three casein sources (intact casein (IN), casein enzyme hydrolysate (EH), and casein acid hydrolysate (AH)) were introduced to cecal contents in combination with inoculated C. jejuni in an in vitro model system incubated for 48 h at 42°C under microaerophilic conditions. Samples were collected at 0, 24, and 48 h. Genomic DNA was extracted and amplified using custom dual-indexed primers, followed by sequencing on an Illumina MiSeq platform. The obtained sequencing data were then analyzed via QIIME2-2021.11. Metabolite extracts were analyzed with ultra-high-performance liquid orbitrap chromatography-mass spectrometry (UHPLC-MS). Statistical analysis of metabolites was conducted using MetaboAnalyst 5.0, while functional analysis was performed using Mummichog 2.0 with a significance threshold set at P < 0.00001. DNA sequencing and metabolomic analyses revealed that C. jejuni was most abundant in the EH group. Microbial diversity and richness improved in casein supplemented groups, with core microbial differences observed, compared to non-supplemented groups. Vitamin B-associated metabolites significantly increased in the supplemented groups, displaying distinct patterns in vitamin B6 and B9 metabolism between EH and AH groups (P < 0.05). Faecalibacterium and Phascolarctobacterium were associated with AH and EH groups, respectively. These findings suggest microbial interactions in the presence of C. jejuni and casein supplementation are influenced by microbial community preferences for casein hydrolysates impacting B vitamin production and shaping competitive dynamics within the cecal microbial community. These findings underscore the potential of nutritional interventions to modulate the poultry GIT microbiota for improved health outcomes. [ABSTRACT FROM AUTHOR]

Background: Information on the microbiome's human pathways and active members that can affect SARS-CoV-2 susceptibility and pathogenesis in the salivary proteome is very scarce. Here, we studied a unique collection of samples harvested from April to June 2020 from unvaccinated patients. Methods: We compared 10 infected and hospitalized patients with severe (n = 5) and moderate (n = 5) coronavirus disease (COVID-19) with 10 uninfected individuals, including non-COVID-19 but susceptible individuals (n = 5) and non-COVID-19 and nonsusceptible healthcare workers with repeated high-risk exposures (n = 5). Results: By performing high-throughput proteomic profiling in saliva samples, we detected 226 unique differentially expressed (DE) human proteins between groups (q-value ≤ 0.05) out of 3376 unambiguously identified proteins (false discovery rate ≤ 1%). Major differences were observed between the non-COVID-19 and nonsusceptible groups. Bioinformatics analysis of DE proteins revealed human proteomic signatures related to inflammatory responses, central cellular processes, and antiviral activity associated with the saliva of SARS-CoV-2-infected patients (p-value ≤ 0.0004). Discriminatory biomarker signatures from human saliva include cystatins, protective molecules present in the oral cavity, calprotectins, involved in cell cycle progression, and histones, related to nucleosome functions. The expression levels of two human proteins related to protein transport in the cytoplasm, DYNC1 (p-value, 0.0021) and MAPRE1 (p-value, 0.047), correlated with angiotensin-converting enzyme 2 (ACE2) plasma activity. Finally, the proteomes of microorganisms present in the saliva samples showed 4 main microbial functional features related to ribosome functioning that were overrepresented in the infected group. Conclusion: Our study explores potential candidates involved in pathways implicated in SARS-CoV-2 susceptibility, although further studies in larger cohorts will be necessary. [ABSTRACT FROM AUTHOR]

Background: Mangrove sediment microbes are increasingly attracting scientific attention due to their demonstrated capacity for diverse bioremediation activities, encompassing a wide range of environmental contaminants. Materials and methods: The microbial communities of five Avicennia marina mangrove sediment samples collected from Al Rayyis White Head, Red Sea (KSA), were characterized using Illumina amplicon sequencing of the 16S rRNA genes. Results: Our study investigated the microbial composition and potential for organohalide bioremediation in five mangrove sediments from the Red Sea. While Proteobacteria dominated four microbiomes, Bacteroidetes dominated the fifth. Given the environmental concerns surrounding organohalides, their bioremediation is crucial. Encouragingly, we identified phylogenetically diverse organohalide-respiring bacteria (OHRB) across all samples, including Dehalogenimonas, Dehalococcoides, Anaeromyxobacter, Desulfuromonas, Geobacter, Desulfomonile, Desulfovibrio, Shewanella and Desulfitobacterium. These bacteria are known for their ability to dechlorinate organohalides through reductive dehalogenation. PICRUSt analysis further supported this potential, predicting the presence of functional biomarkers for organohalide respiration (OHR), including reductive dehalogenases targeting tetrachloroethene (PCE) and 3-chloro-4-hydroxyphenylacetate in most sediments. Enrichment cultures studies confirmed this prediction, demonstrating PCE dechlorination by the resident microbial community. PICRUSt also revealed a dominance of anaerobic metabolic processes, suggesting the microbiome's adaptation to the oxygen-limited environment of the sediments. Conclusion: This study provided insights into the bacterial community composition of five mangrove sediments from the Red Sea. Notably, diverse OHRB were detected across all samples, which possess the metabolic potential for organohalide bioremediation through reductive dehalogenation pathways. Furthermore, PICRUSt analysis predicted the presence of functional biomarkers for OHR in most sediments, suggesting potential intrinsic OHR activity by the enclosed microbial community. [ABSTRACT FROM AUTHOR]

Background: The homodomain-leucine zipper (HD-Zip) is a conserved transcription factor family unique to plants that regulate multiple developmental processes including lignificaion. Stone cell content is a key determinant negatively affecting pear fruit quality, which causes a grainy texture of fruit flesh, because of the lignified cell walls. Results: In this study, a comprehensive bioinformatics analysis of HD-Zip genes in Chinese white pear (Pyrus bretschneideri) (PbHBs) was performed. Genome-wide identification of the PbHB gene family revealed 67 genes encoding PbHB proteins, which could be divided into four subgroups (I, II, III, and IV). For some members, similar intron/exon structural patterns support close evolutionary relationships within the same subgroup. The functions of each subgroup of the PbHB family were predicted through comparative analysis with the HB genes in Arabidopsis and other plants. Cis-element analysis indicated that PbHB genes might be involved in plant hormone signalling and external environmental responses, such as light, stress, and temperature. Furthermore, RNA-sequencing data and quantitative real-time PCR (RT-qPCR) verification revealed the regulatory roles of PbHB genes in pear stone cell formation. Further, co-expression network analysis revealed that the eight PbHB genes could be classified into different clusters of co-expression with lignin-related genes. Besides, the biological function of PbHB24 in promoting stone cell formation has been demonstrated by overexpression in fruitlets. Conclusions: This study provided the comprehensive analysis of PbHBs and highlighted the importance of PbHB24 during stone cell development in pear fruits. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons (PAHs) are highly toxic, carcinogenic substances. On soils contaminated with PAHs, crop cultivation, animal husbandry and even the survival of microflora in the soil are greatly perturbed, depending on the degree of contamination. Most microorganisms cannot tolerate PAH-contaminated soils, however, some microbial strains can adapt to these harsh conditions and survive on contaminated soils. Analysis of the metagenomes of contaminated environmental samples may lead to discovery of PAH-degrading enzymes suitable for green biotechnology methodologies ranging from biocatalysis to pollution control. In the present study, our goal was to apply a metagenomic data search to identify efficient novel enzymes in remediation of PAH-contaminated soils. The metagenomic hits were further analyzed using a set of bioinformatics tools to select protein sequences predicted to encode well-folded soluble enzymes. Three novel enzymes (two dioxygenases and one peroxidase) were cloned and used in soil remediation microcosms experiments. The experimental design of the present study aimed at evaluating the effectiveness of the novel enzymes on short-term PAH degradation in the soil microcosmos model. The novel enzymes were found to be efficient for degradation of naphthalene and phenanthrene. Adding the inorganic oxidant CaO2 further increased the degrading potential of the novel enzymes for anthracene and pyrene. We conclude that metagenome mining paired with bioinformatic predictions, structural modelling and functional assays constitutes a powerful approach towards novel enzymes for soil remediation. [ABSTRACT FROM AUTHOR]

Patterns of single nucleotide polymorphisms (SNPs) in eukaryotic DNA are traditionally attributed to selective pressure, drift, identity descent, or related factors—without accounting for ways in which bias during de novo SNP formation, itself, might contribute. A functional and phenotypic analysis based on evolutionary resilience of DNA points to decreased numbers of non-synonymous SNPs in human and other genomes, with a predominant component of SNP depletion in the human gene pool caused by robust preferences during de novo SNP formation (rather than selective constraint). Ramifications of these findings are broad, belie a number of concepts regarding human evolution, and point to a novel interpretation of evolving DNA across diverse species. [ABSTRACT FROM AUTHOR]

Background: Alpha synuclein (α-synuclein) is coded by SNCA gene and found in a helical form with phospholipids or in an unfolded arrangement in the cytosol and belongs to the synuclein family other than beta synuclein and gamma synuclein. It is a short protein made of 140 amino acids with three domains: an N-terminal lipid binding helix, a non-amyloid-ß component (NAC), and an acidic tail at the C-terminus. α-Synuclein is present in aggregated and fibrillar form in Lewy bodies and its association has been related to multiple system atrophy (MSA), Parkinson's disease (PD), and Dementia with Lewy bodies (DLB). Our objective is to investigate and prioritise the possible nsSNPs in the α-synuclein protein that have been potentially connected to human neurodegenerative diseases. Results: We used the series of computational tools to predict the mutation's harmful effect on three-dimensional structure of α-synuclein based on consensus approach. Our findings pointed to a significant computational blueprint for discovering nsSNPs connected to neurodegenerative illnesses from a large SNP data set while also minimising the expenses of experimentally showing harmful nsSNPs. Conclusions: The prioritised G25S (rs1433622151), V66E (rs1261243630), and V77D (rs745815563) mutations can be employed in additional experimental studies to assess the α-synuclein protein mutation in relation to neurodegenerative illnesses and develop a therapeutics against them. [ABSTRACT FROM AUTHOR]

Amaranth species are C4 plants that are rich in betalains, and they are tolerant to salinity stress. A small family of plant-specific TCP transcription factors are involved in the response to salt stress. However, it has not been investigated whether amaranth TCP1 is involved in salt stress. We elucidated that the growth and physiology of amaranth were affected by salt concentrations of 50–200 mmol·L−1 NaCl. The data showed that shoot and root growth was inhibited at 200 mmol·L−1, while it was promoted at 50 mmol·L−1. Meanwhile, the plants also showed physiological responses, which indicated salt-induced injuries and adaptation to the salt stress. Moreover, AtrTCP1 promoted Arabidopsis seed germination. The germination rate of wild-type (WT) and 35S::AtrTCP1-GUS Arabidopsis seeds reached around 92% by the seventh day and 94.5% by the second day under normal conditions, respectively. With 150 mmol·L−1 NaCl treatment, the germination rate of the WT and 35S::AtrTCP1-GUS plant seeds was 27.0% by the seventh day and 93.0% by the fourth day, respectively. Under salt stress, the transformed 35S::AtrTCP1 plants bloomed when they grew 21.8 leaves after 16.2 days of treatment, which was earlier than the WT plants. The transformed Arabidopsis plants flowered early to resist salt stress. These results reveal amaranth's growth and physiological responses to salt stress, and provide valuable information on the AtrTCP1 gene. [ABSTRACT FROM AUTHOR]

The pil gene cluster for Type IV pilus (Tfp) biosynthesis is commonly present and highly conserved in Streptococcus sanguinis. Nevertheless, Tfp-mediated twitching motility is less common among strains, and the factors determining twitching activity are not fully understood. Here, we analyzed the functions of three major pilin proteins (PilA1, PilA2, and PilA3) in the assembly and activity of Tfp in motile S. sanguinis CGMH010. Using various recombinant pilA deletion strains, we found that Tfp composed of different PilA proteins varied morphologically and functionally. Among the three PilA proteins, PilA1 was most critical in the assembly of twitching-active Tfp, and recombinant strains expressing motility generated more structured biofilms under constant shearing forces compared to the non-motile recombinant strains. Although PilA1 and PilA3 shared 94% identity, PilA3 could not compensate for the loss of PilA1, suggesting that the nature of PilA proteins plays an essential role in twitching activity. The single deletion of individual pilA genes had little effect on the invasion of host endothelia by S. sanguinis CGMH010. In contrast, the deletion of all three pilA genes or pilT, encoding the retraction ATPase, abolished Tfp-mediated invasion. Tfp- and PilT-dependent invasion were also detected in the non-motile S. sanguinis SK36, and thus, the retraction of Tfp, but not active twitching, was found to be essential for invasion. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are a group of endogenous small non-coding RNAs in plants. They play critical functions in various biological processes during plant growth and development. Salvia miltiorrhiza is a well-known traditional Chinese medicinal plant with significant medicinal, economic, and academic values. In order to elucidate the role of miRNAs in S. miltiorrhiza, six small RNA libraries from mature roots, young roots, stems, mature leaves, young leaves and flowers of S. miltiorrhiza and one degradome library from mixed tissues were constructed. A total of 184 miRNA precursors, generating 137 known and 49 novel miRNAs, were genome-widely identified. The identified miRNAs were predicted to play diversified regulatory roles in plants through regulating 891 genes. qRT-PCR and 5′ RLM-RACE assays validated the negative regulatory role of smi-miR159a in SmMYB62, SmMYB78, and SmMYB80. To elucidate the function of smi-miR159a in bioactive compound biosynthesis, smi-miR159a transgenic hairy roots were generated and analyzed. The results showed that overexpression of smi-miR159a caused a significant decrease in rosmarinic acid and salvianolic acid B contents. qRT-PCR analysis showed that the targets of smi-miR159a, including SmMYB62, SmMYB78, and SmMYB80, were significantly down-regulated, accompanied by the down-regulation of SmPAL1, SmC4H1, Sm4CL1, SmTAT1, SmTAT3, SmHPPR1, SmRAS, and SmCYP98A14 genes involved in phenolic acid biosynthesis. It suggests that smi-miR159a is a significant negative regulator of phenolic acid biosynthesis in S. miltiorrhiza. [ABSTRACT FROM AUTHOR]

Low-complexity domains (LCDs) in proteins are typically enriched in one or two predominant amino acids. As a result, LCDs often exhibit unusual structural/biophysical tendencies and can occupy functional niches. However, for each organism, protein sequences must be compatible with intracellular biomolecules and physicochemical environment, both of which vary from organism to organism. This raises the possibility that LCDs may occupy sequence spaces in select organisms that are otherwise prohibited in most organisms. Here, we report a comprehensive survey and functional analysis of LCDs in all known reference proteomes (>21k organisms), with added focus on rare and unusual types of LCDs. LCDs were classified according to both the primary amino acid and secondary amino acid in each LCD sequence, facilitating detailed comparisons of LCD class frequencies across organisms. Examination of LCD classes at different depths (i.e., domain of life, organism, protein, and per-residue levels) reveals unique facets of LCD frequencies and functions. To our surprise, all 400 LCD classes occur in nature, although some are exceptionally rare. A number of rare classes can be defined for each domain of life, with many LCD classes appearing to be eukaryote-specific. Certain LCD classes were consistently associated with identical functions across many organisms, particularly in eukaryotes. Our analysis methods enable simultaneous, direct comparison of all LCD classes between individual organisms, resulting in a proteome-scale view of differences in LCD frequencies and functions. Together, these results highlight the remarkable diversity and functional specificity of LCDs across all known life forms. Author summary: Many protein sequences contain "low-complexity domains" (LCDs), which are regions in the sequence mostly comprised of only one or two different types of amino acids. Since there are 20 main types of amino acids found in natural proteins, many "flavors" of LCDs are possible, with each flavor having unique structural and functional properties. However, the functions and prevalence of each type of LCD across organisms has not been explored extensively. In this study, we divided LCDs into 400 categories based on the one or two amino acids that were most common in each LCD sequence. Then, using a representative set of all known organisms, we examined how prevalent each type of LCD was and which functions were most often linked to each type of LCD. We uncovered LCD functions common to many organisms as well as LCD functions restricted to certain organisms or LCD types. Some organisms had unusually high levels of specific types of LCDs, suggesting that adaptations in these organisms or special conditions in their environment have aided in the tolerance–or even usage–of those LCD types. Our results give both broad and in-depth views of LCDs, their functions, and their frequencies in nature. [ABSTRACT FROM AUTHOR]

Background: Culex pipiens pallens is a well-known mosquito vector for several diseases. Deltamethrin, a commonly used pyrethroid insecticide, has been frequently applied to manage adult Cx. pipiens pallens. However, mosquitoes can develop resistance to these insecticides as a result of insecticide misuse and, therefore, it is crucial to identify novel methods to control insecticide resistance. The relationship between commensal bacteria and vector resistance has been recently recognized. Bacteriophages (= phages) are effective tools by which to control insect commensal bacteria, but there have as yet been no studies using phages on adult mosquitoes. In this study, we isolated an Aeromonas phage vB AhM-LH that specifically targets resistance-associated symbiotic bacteria in mosquitoes. We investigated the impact of Aeromonas phage vB AhM-LH in an abundance of Aeromonas hydrophila in the gut of Cx. pipiens pallens and its effect on the status of deltamethrin resistance. Methods: Phages were isolated on double-layer agar plates and their biological properties analyzed. Phage morphology was observed by transmission electron microscopy (TEM) after negative staining. The phage was then introduced into the mosquito intestines via oral feeding. The inhibitory effect of Aeromonas phage vB AhM-LH on Aeromonas hydrophila in mosquito intestines was assessed through quantitative real-time PCR analysis. Deltamethrin resistance of mosquitoes was assessed using WHO bottle bioassays. Results: An Aeromonas phage vB AhM-LH was isolated from sewage and identified as belonging to the Myoviridae family in the order Caudovirales using TEM. Based on biological characteristics analysis and in vitro antibacterial experiments, Aeromonas phage vB AhM-LH was observed to exhibit excellent stability and effective bactericidal activity. Sequencing revealed that the Aeromonas phage vB AhM-LH genome comprises 43,663 bp (51.6% CG content) with 81 predicted open reading frames. No integrase-related gene was detected in the vB AH-LH genome, which marked it as a potential biological antibacterial. Finally, we found that Aeromonas phage vB AhM-LH could significantly reduce deltamethrin resistance in Cx. pipiens pallens, in both the laboratory and field settings, by decreasing the abundance of Aeromonas hydrophila in their midgut. Conclusions: Our findings demonstrate that Aeromonas phage vB AhM-LH could effectively modulate commensal bacteria Aeromonas hydrophila in adult mosquitoes, thus representing a promising strategy to mitigate mosquito vector resistance. [ABSTRACT FROM AUTHOR]

Within the islets of Langerhans, beta cells orchestrate synchronized insulin secretion, a pivotal aspect of metabolic homeostasis. Despite the inherent heterogeneity and multimodal activity of individual cells, intercellular coupling acts as a homogenizing force, enabling coordinated responses through the propagation of intercellular waves. Disruptions in this coordination are implicated in irregular insulin secretion, a hallmark of diabetes. Recently, innovative approaches, such as integrating multicellular calcium imaging with network analysis, have emerged for a quantitative assessment of the cellular activity in islets. However, different groups use distinct experimental preparations, microscopic techniques, apply different methods to process the measured signals and use various methods to derive functional connectivity patterns. This makes comparisons between findings and their integration into a bigger picture difficult and has led to disputes in functional connectivity interpretations. To address these issues, we present here a systematic analysis of how different approaches influence the network representation of islet activity. Our findings show that the choice of methods used to construct networks is not crucial, although care is needed when combining data from different islets. Conversely, the conclusions drawn from network analysis can be heavily affected by the pre-processing of the time series, the type of the oscillatory component in the signals, and by the experimental preparation. Our tutorial-like investigation aims to resolve interpretational issues, reconcile conflicting views, advance functional implications, and encourage researchers to adopt connectivity analysis. As we conclude, we outline challenges for future research, emphasizing the broader applicability of our conclusions to other tissues exhibiting complex multicellular dynamics. Author summary: Islets of Langerhans, multicellular microorgans in the pancreas, are pivotal for whole-body energy homeostasis. Hundreds of beta cells within these networks synchronize to produce insulin, a crucial hormone for metabolic control. Coordinated activity disruptions in these multicellular networks contribute to irregular insulin secretion, a hallmark of diabetes. Recognizing the significance of collective activity, network science approaches have been increasingly applied in islet research. However, variations in experimental setups, imaging techniques, signal processing, and connectivity analysis methods across different research groups pose challenges for integrating findings into a comprehensive picture. Therefore, we present here a systematic analysis of various approaches impacting results in islet activity network representation. We find that methods for constructing functional connectivity maps aren't critical, but caution is necessary when aggregating data from different islets. Network analysis conclusions are notably influenced by factors such as time series pre-processing, the oscillatory component of signals, and experimental preparation. Despite these challenges, this paper advocates for the adoption of connectivity analysis in future islet research, emphasizing that the insights gained extend beyond pancreatic islets to provide valuable contributions for understanding connectivity in other multicellular systems. [ABSTRACT FROM AUTHOR]

Understanding the influence of cis‐regulatory elements on gene regulation poses numerous challenges given complexities stemming from variations in transcription factor (TF) binding, chromatin accessibility, structural constraints, and cell‐type differences. This review discusses the role of gene regulatory networks in enhancing understanding of transcriptional regulation and covers construction methods ranging from expression‐based approaches to supervised machine learning. Additionally, key experimental methods, including MPRAs and CRISPR‐Cas9‐based screening, which have significantly contributed to understanding TF binding preferences and cis‐regulatory element functions, are explored. Lastly, the potential of machine learning and artificial intelligence to unravel cis‐regulatory logic is analyzed. These computational advances have far‐reaching implications for precision medicine, therapeutic target discovery, and the study of genetic variations in health and disease. [ABSTRACT FROM AUTHOR]

The GO DNA repair system protects against GC → TA mutations by finding and removing oxidized guanine. The system is mechanistically well understood but its origins are unknown. We searched metagenomes and abundantly found the genes encoding GO DNA repair at the Lost City Hydrothermal Field (LCHF). We recombinantly expressed the final enzyme in the system to show MutY homologs function to suppress mutations. Microbes at the LCHF thrive without sunlight, fueled by the products of geochemical transformations of seafloor rocks, under conditions believed to resemble a young Earth. High levels of the reductant H2 and low levels of O2 in this environment raise the question, why are resident microbes equipped to repair damage caused by oxidative stress? MutY genes could be assigned to metagenome-assembled genomes (MAGs), and thereby associate GO DNA repair with metabolic pathways that generate reactive oxygen, nitrogen and sulfur species. Our results indicate that cell-based life was under evolutionary pressure to cope with oxidized guanine well before O2 levels rose following the great oxidation event. [ABSTRACT FROM AUTHOR]

Background: Standard ChIP-seq and RNA-seq processing pipelines typically disregard sequencing reads whose origin is ambiguous ("multimappers"). This usual practice has potentially important consequences for the functional interpretation of the data: genomic elements belonging to clusters composed of highly similar members are left unexplored. Results: In particular, disregarding multimappers leads to the underrepresentation in epigenetic studies of recently active transposable elements, such as AluYa5, L1HS and SVAs. Furthermore, this common strategy also has implications for transcriptomic analysis: members of repetitive gene families, such the ones including major histocompatibility complex (MHC) class I and II genes, are under-quantified. Conclusion: Revealing inherent biases that permeate routine tasks such as functional enrichment analysis, our results underscore the urgency of broadly adopting multimapper-aware bioinformatic pipelines –currently restricted to specific contexts or communities– to ensure the reliability of genomic and transcriptomic studies. [ABSTRACT FROM AUTHOR]

Background: Recent studies have revealed the correlation between serum vitamin D (VD) level and polycystic ovary syndrome (PCOS), but the causality and specific mechanisms remain uncertain. Objective: We aimed to investigate the cause-effect relationship between serum VD and PCOS, and the role of testosterone in the related pathological mechanisms. Methods: We assessed the causality between serum VD and PCOS by using genome-wide association studies (GWAS) data in a bidirectional two-sample Mendelian randomization (TS-MR) analysis. Subsequently, a MR mediation analysis was conducted to examine the mediating action of testosterone in the causality between serum VD and PCOS. Ultimately, we integrated GWAS data with cis-expression quantitative loci (cis-eQTLs) data for gene annotation, and used the potentially related genes for functional enrichment analysis to assess the involvement of testosterone and the potential mechanisms. Results: TS-MR analysis showed that individuals with lower level of serum VD were more likely to develop PCOS (OR = 0.750, 95% CI: 0.587–0.959, P = 0.022). MR mediation analysis uncovered indirect causal effect of serum VD level on the risk of PCOS via testosterone (OR = 0.983, 95% CI: 0.968–0.998, P = 0.025). Functional enrichment analysis showed that several pathways may be involved in the VD-testosterone-PCOS axis, such as steroid hormone biosynthesis and autophagy process. Conclusion: Our findings suggest that genetically predicted lower serum VD level may cause a higher risk of developing PCOS, which may be mediated by increased testosterone production. [ABSTRACT FROM AUTHOR]

In this article, we present a meticulous computational study to foresee the effect of an oxygen-rich macrocycle on the reactivity for C–H activation. For this study, a widely studied nonheme Fe(IV)O molecule with a TMC (1,4,8,11-tetramethyl 1,4,8,11-tetraazacyclotetradecane) macrocycle that is equatorially attached to four nitrogen atoms (designated as N4) and acetonitrile as an axial ligand has been taken into account. For the goal of hetero-substitution, step-by-step replacement of the N4 framework with O atoms, i.e., N4, N3O1, N2O2, N1O3, and O4 systems, has been considered, and dihydroanthracene (DHA) has been used as the substrate. In order to neutralise the system and prevent the self-interaction error in DFT, triflate counterions have also been included in the calculations. The study of the energetics of these C–H bond activation reactions and the potential energy surfaces mapped therefore reveal that the initial hydrogen abstraction, which is the rate-determining step, follows the two-state reactivity (TSR) pattern, which means that the originally excited quintet state falls lower in the transition state and the product. The reaction follows the hydrogen atom transfer (HAT) mechanism, as indicated by the spin density studies. The results revealed a fascinating reactivity order, in which the reactivity increases with the enrichment of the oxygen atom in the equatorial position, namely the order follows N4 < N3O1 < N2O2 < N1O3 < O4. The impacts of oxygen substitution on quantum mechanical tunneling and the H/D kinetic isotope effect have also been investigated. When analysing the causes of this reactivity pattern, a number of variables have been identified, including the reactant-like transition structure, spin density distribution, distortion energy, and energies of the electron acceptor orbital, i.e., the energy of the LUMO (σ*z2), which validate the obtained outcome. Our results also show very good agreement with earlier combined experimental and theoretical studies considering TMC and TMCO-type complexes. The DFT predictions reported here will undoubtedly encourage experimental research in this biomimetic field, as they provide an alternative with higher reactivity in which heteroatoms can be substituted for the traditional nitrogen atom. [ABSTRACT FROM AUTHOR]