Search

Background and Clinical Significance: Fever in the returning traveler is a medical emergency warranting prompt exclusion of potentially life-threatening infections such as malaria. Case Presentation: We describe a case of a febrile returned traveler to South Africa whose prompt initial diagnostic work-up was notable for a false-positive malaria rapid diagnostic test (RDT), and who nevertheless responded quickly to oral atovaquone-proguanil, despite an ultimate diagnosis of African tick bite fever. Subsequent RDT and malaria thick- and thin-film blood examination failed to corroborate a diagnosis of malaria and all other microbiological testing other than rickettsial serology remained non-contributory. Conclusions: The case presented highlights important points regarding diagnostic test performance characteristics and premature diagnostic closure. [ABSTRACT FROM AUTHOR]

Amentoflavone (AF) is a biflavonoid compound found in many plants. In this study, we first demonstrate that AF has a potent antiviral effect against the influenza virus via the inhibition of viral attachment and virucidal effects. The anti-influenza-viral effect of AF was evaluated using green fluorescent protein-tagged Influenza A virus (IAV) with fluorescent microscopy and flow cytometry analysis. AF decreased the GFP expression by viral infection, dose-dependently. Fifty micromoles of AF suppressed the GFP expression by virus infection of up to 70% of untreated infected control cells. Consistently, immunofluorescence results showed the inhibitory effect of AF on viral protein expression. Time-of-addition and hemagglutination assays revealed that AF inhibits viral binding to cells by interfering with the hemagglutinin (HA) of IAV. Furthermore, AF has a virucidal effect and blocks cytopathic effects caused by the Influenza B virus and H3N2 IAV. Additionally, AF represses the neuraminidase (NA) activity of IAV. In silico analysis confirmed the potential interaction of AF with both HA and NA. Our findings indicate that AF has antiviral effects by modulating HA and NA during the attachment and release stages of influenza viral infection. [ABSTRACT FROM AUTHOR]

This article examines the effectiveness of exercise interventions for individuals with Parkinson's disease (PD). It compares the outcomes of endurance exercise, such as walking or biking, with occupation-based exercises, such as boxing or dancing. The results suggest that occupation-based exercises, which hold more meaning for patients, may lead to better treatment outcomes and increased participation. The article emphasizes the importance of providing meaningful options for rehabilitation to PD patients and incorporating neuro-occupation principles into treatment. However, further research is needed to fully understand the impact of different exercise types on PD symptoms. [Extracted from the article]

Streptococcus mutans, the primary cause of dental caries, relies on its ability to create and sustain a biofilm (dental plaque) for survival and pathogenicity in the oral cavity. This study was focused on the antimicrobial biofilm formation control and biofilm dispersal potential of Coumaric acid (CA) against Streptococcus mutans on the dentin surface. The biofilm was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) viability assay, microtiter plate assay, production of extracellular polymeric substances (EPSs), florescence microscopy (surface coverage and biomass μm2) and three-dimensional (3D) surface plots. It was observed that CA at 0.01 mg/mL reduced bacterial growth by 5.51%, whereases at 1 mg/mL, a significant (p < 0.05) reduction (98.37%) was observed. However, at 1 mg/mL of CA, a 95.48% biofilm formation reduction was achieved, while a 73.45% biofilm dispersal (after 24 h. treatment) was achieved against the preformed biofilm. The MTT assay showed that at 1 mg/mL of CA, the viability of bacteria in the biofilm was markedly (p < 0.05) reduced to 73.44%. Moreover, polysaccharide (EPS) was reduced to 24.80 μg/mL and protein (EPS) to 41.47 μg/mL. ImageJ software (version 1.54 g) was used to process florescence images, and it was observed that the biofilm mass was reduced to 213 (μm2); the surface coverage was reduced to 0.079%. Furthermore, the 3D surface plots showed that the untreated biofilm was highly dense, with more fibril-like projections. Additionally, molecular docking predicted a possible interaction pattern of CA (ligand) with the receptor Competence Stimulating Peptide (UA159sp, PDB ID: 2I2J). Our findings suggest that CA has antibacterial and biofilm control efficacy against S. mutans associated with dental plaque under tested conditions. [ABSTRACT FROM AUTHOR]

Ginseng is usually consumed as a daily food supplement to improve health and has been shown to benefit skeletal muscle, improve glucose metabolism, and ameliorate muscle-wasting conditions, cardiovascular diseases, stroke, and the effects of aging and cancers. Ginseng has also been reported to help maintain bone strength and liver (digestion, metabolism, detoxification, and protein synthesis) and kidney functions. In addition, ginseng is often used to treat age-associated neurodegenerative disorders, and ginseng and ginseng-derived natural products are popular natural remedies for diseases such as diabetes, obesity, oxidative stress, and inflammation, as well as fungal, bacterial, and viral infections. Ginseng is a well-known herbal medication, known to alleviate the actions of several cytokines. The article concludes with future directions and significant application of ginseng compounds for researchers in understanding the promising role of ginseng in the treatment of several diseases. Overall, this study was undertaken to highlight the broad-spectrum therapeutic applications of ginseng compounds for health management. [ABSTRACT FROM AUTHOR]

Simple Summary: Hybrids between the critically endangered Siamese crocodile (Crocodylus siamensis) and least-concern saltwater crocodile (C. porosus) pose a significant challenge to conservation efforts due to human activities. Previous studies used microsatellite and mitochondrial DNA data to identify these hybrids, but potential biases and genetic drift within the populations could influence the results. To address these limitations and gain a clearer understanding of the genetic dynamics, we employed DArT sequencing to identify genome-wide single nucleotide polymorphisms (SNPs) in both species and confirm hybrid scenarios. We compared a population of Australian saltwater crocodiles to assess species-specific SNP distribution. Various analytical approaches were used to diagnose hybridization levels, especially in cases with potential backcrossing. Approximately 17.00–26.00% of loci were shared between Siamese and saltwater crocodile genomes. We identified 8051 species-specific SNP loci for Siamese crocodiles and 1288 for saltwater crocodiles. Using a PCR-based approach, three SNP loci were developed as markers, successfully enabling the distinction between species and various levels of hybridization. By combining mitochondrial and nuclear genetic information with species-diagnostic DNA markers, we developed a novel method for conservation prioritization, aiding long-term species survival through reintroduction and management programs. Hybrids between the critically endangered Siamese crocodile (Crocodylus siamensis) and least-concern saltwater crocodile (C. porosus) in captive populations represent a serious challenge for conservation and reintroduction programs due to the impact of anthropogenic activities. A previous study used microsatellite and mitochondrial DNA data to establish the criteria for identifying species and their hybrids; however, the results may have been influenced by biased allelic frequencies and genetic drift within the examined population. To overcome these limitations and identify the true signals of selection, alternative DNA markers and a diverse set of populations should be employed. Therefore, this study used DArT sequencing to identify genome-wide single nucleotide polymorphisms (SNPs) in both species and confirm the genetic scenario of the parental species and their hybrids. A population of saltwater crocodiles from Australia was used to compare the distribution of species-diagnostic SNPs. Different analytical approaches were compared to diagnose the level of hybridization when an admixture was present, wherein three individuals had potential backcrossing. Approximately 17.00–26.00% of loci were conserved between the Siamese and saltwater crocodile genomes. Species-diagnostic SNP loci for Siamese and saltwater crocodiles were identified as 8051 loci and 1288 loci, respectively. To validate the species-diagnostic SNP loci, a PCR-based approach was used by selecting 20 SNP loci for PCR primer design, among which 3 loci were successfully able to differentiate the actual species and different hybridization levels. Mitochondrial and nuclear genetic information, including microsatellite genotyping and species-diagnostic DNA markers, were combined as a novel method that can compensate for the limitations of each method. This method enables conservation prioritization before release into the wild, thereby ensuring sustainable genetic integrity for long-term species survival through reintroduction and management programs. [ABSTRACT FROM AUTHOR]

Simple Summary: Microsatellite markers are widely used molecular markers for genetic studies, but choosing the right set involves a challenging trade-off between effectiveness and cost. The research aims to enhance the widely used ant colony optimization algorithm by integrating marker effectiveness indicators. By considering the genetic properties of the markers such as the polymorphic information content, the study seeks to determine the suitable way to select a reduced set of microsatellites. The approach addresses the accuracy–cost trade-off, aiding genetic assessments, breeding, and conservation efforts with cost-effective solutions. This research provides valuable insights into real-world genetic studies, including breeding programs and conservation initiatives. Microsatellites are polymorphic and cost-effective. Optimizing reduced microsatellite panels using heuristic algorithms eases budget constraints in genetic diversity and population genetic assessments. Microsatellite marker efficiency is strongly associated with its polymorphism and is quantified as the polymorphic information content (PIC). Nevertheless, marker selection cannot rely solely on PIC. In this study, the ant colony optimization (ACO) algorithm, a widely recognized optimization method, was adopted to create an enhanced selection scheme for refining microsatellite marker panels, called the PIC–ACO selection scheme. The algorithm was fine-tuned and validated using extensive datasets of chicken (Gallus gallus) and Chinese gorals (Naemorhedus griseus) from our previous studies. In contrast to basic optimization algorithms that stochastically initialize potential outputs, our selection algorithm utilizes the PIC values of markers to prime the ACO process. This increases the global solution discovery speed while reducing the likelihood of becoming trapped in local solutions. This process facilitated the acquisition of a cost-efficient and optimized microsatellite marker panel for studying genetic diversity and population genetic datasets. The established microsatellite efficiency metrics such as PIC, allele richness, and heterozygosity were correlated with the actual effectiveness of the microsatellite marker panel. This approach could substantially reduce budgetary barriers to population genetic assessments, breeding, and conservation programs. [ABSTRACT FROM AUTHOR]

Jade perch (Scortum barcoo) has an XX/XY sex-determination system (SDS); however, its sex chromosomes and sex-determining region remain unknown. The recent availability of the jade perch chromosome-level genomic data provides a valuable resource for pinpointing the location of functional genes and the whole genomic structure. In this study, we conducted. In silico chromosome mapping of male-specific/linked loci of jade perch and identified a potential 11.18 Mb male-linked region localized on chromosome 19 (SBA19). Repeat annotations of the male-linked region revealed an abundance of transposable elements, particularly Ty3/Gypsy and novel repeats. Sequence analysis of this region identified a remnant of amh gene, which is considered a potential candidate for SDS in many teleosts. A duplicate copy of amh remnant was located at SBA6. These duplicated amh copies were highly similar to those of XX/XY SDS in teleosts, in which one copy of amh was identified on the Y sex chromosome. Taken all together, we hypothesize SBA19 as the putative sex chromosome and the 11.18 Mb male-linked region to be a potential male-determining region. [ABSTRACT FROM AUTHOR]

Simple Summary: Mae Hong Son chicken is a local breed of North Thai domestic chicken widely distributed in Mae Hong Son; however, its genetic characterization, origin, and diversity remain unclear. Here, we studied the socio–cultural, environmental, and genetic aspects of the Mae Hong Son chicken breed, and we investigated its genetic diversity and footprint using the genotyping of 28 microsatellite markers and analyzed mitochondrial D-loop sequencing data. Genetic diversity analysis indicated that the Mae Hong Son chicken population is genetically highly diverse, with 35 haplotypes clustered into haplogroups A, B, E, and F, mostly in the North ecotype. Allelic gene pool patterns showed a unique DNA fingerprint of the Mae Hong Son chicken, as compared to other breeds and red junglefowl. A genetic introgression of some parts of the gene pool of red junglefowl and other indigenous breeds was identified in the Mae Hong Son chicken, supporting the hypothesis of the origin of the Mae Hong Son chicken as a crossbreed between red junglefowl and Thai indigenous village chickens that adapted to the environmental, social, and cultural conditions in its habitat. These findings enrich our understanding of the genetic blueprint, origin, and evolutionary process of the Mae Hong Son chickens and lay the foundation for future studies to improve domestic chickens using this indigenous chicken breed. Understanding the genetic diversity of domestic chicken breeds under the impact of socio–cultural and ecological dynamics is vital for the conservation of natural resources. Mae Hong Son chicken is a local breed of North Thai domestic chicken widely distributed in Mae Hong Son Province, Thailand; however, its genetic characterization, origin, and diversity remain poorly understood. Here, we studied the socio–cultural, environmental, and genetic aspects of the Mae Hong Son chicken breed and investigated its diversity and allelic gene pool. We genotyped 28 microsatellite markers and analyzed mitochondrial D-loop sequencing data to evaluate genetic diversity and assessed spatial habitat suitability using maximum entropy modeling. Sequence diversity analysis revealed a total of 188 genotyped alleles, with overall nucleotide diversity of 0.014 ± 0.007, indicating that the Mae Hong Son chicken population is genetically highly diverse, with 35 (M1–M35) haplotypes clustered into haplogroups A, B, E, and F, mostly in the North ecotype. Allelic gene pool patterns showed a unique DNA fingerprint of the Mae Hong Son chicken, as compared to other breeds and red junglefowl. A genetic introgression of some parts of the gene pool of red junglefowl and other indigenous breeds was identified in the Mae Hong Son chicken, supporting the hypothesis of the origin of the Mae Hong Son chicken. During domestication in the past 200–300 years after the crossing of indigenous chickens and red junglefowl, the Mae Hong Son chicken has adapted to the highland environment and played a significant socio–cultural role in the Northern Thai community. The unique genetic fingerprint of the Mae Hong Son chicken, retaining a high level of genetic variability that includes a dynamic demographic and domestication history, as well as a range of ecological factors, might reshape the adaptation of this breed under selective pressure. [ABSTRACT FROM AUTHOR]

Potential single nucleotide polymorphisms (SNPs) were detected between two chicken breeds (Kashmir favorella and broiler) using deep RNA sequencing. This was carried out to comprehend the coding area alterations, which cause variances in the immunological response to Salmonella infection. In the present study, we identified high impact SNPs from both chicken breeds in order to delineate different pathways that mediate disease resistant/susceptibility traits. Samples (liver and spleen) were collected from Salmonella resistant (K. favorella) and susceptible (broiler) chicken breeds. Salmonella resistance and susceptibility were checked by different pathological parameters post infection. To explore possible polymorphisms in genes linked with disease resistance, SNP identification analysis was performed utilizing RNA seq data from nine K. favorella and ten broiler chickens. A total of 1778 (1070 SNPs and 708 INDELs) and 1459 (859 SNPs and 600 INDELs) were found to be specific to K. favorella and broiler, respectively. Based on our results, we conclude that in broiler chickens the enriched pathways mostly included metabolic pathways like fatty acid metabolism, carbon metabolism and amino acid metabolism (Arginine and proline metabolism), while as in K. favorella genes with high impact SNPs were enriched in most of the immune-related pathways like MAPK signaling pathway, Wnt signaling pathway, NOD-like receptor signaling pathway, etc., which could be a possible resistance mechanism against salmonella infection. In K. favorella, protein–protein interaction analysis also shows some important hub nodes, which are important in providing defense against different infectious diseases. Phylogenomic analysis revealed that indigenous poultry breeds (resistant) are clearly separated from commercial breeds (susceptible). These findings will offer fresh perspectives on the genetic diversity in chicken breeds and will aid in the genomic selection of poultry birds. [ABSTRACT FROM AUTHOR]

Knowledge of the genetic characteristics, origin, and local adaptation of chickens is essential to identify the traits required for chicken breeding programs. Chee Fah and Fah Luang are black-boned chicken breeds reared in Chiang Rai, Thailand. Chickens are an important part of the local economy and socio-culture; however, the genetic diversity, characteristics, and origins of these two breeds have been poorly studied. Here, we investigated the genetic diversity, gene pool, and origin of the Chee Fah and Fah Luang chickens using mitochondrial DNA D-loop (mtDNA D-loop) sequencing and microsatellite genotyping, as well as habitat suitability analysis using maximum entropy modeling. The MtDNA D-loop sequencing and microsatellite genotype analyses indicated that the Chee Fah and Fah Luang chickens shared haplogroups A, B, and CD with Chinese black-boned chickens. Gene pool analysis revealed that the Chee Fah and Fah Luang chickens have distinct genetic patterns compared to Thai domestic chickens and red junglefowl. Some gene pools of red junglefowl and other Thai domestic chickens were observed within the Chee Fah and Fah Luang chicken gene pool structures, suggesting genetic exchange. The data indicate that the Chee Fah and Fah Luang chickens originated from Chinese indigenous black-boned chicken breeds and experienced crossbreeding/hybridization and introgression with red junglefowl and other domestic breeds during domestication. Interestingly, the Chee Fah and Fah Luang chickens from Chiang Rai shared the same allelic gene pool, which was not shared with the Chee Fah and Fah Luang chickens from Mae Hong Son, suggesting at least two gene pool origins in the Chee Fah and Fah Luang chicken populations. Alternatively, different gene pools in the Chee Fah and Fah Luang chickens from different localities might be caused by differences in environmental factors, especially elevation. [ABSTRACT FROM AUTHOR]

Simple Summary: Morphological divergence between Siamese and other crocodiles has been identified by size, number of scales, and patterns of cervical squamation with post-occipital scutes (P.O.). However, a large variation of P.O. has been observed in captive Siamese crocodiles in Thailand, leading to questions about possible crocodile hybrids. The genetic diversity and population structure of Siamese crocodiles were studied using mitochondrial DNA D-loop and microsatellite genotyping. The STRUCTURE plot revealed numerous distinct gene pools, indicating that the crocodiles in each farm descended from distinct lineages. Researchers also discovered evidence of introgression in several individual crocodiles, implying that Siamese and saltwater crocodiles may have hybridized. A schematic protocol for screening hybrids was proposed based on patterns observed in phenotypic and molecular data. Populations of Siamese crocodiles (Crocodylus siamensis) have severely declined because of hunting and habitat fragmentation, necessitating a reintroduction plan involving commercial captive-bred populations. However, hybridization between Siamese and saltwater crocodiles (C. porosus) has occurred in captivity. Siamese crocodiles commonly have post-occipital scutes (P.O.) with 4–6 scales, but 2–6 P.O. scales were found in captives on Thai farms. Here, the genetic diversity and population structure of Siamese crocodiles with large P.O. variations and saltwater crocodiles were analyzed using mitochondrial DNA D-loop and microsatellite genotyping. Possible crocodile hybrids or phenotypic variations were ascertained by comparison with our previous library from the Siam Crocodile Bioresource Project. Siamese crocodiles with <4 P.O. scales in a row exhibit normal species-level phenotypic variation. This evidence encourages the revised description of Siamese crocodiles. Moreover, the STRUCTURE plot revealed large distinct gene pools, suggesting crocodiles in each farm were derived from distinct lineages. However, combining both genetic approaches provides evidence of introgression for several individual crocodiles, suggesting possible hybridization between Siamese and saltwater crocodiles. We proposed a schematic protocol with patterns observed in phenotypic and molecular data to screen hybrids. Identifying non-hybrid and hybrid individuals is important for long-term in situ/ex situ conservation. [ABSTRACT FROM AUTHOR]

Vaccination is widely used to control Infectious Bronchitis in poultry; however, the limited cross-protection and safety issues associated with these vaccines can lead to vaccination failures. Keeping these limitations in mind, the current study explored the antiviral potential of phytocompounds against the Infectious Bronchitis virus using in silico approaches. A total of 1300 phytocompounds derived from fourteen botanicals were screened for their potential ability to inhibit the main protease, papain-like protease or RNA-dependent RNA–polymerase of the virus. The study identified Methyl Rosmarinate, Cianidanol, Royleanone, and 6,7-Dehydroroyleanone as dual-target inhibitors against any two of the key proteins. At the same time, 7-alpha-Acetoxyroyleanone from Rosmarinus officinalis was found to be a multi-target protein inhibitor against all three proteins. The potential multi-target inhibitor was subjected to molecular dynamics simulations to assess the stability of the protein–ligand complexes along with the corresponding reference ligands. The findings specified stable interactions of 7-alpha-Acetoxyroyleanone with the protein targets. The results based on the in silico study indicate that the phytocompounds can potentially inhibit the essential proteins of the Infectious Bronchitis virus; however, in vitro and in vivo studies are required for validation. Nevertheless, this study is a significant step in exploring the use of botanicals in feed to control Infectious Bronchitis infections in poultry. [ABSTRACT FROM AUTHOR]

Silver nanoparticles (Ag-NPs) are most effective against pathogens and have widely been studied as antibacterial agents in commodity clothing, medical textile, and other hygiene products. However, prolonged utilization of silver and rapid mutation in bacterium stains has made them resistant to conventional silver agents. On the other hand, strict compliance against excessive utilization of toxic reagents and the current sustainability drive is forcing material synthesis toward green routes with extended functionality. In this study, we proposed an unprecedented chemical-free green synthesis of bioactive Ag-NPs without the incorporation of any chemicals. Cinnamon essential oil (ECO) was used as a bio-reducing agent with and without the mediation of lime extract. A rapid reaction completion with better shape and size control was observed in the vicinity of lime extract when incorporated into the reaction medium. The interaction of natural metabolites and citrus compounds with nanoparticles was established using Fourier transform infrared spectroscopy (FTIR) and Raman spectroscopy. The application of as-prepared nanoparticles on textiles encompasses extended bioactivity to treated fabric with infused easy-care performance. To the best of our knowledge, this is the first reported instance of utilizing bioactive silver nanoparticles as a functional finish, both as an antimicrobial and as for easy care in the absolute absence of toxic chemicals. The easy-care performance of fabric treated with lime-mediated nanoparticles was found to be 141O, which is around 26% better than bare cotton without any significant loss in fabric strength. Furthermore, to enlighten the sustainability of the process, the development traits were mapped with the United Nations Sustainable Development Goals (SDGs), which show significant influence on SDGs 3, 8, 9, and 14. With the effective suspension of microorganisms, added functionality, and eco-mapping with SDGs with the chemical-free synthesis of nanoparticles, widespread utilization can be found in various healthcare and hygiene products along with the fulfillment of sustainability needs. [ABSTRACT FROM AUTHOR]

The development of long-term symptoms of coronavirus disease 2019 (COVID-19) more than four weeks after primary infection, termed "long COVID" or post-acute sequela of COVID-19 (PASC), can implicate persistent neurological complications in up to one third of patients and present as fatigue, "brain fog", headaches, cognitive impairment, dysautonomia, neuropsychiatric symptoms, anosmia, hypogeusia, and peripheral neuropathy. Pathogenic mechanisms of these symptoms of long COVID remain largely unclear; however, several hypotheses implicate both nervous system and systemic pathogenic mechanisms such as SARS-CoV2 viral persistence and neuroinvasion, abnormal immunological response, autoimmunity, coagulopathies, and endotheliopathy. Outside of the CNS, SARS-CoV-2 can invade the support and stem cells of the olfactory epithelium leading to persistent alterations to olfactory function. SARS-CoV-2 infection may induce abnormalities in innate and adaptive immunity including monocyte expansion, T-cell exhaustion, and prolonged cytokine release, which may cause neuroinflammatory responses and microglia activation, white matter abnormalities, and microvascular changes. Additionally, microvascular clot formation can occlude capillaries and endotheliopathy, due to SARS-CoV-2 protease activity and complement activation, can contribute to hypoxic neuronal injury and blood–brain barrier dysfunction, respectively. Current therapeutics target pathological mechanisms by employing antivirals, decreasing inflammation, and promoting olfactory epithelium regeneration. Thus, from laboratory evidence and clinical trials in the literature, we sought to synthesize the pathophysiological pathways underlying neurological symptoms of long COVID and potential therapeutics. [ABSTRACT FROM AUTHOR]

Excessive high fat diet (HFD) consumption can induce food addiction, which is believed to involve the communication between the hypothalamus and mesolimbic dopaminergic neurons, originating in the ventral tegmental area (VTA) and projecting to the nucleus accumbens (NAc). These brain areas are densely populated with opioid receptors, raising the possibility that these receptors, and particularly mu opioid receptors (MORs), are involved in rewards elicited by palatable food. This study sought to investigate the involvement of MORs in HFD-induced reward and if there is any difference between male and female subjects in this response. We also assessed if exposure to HFD would alter the rewarding action of oxycodone, a relatively selective MOR agonist. The place conditioning paradigm was used as an animal model of reward to determine if short-time (STC, 2 h) or long-time (LTC, 16 h) conditioning with HFD induces reward or alters the rewarding action of oxycodone. Male and female C57BL/6J mice as well as MOR knockout and their wildtype littermates of both sexes were tested for basal place preference on day 1 and then conditioned with an HFD in one chamber and a regular chow diet (RCD) in another chamber for 2 h on alternate days. Three sets of STC were used, followed by a set of LTC. Each set of conditioning consisted of two conditioning with RCD and two conditioning with HFD. Mice were tested for place preference after each set of STC and again after LTC. Controls were conditioned with RCD in both conditioning chambers. Following the last place preference test, mice were treated with oxycodone and conditioned in the HFD-paired chamber and with saline in the RCD-paired chamber for one hour once a day to explore the possibility if the HFD could alter oxycodone reward. The result showed that HFD induced conditioned place preference (CPP) in male but not female subjects. However, oxycodone conditioning elicited reward in both male and female mice of the HFD group but not the control group, showing that prior conditioning with HFD potentiated the rewarding action of oxycodone. The latter response was mediated via MORs, as it was blunted in MOR knockout mice. Similarly, HFD-induced CPP was blunted in male MOR knockout mice, suggesting sexual dimorphism in this response. [ABSTRACT FROM AUTHOR]

Marek's disease virus (MDV), a highly cell-associated oncogenic α-herpesvirus, is the etiological agent of T cell lymphomas and neuropathic disease in chickens known as Marek's disease (MD). Clinical signs of MD include neurological disorders, immunosuppression, and lymphoproliferative lymphomas in viscera, peripheral nerves, and skin. Although vaccination has greatly reduced the economic losses from MD, the molecular mechanism of vaccine-induced protection is largely unknown. To shed light on the possible role of T cells in immunity induced by vaccination, we vaccinated birds after the depletion of circulating T cells through the IP/IV injection of anti-chicken CD4 and CD8 monoclonal antibodies, and challenged them post-vaccination after the recovery of T cell populations post-treatment. There were no clinical signs or tumor development in vaccinated/challenged birds with depleted CD4+ or CD8+ T cells. The vaccinated birds with a combined depletion of CD4+ and CD8+ T cells, however, were severely emaciated, with atrophied spleens and bursas. These birds were also tumor-free at termination, with no virus particles detected in the collected tissues. Our data indicated that CD4+ and CD8+ T lymphocytes did not play a critical role in vaccine-mediated protection against MDV-induced tumor development. [ABSTRACT FROM AUTHOR]

Developing successful conservation programs for genetically depleted species is challenging. Survival and adaptive potential are related to genetic and habitat factors; therefore, conservation programs are designed to minimize risks associated with inbreeding and loss of genetic diversity. The greater mouse-deer (Tragulus napu) is a true forest species that contributes to seed distribution dynamics in forests. However, with continuous demographic decline over the last century in the wild, only captive populations of the greater mouse-deer remain on the Thai mainland. A restoration program initiated 20 years ago has increased their population to more than 100 individuals but maintaining high genetic diversity in a small captive population is crucial for successful recovery. Microsatellite genotyping and mitochondrial D-loop and SRY gene sequence analyses were performed to examine the genetic diversity and population structure in 123 greater mouse-deer (64 females and 59 males). Highly reduced effective captive population size with trends of inbreeding were observed. No historical bottleneck was observed. These conditions have reduced their reproductive fitness and ability to adapt to environmental change, increasing the risk of population decline and eventual extinction. Demographic analyses suggested a recent captive population expansion due to effective animal welfare and reproduction. The results also suggested that population size at equilibrium is the main factor of allelic diversity (number of alleles). Large habitat carrying capacity, representing each fixed captive population size can support the genetic diversity of greater mouse-deer. We also identified suitable habitat areas for reintroduction and long-term in situ conservation of greater mouse-deer using maximum entropy modeling. Based on the environmental variables, species distribution modeling for greater mouse-deer indicated lowland tropical forest regions in the Khlong Saeng-Khao Sok forest complexes as most suitable and requiring urgent habitat improvement. These findings highlight the relevance of careful genetic monitoring and habitat suitability for the long-term conservation of greater mouse-deer and enhance the success of future conservation plans. [ABSTRACT FROM AUTHOR]

Mitochondrial displacement loop (mt D-loop) sequence analyses have greatly improved assessments of genetic diversity, structure, and population dynamics of endangered species threatened by climate change and habitat loss. Tracking population haplotypes of these species using mitochondrial-based markers has opened new avenues for conservation genomics and biodiversity research. Recent studies have used mt D-loop sequences to assess the genetic diversity of the largest land mammal in Asia, the Asian elephant (Elephas maximus), whose populations are rapidly declining. Here, we review haplotype data from mt D-loop sequencing studies and highlight previous population-scale hypotheses pertaining to the origin and diverse genetic profiles of Asian elephants. Retrieving haplotype information from elephant populations can substantially improve estimations of different parameters relevant to their conservation and allow introgression/hybridization dissection of genetic variation to shed light on ongoing evolutionary processes. [ABSTRACT FROM AUTHOR]

The traditional supply chain system included smart objects to enhance intelligence, automation capabilities, and intelligent decision-making. Internet of Things (IoT) technologies are providing unprecedented opportunities to enhance efficiency and reduce the cost of the existing system of the supply chain. This article aims to study the prevailing supply chain system and explore the benefits obtained after smart objects and embedded networks of IoT are implanted. Short-range communication technologies, radio frequency identification (RFID), middleware, and cloud computing are extensively comprehended to conceptualize the smart supply chain management system. Moreover, manufacturers are achieving maximum benefits in terms of safety, cost, intelligent management of inventory, and decision-making. This study also offers concepts of smart carriage, loading/unloading, transportation, warehousing, and packaging for the secure distribution of products. Furthermore, the tracking of customers to convince them to make more purchases and the modification of shops with the assistance of the Internet of Things are thoroughly idealized. [ABSTRACT FROM AUTHOR]

Climate warming-induced glacier recession has resulted in the development and rapid expansion of glacial lakes in the Himalayan region. The increased melting has enhanced the susceptibility for Glacial Lake Outburst Floods (GLOFs) in the region. The catastrophic failure of potentially dangerous glacial lakes could be detrimental to human life and infrastructure in the adjacent low-lying areas. This study attempts to assess the GLOF hazard of Gangabal lake, located in the Upper Jhelum basin of Kashmir Himalaya, using the combined approaches of remote sensing, GIS, and dam break modeling. The parameters, such as area change, ice thickness, mass balance, and surface velocity of the Harmukh glacier, which feeds Gangabal lake, were also assessed using multitemporal satellite data, GlabTop-2, and the Cosi–Corr model. In the worst-case scenario, 100% volume (73 × 106 m3) of water was considered to be released from the lake with a breach formation time (bf) of 40 min, breach width (bw) of 60 m, and producing peak discharge of 16,601.03 m3/s. Our results reveal that the lake area has increased from 1.42 km2 in 1972 to 1.46 km2 in 1981, 1.58 km2 in 1992, 1.61 km2 in 2001, 1.64 km2 in 2010, and 1.66 km2 in 2020. The lake area experienced 17 ± 2% growth from 1972 to 2020 at an annual rate of 0.005 km2. The feeding glacier (Harmukh) contrarily indicated a significant area loss of 0.7 ± 0.03 km2 from 1990 (3.36 km2) to 2020 (2.9 km2). The glacier has a maximum, minimum, and average depth of 85, 7.3, and 23.46 m, respectively. In contrast, the average velocity was estimated to be 3.2 m/yr with a maximum of 7 m/yr. The results obtained from DEM differencing show an average ice thickness loss of 11.04 ± 4.8 m for Harmukh glacier at the rate of 0.92 ± 0.40 m/yr between 2000 and 2012. Assessment of GLOF propagation in the worst-case scenario (scenario-1) revealed that the maximum flood depth varies between 3.87 and 68 m, the maximum flow velocity between 4 and 75 m/s, and the maximum water surface elevation varies between 1548 and 3536 m. The resultant flood wave in the worst-case scenario will reach the nearest location (Naranaag temple) within 90 min after breach initiation with a maximum discharge of 12,896.52 m3 s−1 and maximum flood depth and velocity of 10.54 m and 10.05 m/s, respectively. After evaluation of GLOF impacts on surrounding areas, the area under each inundated landuse class was estimated through the LULC map generated for both scenarios 1 and 2. In scenario 1, the total potentially inundated area was estimated as 5.3 km2, which is somewhat larger than 3.46 km2 in scenario 2. We suggest a location-specific comprehensive investigation of Gangbal lake and Harmukh glacier by applying the advanced hazard and risk assessment models/methods for better predicting a probable future GLOF event. [ABSTRACT FROM AUTHOR]

Illegal wildlife trade is a major threat to global biodiversity. Asian elephants (Elephas maximus) are highly valued by various cultures as religious symbols and tourist attractions, which has led to a high demand for captive elephants. Owing to the unviability of captive breeding programs, several captive elephant populations are maintained by illegally obtaining wild Asian elephants. Morbidity and mortality rates among captive populations are high, whereas reproduction is low. In this study, we examined the genetic diversity among elephants using microsatellite genotyping and mitochondrial D-loop sequences of three captive elephant populations. The study results showed very low nucleotide diversity D-loop sequences and high variations in microsatellite genotyping, with an extensive variation of the gene pool estimates from different populations. This suggests that the optimal male selection during breeding could aid in maintaining the genetic diversity among captive populations. Forward genetic simulation revealed a decreasing genetic diversity in the fixed state within 50 generations. However, largely different gene pools can be effectively used to infer original elephant sources; this would facilitate the development of an identification certificate integration with machine learning and image processing to prevent illegal legislation owing to registration fraud between wild and domestic elephants. Implementing the proposed approaches and recommendations would aid in the mitigation of the illegal capture and domestic trade of wild elephants in Thailand and contribute to the success of future conservation plans in the blueprint of sustainable development goals. [ABSTRACT FROM AUTHOR]

Immunoglobulin-like cell adhesion molecule (IgLON4) is a glycosylphosphatidylinositol-anchored membrane protein that has been associated with neuronal growth and connectivity, and its deficiency has been linked to increased fat mass and low muscle mass. Adequate information on IgLON4 is lacking, especially in the context of skeletal muscle. In this study, we report that IgLON4 is profusely expressed in mouse muscles and is intensely localized on the cell membrane. IgLON4 expression was elevated in CTX-injected mouse muscles, which confirmed its role during muscle regeneration, and was abundantly expressed at high concentrations at cell-to-cell adhesion and interaction sites during muscle differentiation. IgLON4 inhibition profoundly affected myotube alignment, and directional analysis confirmed this effect. Additionally, results demonstrating a link between IgLON4 and lipid rafts during myogenic differentiation suggest that IgLON4 promotes differentiation by increasing lipid raft accumulation. These findings support the notion that a well-aligned environment promotes myoblast differentiation. Collectively, IgLON4 plays a novel role in myogenesis and regeneration, facilitates myotube orientation, and is involved in lipid raft accumulation. [ABSTRACT FROM AUTHOR]

Earias vittella Fabricius is a potential cotton and okra pest in South Asia. The realized heritability, risk assessment, and inheritance mode of Bacillus thuringiensis Kurstaki (Btk) resistance were determined in the Dipel-selected (DIPEL-SEL) E. vittella. The DIPEL-SEL strain had a 127.56-fold rise in Dipel resistance after nine generations compared to the laboratory reference strain (LAB-PK). The overlapping of 95% fiducial limits in the median lethal concentrations (LC50s) of the F1 (DIPEL-SEL♂ × LAB-PK♀) and F1ǂ (DIPEL-SEL♀ × LAB-PK♂) suggested a lack of sex linkage and an autosomal Dipel resistance. The dominance (DLC) values for the F1 (0.86) and F1ǂ (0.94) indicated incompletely dominant resistance to Dipel. Backcrossing of the F1♀ × Lab-PK♂ revealed a polygenic response of resistance to Dipel. The realized heritability estimation (h2) of resistance to Dipel was 0.19. With 20% to 90% selection mortality, the generations required for a tenfold increase in LC50 of Dipel were 4.7–22.8, 3.1–14.9, and 2.3–11.1 at h2 of 0.19, 0.29, and 0.39, respectively, and a constant slope of 1.56. At slope values of 2.56 and 3.56 with a constant h2 = 0.19, 7.7–37.4 and 10.6–52.0 generations were needed to increase the tenfold LC50 of Dipel in the DIPEL-SEL E. vittella. It is concluded that the DIPEL-SEL E. vittella has an autosomal, incompletely dominant, and polygenic nature of resistance. The h2 of 0.19 suggested that a high proportion of phenotypic variation for the Dipel resistance in E. vittella was heritable genetic variation. The present results will support the creation of an effective and suitable resistance management plan for better control of E. vittella. [ABSTRACT FROM AUTHOR]

The Siamese fighting fish (Betta splendens) is a well-known ornamental fish and emerging model species for studying animal morphology, physiology, and behavior. A key concern of betta inbreeding is the decline in genetic diversity resulting from commercial breeding programs. Therefore, it is essential to develop markers for understanding the genetic bases of the domestication and phenotypic diversification of this species. We utilized the previously assembled genome of Siamese fighting fish to identify and characterize microsatellites and compare their genomic organization across different species. We annotated 812,134 microsatellite loci spanning 30.70 Mb, accounting for 6.57% of the Siamese fighting fish genome. We performed in silico polymorphism screening of microsatellites in the Siamese fighting fish and related species and present these sequences as candidate markers for cross-species amplification. In addition, we successfully validated two microsatellite loci using PCR-based assays in different species, which can promote further genetic characterization of diverse betta lineages. The set of polymorphic markers identified in this study may facilitate the assessment of genetic diversity and population structure and marker-assisted selection, among other applications. [ABSTRACT FROM AUTHOR]

Bats are important reservoir hosts of emerging viruses. Recent viral outbreaks and pandemics have resulted in an increased research focus on the genetic diversity, population structure, and distribution of bat species. Lyle's flying fox (Pteropus lylei) is widely distributed throughout central Thailand, with most colonies congregating in temples within proximity to humans. A lack of knowledge regarding the genetic connectivity among different colonies hinders the investigation of zoonotic disease epidemiology and wildlife management. In this study, we hypothesized that genetic material may be exchanged between Lyle's flying fox colonies that live in proximity. We assessed the mitochondrial displacement loop and cytochrome b nucleotide sequences of samples collected from 94 individuals from ten colonies across different roosting sites and detected limited genetic differentiation but increased nucleotide divergence within colonies. This suggests that genetic connectivity among Lyle's flying fox colonies has experienced frequent and recent gene flow. These findings indicate that this species has maintained demographic equilibrium in a stable population, with a slight expansion event in certain populations. These data provide insights into the dynamics of bat populations, and the genetic knowledge gained presents opportunities for the improved monitoring of bat population structure. [ABSTRACT FROM AUTHOR]

Myostatin (MSTN), a negative regulator of muscle mass, is reported to be increased in conditions linked with muscle atrophy, sarcopenia, and other muscle-related diseases. Most pharmacologic approaches that treat muscle disorders are ineffective, emphasizing the emergence of MSTN inhibition. In this study, we used computational screening to uncover natural small bioactive inhibitors from the Traditional Chinese Medicine database (~38,000 compounds) for the MSTN protein. Potential ligands were screened, based on binding affinity (150), physicochemical (53) and ADMET properties (17). We found two hits (ZINC85592908 and ZINC85511481) with high binding affinity and specificity, and their binding patterns with MSTN protein. In addition, molecular dynamic simulations were run on each complex to better understand the interaction mechanism of MSTN with the control (curcumin) and the hit compounds (ZINC85592908 and ZINC85511481). We determined that the hits bind to the active pocket site (Helix region) and trigger conformational changes in the MSTN protein. Since the stability of the ZINC85592908 compound was greater than the MSTN control, we believe that ZINC85592908 has therapeutic potential against the MSTN protein and may hinder downstream singling by inhibiting the MSTN protein and increasing myogenesis in the skeletal muscle tissues. [ABSTRACT FROM AUTHOR]

The domestication of wild animals represents a major milestone for human civilization. Chicken is the largest domesticated livestock species and used for both eggs and meat. Chicken originate from the red junglefowl (Gallus gallus). Its adaptability to diverse environments and ease of selective breeding provides a unique genetic resource to address the challenges of food security in a world impacted by climatic change and human population growth. Habitat loss has caused population declines of red junglefowl in Thailand. However, genetic diversity is likely to remain in captive stocks. We determine the genetic diversity using microsatellite genotyping and the mitochondrial D-loop sequencing of wild red junglefowl. We identified potential distribution areas in Thailand using maximum entropy models. Protected areas in the central and upper southern regions of Thailand are highly suitable habitats. The Bayesian clustering analysis of the microsatellite markers revealed high genetic diversity in red junglefowl populations in Thailand. Our model predicted that forest ranges are a highly suitable habitat that has enabled the persistence of a large gene pool with a nationwide natural distribution. Understanding the red junglefowl allows us to implement improved resource management, species reintroduction, and sustainable development to support food security objectives for local people. [ABSTRACT FROM AUTHOR]

Centromeric satellite DNA (cen-satDNA) consists of highly divergent repeat monomers, each approximately 171 base pairs in length. Here, we investigated the genetic diversity in the centromeric region of two primate species: long-tailed (Macaca fascicularis) and rhesus (Macaca mulatta) macaques. Fluorescence in situ hybridization and bioinformatic analysis showed the chromosome-specific organization and dynamic nature of cen-satDNAsequences, and their substantial diversity, with distinct subfamilies across macaque populations, suggesting increased turnovers. Comparative genomics identified high level polymorphisms spanning a 120 bp deletion region and a remarkable interspecific variability in cen-satDNA size and structure. Population structure analysis detected admixture patterns within populations, indicating their high divergence and rapid evolution. However, differences in cen-satDNA profiles appear to not be involved in hybrid incompatibility between the two species. Our study provides a genomic landscape of centromeric repeats in wild macaques and opens new avenues for exploring their impact on the adaptive evolution and speciation of primates. [ABSTRACT FROM AUTHOR]

The peritoneal cavity is a common site of metastatic spread from colorectal cancer (CRC). Patients with peritoneal metastases (PM) often have aggressive underlying tumor biology and poor survival. While only a minority of patients with CRC have potentially resectable disease, the high overall incidence of CRC makes management of PM a common clinical problem. In this population, cytoreductive surgery (CRS)-hyperthermic intraperitoneal chemotherapy (HIPEC) is the only effective therapy for appropriately selected patients. In this narrative review, we summarize the existing literature on CRS-HIPEC in colorectal PM. Recent prospective clinical trials have shown conflicting evidence regarding the benefit of HIPEC perfusion in addition to CRS. Current strategies to prevent PM in those at high-risk have been shown to be ineffective. Herein we will provide a framework for clinicians to understand and apply these data to treat this complex disease presentation. [ABSTRACT FROM AUTHOR]

Fishes provide a unique and intriguing model system for studying the genomic origin and evolutionary mechanisms underlying sex determination and high sex-chromosome turnover. In this study, the mode of sex determination was investigated in Siamese fighting fish, a species of commercial importance. Genome-wide SNP analyses were performed on 75 individuals (40 males and 35 females) across commercial populations to determine candidate sex-specific/sex-linked loci. In total, 73 male-specific loci were identified and mapped to a 5.6 kb region on chromosome 9, suggesting a putative male-determining region (pMDR) containing localized dmrt1 and znrf3 functional sex developmental genes. Repeat annotations of the pMDR revealed an abundance of transposable elements, particularly Ty3/Gypsy and novel repeats. Remarkably, two out of the 73 male-specific loci were located on chromosomes 7 and 19, implying the existence of polygenic sex determination. Besides male-specific loci, five female-specific loci on chromosome 9 were also observed in certain populations, indicating the possibility of a female-determining region and the polygenic nature of sex determination. An alternative explanation is that male-specific loci derived from other chromosomes or female-specific loci in Siamese fighting fish recently emerged as new sex-determining loci during domestication and repeated hybridization. [ABSTRACT FROM AUTHOR]

Simple Summary: Treatment of pancreas ductal adenocarcinoma (PDAC) remains challenging due to the late stage of presentation, limited efficacy of cytotoxic chemotherapies, and aggressive tumor biology. Novel therapeutic targets are desperately needed. The voltage-gated potassium channel, Kv1.3, is one such unique target. It has been extensively studied in many cancers but less is known in pancreas cancer. In this study, we evaluated the tissue expression of Kv1.3 in resected PDAC and tumor inhibition using novel Kv1.3 inhibitors developed by our group (PCARBTP and PAPTP) with cytotoxic chemotherapies. We found that Kv1.3 is expressed in early stage, non-metastatic, resectable pancreas cancer specimens. Treatment with novel mitochondrial Kv1.3 inhibitors resulted in 95% reduced tumor growth when combined with cytotoxic chemotherapies. This near complete eradication of tumors using this treatment strategy shows that Kv1.3 represents an innovative therapeutic target for pancreas cancer therapy. Pancreas ductal adenocarcinoma (PDAC) is one the most aggressive cancers and associated with very high mortality, requiring the development of novel treatments. The mitochondrial voltage-gated potassium channel, Kv1.3 is emerging as an attractive oncologic target but its function in PDAC is unknown. Here, we evaluated the tissue expression of Kv1.3 in resected PDAC from 55 patients using immunohistochemistry (IHC) and show that all tumors expressed Kv1.3 with 60% of tumor specimens having high Kv1.3 expression. In Pan02 cells, the recently developed mitochondria-targeted Kv1.3 inhibitors PCARBTP and PAPTP strongly reduced cell survival in vitro. In an orthotopic pancreas tumor model (Pan02 cells injected into C57BL/6 mice) in immune-competent mice, injection of PAPTP or PCARBTP resulted in tumor reductions of 87% and 70%, respectively. When combined with clinically used Gemcitabine plus Abraxane (albumin-bound paclitaxel), reduction reached 95% and 80% without resultant organ toxicity. Drug-mediated tumor cell death occurred through the p38-MAPK pathway, loss of mitochondrial membrane potential, and oxidative stress. Resistant Pan02 clones to PCARBTP escaped cell death through upregulation of the antioxidant system. In contrast, tumor cells did not develop resistance to PAPTP. Our data show that Kv1.3 is highly expressed in resected human PDAC and the use of novel mitochondrial Kv1.3 inhibitors combined with cytotoxic chemotherapies might be a novel, effective treatment for PDAC. [ABSTRACT FROM AUTHOR]

Simple Summary: The primary characteristics of cancer cachexia are weakness, weight loss, atrophy, fat reduction, and systemic inflammation. Cachexia is strongly associated with cancers involving the lungs, pancreas, esophagus, stomach, and liver, which account for half of all cancer deaths. TGF-β, MSTN, activin, IGF-1/PI3K/AKT, and JAK-STAT signaling pathways are known to underlie muscle atrophy and cachexia. Anamorelin (appetite stimulation), megestrol acetate, eicosapentaenoic acid, phytocannabinoids, targeting MSTN/activin, and molecules targeting proinflammatory cytokines, such as TNF-α and IL-6, are being tested as treatment options for cancer cachexia. Cancer cachexia is a condition marked by functional, metabolic, and immunological dysfunctions associated with skeletal muscle (SM) atrophy, adipose tissue loss, fat reduction, systemic inflammation, and anorexia. Generally, the condition is caused by a variety of mediators produced by cancer cells and cells in tumor microenvironments. Myostatin and activin signaling, IGF-1/PI3K/AKT signaling, and JAK-STAT signaling are known to play roles in cachexia, and thus, these pathways are considered potential therapeutic targets. This review discusses the current state of knowledge of the molecular mechanisms underlying cachexia and the available therapeutic options and was undertaken to increase understanding of the various factors/pathways/mediators involved and to identify potential treatment options. [ABSTRACT FROM AUTHOR]

Summary: Recent studies have proposed that adequate intake of Vitamin K (VK) is associated with a low risk of fracture and high bone mineral density (BMD) to improve skeletal health in adults. This systematic review was designed to summarize the most relevant and updated evidence discussing the relationship between VK and bone. It explores the effect of VK deficiency and its supplementation on various bone parameters. Methods: The distinct databases such as PubMed, the Cochrane Library, Google Scholar, National Clinical Trials, Current Controlled Trials, and Clinical Trials were searched up to Jan 2020 to identify eligible trials. All relevant randomized controlled trial studies with any oral dosage form of VK supplement administered for at least six months and assessing BMD or fracture in adults were extracted. Finally, two independent reviewers identified 20 relevant citations for the systematic review and extracted data in tabular form. Results: The meta-analysis was performed with all studies, including postmenopausal and osteoporotic females, for both total clinical and vertebral fracture outcomes. The quantitative analysis showed that the odds ratios (OR) of any fracture were lower for VK as compared to control [OR 0.42 (95% CI 0.27 to 0.66)] for vertebral fractures and OR of 0.44 (95% CI 0.23 to 0.88) for clinical fracture. For the BMD, a meta-analysis of the pooled effect of interventional studies suggested a non-significant association between the use of VK and improvement in femoral BMD (CI 95%, p = 0.08 [−0.03–0.20]). Conclusion: VK decreases general fracture risk, and it can be an option to counter bone loss disorders. However, insufficient evidence is available regarding the significant impact of VK on femoral neck BMD. Therefore, further studies are required to establish the therapeutic value of VK as a treatment for osteoporosis. [ABSTRACT FROM AUTHOR]

The use of peptides as drugs has progressed over time and continues to evolve as treatment paradigms change and new drugs are developed. Myostatin (MSTN) inhibition therapy has shown great promise for the treatment of muscle wasting diseases. Here, we report the MSTN-derived novel peptides MIF1 (10-mer) and MIF2 (10-mer) not only enhance myogenesis by inhibiting MSTN and inducing myogenic-related markers but also reduce adipogenic proliferation and differentiation by suppressing the expression of adipogenic markers. MIF1 and MIF2 were designed based on in silico interaction studies between MSTN and its receptor, activin type IIB receptor (ACVRIIB), and fibromodulin (FMOD). Of the different modifications of MIF1 and MIF2 examined, Ac-MIF1 and Ac-MIF2-NH2 significantly enhanced cell proliferation and differentiation as compared with non-modified peptides. Mice pretreated with Ac-MIF1 or Ac-MIF2-NH2 prior to cardiotoxin-induced muscle injury showed more muscle regeneration than non-pretreated controls, which was attributed to the induction of myogenic genes and reduced MSTN expression. These findings imply that Ac-MIF1 and Ac-MIF2-NH2 might be valuable therapeutic agents for the treatment of muscle-related diseases. [ABSTRACT FROM AUTHOR]

Transposable elements (TEs) comprise a substantial portion of eukaryotic genomes. They have the unique ability to integrate into new locations and serve as the main source of genomic novelties by mediating chromosomal rearrangements and regulating portions of functional genes. Recent studies have revealed that TEs are abundant in sex chromosomes. In this review, we propose evolutionary relationships between specific TEs, such as Ty3/Gypsy, and sex chromosomes in different lineages based on the hypothesis that these elements contributed to sex chromosome differentiation processes. We highlight how TEs can drive the dynamics of sex-determining regions via suppression recombination under a selective force to affect the organization and structural evolution of sex chromosomes. The abundance of TEs in the sex-determining regions originates from TE-poor genomic regions, suggesting a link between TE accumulation and the emergence of the sex-determining regions. TEs are generally considered to be a hallmark of chromosome degeneration. Finally, we outline recent approaches to identify TEs and study their sex-related roles and effects in the differentiation and evolution of sex chromosomes. [ABSTRACT FROM AUTHOR]

Cultured meat production is an evolving method of producing animal meat using tissue engineering techniques. Cells, chemical factors, and suitable biomaterials that serve as scaffolds are all essential for the cultivation of muscle tissue. Scaffolding is essential for the development of organized meat products resembling steaks because it provides the mechanical stability needed by cells to attach, differentiate, and mature. In in vivo settings, extracellular matrix (ECM) ensures substrates and scaffolds are provided for cells. The ECM of skeletal muscle (SM) maintains tissue elasticity, creates adhesion points for cells, provides a three-dimensional (3D) environment, and regulates biological processes. Consequently, creating mimics of native ECM is a difficult task. Animal-derived polymers like collagen are often regarded as the gold standard for producing scaffolds with ECM-like properties. Animal-free scaffolds are being investigated as a potential source of stable, chemically defined, low-cost materials for cultured meat production. In this review, we explore the influence of ECM on myogenesis and its role as a scaffold and vital component to improve the efficacy of the culture media used to produce cultured meat. [ABSTRACT FROM AUTHOR]

Simple Summary: Subclinical mastitis represents a significant disease in dairy animals and negatively impacts udder health. Genetics, pathogens, and poor health and management procedures in dairy animals contribute primarily to this disease. Animal genetics plays a major role in disease resistance and susceptibility. Studying single-nucleotide polymorphisms in genes helps to detect resistant and susceptible animals. Transferrin is one of the important glycoproteins involved in the innate immune system that prevents iron availability to pathogens. Several studies have reported polymorphism in the transferrin gene in dairy animals with mastitis, but no detailed information on in silico tools is available for identification and verification. So, this study was carried out to detect polymorphism in the transferrin gene in healthy and mastitic cows, and to use various in silico based tools and software to find the impact of single-nucleotide polymorphisms (SNPs) on animal health. The results indicated three SNPs were located in the transferrin gene of Holstein Friesian cross-bred dairy cows. Moreover, the use of online computational tools provided significant knowledge regarding whether the SNPs would be deleterious, damaging, benign, neutral, or affect protein stability and function. Dairy cattle with a high milk yield are susceptible to many infectious diseases, such as mastitis. Subclinical mastitis (SCM) is the most prevalent form of mastitis that predominantly affects animal health, and causes adverse effects on the quality and quantity of milk. In dairy animals, subclinical mastitis often remains undetected, as no gross changes in udder characteristics are visible. In the present study, 135 Holstein Friesian dairy animals were selected and screened as healthy (n = 25) and mastitic (n = 110) based on diagnostic tests such as the California mastitis test, pH, electrical conductivity, and somatic cell count. In this study, the somatic cell count was used as a gold-standard test in differentiating subclinical mastitis animals from healthy ones. The present study was carried out to study polymorphisms in the bovine transferrin gene in cows (with subclinical mastitis and healthy). For the early detection of resistant/or susceptible animals, a useful marker could be provided by the detection of single-nucleotide polymorphisms (SNPs) in the transferrin gene, which are often associated with mammary innate immune response. The sequencing results revealed three nucleotide substitutions: two transversions (230 A > C, 231 C > A) and one transition (294 A > G) in susceptible cows as compared to disease-free subjects. The nucleotide variations at position 230 (GAC > GCA) and 231 (GAC > GCA) were nonsynonymous, and corresponded to an amino acid change from aspartic acid to alanine; whereas at position 294 (GAA > GAG), the mutation was synonymous. In the present study, many in silico tools were taken into consideration to determine the effect of SNPs on protein structure and function. The PROVEAN tool found the amino acid substitution to be neutral and deleterious. PolyPhen-2 revealed the amino acid variations at positions 320 and 321 to most likely be damaging; and at the 341 position, the variations were benign. The I-Mutant and MUpro tools found that the protein stability decreased for nonsynonymous variations. The SIFT tool revealed the protein function was likely to be affected in nonsynonymous variations, with no change in the case of synonymous ones. Phylogenetic analysis of the bovine transferrin gene revealed a close relation of the CA allele with the Bos taurus transferrin, while the G allele was closely related to a cross of Bos indicus × Bos taurus serotransferrins, followed by the Bison bison transferrin. The least relation was shown by both alleles to Capra hircus, Ovis aries, and Bubalus bubalis. [ABSTRACT FROM AUTHOR]

Safety and reliability of electrical actuators are essential for success of all electric and more electric aircrafts (MEA). Torque limiters improve the reliability of electromechanical actuators (EMA) by restricting the amount of force experienced by the actuator drive train components. If transmitted torque in the shaft exceeds a limit, it gives way in a controlled manner. This protects the actuator from potential failure and jamming. In this paper, different types of existing torque limiters are investigated for their suitability in aerospace EMA application and further integration within the electric motor. They classified based on the torque transmission mechanism and each type is described in detail. Operating principle and basic characteristics are reported. Comparative evaluation of commercially available devices is presented. It is found that those based on friction based and permanent magnet are most suitable due to their good torque density, reliability and high speed capability. Further, based on the characteristics, integration of torque limiter within the actuator motor is investigated in this paper. An example actuator motor is considered for integration. Different integration options suitable for the different types of torque limiting devices are described. Reduction in overall volume is shown for the integration options. Such integration can lead to improved reliability as well as higher power density resulting in next-generation actuator electrical drives for MEA. [ABSTRACT FROM AUTHOR]

Simple Summary: The evolutionary patterns and phylogenetic utility of duplicate control regions (CRs) in 72 individuals of Varanus salvator macromaculatus and other varanids have been observed. Divergence of the two CRs from each individual revealed a pattern of independent evolution in CRs of varanid lineage. This study is a first step towards developing new phylogenetic evolutionary models of the varanid lineage, with accurate evolutionary inferences to provide basic insights into the biology of mitogenomes. Duplicate control regions (CRs) have been observed in the mitochondrial genomes (mitogenomes) of most varanids. Duplicate CRs have evolved in either concerted or independent evolution in vertebrates, but whether an evolutionary pattern exists in varanids remains unknown. Therefore, we conducted this study to analyze the evolutionary patterns and phylogenetic utilities of duplicate CRs in 72 individuals of Varanus salvator macromaculatus and other varanids. Sequence analyses and phylogenetic relationships revealed that divergence between orthologous copies from different individuals was lower than in paralogous copies from the same individual, suggesting an independent evolution of the two CRs. Distinct trees and recombination testing derived from CR1 and CR2 suggested that recombination events occurred between CRs during the evolutionary process. A comparison of substitution saturation showed the potential of CR2 as a phylogenetic marker. By contrast, duplicate CRs of the four examined varanids had similar sequences within species, suggesting typical characteristics of concerted evolution. The results provide a better understanding of the molecular evolutionary processes related to the mitogenomes of the varanid lineage. [ABSTRACT FROM AUTHOR]

Pituitary adenylyl cyclase activating polypeptide (PACAP) belongs to the vasoactive intestinal polypeptide (VIP)/secretin/glucagon superfamily. PACAP is present in two forms (PACAP-38 and PACAP-27) and binds to three guanine-regulatory (G) protein-coupled receptors (PAC1, VPAC1, and VPAC2). PACAP is expressed in the central and peripheral nervous systems, with high PACAP levels found in the hypothalamus, a brain region involved in feeding and energy homeostasis. PAC1 receptors are high-affinity and PACAP-selective receptors, while VPAC1 and VPAC2 receptors show a comparable affinity to PACAP and VIP. PACAP and its receptors are expressed in the central and peripheral nervous systems with moderate to high expression in the hypothalamus, amygdala, and other limbic structures. Consistent with their expression, PACAP is involved in several physiological responses and pathological states. A growing body of literature suggests that PACAP regulates food intake in laboratory animals. However, there is no comprehensive review of the literature on this topic. Thus, the purpose of this article is to review the literature regarding the role of PACAP and its receptors in food intake regulation and to synthesize how PACAP exerts its anorexic effects in different brain regions. To achieve this goal, we searched PubMed and reviewed 68 articles regarding the regulatory action of PACAP on food intake. Here, we present the literature regarding the effect of exogenous PACAP on feeding and the role of endogenous PACAP in this process. We also provide evidence regarding the effect of PACAP on the homeostatic and hedonic aspects of food intake, the neuroanatomical sites where PACAP exerts its regulatory action, which PACAP receptors may be involved, and the role of various signaling pathways and neurotransmitters in hypophagic effects of PACAP. [ABSTRACT FROM AUTHOR]

Simple Summary: HER2 may contribute to immune evasion in gastric cancer that is associated with PD-L1 expression. Autologous organoid/immune cell co-cultures serve as an appropriate in vitro model to study the effects of anti-HER2 targeted therapy in combination with anti-PD1 immune checkpoint inhibition and may be used as an ex vivo tool for precision medicine. (1) Background: The expression of programmed death-ligand 1 (PD-L1), which interacts with programmed cell death protein 1 (PD-1) on cytotoxic T lymphocytes (CTLs), enables tumors to escape immunosurveillance. The PD-1/PD-L1 interaction results in the inhibition of CTL proliferation, and effector function, thus promoting tumor cell evasion from immunosurveillance and cancer persistence. Despite 40% of gastric cancer patients exhibiting PD-L1 expression, only a small subset of patients responds to immunotherapy. Human epidermal growth factor receptor2 (HER2) is one of the critical regulators of several solid tumors, including metastatic gastric cancer. Although half of PD-L1-positive gastric tumors co-express HER2, crosstalk between HER2 and PD-1/PD-L1 in gastric cancer remains undetermined. (2) Methods: Human gastric cancer organoids (huTGOs) were generated from biopsied or resected tissues and co-cultured with CTLs and myeloid-derived suppressor cells (MDSCs). Digital Spatial Profiling (DSP) was performed on FFPE tissue microarrays of numerous gastric cancer patients to examine the protein expression of immune markers. (3) Results: Knockdown of HER2 in PD-L1/HER2-positive huTGOs led to a concomitant decrease in PD-L1 expression. Similarly, in huTGOs/immune cell co-cultures, PD-L1 expression decreased in huTGOs and was correlated with an increase in CTL proliferation which enhanced huTGO death. Treatment with Nivolumab exhibited similar effects. However, a combinatorial treatment with Mubritinib and Nivolumab was unable to inhibit HER2 expression in co-cultures containing MDSCs. (4) Conclusions: Our study suggested that co-expression of HER2 and PD-L1 may contribute to tumor cell immune evasion. In addition, autologous organoid/immune cell co-cultures can be exploited to effectively screen responses to a combination of anti-HER2 and immunotherapy to tailor treatment for gastric cancer patients. [ABSTRACT FROM AUTHOR]

The snakeskin gourami (Trichopodus pectoralis) has a high meat yield and is one of the top five aquaculture freshwater fishes in Thailand. The species is not externally sexually dimorphic, and its sex determination system is unknown. Understanding the sex determination system of this species will contribute to its full-scale commercialization. In this study, a cytogenetic analysis did not reveal any between-sex differences in chromosomal patterns. However, we used genotyping-by-sequencing to identify 4 male-linked loci and 1 female-linked locus, indicating that the snakeskin gourami tends to exhibit an XX/XY sex determination system. However, we did not find any male-specific loci after filtering the loci for a ratio of 100:0 ratio of males:females. This suggests that the putative Y chromosome is young and that the sex determination region is cryptic. This approach provides solid information that can help identify the sex determination mechanism and potential sex determination regions in the snakeskin gourami, allowing further investigation of genetic improvements in the species. [ABSTRACT FROM AUTHOR]

Comparative chromosome maps investigating sex chromosomal linkage groups in amniotes and microsatellite repeat motifs of a male house gecko lizard (Hemidactylus frenatus, HFR) and a flat-tailed house gecko lizard (H. platyurus, HPL) of unknown sex were examined using 75 bacterial artificial chromosomes (BACs) from chicken and zebra finch genomes. No massive accumulations of microsatellite repeat motifs were found in either of the gecko lizards, but 10 out of 13 BACs mapped on HPL chromosomes were associated with other amniote sex chromosomes. Hybridization of the same BACs onto multiple different chromosome pairs suggested transitions to sex chromosomes across amniotes. No BAC hybridization signals were found on HFR chromosomes. However, HFR diverged from HPL about 30 million years ago, possibly due to intrachromosomal rearrangements occurring in the HFR lineage. By contrast, heterochromatin likely reshuffled patterns between HPL and HFR, as observed from C-positive heterochromatin distribution. Six out of ten BACs showed partial homology with squamate reptile chromosome 2 (SR2) and snake Z and/or W sex chromosomes. The gecko lizard showed shared unrelated sex chromosomal linkages—the remnants of a super-sex chromosome. A large ancestral super-sex chromosome showed a correlation between SR2 and snake W sex chromosomes. [ABSTRACT FROM AUTHOR]

Sex determination systems (SDSs) in anurans are diverse and have undergone independent evolutionary transitions among species. The mode of sexual reproduction of the rice field frog (Hoplobatrachus rugulosus)—an economically viable, edible amphibian species—is not well known. Previous studies have proposed that threshold temperature conditions may determine sex in these frogs. To elucidate the SDS in H. rugulosus, we karyotyped 10 male and 12 female frogs, and performed fluorescence in situ hybridization combined with sequencing analyses using DArTseq™. Our results revealed a highly conserved karyotype with no sex chromosome heteromorphism, and the sequencing analyses did not identify any consistent sex-linked loci, supporting the hypothesis of temperature-dependent sex determination. The results of this study, and others, on SDSs in the rice field frog and related species also provide support for the theory that heteromorphic sex chromosomes may lead to an evolutionary trap that prevents variable SDSs. These findings add important information to the body of knowledge on H. rugulosus and are likely to have a significant impact on the productivity and economic success of rice field frog farming. [ABSTRACT FROM AUTHOR]

The world's population continues to increase, meaning we require more consistent protein supply to meet demand. Despite the availability of plant-based protein alternatives, animal meat remains a popular, high-quality protein source. Research studies have focused on cultured meat (meat grown in vitro) as a safe and more efficient alternative to traditional meat. Cultured meat is produced by in vitro myogenesis, which involves the processing of muscle satellite and mature muscle cells. Meat culture efficiency is largely determined by the culture conditions, such as the cell type and cell culture medium used and the biomolecular composition. Protein production can be enhanced by providing the optimum biochemical and physical conditions for skeletal muscle cell growth, while myoblasts play important roles in skeletal muscle formation and growth. This review describes the cell types used to produce cultured meat and the biological effects of various myokines and cytokines, such as interleukin-6, leukemia inhibitory factor, interleukin-4, interleukin-15, and interleukin-1β, on skeletal muscle and myogenesis and their potential roles in cultured meat production. [ABSTRACT FROM AUTHOR]

The skeletal muscle (SM) is the largest organ in the body and has tremendous regenerative power due to its myogenic stem cell population. Myostatin (MSTN), a protein produced by SM, is released into the bloodstream and is responsible for age-related reduced muscle fiber development. The objective of this study was to identify the natural compounds that inhibit MSTN with therapeutic potential for the management of age-related disorders, specifically muscle atrophy and sarcopenia. Sequential screening of 2000 natural compounds was performed, and dithymoquinone (DTQ) was found to inhibit MSTN with a binding free energy of −7.40 kcal/mol. Furthermore, the docking results showed that DTQ reduced the binding interaction between MSTN and its receptor, activin receptor type-2B (ActR2B). The global energy of MSTN-ActR2B was found to be reduced from −47.75 to −40.45 by DTQ. The stability of the DTQ–MSTN complex was subjected to a molecular dynamics analysis for up to 100 ns to check the stability of the complex using RMSD, RMSF, Rg, SASA, and H-bond number. The complex was found to be stable after 10 ns to the end of the simulation. These results suggest that DTQ blocks MSTN signaling through ActR2B and that it has potential use as a muscle growth-promoting agent during the aging process. [ABSTRACT FROM AUTHOR]

With more than 70,000 living species, vertebrates have a huge impact on the field of biology and research, including karyotype evolution. One prominent aspect of many vertebrate karyotypes is the enigmatic occurrence of tiny and often cytogenetically indistinguishable microchromosomes, which possess distinctive features compared to macrochromosomes. Why certain vertebrate species carry these microchromosomes in some lineages while others do not, and how they evolve remain open questions. New studies have shown that microchromosomes exhibit certain unique characteristics of genome structure and organization, such as high gene densities, low heterochromatin levels, and high rates of recombination. Our review focuses on recent concepts to expand current knowledge on the dynamic nature of karyotype evolution in vertebrates, raising important questions regarding the evolutionary origins and ramifications of microchromosomes. We introduce the basic karyotypic features to clarify the size, shape, and morphology of macro- and microchromosomes and report their distribution across different lineages. Finally, we characterize the mechanisms of different evolutionary forces underlying the origin and evolution of microchromosomes. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate fibromodulin (FMOD) and myostatin (MSTN) gene expressions during skeletal muscle aging and to understand their involvements in this process. The expressions of genes related to muscle aging (Atrogin 1 and Glb1), diabetes (RAGE and CD163), and lipid accumulation (CD36 and PPARγ) and those of FMOD and MSTN were examined in CTX-injected, aged, MSTN−/−, and high-fat diet (HFD) mice and in C2C12 myoblasts treated with ceramide or grown under adipogenic conditions. Results from CTX-injected mice and gene knockdown experiments in C2C12 cells suggested the involvement of FMOD during muscle regeneration and myoblast proliferation and differentiation. Downregulation of the FMOD gene in MSTN−/− mice, and MSTN upregulation and FMOD downregulation in FMOD and MSTN knockdown C2C12 cells, respectively, during their differentiation, suggested FMOD negatively regulates MSTN gene expression, and MSTN positively regulates FMOD gene expression. The results of our in vivo and in vitro experiments indicate FMOD inhibits muscle aging by negatively regulating MSTN gene expression or by suppressing the action of MSTN protein, and that MSTN promotes muscle aging by positively regulating the expressions of Atrogin1, CD36, and PPARγ genes in muscle. [ABSTRACT FROM AUTHOR]

The distinctive biology and unique evolutionary features of snakes make them fascinating model systems to elucidate how genomes evolve and how variation at the genomic level is interlinked with phenotypic-level evolution. Similar to other eukaryotic genomes, large proportions of snake genomes contain repetitive DNA, including transposable elements (TEs) and satellite repeats. The importance of repetitive DNA and its structural and functional role in the snake genome, remain unclear. This review highlights the major types of repeats and their proportions in snake genomes, reflecting the high diversity and composition of snake repeats. We present snakes as an emerging and important model system for the study of repetitive DNA under the impact of sex and microchromosome evolution. We assemble evidence to show that certain repetitive elements in snakes are transcriptionally active and demonstrate highly dynamic lineage-specific patterns as repeat sequences. We hypothesize that particular TEs can trigger different genomic mechanisms that might contribute to driving adaptive evolution in snakes. Finally, we review emerging approaches that may be used to study the expression of repetitive elements in complex genomes, such as snakes. The specific aspects presented here will stimulate further discussion on the role of genomic repeats in shaping snake evolution. [ABSTRACT FROM AUTHOR]