Evaluation of the anti-depressant potential of metformin in conditioned defeat model in golden Syrian hamsters

Background: Depression is a prevalent mood condition that has an impact on daily functioning. Globally, depression affects 264 million people. The current pharmacotherapy of depression has a lot of shortcomings. Therefore, there is a need to explore newer therapy that alleviate the symptoms of depression. Metformin was found to possess antioxidant potential and hypothesized to decrease the levels of branched-chain amino-acids essential for tryptophan uptake (precursor for serotonin synthesis). The study was designed to validate the efficacy of metformin as an anti-depressant in conditioned defeat model in male golden Syrian hamsters using open field test (OFT), forced swim test (FST) and Serum serotonin levels. Methods: After obtaining IAEC approval, the study was carried out using 8 golden Syrian hamsters each that were randomly assigned to four groups. The disease control group received 1mL normal saline, positive control was given fluoxetine 12 mg/kg, two groups of metformin 240 mg/kg given pre-insult and post-insult. The variables assessed on every third day included OFT and FST. Following the behavioral tests, serotonin-ELISA was done. To analyse the outcomes, appropriate statistical tests were applied. Results: On standardization, the model was established to a 16-day model. Further, results highlighted a significant difference in OFT, FST and serotonin levels with the metformin group and fluoxetine compared to disease control (p<0.001). However, no significant difference was observed between the fluoxetine and metformin groups (p>0.05), signifying the comparable results. Conclusions: Metformin (240 mg/kg) alleviated the depressive symptoms by modulating both behavioral and serotonin levels

The retrograde IFT dynein is required for normal function of diverse mechanosensory cilia in Drosophila

IntroductionCilia biogenesis relies on intraflagellar transport (IFT), a conserved transport mechanism which functions bi-directionally to bring protein complexes to the growing ciliary tip and recycle signaling and transport proteins between the cilium and cell body. In Drosophila, anterograde IFT is critical for assembly of sensory cilia in the neurons of both chordotonal (ch) organs, which have relatively long ciliary axonemes, and external sensory (es) organs, which have short axonemal segments with microtubules in distal sensory segments forming non-axonemal bundles. We previously isolated the beethoven (btv) mutant in a mutagenesis screen for auditory mutants. Although many btv mutant flies are deaf, some retain a small residual auditory function as determined both by behavior and by auditory electrophysiology.ResultsHere we molecularly characterize the btv gene and demonstrate that it encodes the IFT-associated dynein-2 heavy chain Dync2h1. We also describe morphological changes in Johnston’s organ as flies age to 30 days, and we find that morphological and electrophysiological phenotypes in this ch organ of btv mutants become more severe with age. We show that NompB protein, encoding the conserved IFT88 protein, an IFT complex B component, fails to be cleared from chordotonal cilia in btv mutants, instead accumulating in the distorted cilia. In macrochaete bristles, a class of es organ, btv mutants show a 50% reduction in mechanoreceptor potentials.DiscussionThus, the btv-encoded Dync2h1 functions as the retrograde IFT motor in the assembly of long ciliary axonemes in ch organs and is also important for normal function of the short ciliary axonemes in es organs

Mouse Gestation Length Is Genetically Determined

Background: Preterm birth is an enormous public health problem, affecting over 12 % of live births and costing over $26 billion in the United States alone. The causes are complex, but twin studies support the role of genetics in determining gestation length. Despite widespread use of the mouse in studies of the genetics of preterm birth, there have been few studies that actually address the precise natural gestation length of the mouse, and to what degree the timing of labor and birth is genetically determined. Methodology/Principal Findings: To further develop the mouse as a genetic model of preterm birth, we developed a highthroughput monitoring system and measured the gestation length in 15 inbred strains. Our results show an unexpectedly wide variation in overall gestation length between strains that approaches two full days, while intra-strain variation is quite low. Although litter size shows a strong inverse correlation with gestation length, genetic difference alone accounts for a significant portion of the variation. In addition, ovarian transplant experiments support a primary role of maternal genetics in the determination of gestation length. Preliminary analysis of gestation length in the C57BL/6J-Chr # A/J /NaJ chromosome substitution strain (B.A CSS) panel suggests complex genetic control of gestation length. Conclusions/Significance: Together, these data support the role of genetics in regulating gestation length and present th

A pleiotropic missense variant in SLC39A8 is associated with Crohn's disease and human gut microbiome composition

Genome-wide association studies have identified 200 inflammatory bowel disease (IBD) loci, but the genetic architecture of Crohn's disease (CD) and ulcerative colitis remain incompletely defined. Here, we aimed to identify novel associations between IBD and functional genetic variants using the Illumina ExomeChip (San Diego, CA)

Avian Colibacillosis and Salmonellosis: A Closer Look at Epidemiology, Pathogenesis, Diagnosis, Control and Public Health Concerns

Avian colibacillosis and salmonellosis are considered to be the major bacterial diseases in the poultry industry world-wide. Colibacillosis and salmonellosis are the most common avian diseases that are communicable to humans. This article provides the vital information on the epidemiology, pathogenesis, diagnosis, control and public health concerns of avian colibacillosis and salmonellosis. A better understanding of the information addressed in this review article will assist the poultry researchers and the poultry industry in continuing to make progress in reducing and eliminating avian colibacillosis and salmonellosis from the poultry flocks, thereby reducing potential hazards to the public health posed by these bacterial diseases

A Survey of the Challenges Faced by Individuals with Disabilities and Unpaid Caregivers during the COVID-19 Pandemic

The COVID-19 pandemic negatively affected many individuals. In particular, it is likely that individuals with disabilities and unpaid caregivers were disproportionately affected, however, its exact impact is largely unknown. The primary objective of this work was to identify challenges faced by individuals with disabilities and unpaid caregivers. A secondary objective was to identify potential solutions to the major challenges experienced by both populations. Two surveys were administered online to individuals with disabilities and unpaid caregivers, respectively between September 2020 and January 2021. We used an inductive thematic analysis within an interpretivist paradigm to analyze survey responses. A total of 111 survey responses were collected amongst both surveys. Separate thematic maps were created for individuals with disabilities and unpaid caregivers, and maps were drawn to compare challenges. Potential solutions to mitigate the challenges experienced by both populations include revising financial assistance programs and improving awareness of support programs that are available

Determination of Multiple Spring Constants, Gaps and Pull Down Voltages in MEMS CRAB Type Microaccelerometer Using Near Pull Down Capacitance Voltage Measurements

A simple experimental method based on capacitance voltage (CV) measurements is presented to extract the spring constants (k) different actuation voltages and gaps, in crab type capacitive MEMS accelerometer sensors. It is shown that in addition to main spring action provided by the legs of the structure, the additional spring constants related to the interaction of main spring-proof mass joint and corner region of the proof mass also contribute to change in capacitance. The proposed approach is used in resolving and measuring these model parameters simultaneously because all of them can be extracted from the just one CV measurement. It is found that this additional k varies by more than a factor of 10 across the 6-inch wafer. Furthermore, zero bias capacitance C0, zero bias gap g0, main spring constant k and initial pull down voltage Vpd1 vary by factors of 2.4, 2.38, 30 and 3 respectively. The method also allows us to extract different values of pull down and spring constants associated with different regions of crab structure. The experimental results agree well with the theoretical predictions and reported trends in literatures. The method is routinely applied while fabricating the actual prototype sensors fabricated in our laboratory

Supporting conditional mouse mutagenesis with a comprehensive cre characterization resource.

Full realization of the value of the loxP-flanked alleles generated by the International Knockout Mouse Consortium will require a large set of well-characterized cre-driver lines. However, many cre driver lines display excision activity beyond the intended tissue or cell type, and these data are frequently unavailable to the potential user. Here we describe a high-throughput pipeline to extend characterization of cre driver lines to document excision activity in a wide range of tissues at multiple time points and disseminate these data to the scientific community. Our results show that the majority of cre strains exhibit some degree of unreported recombinase activity. In addition, we observe frequent mosaicism, inconsistent activity and parent-of-origin effects. Together, these results highlight the importance of deep characterization of cre strains, and provide the scientific community with a critical resource for cre strain information

Data_Sheet_1_The retrograde IFT dynein is required for normal function of diverse mechanosensory cilia in Drosophila.pdf

IntroductionCilia biogenesis relies on intraflagellar transport (IFT), a conserved transport mechanism which functions bi-directionally to bring protein complexes to the growing ciliary tip and recycle signaling and transport proteins between the cilium and cell body. In Drosophila, anterograde IFT is critical for assembly of sensory cilia in the neurons of both chordotonal (ch) organs, which have relatively long ciliary axonemes, and external sensory (es) organs, which have short axonemal segments with microtubules in distal sensory segments forming non-axonemal bundles. We previously isolated the beethoven (btv) mutant in a mutagenesis screen for auditory mutants. Although many btv mutant flies are deaf, some retain a small residual auditory function as determined both by behavior and by auditory electrophysiology.ResultsHere we molecularly characterize the btv gene and demonstrate that it encodes the IFT-associated dynein-2 heavy chain Dync2h1. We also describe morphological changes in Johnston’s organ as flies age to 30 days, and we find that morphological and electrophysiological phenotypes in this ch organ of btv mutants become more severe with age. We show that NompB protein, encoding the conserved IFT88 protein, an IFT complex B component, fails to be cleared from chordotonal cilia in btv mutants, instead accumulating in the distorted cilia. In macrochaete bristles, a class of es organ, btv mutants show a 50% reduction in mechanoreceptor potentials.DiscussionThus, the btv-encoded Dync2h1 functions as the retrograde IFT motor in the assembly of long ciliary axonemes in ch organs and is also important for normal function of the short ciliary axonemes in es organs.</p