Comparative genomic diversity analysis of copy number variations (CNV) in indicine and taurine cattle thriving in Europe and Indian subcontinent.

Copy number variations (CNVs) include deletions, duplications, and insertions that are larger than 50 bp in size causing structural variation responsible for diversity, adaptation, and breed development. Indian cattle breeds are highly diverse from the taurine breeds. The pattern of CNVRs in 191 animals belonging to 39 cattle breeds (four Indicine and 35 Taurine) was studied based on Illumina 777K BovineHD chip data. The Indicine breeds revealed 2590 CNVs and 335 copy number variation regions (CNVRs) in autosomes. Out of the identified CNVs, 50 were found to be novel. Structure analysis revealed admixed nature of Siri. Neighbor joining tree from CNVR data showed that hot (Kankrej and Hallikar) and cold (Ladakhi and Siri) adapted cattle breeds clustered separately. CNVR of Indian and European breeds revealed that Balkan and Italian breeds of Podolian group are admixed with Indian cattle breeds corroborating indicine introgression (6.1-13.5%). CNVRs spanning the regions of olfactory receptors and immune system genes were identified. AMOVA revealed 9% variation among populations which is 2% greater than SNP based studies showing higher inclusion of variation by CNVR. Detailed analysis of CNVs/CNVRs in Indian cattle adapted to hot and cold climate, and their diversity among worldwide cattle is presented in this study.

Exploring haplotype block structure, runs of homozygosity, and effective population size among dairy cattle breeds of India.

The present study aimed to explore haplotype structure, runs of homozygosity (ROH), effective population size and persistence of gametic phase among three indigenous dairy cattle breeds, viz., Sahiwal (n = 19), Tharparkar (n = 17), and Gir (n = 16) by using BovineHD single nucleotide polymorphism (SNP) genotyping assay. The filtered SNPs after quality control ranged from 44% in Sahiwal to 53% in Gir. The highest number of haplotype blocks was observed in Tharparkar (15,640) and the lowest in Sahiwal (8027) spanning 17.3% and 7.8% of genome, respectively. The average block length was found close to 26 kb which suggests that multiple recombination events fragmented the ancestral haplotypes into smaller sizes. Gir cattle had the largest number of runs of homozygosity (ROH) regions (1762) followed by Tharparkar (1528) and Sahiwal (1138). Without pedigree information, inbreeding coefficients estimated from ROH (FROH) revealed that Gir had the highest FROH (0.099) proposing more inbreeding rate in this population. Effective population size (Ne) decreased slowly over the last 60 generations and at 13 generations ago; Ne was estimated as 70 for all the three dairy breeds. The highest gametic phase correlation (r = 0.78) was observed for Sahiwal and Tharparkar breed pair suggesting formulation of multi-breed reference population for successful implementation of genomic selection among dairy breeds. The decline in effective population size among native Indian cattle breeds may help in formulating strategies for conservation and genetic improvement of native germplasm for future use.

Fabrication and analysis of enhanced thermal stability and high-sensitivity turnaround point long-period fiber grating.

This paper presents a what we believe is a novel method to fabricate turnaround point long-period gratings (TAP-LPGs) possessing enhanced thermal stability and high sensitivity. It is shown by analysis and by experiment that LPG resonance in photosensitive fibers can be controlled partially by UV fluence and thermal annealing. TAP-LPGs with enhanced thermal stability were fabricated by following three steps: (I) finding grating period versus writing UV fluence for TAP operation; (II) writing gratings at a relatively higher period with higher fluence, in which case the resonance is out of phase; (III) controlled annealing so that the postannealed LPG operates at/near TAP. The thermal stability is enhanced. The average temperature sensitivity of dual peak resonance measured for a typical TAP-LPG in the temperature interval of 70°C-240°C is about 2.3 nm/°C. This study will be useful for the development of high temperature TAP-LPG sensors.

Altered synaptic glutamate homeostasis contributes to cognitive decline in young APP/PSEN1 mice.

Non-convulsive epileptiform activity is a common and under-studied comorbidity of Alzheimer's disease that may significantly contribute to onset of clinical symptoms independently of other neuropathological features such as ß-amyloid deposition. We used repeated treatment with low dose kainic acid (KA) to trigger sub-threshold epileptiform activity in young (less than 6 months) wild-type (WT) and APP/PSEN1 mice to test the role of disruption to the glutamatergic system in epileptiform activity changes and the development of memory deficits. Short-term repeated low-dose KA (five daily treatments with 5 mg/kg, IP) impaired long-term potentiation in hippocampus of APP/PSEN1 but not WT mice. Long-term repeated low-dose KA (fourteen weeks of bi-weekly treatment with 7.5-10 mg/kg) led to high mortality in APP/PSEN1 mice. KA treatment also impaired memory retention in the APP/PSEN1 mice in a Morris water maze task under cognitively challenging reversal learning conditions where the platform was moved to a new location. Four weeks of bi-weekly treatment with 5 mg/kg KA also increased abnormal spike activity in APP/PSEN1 and not WT mice but did not impact sleep/wake behavioral states. These findings suggest that hyperexcitability in Alzheimer's disease may indeed be an early contributor to cognitive decline that is independent of heavy ß-amyloid-plaque load, which is absent in APP/PSEN1 mice under 6 months of age.

An Improved Calibration Approach for Traveling Wave Ion Mobility Spectrometry: Robust, High-Precision Collision Cross Sections.

The combination of ion-mobility (IM) separation with mass spectrometry (MS) has impacted global measurement efforts in areas ranging from food analysis to drug discovery. Reasons for the broad adoption of IM-MS include its significantly increased peak capacity, duty-cycle, and ability to reconstruct fragmentation data in parallel, all of which greatly enable the analyses of complex mixtures. More fundamentally, however, measurements of ion-gas molecule collision cross sections (CCSs) are used to support compound identification and quantitation efforts as well as study the structures of large biomolecules. As the first commercialized form of IM-MS, Traveling Wave Ion Mobility (TWIM) devices are operated at low pressures (∼3 mbar) and voltages, are relatively short (∼25 cm), and separate ions on a timescale of tens of milliseconds. These qualities make TWIM ideally suited for hybridization with MS. Owing to the complicated motion of ions in TWIM devices, however, IM transit times must be calibrated to enable CCS measurements. Applicability of these calibrations has hitherto been restricted to primarily singly charged small molecules and some classes of large, multiply charged ions under a significantly narrower range of instrument conditions. Here, we introduce and extensively characterize a dramatically improved TWIM calibration methodology. Using over 2500 experimental TWIM data sets, covering ions that span over 3.5 orders of magnitude of molecular mass, we demonstrate robust calibrations for a significantly expanded range of instrument conditions, thereby opening up new analytical application areas and enabling the expansion of high-precision CCS measurements for both existing and next-generation TWIM instrumentation.

Molecular characterization of N-methyl-d-aspartate receptor from Bemisia tabaci.

The N-methyl-d-aspartate receptors (NMDARs) are ionotropic ligand gated channels that are highly permeable to calcium ions. In insects, NMDARs are associated with glutamatergic neurotransmission governing diverse physiological and biological processes like vitellogenesis and ovarian development. Therefore, NMDAR may act as attractive target for insect pest control. In present study, we performed structural and functional characterization of NMDARs in Bemisia tabaci, a highly invasive crop pest and potent virus vector. We identified that NMDAR consists of three subunits each encoded by single gene in whiteflies which are highly conserved among different insect orders. Expression analysis suggests that subunit 1 (BtNR1) and subunit 2 (BtNR2) are the main functional units. External supplementation of NMDAR ligand or BtNRs silencing was lethal to insects, which suggested that NMDAR function is highly balanced in whiteflies.

Molecular characterization, computational analysis and expression profiling of Dmrt1 gene in Indian major carp, Labeo rohita (Hamilton 1822).

Sexual dimorphism of fish morphology, physiology and behavior is diverse and complex in nature. Doublesex and mab-3 related transcription factor (Dmrt) is a large protein family whose function is sexual development and differentiation in vertebrates. Here, we report a full-length cDNA sequence of Labeo rohita (rohu) Dmrt1 of 907 bp length having 798 bp of open reading frame encoding 265 amino acids. The molecular weight of rohu DMRT1 protein was found to be 28.74 KDa and isoelectric point was 7.53. DMRT1 protein contains 23 positively and 24 negatively charged amino acids with a GRAVY score of -0.618. A characteristic DM domain was found in DMRT1 protein, which is a novel DNA-binding domain. Phylogenetic analysis showed maximum similarity with Cyprinus carpio when compared with DMRT1 of other vertebrates. Molecular docking study identified active sites to be targeted for drug designing. Rohu DMRT1 was observed to interact with other proteins such as FOXL2, CYP19a1a, AMH and SOX9a. Differential expression study revealed higher expression in testis tissue implying its role in male sex differentiation and testicular development. The information generated in the present work could facilitate further research to resolve the issues related to gonadal maturation and reproduction of commercially important aquaculture species.

Biogenic link to the recent increase in atmospheric methane over India.

Methane (CH4) is a prominent Greenhouse Gas (GHG) and its global atmospheric concentration has increased significantly since the year 2007. Anthropogenic CH4 emissions are projected to be 9390 million metric tonnes by 2020. Here, we present the long-term changes in atmospheric methane over India and suggest possible alternatives to reduce soil emissions from paddy fields. The increase in atmospheric CH4 concentrations from 2009 to 2020 in India is significant, about 0.0765 ppm/decade. The Indo-Gangetic Plains, Peninsular India and Central India show about 0.075, 0.076 and 0.074 ppm/decade, respectively, in 2009-2020. Seasonal variations in CH4 emissions depend mostly on agricultural activities and meteorology, and contribution during the agricultural intensive period of Kharif-Rabi (i.e., June-December) is substantial in this regard. The primary reason for agricultural soil emissions is the application of chemical fertilizers to improve crop yield. However, for rice farming, soil amendments involving stable forms of carbon can reduce GHG emissions and improve soil carbon status. High crop production in pot culture experiment resulted in lower potential yield-scaled GHG emissions in rice with biochar supplement. The human impact of global warming induced by agricultural activities could be reduced by using biochar as a natural solution.

Genomewide identification and annotation of SNPs in Bubalus bubalis.

The present study was carried out to identify and annotate the genome wide SNPs in Murrah buffalo genome. A total of 21.2 million raw reads from 4 pooled female Murrah buffalo samples were obtained using restriction enzyme digestion followed by sequencing with Illumina Hiseq 2000. After quality filtration, the reads were aligned to Murrah buffalo genome (ICAR-NBAGR) and Water buffalo genome (UMD_CASPUR_WB_2.0) which resulted in 99.37% and 99.67% of the reads aligning, respectively. A total of 130,688 high quality SNPs along with 35,110 indels were identified versus the Murrah bufffalo genome. Similarly 219,856 high quality SNPs along with 15,201 indels were identified versus the Water buffalo genome. We report 483 SNPs in 66 genes affecting Milk Production, 436 SNPs in 38 genes affecting fertility and 559 SNPs in 72 genes affecting other major traits. The average genome coverage was 13.4% and 14.8% versus the Murrah and Water buffalo genomes, respectively.

Genome-wide discovery of SNPs in candidate genes related to production and fertility traits in Sahiwal cattle.

The present study was carried out to identify genome-wide genetic markers and variants in candidate genes for production and reproduction traits in Sahiwal cattle using a cost-effective reduced representation sequencing method. A total of 258,231 genome-wide SNPs were identified in Sahiwal cattle with reference to Bos indicus genome, of which 150,231 were novel SNPs. Among the high-confidence SNPs identified, 91.86% and 27.30% were genotyped in 50% and 100% of the samples. Mapping of the identified SNPs revealed 525 SNPs in candidate genes related to production traits while 333 SNPs were mapped to candidate genes related to reproduction traits. The SNPs identified in this study will facilitate further insights on tropical adaptation, domestication history and population structure of indigenous cattle. The variants in candidate genes identified in this study will serve as useful genetic tools, in the quest for phenotype modifying nucleotide change and help in designing appropriate genetic improvement programs.

Morphometric evaluation of Anterior Cerebral Artery (on Digital Subtraction Angiography)-Potential implications.

PURPOSE: The aim of the present study was to perform a morphometric analysis of ACA and to establish significant differences, if any, with sex and age via Digital Subtraction Angiography (DSA). METHODS: This cross-sectional study was conducted on 70 patients (>20 years) for the evaluation of ACA by Digital Subtraction Angiography done on a Philips biplane system clarity (Allura FD20/20). Length and diameter of ACA were taken manually on the DSA console using auto-calibration. Statistical analysis was done. RESULT: Mean diameter and length of ACA was found to be greater in female. The f-ratio value for diameter and length of the same was 1.43 and 0.92 respectively. The length of ACA was found to be statistically significant for different age groups. The mean length of ACA followed a decreasing trend with age, whereas mean diameter of ACA was nearly the same in all the age groups. CONCLUSION: The results of our study show that the length of ACA was found to be statistically significant for different age groups.

Pattern of Dental Problems among Patients Visiting a Dental Hospital during COVID-19 Pandemic.

Background Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Nepal is a part of this worldwide corona virus disease. In this critical situation, the patients have a sense of insecurity visiting dental hospital. Objective To assess the pattern of dental problems in patients visiting a dental college during COVID-19. Method A descriptive cross-sectional study was conducted in Dental Hospital of Kathmandu Medical College and Teaching Hospital from May to August 2020. The patients visiting the Dental hospital were assessed for dental problems. Data were analyzed in Statistical Package of Social Sciences version 20. Frequency and percentage for pattern of dental problems were calculated. Result Most of the patients of age group of 14 to 31 years 530 (36.53%) had dental problems during the survey period. Out of total patients having dental emergency, 739 (50.93%) were males and 712 (49.07%) were females. Majority 545 (37.56%) visited the dental hospital for endodontic consultation followed by emergency consultation for oral surgical procedures 298 (20.54%). Least consulted dental emergency condition was prosthodontic consultation 18 (1.24%). Conclusion The study findings showed that the major dental problems in patients causing emergency visit to dental hospital during COVID-19 pandemic period were dental pain and swelling requiring endodontic consultation and the least need felt is prosthodontic consultation.

Bifunctional cross-linking approaches for mass spectrometry-based investigation of nucleic acids and protein-nucleic acid assemblies.

With the goal of expanding the very limited toolkit of cross-linking agents available for nucleic acids and their protein complexes, we evaluated the merits of a wide range of bifunctional agents that may be capable of reacting with the functional groups characteristic of these types of biopolymers. The survey specifically focused on the ability of test reagents to produce desirable inter-molecular conjugates, which could reveal the identity of interacting components and the position of mutual contacts, while also considering a series of practical criteria for their utilization as viable nucleic acid probes. The survey employed models consisting of DNA, RNA, and corresponding protein complexes to mimic as close as possible typical applications. Denaturing polyacrylamide gel electrophoresis (PAGE) and mass spectrometric (MS) analyses were implemented in concert to monitor the formation of the desired conjugates. In particular, the former was used as a rapid and inexpensive tool for the efficient evaluation of cross-linker activity under a broad range of experimental conditions. The latter was applied after preliminary rounds of reaction optimization to enable full-fledged product characterization and, more significantly, differentiation between mono-functional and intra- versus inter-molecular conjugates. This information provided the feedback necessary to further optimize reaction conditions and explain possible outcomes. Among the reagents tested in the study, platinum complexes and nitrogen mustards manifested the most favorable characteristics for practical cross-linking applications, whereas other compounds provided inferior yields, or produced rather unstable conjugates that did not survive the selected analytical conditions. The observed outcomes will help guide the selection of the most appropriate cross-linking reagent for a specific task, whereas the experimental conditions described here will provide an excellent starting point for approaching these types of applications. As a whole, the results of the survey clearly emphasize that finding a universal reagent, which may afford excellent performance with all types of nucleic acid substrates, will require extending the exploration beyond the traditional chemistries employed to modify the constitutive functional groups of these vital biopolymers.

Selective photoionization of lithium isotopes in a hollow cathode lamp: a feasibility study for a laser ion source and detector.

Two-step selective photoionization of lithium isotopes is carried out in a hollow cathode (HC) discharge lamp using a nitrogen-laser-pumped homemade tunable dye laser (∼0.2 cm-1, 7 ns, 640-680 nm). The HC lamp is developed in-house and used as a lithium ion source as well as a detector. The dark space region of HC discharge is illuminated by a dye laser exciting pulse followed by an ionizing radiation from the nitrogen laser. The high electric field (∼kV/cm) present in HC dark space is exploited for fast charge collection, produced by the simultaneous interaction of exciting and ionizing laser beams with sputtered lithium atoms, enabling the detection of photoionization signal. Photoionization signals with a high signal-to-noise ratio are obtained without using any amplifier. Effects of the ionizing laser pulse energy and the precise tuning of the dye laser on lithium photoionization signal, across 670.780 nm (S1/22→P1/2,3/22) transition, are studied. The fine structure of lithium is clearly identified, and its two isotopes (Li7,6) are fairly resolved in the measured photoionization spectrum. Using a saturation technique, the photoionization cross section and the number density of lithium atoms for the Li7 (P3/22) excited level are also measured as 18.5±2.4 Mb, N0∼1.7×109 (atoms/cm3). The results obtained infer that HC-lamp-based photoionization is an easier and cost-effective way of selective photoionization of lithium atoms, and it can be applied for other elements also.

Evaluation of Bovine High-Density SNP Genotyping Array in Indigenous Dairy Cattle Breeds.

In total 52 samples of Sahiwal ( 19 ), Tharparkar ( 17 ), and Gir ( 16 ) were genotyped by using BovineHD SNP chip to analyze minor allele frequency (MAF), genetic diversity, and linkage disequilibrium among these cattle. The common SNPs of BovineHD and 54K SNP Chips were also extracted and evaluated for their performance. Only 40%-50% SNPs of these arrays was found informative for genetic analysis in these cattle breeds. The overall mean of MAF for SNPs of BovineHD SNPChip was 0.248 ± 0.006, 0.241 ± 0.007, and 0.242 ± 0.009 in Sahiwal, Tharparkar and Gir, respectively, while that for 54K SNPs was on lower side. The average Reynold's genetic distance between breeds ranged from 0.042 to 0.055 based on BovineHD Beadchip, and from 0.052 to 0.084 based on 54K SNP Chip. The estimates of genetic diversity based on HD and 54K chips were almost same and, hence, low density chip seems to be good enough to decipher genetic diversity of these cattle breeds. The linkage disequilibrium started decaying (r2 < 0.2) at 140 kb inter-marker distance and, hence, a 20K low density customized SNP array from HD chip could be designed for genomic selection in these cattle else the 54K Bead Chip as such will be useful.

Self-Perception of Halitosis among Undergraduate Students of Kathmandu University School of Medical Sciences - A Questionnaire Based Study.

Background Halitosis is a frequently reported oral health problem worldwide with a prevalence rate of 10-30% in the general population. It is defined as the disagreeable or foul smelling breath originating consistently from a person's oral cavity. It not only effects the normal daily life activities of the patient but also bring humiliation, reduced self- esteem, ultimately resulting into decreased quality of life. Objective To determine the self-perception of halitosis among undergraduate students of different medical branches of Kathmandu University School of Medical Sciences (KUSMS); Kavre, Nepal. Method A descriptive cross-sectional epidemiological survey was conducted among undergraduate students of Physiotherapy, B.Sc Nursing, Bachelor of Nursing Sciences (BNS), MBBS and BDS program of Kathmandu University School of Medical Sciences, Dhulikhel. A self-administered questionnaire was developed and were distributed among 500 undergraduate students. Result Out of total 500 distributed questionnaires, 406 were completely filled and returned giving an overall response of 81.2%, in which 70 (89.7%) male and 280 (85.4%) female students from different medical branches were aware of the term halitosis. Among them 29 (7.14%) of students think that they suffer from halitosis. Similarly 178 (43.84%) students had severe impact of halitosis on their social life while 153 (37.68%) and 62 (15.27%) students had moderate and mild impact respectively. Conclusion Due to the multifactorial complexity of halitosis, further longitudinal studies including objective assessment of malodor are required to determine its prevalence and to further investigate the association of this problem with other etiological factors in the context of Nepal. Also, curriculum of different fields should be modified to include this simple but very necessary topic.

Hyperfine structure studies of neutral europium transitions at 601.815 and 580.027 nm by saturation absorption spectroscopy.

We report Doppler-free spectroscopy of neutral europium carried out using the saturation absorption technique. In the present experiment, Eu/Ne hollow cathode discharge is used as an atomic vapor source of europium. The Eu transition 4f76s2(S87/2°)→4f76s6p(P89/2) at 601.815 nm and 4f75d6s(aD1013/2°)→4f75d6p(zD811/2) at 580.027 nm are investigated. The frequency separation between the adjacent hyperfine transitions as well as hyperfine structure (HFS) constants are calculated from the obtained experimental spectra. The HFS constant obtained for the state 4f76s6p(P89/2) are A151=664.8 MHz; B151=293.5 MHz, and for state 4f75d6p(zD811/2), the values are A151=7.6 MHz; B151=-60 MHz. These obtained values are in good agreement with the results reported in the literature using laser induced atomic beam fluorescence technique.

Immunomodulatory basis of antioxidant therapy and its future prospects: an appraisal.

Antioxidants are agents which can modulate oxidant-antioxidant profile of body system by neutralizing pro-oxidant molecules. The current scientific knowledge on mechanisms of antioxidant activity of biomolecules was critically reviewed with a special emphasis on immunomodulation. The immuno-oxidative wreckage of animals in various disease conditions and the role of biomodulators in curbing the oxidative stress through immune pathways were analyzed. The critical role of immunomodulatory mechanisms in controlling oxidative damage was identified. Selection of antioxidant therapy considering the immunopharmacology of the drug as well as immunological basis of disease may reduce treatment failure and adverse health effects. Hence, it is suggested that future studies on antioxidants may focus on the immuno-oxidative pathobiology to better understand its clinical effects and effective disease management.

Comparative Study to Determine the efficacy of Zinc Oxide Eugenol and Alveogyl in Treatment of Dry Socket.

Background Dry socket is one of the most common complications following permanent tooth extraction, especially mandibular third molar. Management remains controversial and different authors have shown different results with the use of zinc oxide eugenol and AlveogylTM, some preferring AlveogylTM over zinc oxide eugenol. Objective To determine the incidence, possible risk factors and compare the effectiveness of two most commonly used agents (Zinc oxide eugenol and AlveogylTM) for management of dry socket. Method Dry socket patients were randomly divided into two groups. Various risk factors were recorded through proper history. After thorough irrigation with normal saline, zinc oxide eugenol paste mixed with cotton pellet was placed in one group whereas AlveogylTM was placed in another group. Intensity of pain was recorded on visual analogue scale of Zero to ten. Pain score was recorded at the time of diagnosis, thirty and sixty minutes after placement of medication and on second, fifth, seventh and tenth day. The medication was changed every day until the pain subsided. The data were collected and analyzed using SPPS software (version 20). Result Incidence of dry socket was 4.70%, more common in males (59.09%). It was more common after extraction mandibular third molar. Initial and final pain relief on visual analogue scale was better with use of zinc oxide eugenol. Conclusion Zinc oxide Eugenol paste is more effective in management of dry socket for early as well as final pain relief compared to AlveogylTM.

Mapping of protein-protein interaction network of Alexander disease.

Alexander disease (ALXD) is slowly progressive neurodegenerative disorder which affects white matter of the central nervous system. The main cause of disorder is mutation in GFAP gene and mutation in some other genes were also reported. This study was aimed at getting a better insight into ALXD pathogenesis and identifying the important functional and highly interconnected nodes in human protein interaction network, identifying the important sub-networks in the system could be helpful in understanding the underlying molecular mechanism. The topological analysis of human protein interaction network strategy to identify highly interconnected sub-network modules from which six proteins are found i.e. GFAP, PLEC, CRYAB, NDUFV1, CASP3 and MAPK14 plays important role in disease. Further, the enrichment analysis of interaction network identifies crucial pathways in which most of the diseased proteins overlaps. Through system biology approach, the undirected human protein interaction network of ALXD is buildup with the help of Cytoscape tool and its various plugins helps to investigate network further. The systematic approach suggests the finding of previously known proteins, GFAP, PLEC, CRYAB, NDUFV1, CASP3 and MAPK14 can be used as a drug targets and potential treatment discovered also enrichment analysis will provide guidance for the future study on Alexander disease.