Comparison of intranasal dexmedetomidine and ketamine for paediatric premedication: A randomized study.

INTRODUCTION AND OBJECTIVES: Paediatric patients are given premedication in order to decrease preoperative anxiety, allow smooth induction, and prevent postoperative psychological insult and behavioural changes. A child friendly method of administration is desirable. We compared intranasal administration of dexmedetomidine and ketamine in the operating room environment, to evaluate the Faces, Legs, Activity, Cry and Consolability (FLACC) score at the time of establishing intravenous access for induction of general anaesthesia. METHODS: This prospective, double-blind, randomized controlled trial was conducted at a tertiary care center. One hundred patients, 2-10 years of age, ASA physical status 1 & 2, scheduled for general anaesthesia were enrolled. Patient's presedation behaviour was assessed by the modified Yale Preoperative Anxiety Scale Short Form (mYPAS-SF). Patients in Group D received Dexmedetomidine 1 mcg/kg intranasally, and patients in Group K received Ketamine 5 mg/kg intranasally. After 45 min, patients were transferred to the operating table where intravenous cannulation was carried out and the response to needle insertion was assessed by FLACC scale. Vital signs, including the pulse-oximetry, heart rate and respiratory rate were monitored. Side effects such as nausea, vomiting, and agitation were also recorded. RESULTS: A significantly higher FLACC score was seen in Group D as compared to Group K (p = 0.001). The mean heart rate between two groups was found to be significantly (p = 0.001) lower in Group D compared to Group K. However, the proportion of adverse events was 8% in patients who received ketamine. CONCLUSIONS: Intranasal ketamine in a dose of 5 mg/kg is clinically more effective as premedication in children aged 2-10 years in comparison with intranasal dexmedetomidine in a dose of 1 mcg/kg.

Measurement of ultrasonic pulse velocity with improved accuracy using automatic threshold error correction.

Ultrasonic Pulse Velocity (UPV) measurement is extensively used to monitor the strength and health of concrete structures as per American Society for Testing and Materials C 597 - 09. The commercially available UPV measurement systems work on the basis of single threshold detection of the received signal. Therefore, measurement accuracy is affected due to threshold error. The effect is sensitive to the signal amplitude reaching the threshold comparator and, hence, receiver gain. It is observed that a UPV tester operating at 50 kHz to test concrete might generate an error of up to 10% in the ultrasonic transit time measurement of 50 µs. Hence, it is of great concern and needs to be improved. In this article, the UPV measurement circuit capable of detecting and compensating the threshold error is described. The threshold error correction is achieved with the help of two threshold comparators and two hybrid counters. The circuit developed minimizes the threshold error for wide receiver gain. The measurement carried out with the developed system shows significant improvement, having deviations within 100 ns.

Development of sweep frequency ultrasonic interferometer for high precision velocity measurement in liquids.

An ultrasonic interferometer with variable separation between the transducer and reflector is widely used for the measurement of ultrasonic propagation velocity in liquids. The inherent limitation of such an interferometer is due to the mechanical movement of its reflector for ultrasonic wavelength measurement in a liquid medium. It is observed that the ultrasonic velocity measurement precision is adversely affected at higher frequencies compared to lower ones. For instance, in our experimentation, a standard deviation of ±21.5 m/s (±1.43%) was obtained for velocity measurement at 1.84 MHz with the consideration of two consecutive maxima, which increases drastically to ±76.8 m/s (±5.12%) at 9.4 MHz. These measurements can significantly be improved by considering many maxima and averaging for wavelength estimation. However, it still requires design attention and improvement, particularly for higher frequencies. In this article, a sweep-frequency based ultrasonic interferometer design with a fixed separation for liquid characterization is proposed and described. This technique overcomes the limitations of mechanical movement systems and also provides a better and uniform precision for lower as well as higher frequencies. The functionality of the developed sweep frequency method was tested in water, carbon tetrachloride, ethylene glycol, and glycerol, which shows good agreement with literature values. The velocity measurement in double distilled water by the developed technique at 1 Hz sweep resolution has shown an improved standard deviation of ±0.74 m/s (±0.05%) at 9.4 MHz.

Design and development of mechanical test bench for testing and calibration of multiple blood pressure measuring devices.

Blood pressure (BP) measurement is an important physiological parameter for human health monitoring, which plays a significant role in the diagnosis of many incurable diseases. However, due to inaccuracies in the different types of BP measuring devices, the calibration of these BP measuring instruments is a major concern for a medical practitioner. Currently, these devices' calibration, testing, and validation are performed using rigorous methods with complex clinical trials and following the available documentary standards. This article describes the design and development of an indigenous mechanical test bench (MTB) system for the testing and calibration of multiple BP devices, as per International Organization of Legal Metrology (OIML) recommended documents e.g., OIML R 16-1 and OIML R 16-2. The developed system can test and calibrate 20 BP devices, simultaneously. The traceability of the developed MTB is established by performing its calibration against the Air Piston Gauge, a national primary vacuum standard. The estimated expanded measurement uncertainty evaluated is found to be ±0.11 mmHg, which is almost one order better than the measurement uncertainty required for the test and calibration of BP measuring instruments as per standard. The MTB has successfully been used to test and calibrate several BP measuring instruments. The data of one such device is reported herein as an indicator of the performance process. The calibration of these BP measuring instruments was performed in the static mode, and the estimated expanded measurement uncertainty was found to be ±1.25 mmHg. The developed MTB system would prove to be an excellent instrument for calibration laboratories, hospitals, regulatory agencies, and other users to test and calibrate 20 BP measuring devices simultaneously and cost-effectively.

Identification of novel polymorphism in mammary-derived growth inhibitor gene of water buffalo and its expression analysis in the mammary gland.

Mammary-derived growth inhibitor (MDGI), a member of the lipophilic family of fatty acid-binding proteins, plays an important role in the development, regulation, and differentiation of the mammary gland. The aim of the study was to identify polymorphism in the MDGI gene and its expression analysis in the mammary gland at various stages of lactation, in Indian buffalo. Nucleotide sequence analysis of MDGI gene in different breeds of riverine and swamp buffaloes revealed a total of 16 polymorphic sites and one Indel. Different transcription factor binding sites were predicted for buffalo MDGI gene promoter sequence, using online tools and in-silico analysis indicating that the SNPs in this region can impact the gene expression regulation. Phylogenetic analysis exhibited the MDGI of buffalo being closer to other ruminants like cattle, yak, sheep, and goats. Further, the expression analysis revealed that buffalo MDGI being highly expressed in well-developed mammary glands of lactating buffalo as compared to involution/non-lactating and before functional development to start the milk production stage in heifers. Stage-specific variation in expression levels signifies the important functional role of the MDGI gene in mammary gland development and milk production in buffalo, an important dairy species in Southeast Asia.

Advent of Proteomic Tools for Diagnostic Biomarker Analysis in Alzheimer's Disease.

Locating remedies for Alzheimer's disease (AD) has been majorly restricted by the inefficiency to establish a definitive detection model for early-stage diagnosis of pathological events. This current lapse in AD diagnosis also limits the therapeutic efficiency of the drugs, which might have been effective if given at the earlier stages of the disease. The indicated situation directs towards the burgeoned need for an effective biomarker technique that will help in early detection of AD and would be imminently useful to facilitate improved diagnosis and stimulate therapeutic trials. Till date, the major biomarkers, specifically associated with AD detection, may help in determining the early-stage AD diagnosis and identifying alterations in the cellular proteome, offering deeper insight into disease etiology. Currently existing multidisciplinary clinical diagnosis of AD is a very tedious, expensive procedure and requires highly trained and skilled professionals who are rarely available outside the specialty clinics. Mutations in amyloid precursor protein (APP) or Presenilin 1 and 2 (PSEN1 and PSEN2) are some biomarkers acting as critical checkpoints for AD diagnosis. However, the presence of some associated biomarkers in cerebrospinal fluid (CSF) such as total-Tau (tTau), phosphorylated- Tau (pTau) 181 and Amyloid-ß (Aß) 1-42 using structural or functional imaging techniques is considered for confirmatory diagnosis of AD. Furthermore, the molecular diagnosis of AD incorporates various sophisticated techniques including immuno-sensing, machine learning, nano conjugation-based detections, etc. In the current review description, we have summarized the various diagnostic approaches and their relevance in mitigating the long-standing urgency of targeted diagnostic tools for detection of AD.

Identification of novel polymorphism in buffalo stanniocalcin-1 gene and its expression analysis in mammary gland under different stages of lactation.

Stanniocalcin-1 (STC1) is secreted by the variety of tissues having a major role in the regulation of calcium ions in the involuting mammary gland. The present work aims to sequence and structural characterization as well as expression profiling of STC1 gene in buffalo. Polymorphism identified in the 3-untranslated region (UTR) was analysed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) genotyping in riverine and swamp buffaloes. Expression profiling of STC1 was performed in different lactation stages of mammary gland and peripheral blood mononuclear cells to study the impact of 3'-UTR polymorphism on its expression. Different polymorphic sites were detected in the entire coding and noncoding regions of riverine and swamp buffaloes, including two INDELs. An identified polymorphic nucleotide locus A324G, having target sites for two miRNAs, namely bta-miR-2382 and bta-miR-1343, reported in cattle, was genotyped by PCR-RFLP to reveal variable allelic distribution among swamp and riverine buffaloes. Gene expression profiling across buffalo mammary tissues representing different lactation stages showed maximum expression of the STC1 gene in the involuting mammary gland. Ruminants' specific genetic variation has been observed in STC1 and its implication in buffalo mammary gland involution as well as coregulation of gene expression through miRNA binding in the 3'-UTR is suggested.

Improved ultrasonic interferometer technique for propagation velocity and attenuation measurement in liquids.

Propagation velocity and attenuation are the two basic parameters used for the ultrasonic investigations of liquids. An ultrasonic interferometer is a widely used tool as a cost effective solution for propagation velocity measurement. The ultrasonic attenuation measurements are not possible using the existing interferometers commercially available in the market. Ultrasonic attenuation can be measured using the pulse echo method, which is relatively complex and expensive. Generally, in interferometers, a radio frequency voltage of more than 100 V is used to excite the piezoelectric transducer. In this article, an improved design of the ultrasonic interferometer with low (5 V) rf voltage excitation is discussed. The proposed design has several advantages over existing systems. The low voltage excitation reduces heating of the sample under study. Detection of the received signal is done directly at the transducer. The critical effects of a coaxial cable in rf detection are minimized by dc detection at the transducer node. The impedance response of the transducer is used for the detection of nodes and antinodes for attenuation and velocity measurements. The use of an instrumentation amplifier enables one to amplify the extremely small voltage changes across the transducer due to interference. The developed method has the capability to measure attenuation due to high receiver sensitivity. The technique has been validated for the propagation velocity and attenuation measurement in standard samples of water and other liquids. The results thus obtained have been compared with the literature and the conventional pulse echo technique which shows close agreement.

Real-time implementation of Kalman filter to improve accuracy in the measurement of time of flight in an ultrasonic pulse-echo setup.

In this paper, we demonstrate a hardware implementation of Kalman filter to enhance accuracy in the measurements of time-of-flight in an ultrasonic pulse echo technique (operated at 10 MHz). Pulser-receivers and other respective circuit units are designed using off-the-shelf electronic components. The advanced reduced instruction-set computing machine processor based Raspberry Pi single board computer is used to implement the Kalman filter and control various processes. Additionally, a graphical user interface is designed using Qt software, under the Debian open source operating system. The software has capability to measure and display the time-of-flight and ultrasonic propagation velocity in a liquid under test. The designed system with the Kalman filter exhibited an extremely small error of about 0.01% in the time-of-flight measurements compared with other systems. The functionality of the developed approach to measure time of flight and thereby ultrasonic velocity with significant improvement has been discussed in this article. It was experimentally verified that by improving other parameters such as the separation between the transducer and the reflector and cell structure, significant improvement in the accuracy of ultrasonic velocity in the liquid under test is achieved.

Sequence-based structural analysis and evaluation of polymorphism in buffalo Nod-like receptor-1 gene.

In this study, we have sequence characterized and analyzed the polymorphism in buffalo NOD1 (nucleotide-binding oligomerization domain 1) gene as well as its expression analysis. Full-length sequence analysis of NOD1 revealed this gene in buffalo being conserved with respect to the domain structures, similar to other species. Alternate splice variants having exon3 skipping also identified for the first time in the gene expressed in buffalo-purified peripheral blood mononuclear cells (PBMCs). Phylogenetically ruminant species were found to be clustering together and buffalo displaying maximum similarity with cattle. Sequencing of NOD1 across 12 Indian buffalo breeds identified 23 polymorphic sites within coding region, among which 16 were synonymous and 7 changes found to be non-synonymous. Four SNPs (single nucleotide polymorphisms) of them were genotyped in 393 animals belonging to 12 riverine, swamp and hybrid (riverine × swamp) buffalo populations of diverse phenotypes and utilities, showing variable allelic frequencies. Principal component analysis revealed, riverine and swamp buffaloes being distinctly placed with the distribution of breeds within the group based on the geographical isolation. Further, quantitative real-time PCR detected NOD1 expression in multiple tissues with PBMCs and lungs showing highest expression among the tissues examined. Structural analysis based on the translated amino acid sequence of buffalo NOD1 identified four protein interaction motifs LxxLL important for ligand binding. Molecular interaction analysis of iE-DAP and NOD1-LRR and their complex stability and binding-free energy studies indicated variable binding energies in buffalo and cattle NOD1. Overall, the study reveals unique structural features in buffalo NOD1, important for species-specific ligand interaction.

PCR-SSCP analysis of MDGI gene and its association with milk production traits in river buffalo (Bubalus bubalis).

In this study, we investigated the genetic variation within 3'UTR of Mammary-Derived Growth Inhibitor (MDGI) gene of buffalo using PCR-SSCP and sequencing; and also analyzed association of polymorphism with the milk production traits. The study revealed two conformational patterns, 'A' and 'B' among 234 Mehsana buffaloes maintained with their records in the field and at farm. The frequency of SSCP variant 'A' was found to be invariably high in the buffalo population under study. Further, association analysis of SSCP variants with various milk production and milk quality traits indicated no significant effect on any of the traits investigated. Sequencing of SSCP variant 'A' showed homozygous G/G and A/A and 'B' had heterozygous G/C and A/G at positions +124 and +140 respectively, in the 3'UTR of buffalo MDGI. The preliminary results showed the substantial variations in the distribution of SSCP variants' frequencies within Mehsana buffaloes, however these variants had non-significant association with milk yield, fat yield and fat percentage in Mehsana buffaloes.

Identification of genetic variation in NOD-like receptor 2 gene and influence of polymorphism on gene structure and function in buffalo (Bubalus bubalis).

Nucleotide-binding oligomerization domain (NOD)-like receptor 2 is one of the important mediators of innate as well as adaptive immune response to microbial infections. In this study, NOD-like receptor-2 was characterized by determining the full gene sequence and analyzing genetic diversity in Indian buffaloes. Sequence analysis of buffalo NOD2 revealed 3042 nucleotides long ORF, encoding 1013 amino acids from 12 exons. Domain structure analysis indicated existence of 8 leucine-rich repeat (LRR) domains in buffalo, cattle, sheep and mouse, along with central NACHT/NOD domain and two N-terminal CARD domains. Comparative sequence analysis among different buffalo breeds identified 46 polymorphic sites in NOD2 gene. Among coding region SNPs, 10 were non-synonymous, 7 synonymous and 3 were present in 5'UTR. Genotyping of two nsSNPs, revealed significant differences in the allele frequencies, distinguishing swamp and riverine buffaloes, having different utilities. Association analysis with mastitis in dairy buffaloes indicated significant variation in allelic frequencies at G1135A locus, between mastitis affected and non-affected animals. Further, NOD2 gene expression was quantified in different riverine buffalo tissues, using real-time PCR and lymph node displayed highest expression, compared to others organs included in the study. Overall, the study revealed buffalo NOD2 gene attributes, important to understand species specific immune response in ruminants.

Expression Analysis of Genes Associated with Prolificacy in FecB Carrier and Noncarrier Indian Sheep.

The effect of FecB mutation on the gene expression in FecB carrier and noncarrier estrous synchronized ewes, has been analyzed. For this study the whole ovarian tissues and Graafian follicles were collected from estrus synchronized FecB carrier Garole, and non-carrier Deccani Indian sheep, showing remarkable differences in the numbers of preovulatory follicles among two groups. Eleven potential candidate genes (BMP15, GDF9, BMP4, BMP7, BMPR1B, BMPR1A, SMAD9, LHCGR, FSHR, IGF1R, and STAT5) were selected for their expression analysis by SybrGreen based real-time PCR, across ovaries and Graafian follicles of different fecundity groups, for having better insights into the effect of FecB genotypes on follicular development. Variable expression was observed for almost all the genes included in the present study among high and low fecundity groups that was most significant for the BMP7, BMP4, LHCGR, and FSHR transcripts in the ovarian follicles of high and low fecundity ewes, indicating their importance in governing the fecundity in FecB carrier, Indian Garole sheep. BMP4 expression among the genes studied was significantly higher in FecB carrier Garole sheep. This study confirms the changes in mRNA expression of the genes implicated in follicular development in FecB carrier and noncarrier Indian sheep breeds.

High genetic diversity and distribution of Bubu-DQA alleles in swamp buffaloes (Bubalus bubalis carabanesis): identification of new Bubu-DQA loci and haplotypes.

In this study, genetic diversity analysis of MHC class II-DQA locus helped in identification of 25 new Bubu-DQA nucleotide sequences in swamp buffaloes (Bubalus bubalis carabanesis, Bubu). Phylogenetic analysis revealed the distribution of the buffalo DQA sequences in two major clusters of DQA1 and DQA2 genes, sharing common lineages with corresponding cattle alleles, possibly due to trans-species evolution. However, a highly divergent sequence, Bubu-DQA*2501, homologous to cattle (BoLA) DQA3 allele, was identified, indicating the existence of an additional locus; putative DQA3 in buffalo. PCR-RFLP analysis revealed extensive duplication of DQA locus in swamp buffaloes, sharing DQA1, DQA2, and DQA3 alleles in different combinations in duplicated haplotypes. Higher dN than dS values and Wu-Kabat variability at peptide-binding regions in Bubu-DQA indicated high polymorphism with balancing selection. Levels of genetic diversity within DQA sequences and duplication in a small population of swamp buffalo indicate the genetic richness of the species, important for fitness.

Molecular Characterization of Buffalo Haptoglobin: Sequence Based Structural Comparison Indicates Convergent Evolution Between Ruminants and Human.

Haptoglobin (Hp) protein has high affinity for hemoglobin (Hb) binding during intravascular hemolysis and scavenges the hemoglobin induced free radicals. Earlier reports indicate about uniqueness of Hp molecule in human and cattle, but in other animals, it is not much studied. In this paper, we characterized buffalo Hp molecule and determined its molecular structure, evolutionary importance, and tissue expression. Comparative analysis and predicted domain structure indicated that the buffalo Hp has an internal duplicated region in α-chain only similar to an alternate Hp2 allele in human. This duplicated part encoded for an extra complement control protein CCP domain. Phylogenetic analysis revealed that buffalo and other ruminants were found to group together separated from all other non-ruminants, including human. The key amino acid residues involved in Hp and Hb as well as Hp and macrophage scavenger receptor, CD163 interactions in buffalo, depicted a significant variation in comparison to other non-ruminant species. Constitutive expression of Hp was also confirmed across all the vital tissues of buffalo, for the first time. Results revealed that buffalo Hp is both structurally and functionally conserved, having internal duplication in α-chain similar to human Hp2 and other ruminant species, which might have evolved separately as a convergent evolutionary process. Furthermore, the presence of extra Hp CCP domain possibly in all ruminants may have an effect during dimerization of molecule in these species.

Genetic diversity analysis of buffalo fatty acid synthase (FASN) gene and its differential expression among bovines.

Fatty Acid Synthase (FASN) gene seems to be structurally and functionally different in bovines in view of their distinctive fatty acid synthesis process. Structural variation and differential expression of FASN gene is reported in buffalo (Bubalus bubalis), a bovine species close to cattle, in this study. Amino acid sequence and phylogenetic analysis of functionally important thioesterase (TE) domain of FASN revealed its conserved nature across mammals. Amino acid residues at TE domain, responsible for substrate binding and processing, were found to be invariant in all the mammalian species. A total of seven polymorphic nucleotide sites, including two in coding region of TE domain were identified across the 10 buffalo populations of riverine and swamp types. G and C alleles were found almost fixed at g18996 and g19056 loci, respectively in riverine buffaloes. Principal component analysis of three SNPs (g18433, g18996 and g19056) revealed distinct classification of riverine and swamp buffalo populations. Reverse Transcription-PCR amplification of mRNA corresponding to exon 8-10 region of buffalo FASN helped in identification of two transcript variants; one transcript of 565 nucleotides and another alternate transcript of 207 nucleotides, seems to have arisen through alternative splicing. Both the transcripts were found to be expressed in most of the vital tissues of buffalo with the highest expression in mammary gland. Semi-quantitative and real-time expression analysis across 13 different buffalo tissues revealed its highest expression in lactating mammary gland. When compared, expression of FASN was also found to be higher in liver, adipose and skeletal muscle of buffalo tissues, than cattle. However, the FASN expression was highest in adipose among the three tissues in both the species. Results indicate structural and functional distinctiveness of bovine FASN. Presence of alternate splicing in buffalo FASN also seems to be a unique phenomenon to the bovines, probably associated with mRNA based regulation of the biological functions of FASN in these species.

MARKER ASSISTED EVALUATION OF MORPHOLOGICAL AND GENETIC ATTRIBUTES OF SUB-POPULATIONS OF NILI-RAVI BUFFALO: A VULNERABLE DAIRY TYPE RIVERINE BREED OF INDIA.

In the present study, we report the distribution of true to type and atypical Nili-Ravi buffalo, a vulnerable dairy type riverine breed of North India and its underlying genetic structure. Out of total investigated buffaloes 73.5% had bilateral wall eyes while 5.4% had unilateral wall eyes and 21.1% had no wall eyes. 41.15% of Nili-Ravi buffaloes maintained in the breeding farm were having typical true to the type characteristics (both eyes walled, white markings in forehead, muzzle/chin, all the four legs and tail) while only 28.5% of Nili-Ravi buffaloes were true to the type under field conditions. Genotypic data were generated in four groups of Nili-Ravi buffalo (FMTNR--Typical Nili-Ravi from farm; FMANR--Atypical Nili-Ravi from farm; FDTNR--Typical Nili-Ravi from field; FDANR--Atypical Nili-Ravi from field) at 16 microsatellite loci. Comparative genetic analysis of various groups of Nili-Ravi buffaloes with Murrah revealed significant between group differences with an estimated global F(ST) of 0.063. Pair-wise F(ST) values ranged from 0.003 (between FDTNR and FDANR) to 0.112 (between FMTNR and FDTNR). Phylogenetic analysis and multi-dimensional scaling revealed clustering of FDTNR and FDANR together while FMTNR and FMANR clustered separately with Murrah in between farm and field Nili-Ravi buffaloes. Based on the results, the paper also proposes three pronged strategy for conservation and sustainable genetic improvement of Nili-Ravi buffalo in India.

Association analysis of polymorphism in thyroglobulin gene promoter with milk production traits in riverine buffalo (Bubalus bubalis).

Polymorphism within the promoter region of bovine thyroglobulin has been reported to be associated with milk and meat quality. In this study, we investigated the genetic variation within thyroglobulin promoter region of swamp and riverine buffaloes using PCR-SSCP technique and sequencing, and also analyzing association of polymorphism with the milk production traits. The study revealed four conformational patterns, A, B, C, and D among 323 buffaloes of two riverine breeds and different swamp populations. The frequency of SSCP variant 'A' was found to be invariably high among all buffalo populations. Variant 'C' was found to be absent in pure swamp population and present with higher frequency among riverine dairy breeds Mehsana and Nili Ravi. Frequency of D variant was observed to be highest in buffalo population, representing riverine and hybrid types. Sequencing of three representative PCR products of each of the SSCP variants, revealed three polymorphic sites responsible, 33C > T, 176G > T and 221C > T, in the buffalo TG promoter region. Further, association studies of SSCP variants with various milk production and milk quality traits indicated significant effect on fat percentage in buffaloes belonging to Mehsana and Nili Ravi dairy breeds. The preliminary results also showed the substantial variations in the distribution of SSCP variants' frequencies across swamp and riverine buffaloes, two distinct populations being reared for meat and milk production, respectively.

Genetic analysis of river, swamp and hybrid buffaloes of north-east India throw new light on phylogeography of water buffalo (Bubalus bubalis).

This study analysed buffaloes from north-east India and compared their nuclear and mitochondrial DNA variations with buffaloes of mainland India, China, Mediterranean and South-East Asia. Microsatellite genotypes of 338 buffaloes including 210 from six north-east Indian buffalo populations and three mainland Indian breeds were analysed to evaluate their genetic structure and evolutionary relationships. Phylogenetic analysis and multidimensional scaling plot of pairwise FST revealed the clustering of all swamp-type buffaloes of north-east India with Lower Assamese (significantly hybrid type) buffaloes in one plane and all the mainland river buffaloes in another plane while the upper Assamese buffaloes being distinct from both these clusters. Analysis of mtDNA D-loop region of 530-bp length was performed on 345 sequences belonging to 23 buffalo populations from various geographical regions to establish the phylogeography of Indian water buffalo. The swamp buffaloes of north-east India clustered with both the lineages of Chinese swamp buffalo. Multidimensional scaling display of pairwise FST derived from mitochondrial DNA data showed clustering of upper Assamese, Chilika and Mediterranean buffaloes distinctly from all the other Indian buffalo populations. Median-joining network analysis further confirmed the distinctness and ancestral nature of these buffaloes. The study revealed north-east region of India forming part of the wider hybrid zone of water buffalo that may probably extend from north-east India to South-East Asia.

Virtual screening and discovery of novel aurora kinase inhibitors.

Cancer remains one of the major contributors to human mortality and a hazard to human growth. The search for a new treatment continues unabated. Aurora kinases play an important role in cell cycle, and thus a potential target for the treatment of cancer. In the present work, we aim to discover potential leads against aurora kinase using various rational methods of drug discovery. The available crystal complexes of AKs were analyzed for their interactions and quantified with glide-extra precision (XP) docking. About 20 crystal pdb were selected from the protein databank based on the resolution factor, R-factor and R-value. And after docking with the native ligands, the RMSD value was calculated, wherein the protein with the least RMSD was found to be 3UOK which was further used for our screening of small molecules from the in-house database by molecular docking. Fragments which were found to possess the best interactions were considered for the synthesis with characterization, and biological activity was carried out against breast cancer and colorectal cancer cell lines to assess the inhibitory capability of synthesized compounds. Molecule with the molecular id IS2 i.e. (3E)-3-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)-2H chromene-2,4(3H)-dione was found to possess inhibitory activity with an IC50 of 1.324 nM and 5.785 µM for breast cell line and colorectal cell line studies, respectively.