Deep Learning-Based Ensembling Technique to Classify Alzheimer's Disease Stages Using Functional MRI.

The major issue faced by elderly people in society is the loss of memory, difficulty learning new things, and poor judgment. This is due to damage to brain tissues, which may lead to cognitive impairment and eventually Alzheimer's. Therefore, the detection of such mild cognitive impairment (MCI) becomes important. Usually, this is detected when it is converted into Alzheimer's disease (AD). AD is irreversible and cannot be cured whereas mild cognitive impairment (MCI) can be cured. The goal of this research is to diagnose Alzheimer's patients for timely treatment. For this purpose, functional MRI images from the publicly available dataset are used. Various deep-learning models have been used by the scientific community for the automatic detection of Alzheimer's subjects. These include the binary classification of scans of patients into MCI and AD stages, and limited work is carried out for multiclass classification of Alzheimer's disease up to six different stages. This study is divided into two steps. In the first step, a binary classification of the subject's scan is performed using Custom CNN. The second step involves the use of different deep learning models along with Custom CNN for multiclass classification of a subject's scan into one of the six stages of Alzheimer's disease. The models are evaluated based on different evaluation metrics, and the overall result of the models is improved using the max-voting ensembling technique. The experimental results show that an overall average accuracy of 98.8% is achieved for Alzheimer's stages classification.

Ribavirin inhibits the replication of infectious bursal disease virus predominantly through depletion of cellular guanosine pool.

Introduction: The antiviral activity of different mutagens against single-stranded RNA viruses is well documented; however, their activity on the replication of double-stranded RNA viruses remains unexplored. This study aims to investigate the effect of different antivirals on the replication of a chicken embryo fibroblast-adapted Infectious Bursal Disease virus, FVSKG2. This study further explores the antiviral mechanism utilized by the most effective anti-IBDV agent. Methods: The cytotoxicity and anti-FVSKG2 activity of different antiviral agents (ribavirin, 5-fluorouracil, 5-azacytidine, and amiloride) were evaluated. The virus was serially passaged in chicken embryo fibroblasts 11 times at sub-cytotoxic concentrations of ribavirin, 5-fluorouracil or amiloride. Further, the possible mutagenic and non-mutagenic mechanisms utilized by the most effective anti-FVSKG2 agent were explored. Results and Discussion: Ribavirin was the least cytotoxic on chicken embryo fibroblasts, followed by 5-fluorouracil, amiloride and 5-azacytidine. Ribavirin inhibited the replication of FVSKG2 in chicken embryo fibroblasts significantly at concentrations as low as 0.05 mM. The extinction of FVSKG2 was achieved during serial passage of the virus in chicken embryo fibroblasts at ≥0.05 mM ribavirin; however, the emergence of a mutagen-resistant virus was not observed until the eleventh passage. Further, no mutation was observed in 1,898 nucleotides of the FVSKG2 following its five passages in chicken embryo fibroblasts in the presence of 0.025 mM ribavirin. Ribavarin inhibited the FVSKG2 replication in chicken embryo fibroblasts primarily through IMPDH-mediated depletion of the Guanosine Triphosphate pool of cells. However, other mechanisms like ribavirin-mediated cytokine induction or possible inhibition of viral RNA-dependent RNA polymerase through its interaction with the enzyme's active sites enhance the anti-IBDV effect. Ribavirin inhibits ds- RNA viruses, likely through IMPDH inhibition and not mutagenesis. The inhibitory effect may, however, be augmented by other non-mutagenic mechanisms, like induction of antiviral cytokines in chicken embryo fibroblasts or interaction of ribavirin with the active sites of RNA-dependent RNA polymerase of the virus.

Mesenchymal stem cells derived from bone marrow and adipose tissue for repairing acute sciatic nerve injury in a rabbit model.

Peripheral nerve injury is one of the common disabling clinical conditions and around 50% of the cases end up in permanent impairment. Due to the lack of effective treatment options regenerative medicine employing stem cells is being evaluated. The presented study evaluated and compared regeneration potential of mesenchymal stem cells (MSCs) derived from bone marrow (BM) and adipose tissue (AD) in acute rabbit sciatic nerve injury (axonotmesis) model. A total of n = 54 grey giant rabbits were made subject of the study and divided equally into 3 groups: Control, BM-MSCs in Collagen I and AD-MSCs in Collagen I as per the treatment given. Iliac crest BM and omental AD was harvested from the same donor for isolation and culture of MSCs. The repair of sciatic nerve injury was evaluated on days 60 and 90. The clinical and histopathological scores and SEM morphology was better in cell treated groups as compared to the control. Morphology and histological studies revealed injured nerve in different levels of regenerative process. Gene expression was more than double for N-Cadherin in cell treated groups as compared to the control, especially at day 60. Between cell treated groups, BM-MSCs group showed better response as compared to the AD-MSCs, although statistically non-significant (p > 0.05). Incomplete nerve regeneration observed under various diagnostic parameters was in compliance to the incomplete clinical recovery at day 90. It was concluded that MSCs may improve sciatic nerve healing but fall short of complete regeneration at day 90, although BM-MSCs may have an edge over AD-MSCs.

Mesenchymal stem cells: A promising antimicrobial therapy in veterinary medicine.

Growing antimicrobial resistance (AMR) is a threat to human and animal populations citing the limited available options. Alternative antimicrobial options or functional enhancement of currently available antimicrobials remains only options. One of the potential options seems stem cells especially the mesenchymal stem cells (MSCs) that show antimicrobial properties. These cells additionally have pro-healing effects that may plausibly improve healing outcomes. MSCs antimicrobial actions are mediated either through direct cell-cell contact or their secretome that enhances innate immune mediated antimicrobial activities. These cells synergistically enhance efficacy of currently available antimicrobials especially against the biofilms. Reciprocal action from antimicrobials on the MSCs functionality remains poorly understood. Currently, the main limitation with MSCs based therapy is their limited efficacy. This demands further understanding and can be enhanced through biotechnological interventions. One of the interventional options is the 'priming' to enhance MSCs resistance and specific expression potential. The available literature shows potential antimicrobial actions of MSCs both ex vivo as well as in vivo. The studies on veterinary species are very promising although limited by number and extensiveness in details for their utility as standard therapeutic agents. The current review aims to discuss the role of animals in AMR and the potential antimicrobial actions of MSCs in veterinary medicine. The review also discusses the limitations in their utilization as standard therapeutics.

Isolation, in vitro expansion and characterization of ovine fetal adnexa-derived mesenchymal stem cells reveals a source dependent trilineage differentiation and growth kinetics.

This study was designed to isolate, cultivate, characterize and evaluate the growth kinetics of mesenchymal stem cells (MSCs) derived from fetal adnexa of sheep. The gravid uteri of ewes were collected from a local abattoir. The MSCs isolated from different fetal regions (Wharton's Jelly [oWJ], cord blood [oCB], amniotic fluid [oAF] and amniotic Sac [oAS]) were expanded in vitro and characterized for surface and pluripotency markers. The growth kinetics of MSCs was compared at 3rd and 5th passages. Similarly, the colony-forming efficiency (CFE) assay was performed at 3rd passage. The fetal adnexa-derived ovine MSCs showed the expression of CD73, CD90 and CD105. Similarly, the MSCs also expressed pluripotency markers, OCT4 and SOX2. Besides, cells also differentiated into osteogenic, chondrogenic and adipogenic lineages. The MSCs in culture showed a typical growth curve with initial lag phase, an exponential phase, a plateau phase and a decline phase. The growth rate was highest in oAF-MSCs at P5. The population doubling time (PDT) was highest in oAS-MSCs (87.28 ± 3.24 h), whereas the colony number was highest in oAF-MSCs (53.67 ± 4.06). The study reveals that oAF-MSCs were superior which outperformed other MSCs indicating that oAF-derived MSCs could be utilized for regenerative medicine.

Experimental Investigation of Engine Valve Train Friction Considering Effects of Operating Conditions and WPC Surface Treatment.

Reduction in friction ensures fuel economy, control on emissions and durability of components in internal combustion engines. A modern gasoline internal combustion engine was instrumented to determine the friction values at the cam-roller interface considering the effects of surface treatment and engine operating state. A series of tests under different operating speeds and lubricant inlet temperatures were undertaken using both an original surface roller and a Wonder Process Craft (WPC) surface-treated engine roller. The results clearly revealed a substantial reduction in friction magnitude for the WPC surface-treated engine roller in comparison to the original roller while operating under similar conditions, indicating their strong potential for employment in engines. An increase in friction with the rise in temperature was also observed for both types of rollers, whereas increased lubricant entraining velocity due to higher operating speed had the opposite impact. A considerable reduction in frictional drive torque ranging from 8% to 28% was observed by employing the WPC-treated roller in comparison to original/untreated roller at various operating conditions, which signifies the strong potential for employment of WPC surface treatment in the roller/follower valve train engines.

An Investigation of the Antiviral Potential of Phytocompounds against Avian Infectious Bronchitis Virus through Template-Based Molecular Docking and Molecular Dynamics Simulation Analysis.

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.

Adult Stem Cell Research in Light of the Bovine Mammary Gland Regenerative Medicine.

The bovine mammary gland has vital importance in the dairy sector, as it is considered a source of basic dairy product, milk. Mammary gland affections are widespread, which affect the dairy industry economically and pose a potential public health hazard. Current therapeutic options are ineffective in controlling the infection and regenerating the gland effectively. Antimicrobials commonly used against mastitis make their way into the milk . In order to find a solution to these problems, advanced therapeutic options, like the one for stem cells, are considered. Mammary gland stem cells (MaSCs) are considered to maintain tissue homeostasis. The characterization of these cells and their derived lineages (progenitor cells and mammary epithelial cells) may potentially provide the physiological status or production potential of the gland. However, current isolation methods are cumbersome and fall short to isolate a pure line of cattle MaSCs from progenitors or other differentiated epithelial cells. An alternative to the therapeutic application of MaSCs is the mesenchymal stem cell (MSC). These cells can potentially control microbial infection, show anti-inflammatory and other pro-healing effects, and furthermore enhance mammary epithelial cell secretory potential to ensure tissue regeneration. The current review focuses on MaSCs and MSCs properties in light of the bovine mammary gland regeneration.

Cryopreserved allogeneic bone marrow mesenchymal stem cells show better osteochondral defect repair potential than adipose tissue mesenchymal stem cells.

Mesenchymal stem cells (MSCs) due to their characteristic properties have a potential to treat osteoarthritis, one of the major growing joint problems. MSCs show differential ex vivo chondrogenic potential on the basis of source that remains to be validated under in vivo environment. This study compared chondrogenic potential of MSCs derived from two common sources, adipose tissue (AD) and bone marrow (BM) under ex vivo and in vivo environments. The randomized placebo controlled osteochondral defect (OCD) study divided n = 72 rabbits equally into Control, AD-MSCs and BM-MSCs groups. Ex vivo chondrogenic induction resulted in an increased aggrecan fold expression in BM-MSCs and AD-MSCs. The former cell type had significantly (p<0.05) higher fold expression as compared to the latter. The cell treated OCDs had significantly reduced gene expression for inflammatory markers (IL-6, IL-8 and TNF-α) as compared to the control. In OCD study, radiography, MRI, gross observation, histopathology and SEM revealed that the cell treated defects were early filled by the tissue that had better surface architecture and matrices as compared to the control. BM-MSCs treated defects had better scores especially for gross and histopathology than the AD-MSCs. Gene expression for osteochondral regulation and cartilaginous matrices was higher in BM-MSCs group while only for matrices including the Col I in AD-MSCs as compared to the control. It was concluded that OCD in the cell treated groups are filled early with mostly a fibrocartilaginous to hyaline tissue. BM-MSCs may have an edge over AD-MSCs in OCD repair.

Comparative RNA-Seq analysis reveals insights in Salmonella disease resistance of chicken; and database development as resource for gene expression in poultry.

Salmonella, one of the major infectious diseases in poultry, causes considerable economic losses in terms of mortality and morbidity, especially in countries that lack effective vaccination programs. Besides being resistant to diseases, indigenous chicken breeds are also a potential source of animal protein in developing countries. For understanding the disease resistance, an indigenous chicken line Kashmir faverolla, and commercial broiler were selected. RNA-seq was performed after challenging the chicken with Salmonella Typhimurium. Comparative differential expression results showed that following infection, a total of 3153 genes and 1787 genes were differentially expressed in the liver and spleen, respectively. The genes that were differentially expressed included interleukins, cytokines, NOS2, Avß-defensins, toll-like receptors, and other immune-related gene families. Most of the genes and signaling pathways involved in the innate and adaptive immune responses against bacterial infection were significantly enriched in the Kashmir faverolla. Pathway analysis revealed that most of the enriched pathways were MAPK signaling pathway, NOD-like receptor signaling pathway, TLR signaling pathway, PPAR signaling pathway, endocytosis, etc. Surprisingly some immune-related genes like TLRs were upregulated in the susceptible chicken breed. On postmortem examination, the resistant birds showed small lesions in the liver compared to large necrotic lesions in susceptible birds. The pathological manifestations and RNA sequencing results suggest a balancing link between resistance and infection tolerance in Kashmir faverolla. Here we also developed an online Poultry Infection Database (https://skuastk.org/pif/index.html), the first publicly available gene expression resource for disease resistance in chickens. The available database not only shows the data for gene expression in chicken tissues but also provides quick search, visualization and download capacity.

Cryopreserved allogeneic mesenchymal stem cells enhance wound repair in full thickness skin wound model and cattle clinical teat injuries.

The study was aimed to evaluate and compare the healing potential of mesenchymal stem cells (MSCs) derived from two common sources (iliac crest derived bone marrow and omental fat) in a full thickness skin wound model. Bone marrow derived MSCs clinical efficacy in the repair of cattle teat fistulae (cutaneous and muco-cutaneous wounds) was also evaluated. In a completely randomized placebo controlled experimental full thickness skin wound model, n=36 were randomly divided into three equal groups: groups I, II and III receiving Phosphate buffered saline (PBS), BM-MSCs and adipose tissue MSCs (AD-MSCs), respectively. Grossly early reduction in inflammation and enhanced epithelialization in the cell-treated groups as compared to the control was seen. Microscopy, ultramicroscopy, gene expression analysis and mechanical testing revealed better and early matrix formation with a reduced scar formation and a higher tensile strength in the cell-treated groups as compared to the control. An overall comparable healing in the cell treated groups was observed, although BM-MSCs had led to the better matrix formation tending to scarless healing while the AD-MSCs had led to the early wound closure with a good tissue strength. In the case controlled bovine clinical teat injuries study (n=17) repaired surgically, BM-MSCs (n=13) or PBS (n=4) was injected locally. In surgico-MSCs treated cases, 84.6% non-recurrence rate was observed as compared to the 50% seen in the control. It was concluded that MSCs irrespective of the donor tissue have potential to improve healing of full thickness cutaneous wounds and/ fistulae.

Mammary epithelial cell transcriptome reveals potential roles of lncRNAs in regulating milk synthesis pathways in Jersey and Kashmiri cattle.

BACKGROUND: Long noncoding RNAs (lncRNAs) are now proven as essential regulatory elements, playing diverse roles in many biological processes including mammary gland development. However, little is known about their roles in the bovine lactation process. RESULTS: To identify and characterize the roles of lncRNAs in bovine lactation, high throughput RNA sequencing data from Jersey (high milk yield producer), and Kashmiri cattle (low milk yield producer) were utilized. Transcriptome data from three Kashmiri and three Jersey cattle throughout their lactation stages were utilized for differential expression analysis. At each stage (early, mid and late) three samples were taken from each breed. A total of 45 differentially expressed lncRNAs were identified between the three stages of lactation. The differentially expressed lncRNAs were found co-expressed with genes involved in the milk synthesis processes such as GPAM, LPL, and ABCG2 indicating their potential regulatory effects on milk quality genes. KEGG pathways analysis of potential cis and trans target genes of differentially expressed lncRNAs indicated that 27 and 48 pathways were significantly enriched between the three stages of lactation in Kashmiri and Jersey respectively, including mTOR signaling, PI3K-Akt signaling, and RAP1 signaling pathways. These pathways are known to play key roles in lactation biology and mammary gland development. CONCLUSIONS: Expression profiles of lncRNAs across different lactation stages in Jersey and Kashmiri cattle provide a valuable resource for the study of the regulatory mechanisms involved in the lactation process as well as facilitate understanding of the role of lncRNAs in bovine lactation biology.

Expression of lncRNAs in response to bacterial infections of goat mammary epithelial cells reveals insights into mammary gland diseases.

Mastitis or inflammation of the mammary gland is a highly economic and deadly alarming disease for the dairy sector as well as policymakers caused by microbial infection. Transcriptomic and proteomic approaches have been widely employed to identify the underlying molecular mechanisms of bacterial infections in the mammary gland. Numerous differentially expressed mRNAs, miRNAs, and proteins together with their associated signaling pathways have been identified during bacterial infection, paving the way for analysis of their biological functions. Long noncoding RNAs (lncRNAs) are important regulators of multiple biological processes. However, little is known regarding their role in bacterial infection in mammary epithelial cells. Hence, RNA-sequencing was performed by infecting primary mammary epithelial cells (pMECs) with both gram-negative (E. coli) and gram-positive bacteria (S. aureus). Using stringent pipeline, a set of 1957 known and 1175 novel lncRNAs were identified, among which, 112 lncRNAs were found differentially expressed in bacteria challenged PMECs compared with the control. Additionally, potential targets of the lncRNAs were predicted in cis- and trans-configuration. KEGG analysis revealed that DE lncRNAs were associated with at least 15 immune-related pathways. Therefore, our study revealed that bacterial challenge triggers the expression of lncRNAs associated with immune response and defense mechanisms in goat mammary epithelial cells.

A multiepitope vaccine candidate against infectious bursal disease virus using immunoinformatics-based reverse vaccinology approach.

Infectious bursal disease virus is the causative agent of infectious bursal disease (Gumboro disease), a highly contagious immunosuppressive disease of chicken with a substantial economic impact on small- and large-scale poultry industries worldwide. Currently, live attenuated vaccines are widely used to control the disease in chickens despite their issues with safety (immunosuppression and bursal atrophy) and efficiency (breaking through the maternally-derived antibody titer). To overcome the drawbacks, the current study has, for the first time, attempted to construct a computational model of a multiepitope based vaccine candidate against infectious bursal disease virus, which has the potential to overcome the safety and protection issues found in the existing live-attenuated vaccines. The current study used a reverse vaccinology based immunoinformatics approach to construct the vaccine candidate using major and minor capsid proteins of the virus, VP2 and VP3, respectively. The vaccine construct was composed of four CD8+ epitopes, seven CD4+ T-cell epitopes, 11 B-cell epitopes and a Cholera Toxin B adjuvant, connected using appropriate flexible peptide linkers. The vaccine construct was evaluated as antigenic with VaxiJen Score of 0.6781, immunogenic with IEDB score of 2.89887 and non-allergenic. The 55.64 kDa construct was further evaluated for its physicochemical characteristics, which revealed that it was stable with an instability index of 16.24, basic with theoretical pI of 9.24, thermostable with aliphatic index of 86.72 and hydrophilic with GRAVY score of -0.256. The docking and molecular dynamics simulation studies of the vaccine construct with Toll-like receptor-3 revealed fair structural interaction (binding affinity of -295.94 kcal/mol) and complex stability. Further, the predicted induction of antibodies and cytokines by the vaccine construct indicated the possible elicitation of the host's immune response against the virus. The work is a significant attempt to develop next-generation vaccines against the infectious bursal disease virus though further experimental studies are required to assess the efficacy and protectivity of the proposed vaccine candidate in vivo.

A recurrent homozygous missense mutation in CCDC103 causes asthenoteratozoospermia due to disorganized dynein arms / 亚洲男科学杂志(英文版)

Asthenoteratozoospermia is one of the most severe types of qualitative sperm defects. Most cases are due to mutations in genes encoding the components of sperm flagella, which have an ultrastructure similar to that of motile cilia. Coiled-coil domain containing 103 (CCDC103) is an outer dynein arm assembly factor, and pathogenic variants of CCDC103 cause primary ciliary dyskinesia (PCD). However, whether CCDC103 pathogenic variants cause severe asthenoteratozoospermia has yet to be determined. Whole-exome sequencing (WES) was performed for two individuals with nonsyndromic asthenoteratozoospermia in a consanguineous family. A homozygous CCDC103 variant segregating recessively with an infertility phenotype was identified (ENST00000035776.2, c.461A>C, p.His154Pro). CCDC103 p.His154Pro was previously reported as a high prevalence mutation causing PCD, though the reproductive phenotype of these PCD individuals is unknown. Transmission electron microscopy (TEM) of affected individuals' spermatozoa showed that the mid-piece was severely damaged with disorganized dynein arms, similar to the abnormal ultrastructure of respiratory ciliary of PCD individuals with the same mutation. Thus, our findings expand the phenotype spectrum of CCDC103 p.His154Pro as a novel pathogenic gene for nonsyndromic asthenospermia.

Friction and Wear Performance Evaluation of Bio-Lubricants and DLC Coatings on Cam/Tappet Interface of Internal Combustion Engines.

The environmental concerns associated with artificially formulated engine oils have forced a shift towards bio-based lubricants. The deposition of hard coatings on engine components and migrating to environmentally friendly green lubricants can help in this regard. Chemically modified forms of vegetable oils, with better low-temperature characteristics and enhanced thermo-oxidative stability, are suitable substitutes to conventional lubricant base oils. The research presented in this manuscript was undertaken to experimentally investigate the wear and friction performance of a possible future generation of an environmentally friendly bio-based lubricant as a potential replacement for conventional engine lubricants. In order to quantify the tribological benefits which can be gained by the deposition of DLC coatings, (an (a-C:H) hydrogenated DLC coating and an (a-C:H:W) tungsten-doped DLC coating) were applied on the cam/tappet interface of a direct acting valve train assembly of an internal combustion engine. The tribological correlation between DLC-coated engine components, lubricant base oils and lubricant additives have been thoroughly investigated in this study using actual engine operating conditions. Two additive-free base oils (polyalphaolefines (PAO) and chemically-modified palm oil (TMP)) and two multi-additive-containing lubricants were used in this investigation. Real-time drive torque was measured to determine the friction force, detailed post-test analysis was performed, which involved the use of a specialized jig to measure camlobe wear. An optical profilometer was used to measure the wear on the tappet, high-resolution scanning electron microscopy was employed to study the wear mechanism and energy-dispersive X-ray spectroscopy was performed on the tested samples to qualitatively access the degradation of the coating. When using additive-free TMP, a low friction coefficient was observed for the cam/tappet interface. The presence of additives further improved the friction characteristics of TMP, resulting in reduced average friction torque values. A tremendous enhancement in wear performance was recorded with a-C:H-coated parts and the coating was able to withstand the test conditions with little or no delamination.

SNPs in Mammary Gland Epithelial Cells Unraveling Potential Difference in Milk Production Between Jersey and Kashmiri Cattle Using RNA Sequencing.

Deep RNA sequencing experiment was employed to detect putative single nucleotide polymorphisms (SNP) in mammary epithelial cells between two diverse cattle breeds (Jersey and Kashmiri) to understand the variations in the coding regions that reflect differences in milk production traits. The low milk-producing Kashmiri cattle are being replaced by crossbreeding practices with Jersey cattle with the aim of improving milk production. However, crossbred animals are prone to infections and various other diseases resulting in unsustainable milk production. In this study, we tend to identify high-impact SNPs from Jersey and Kashmiri cows (utilizing RNA-Seq data) to delineate key pathways mediating milk production traits in both breeds. A total of 607 (442 SNPs and 169 INDELs) and 684 (464 SNPs and 220 INDELs) high-impact variants were found specific to Jersey and Kashmir cattle, respectively. Based on our results, we conclude that in Jersey cattle, genes with high-impact SNPs were enriched in nucleotide excision repair pathway, ABC transporter, and metabolic pathways like glycerolipid metabolism, pyrimidine metabolism, and amino acid synthesis (glycine, serine, and threonine). Whereas, in Kashmiri cattle, the most enriched pathways include endocytosis pathway, innate immunity pathway, antigen processing pathway, insulin resistance pathway, and signaling pathways like TGF beta and AMPK which could be a possible defense mechanism against mammary gland infections. A varied set of SNPs in both breeds, suggests a clear differentiation at the genomic level; further analysis of high-impact SNPs are required to delineate their effect on these pathways.

Wheat growth and nutrient uptake after phosphorus and potassium applications in saline-sodic field of semi-arid region / Crescimento do trigo e absorção de nutrientes após aplicações de fósforo e potássio em campo salino-sódico do semi-árido

Nutrient deficiency is a limiting factor in saline-sodic soils resulting in low crop production. The study investigated wheat response to P and K added to soils. The K was applied at 0 (K0), 75 (K1), 150 (K2) kg K2O ha-1 as K2S04 and at (0 (P0), 60 (P1), 120 (P2) kg P2O5 ha-1 as (NH4)2HPO4 in three replications under two-factorial randomized complete block (RCB) design. Both treatments significantly enhanced wheat grain (118%) and dry matter yield (60%) at P2K2 compared to control. The P treatments significantly affected leaf P, Mg, SO4, Ca:P, SO4:P ratios and soil P, Ca:P, Cl:P and SO4:P ratios, while K on leaf K, Na, Ca, SO4 concentration, K:Na, K:Ca, SO4:P,Ca:P ratios and soil pH, Na, K, Ca, SO4 concentrations, SAR, Na:K, Ca:K and Na:Ca ratios. Leaf Na was decreased to 85.3 mmol (+) kg-1 at K2 compared to 105.3 mmol (+) kg-1at P2K0. Negative correlation (R2=0.906) of leaf K:Na was found with leaf Na concentration. The correlation of dry matter was higher (R2=0.851) with leaf K:Na ratio than grain yield (R2=0.392). It is concluded that the addition of K and P addition shows beneficial effects in improving crop nutrition and wheat yield in the saline-sodic soil environment.

A deficiência de nutrientes é um fator limitante em solos salino-sódicos, resultando em baixa produção agrícola. O estudo investigou a resposta do trigo ao P e K adicionados ao solo. O K foi aplicado em 0 (K0), 75 (K1), 150 (K2) kg K2O ha-1 como K2S04 e em (0 (P0), 60 (P1), 120 (P2) kg P2O5 ha-1 como (NH4)2HPO4 em três repetições sob delineamento de blocos completos casualizados (RCB) de dois fatores. Ambos os tratamentos aumentaram significativamente o rendimento de grãos de trigo (118%) e de matéria seca (60%) em P2K2 em comparação com o controle. Os tratamentos com P afetaram significativamente o P foliar, Mg, SO4, as razões Ca:P, SO4:P e o P do solo, e as razões Ca:P, Cl:P e SO4:P, enquanto K no K foliar, Na, Ca, concentração de SO4, razões K:Na, K:Ca, SO4:P, Ca:P e pH do solo, Na, K, Ca, concentrações de SO4, SAR, razões Na:K, Ca:K e Na:Ca. O Na da folha foi reduzido para 85,3 mmol (+) kg-1 em K2 em comparação com 105,3 mmol (+) kg-1 em P2K0. Correlação negativa (R2 = 0,906) do K:Na na folha foi encontrada com a concentração de Na na folha. A correlação da matéria seca foi maior (R2 = 0,851) com a relação K:Na da folha do que rendimento de grãos (R2 = 0,392). Conclui-se que a adição de K e P apresenta efeitos benéficos na melhoria da nutrição da cultura e na produtividade do trigo em solo salino-sódico

Deep Insights in Circular RNAs: from biogenesis to therapeutics.

ABSTRACT: Circular RNAs (circRNAs) have emerged as a universal novel class of eukaryotic non-coding RNA (ncRNA) molecules and are becoming a new research hotspot in RNA biology. They form a covalent loop without 5' cap and 3' tail, unlike their linear counterparts. Endogenous circRNAs in mammalian cells are abundantly conserved and discovered so far. In the biogenesis of circRNAs exonic, intronic, reverse complementary sequences or RNA-binding proteins (RBPs) play a very important role. Interestingly, the majority of them are highly conserved, stable, resistant to RNase R and show developmental-stage/tissue-specific expression. CircRNAs play multifunctional roles as microRNA (miRNA) sponges, regulators of transcription and post-transcription, parental gene expression and translation of proteins in various diseased conditions. Growing evidence shows that circRNAs play an important role in neurological disorders, atherosclerotic vascular disease, and cancer and potentially serve as diagnostic or predictive biomarkers due to its abundance in various biological samples. Here, we review the biogenesis, properties, functions, and impact of circRNAs on various diseases.