Parkinson's: A Disease of Aberrant Vesicle Trafficking.

Parkinson's disease (PD) is a leading cause of neurodegeneration that is defined by the selective loss of dopaminergic neurons and the accumulation of protein aggregates called Lewy bodies (LBs). The unequivocal identification of Mendelian inherited mutations in 13 genes in PD has provided transforming insights into the pathogenesis of this disease. The mechanistic analysis of several PD genes, including α-synuclein (α-syn), leucine-rich repeat kinase 2 (LRRK2), PTEN-induced kinase 1 (PINK1), and Parkin, has revealed central roles for protein aggregation, mitochondrial damage, and defects in endolysosomal trafficking in PD neurodegeneration. In this review, we outline recent advances in our understanding of these gene pathways with a focus on the emergent role of Rab (Ras analog in brain) GTPases and vesicular trafficking as a common mechanism that underpins how mutations in PD genes lead to neuronal loss. These advances have led to previously distinct genes such as vacuolar protein-sorting-associated protein 35 (VPS35) and LRRK2 being implicated in a common signaling pathway. A greater understanding of these common nodes of vesicular trafficking will be crucial for linking other PD genes and improving patient stratification in clinical trials underway against α-syn and LRRK2 targets.

SARS-CoV-2 infects cells lining the blood-retinal barrier and induces a hyperinflammatory immune response in the retina via systemic exposure.

SARS-CoV-2 has been shown to cause wide-ranging ocular abnormalities and vision impairment in COVID-19 patients. However, there is limited understanding of SARS-CoV-2 in ocular transmission, tropism, and associated pathologies. The presence of viral RNA in corneal/conjunctival tissue and tears, along with the evidence of viral entry receptors on the ocular surface, has led to speculation that the eye may serve as a potential route of SARS-CoV-2 transmission. Here, we investigated the interaction of SARS-CoV-2 with cells lining the blood-retinal barrier (BRB) and the role of the eye in its transmission and tropism. The results from our study suggest that SARS-CoV-2 ocular exposure does not cause lung infection and moribund illness in K18-hACE2 mice despite the extended presence of viral remnants in various ocular tissues. In contrast, intranasal exposure not only resulted in SARS-CoV-2 spike (S) protein presence in different ocular tissues but also induces a hyperinflammatory immune response in the retina. Additionally, the long-term exposure to viral S-protein caused microaneurysm, retinal pigmented epithelium (RPE) mottling, retinal atrophy, and vein occlusion in mouse eyes. Notably, cells lining the BRB, the outer barrier, RPE, and the inner barrier, retinal vascular endothelium, were highly permissive to SARS-CoV-2 replication. Unexpectedly, primary human corneal epithelial cells were comparatively resistant to SARS-CoV-2 infection. The cells lining the BRB showed induced expression of viral entry receptors and increased susceptibility towards SARS-CoV-2-induced cell death. Furthermore, hyperglycemic conditions enhanced the viral entry receptor expression, infectivity, and susceptibility of SARS-CoV-2-induced cell death in the BRB cells, confirming the reported heightened pathological manifestations in comorbid populations. Collectively, our study provides the first evidence of SARS-CoV-2 ocular tropism via cells lining the BRB and that the virus can infect the retina via systemic permeation and induce retinal inflammation.

Genomic surveillance uncovers a pandemic clonal lineage of the wheat blast fungus.

Wheat, one of the most important food crops, is threatened by a blast disease pandemic. Here, we show that a clonal lineage of the wheat blast fungus recently spread to Asia and Africa following two independent introductions from South America. Through a combination of genome analyses and laboratory experiments, we show that the decade-old blast pandemic lineage can be controlled by the Rmg8 disease resistance gene and is sensitive to strobilurin fungicides. However, we also highlight the potential of the pandemic clone to evolve fungicide-insensitive variants and sexually recombine with African lineages. This underscores the urgent need for genomic surveillance to track and mitigate the spread of wheat blast outside of South America and to guide preemptive wheat breeding for blast resistance.

Viral infections and pathogenesis of glaucoma: a comprehensive review.

Glaucoma is a leading cause of irreversible blindness worldwide, caused by the gradual degeneration of retinal ganglion cells and their axons. While glaucoma is primarily considered a genetic and age-related disease, some inflammatory conditions, such as uveitis and viral-induced anterior segment inflammation, cause secondary or uveitic glaucoma. Viruses are predominant ocular pathogens and can impose both acute and chronic pathological insults to the human eye. Many viruses, including herpes simplex virus, varicella-zoster virus, cytomegalovirus, rubella virus, dengue virus, chikungunya virus, Ebola virus, and, more recently, Zika virus (ZIKV) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), have been associated with sequela of either primary or secondary glaucoma. Epidemiological and clinical studies suggest the association between these viruses and subsequent glaucoma development. Despite this, the ocular manifestation and sequela of viral infections are not well understood. In fact, the association of viruses with glaucoma is considered relatively uncommon in part due to underreporting and/or lack of long-term follow-up studies. In recent years, literature on the pathological spectrum of emerging viral infections, such as ZIKV and SARS-CoV-2, has strengthened this proposition and renewed research activity in this area. Clinical studies from endemic regions as well as laboratory and preclinical investigations demonstrate a strong link between an infectious trigger and development of glaucomatous pathology. In this article, we review the current understanding of the field with a particular focus on viruses and their association with the pathogenesis of glaucoma.

Rapid mini-chromosome divergence among fungal isolates causing wheat blast outbreaks in Bangladesh and Zambia.

The fungal pathogen, Magnaporthe oryzae Triticum pathotype, causing wheat blast disease was first identified in South America and recently spread across continents to South Asia and Africa. Here, we studied the genetic relationship among isolates found on the three continents. Magnaporthe oryzae strains closely related to a South American field isolate B71 were found to have caused the wheat blast outbreaks in South Asia and Africa. Genomic variation among isolates from the three continents was examined using an improved B71 reference genome and whole-genome sequences. We found strong evidence to support that the outbreaks in Bangladesh and Zambia were caused by the introductions of genetically separated isolates, although they were all close to B71 and, therefore, collectively referred to as the B71 branch. In addition, B71 branch strains carried at least one supernumerary mini-chromosome. Genome assembly of a Zambian strain revealed that its mini-chromosome was similar to the B71 mini-chromosome but with a high level of structural variation. Our findings show that while core genomes of the multiple introductions are highly similar, the mini-chromosomes have undergone marked diversification. The maintenance of the mini-chromosome and rapid genomic changes suggest the mini-chromosomes may serve important virulence or niche adaptation roles under diverse environmental conditions.

Rmg10, a novel wheat blast resistance gene derived from Aegilops tauschii.

Wheat blast, caused by Pyricularia oryzae (syn. Magnaporthe oryzae) pathotype Triticum (MoT), is a devastating disease that can result in up to 100% yield loss in affected fields. To find new resistance genes against wheat blast, we screened 199 accessions of Aegilops tauschii Coss., the D genome progenitor of common wheat (Triticum aestivum L.) by seedling inoculation assays with Brazilian MoT isolate Br48, and found 14 resistant accessions. A synthetic hexaploid wheat line (Ldn/KU-2097) derived from a cross between the T. turgidum cultivar 'Langdon' (Ldn) and resistant Ae. tauschii accession KU-2097 exhibited resistance in seedlings and spikes against Br48. In an F2 population derived from 'Chinese Spring' (CS) × Ldn/KU-2097, resistant and susceptible individuals segregated in a 3:1 ratio, suggesting that the resistance from KU-2097 is controlled by a single dominant gene. We designated this gene Rmg10. Genetic mapping using an F2:3 population from the same cross mapped the RMG10 locus to the short arm of chromosome 2D. Rmg10 was ineffective against Bangladesh isolates but effective against Brazilian isolates. Field tests in Bolivia showed increased spike resistance in a synthetic octaploid wheat line produced from a cross between common wheat cultivar 'Gladius' and KU-2097. These results suggest that Rmg10 would be beneficial in farmers' fields in South America.

Selection of reference genes for normalizing gene expression data across seasons in spermatozoa of water buffalo (Bubalus bubalis).

Selection of the most stably expressed reference genes is key to monitoring accurate target gene expression across any tissue or cell type. The mRNA in spermatozoa stores valuable information related to changes in spermatogenesis due to variations in environmental conditions, especially during heat stress, which affects various sperm functions. Semen quality in buffalo bulls is significantly influenced by the seasons. In the study, a panel of nine genes was evaluated to identify the most stably expressed internal control gene (ICG) for the normalization of real-time gene expression data generated across various seasons for Murrah buffalo bulls' spermatozoa. Sperm cells were purified from the semen samples collected during different seasons, with temperature-humidity index (THI) ranging from 80.80 ± 1.47 (hot summer) to 55.88 ± 1.98 (winter), using the BoviPure™ gradient purification method. The RNA isolated from the purified spermatozoa fraction was quality checked prior to reverse transcription and subjected to qPCR (quantitative real-time PCR) based expression analysis. An automated 'endoGene' pipeline was employed to apply the geNorm, NormFinder, and BestKeeper algorithms for data analysis. The result indicated that GAPDH and PP1A were the most stably expressed among the gene panel, whereas ATPSF1 and ACTB were the two least stable expressed reference genes. Further, the most suitable ICGs identified were validated by normalization of real time expression data of heat stress and sperm quality genes, HSFY2 and AKAP4, respectively. The genes identified would help in generating the most reliable results for the expression profiling of the genes dictating sperm quality and heat stress cope-up mechanism in buffalo spermatozoa, collected during different seasons.

Novel technique for laparoscopic common bile duct exploration using flexible videobronchoscope to study on clinical outcomes of single-stage (laparoscopic cholecystectomy and laparoscopic common bile duct exploration) versus dual-stage (endoscopic retrograde cholangiopancreatography followed by laparoscopic cholecystectomy) for cholelithiasis with choledocholithiasis - Prospective study in a tertiary care centre (BRACE study - BRonchoscope Assisted Common bile duct Exploration Study).

INTRODUCTION: This study aimed to study on clinical outcomes of single-stage (laparoscopic cholecystectomy [LC] and laparoscopic common bile duct [CBD] exploration using flexible videobronchoscope) versus dual-stage (endoscopic retrograde cholangiopancreatography followed by laparoscopic cholecystectomy) for cholelithiasis with choledocholithiasis-prospective study in a tertiary care centre (BRACE STUDY-Bronchoscope-Assisted CBD Exploration [CBDE] Study). PATIENTS AND METHODS: Between April 2022 and April 2023, patients who underwent LC with laparoscopic CBDE and endoscopic retrograde cholangiopancreatography (ERCP) followed by LC participated in this single-centre prospective research. The Institute Ethics Committee granted its approval after receiving an ethical review. The primary endpoint of the proposed research was the removal of the gall bladder and CBD stones. The secondary outcomes studied were complications using the Clavien-Dindo score, cost-effectiveness, patient satisfaction score and post-procedure duration of hospital stay. RESULTS: A total of 168 patients were included in the study. The success rate of LC with laparoscopic CBD exploration using a flexible videobronchoscope (Group 1) was significantly higher as compared to ERCP f/b LC (Group 2) (96.4% vs. 84.5%, P value = 0.02). Out of the 84 patients in Group 1, direct choledochotomies were performed on 83 of them. Group 1 had a considerably shorter hospital stay (4.6 ± 2.4 vs. 5.3 ± 6.2 days; P = 0.03). Both the cost (P = 0.002) and the number of procedures per patient (P < 0.001) were considerably higher in Group 2. Major complications (Clavien-Dindo grade 3 and above) were significantly higher in Group 2 (P = 0.04). Patient satisfaction in Group 1 scored more favourably than those in Group 2 (2.26 ± 0.3 vs. 1.92 ± 0.7; P = 0.006). CONCLUSION: For concurrent gall bladder and CBD stones, single-stage management by LCBDE using a flexible videobronchoscope has a significantly better primary outcome and lower major complications than dual-stage management. The single-stage strategy also has advantages in terms of a shorter hospital stay, the need for fewer procedures, cost efficiency and patient satisfaction.

Butyrate Ameliorates Intraocular Bacterial Infection by Promoting Autophagy and Attenuating the Inflammatory Response.

Despite an important link between the gut and ocular health, the role of the gut-eye axis remains elusive in ocular infections. In this study, we investigated the role of butyrate, a gut microbial metabolite, in the pathobiology of intraocular bacterial (Staphylococcus aureus) infection, endophthalmitis. We found that intravitreal administration of butyrate derivatives, sodium butyrate (NaB), or phenylbutyrate (PBA) reduced intraocular bacterial growth and retinal inflammatory response. The ocular tissue architecture and retinal function were preserved in butyrate-treated eyes. In cultured mouse bone marrow-derived macrophages (BMDMs) and human retinal Müller glia, NaB or PBA treatment reduced S. aureus-induced inflammatory response by inhibiting NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome. However, in vivo data showed NLRP3-independent effects of butyrate. The butyrate-treated mouse retina and cells exhibited induced expression of antimicrobial molecules CRAMP (LL37) and S100A7/A8, resulting in increased bacterial phagocytosis and killing. Moreover, butyrate treatment enhanced AMP-activated protein kinase (AMPK)-dependent autophagy and promoted the co-localization of CRAMP in autophagosomes, indicating autophagy-mediated bacterial killing. Furthermore, pharmacological inhibition of autophagy in mice revealed its role in butyrate-mediated protection. Finally, butyrate exhibited synergy with antibiotic in promoting endophthalmitis resolution. Collectively, our study demonstrated the protective mechanisms of butyrate in ameliorating bacterial endophthalmitis. Therefore, butyrate derivatives could be explored as immunomodulatory and anti-bacterial therapeutics to improve visual outcomes in ocular bacterial infections.

Haplotype-tagged SNPs improve genomic prediction accuracy for Fusarium head blight resistance and yield-related traits in wheat.

KEY MESSAGE: Linkage disequilibrium (LD)-based haplotyping with subsequent SNP tagging improved the genomic prediction accuracy up to 0.07 and 0.092 for Fusarium head blight resistance and spike width, respectively, across six different models. Genomic prediction is a powerful tool to enhance genetic gain in plant breeding. However, the method is accompanied by various complications leading to low prediction accuracy. One of the major challenges arises from the complex dimensionality of marker data. To overcome this issue, we applied two pre-selection methods for SNP markers viz. LD-based haplotype-tagging and GWAS-based trait-linked marker identification. Six different models were tested with preselected SNPs to predict the genomic estimated breeding values (GEBVs) of four traits measured in 419 winter wheat genotypes. Ten different sets of haplotype-tagged SNPs were selected by adjusting the level of LD thresholds. In addition, various sets of trait-linked SNPs were identified with different scenarios from the training-test combined and only from the training populations. The BRR and RR-BLUP models developed from haplotype-tagged SNPs had a higher prediction accuracy for FHB and SPW by 0.07 and 0.092, respectively, compared to the corresponding models developed without marker pre-selection. The highest prediction accuracy for SPW and FHB was achieved with tagged SNPs pruned at weak LD thresholds (r2 < 0.5), while stringent LD was required for spike length (SPL) and flag leaf area (FLA). Trait-linked SNPs identified only from training populations failed to improve the prediction accuracy of the four studied traits. Pre-selection of SNPs via LD-based haplotype-tagging could play a vital role in optimizing genomic selection and reducing genotyping costs. Furthermore, the method could pave the way for developing low-cost genotyping methods through customized genotyping platforms targeting key SNP markers tagged to essential haplotype blocks.

Dynamic assessment of oropharynx with ultrasonography as a screening tool for obstructive sleep apnea.

Ultrasonography is an easily available and portable tool to assess the dynamic changes in the upper airway and surrounding soft tissue. This study aimed to evaluate the utility of oropharynx ultrasonography as a screening tool for obstructive sleep apnea (OSA). The study sequentially enrolled overweight individuals (body mass index >25 kg/m2 ) and subjected them to OSA screening tools (Berlin questionnaire, Epworth Sleepiness Scale and STOP-Bang scores), ultrasonography of the oropharynx followed by overnight polysomnography. A total of 30 healthy individuals were also recruited as controls. Detailed dynamic and static ultrasonography measurements of the oropharynx and surrounding tissue were done. The diagnostic ability of various ultrasonography parameters to detect OSA was determined using receiver operating characteristic curve analysis. A total of 63 subjects were enrolled, with 33 in the OSA group and 30 in non-OSA overweight group. All baseline characteristics were similar in the two groups. Except for the dynamic measurements of oropharynx (Retropalatal% change-inspiration, retropalatal% change-Muller manoeuvre, retroglossal% change-inspiration, and retroglossal% change-Muller manoeuvre) all other parameters were similar in the OSA and non-OSA overweight subjects. The area under the receiver operating characteristic curve was highest for retropalatal% change-inspiration: 0.989, followed by retropalatal% change-Muller manoeuvre: 0.988. Both were also significant predictors of OSA with odds ratios of 0.338 (p = 0.003; 95% confidence interval [CI] 0.164-0.696) and 0.346 (p = 0.018; 95% CI 0.143-0.837), respectively. Ultrasonography provides a near complete picture of the dynamic changes and collapsibility of the oropharynx and can be an effective tool in screening for OSA.

Heterologous expression and characterization of ToxA1 haplotype from India and its interaction with Tsn1 for spot blotch susceptibility in spring wheat.

BACKGROUND: ToxA, a necrotrophic effector protein, is present in the genome of fungal species like Parastagnospora nodorum, Pyrenophora tritici-repentis and Bipolaris sorokiniana. Tsn1 is the sensitivity gene in the host whose presence indicates more susceptibility to ToxA carrying pathogen, and ToxA-Tsn1 interaction follows an inverse gene-for-gene relationship. METHODS AND RESULTS: The present study involved cloning and expressing the ToxA1 haplotype from B. sorokiniana. It was found that the amplicon exhibited an expected product size of 471 bp. Sequence analysis of the ToxA1 nucleotide sequence revealed the highest identity, 99.79%, with P. tritici-repentis. The protein expression analysis showed peak expression at 16.5 kDa. Phylogenetic analysis of the ToxA1 sequence from all the Bipolaris isolates formed an independent clade along with P. tritici-repentis and diverged from P. nodorum. ToxA-Tsn1 interaction was studied in 18 wheat genotypes (11 Tsn1 and 7 tsn1) at both seedling and adult stages, validating the inverse gene-for-gene relationship, as the toxin activity was highest in the K68 genotype (Tsn1) and lowest in WAMI280 (tsn1). CONCLUSION: The study indicates that the haplotype ToxA1 is prevailing in the Indian population of B. sorokiniana. It would be desirable for wheat breeders to select genotypes with tsn1 locus for making wheat resistant to spot blotch.

Development and validation of most efficient RNA isolation method from buffalo bull spermatozoa.

BACKGROUND: Being highly fragmented and low in concentration, isolation of good quality RNA from sperm cells is a big challenge. Attempts have been made to evaluate various sperm RNA isolation methods from purified buffalo bull sperm cells. METHODS: Both, non-membrane and membrane-based methods have been evaluated for isolating RNA from Murrah buffalo sperms and compared for their respective efficacies. The traditional TRIzol, TRIzol-heat lysed (H-TRIzol) and cocktail of TCEP-RLT lysis buffer (Qiagen RNeasy mini kit)-TRIzol (C-TRIzol) based isopropanol isolation methods have been evaluated. RESULTS: H-TRIzol yielded best results among conventional methods. The combined T-RLT RNA isolation protocol yielded best quality and quantity compared to other membrane-based methods, due to high lytic property of cocktail of lysis reagents, necessary for complete breakdown of sperm membrane and RNA binding membrane for RNA isolation. Combined lysis performed by treatment with RLT-T and T-RLT differing in order of reagents used were also evaluated. T-RLT combination giving better results compared to RLT-T due to high gDNA contamination and membrane clogging in later protocol steps. CONCLUSION: Overall, in terms of total RNA quantity and quality per million spermatozoa, the heat-lysed TRIzol method (H-TRIzol) performs best among RNA separation techniques employed and is also quite easy to perform. This comparative evaluation of sperm RNA isolation protocols can be useful in deciding the best protocol for isolation of good quality and high concentration sperm RNA from buffalo semen, for transcriptome and other downstream studies.

Evaluation of Growth Responses of Lettuce and Energy Efficiency of the Substrate and Smart Hydroponics Cropping System.

Smart sensing devices enabled hydroponics, a concept of vertical farming that involves soilless technology that increases green area. Although the cultivation medium is water, hydroponic cultivation uses 13 ± 10 times less water and gives 10 ± 5 times better quality products compared with those obtained through the substrate cultivation medium. The use of smart sensing devices helps in continuous real-time monitoring of the nutrient requirements and the environmental conditions required by the crop selected for cultivation. This, in turn, helps in enhanced year-round agricultural production. In this study, lettuce, a leafy crop, is cultivated with the Nutrient Film Technique (NFT) setup of hydroponics, and the growth results are compared with cultivation in a substrate medium. The leaf growth was analyzed in terms of cultivation cycle, leaf length, leaf perimeter, and leaf count in both cultivation methods, where hydroponics outperformed substrate cultivation. The results of the 'AquaCrop simulator also showed similar results, not only qualitatively and quantitatively, but also in terms of sustainable growth and year-round production. The energy consumption of both the cultivation methods is compared, and it is found that hydroponics consumes 70 ± 11 times more energy compared to substrate cultivation. Finally, it is concluded that smart sensing devices form the backbone of precision agriculture, thereby multiplying crop yield by real-time monitoring of the agronomical variables.

Genomic Prediction of Resistance to Tan Spot, Spot Blotch and Septoria Nodorum Blotch in Synthetic Hexaploid Wheat.

Genomic prediction combines molecular and phenotypic data in a training population to predict the breeding values of individuals that have only been genotyped. The use of genomic information in breeding programs helps to increase the frequency of favorable alleles in the populations of interest. This study evaluated the performance of BLUP (Best Linear Unbiased Prediction) in predicting resistance to tan spot, spot blotch and Septoria nodorum blotch in synthetic hexaploid wheat. BLUP was implemented in single-trait and multi-trait models with three variations: (1) the pedigree relationship matrix (A-BLUP), (2) the genomic relationship matrix (G-BLUP), and (3) a combination of the two matrices (A+G BLUP). In all three diseases, the A-BLUP model had a lower performance, and the G-BLUP and A+G BLUP were statistically similar (p ≥ 0.05). The prediction accuracy with the single trait was statistically similar (p ≥ 0.05) to the multi-trait accuracy, possibly due to the low correlation of severity between the diseases.

Utility and timing of the respiratory rate-oxygenation index in the prediction of high-flow oxygen therapy failure in acute hypoxemic respiratory failure of infective etiology: a prospective observational study.

During and following the COVID-19 pandemic, the world has witnessed a surge in high-flow oxygen therapy (HFOT) use. The ability to provide high oxygenation levels with remarkable comfort levels has been the grounds for the same. Despite the advantages, delays in intubation leading to poor overall outcomes have been noticed in subgroups of patients on HFOT. The respiratory rate-oxygenation (ROX) index has been proposed to be a useful indicator to predict HFOT success. In this study, we have examined the utility of the ROX index prospectively in cases of acute hypoxemic respiratory failure (AHRF) due to infective etiologies. A total of 70 participants were screened, and 55 were recruited for the study. The majority of participants were males (56.4%), with diabetes mellitus being the most common comorbidity (29.1%). The mean age of the study subjects was 46.27±15.6 years. COVID-19 (70.9%) was the most common etiology for AHRF, followed by scrub typhus (21.8%). 19 (34.5%) experienced HFOT failure, and 9 (16.4%) subjects died during the study period. Demographic characteristics did not differ between either of the two groups (HFOT success versus failure and survived group versus expired group). The ROX index was significantly different between the HFOT success versus failure group at baseline, 2, 4, 6, 12, and 24 hours. The best cut-offs of the ROX index at baseline and 2 hours were 4.4 (sensitivity 91.7%, specificity 86.7%) and 4.3 (sensitivity 94.4% and specificity 86.7%), respectively. The ROX index was found to be an efficient tool in predicting HFOT failure in cases of AHRF with infective etiology.

Nonsmoker COPD represents a clinically Distinct Phenotype: A Prospective Observational Study.

BACKGROUND: Chronic obstructive lung disease (COPD) has been characterized as a smoker's disease, which has resulted in the usual exclusion of never-smokers from COPD studies. It is now recognized that never-smokers account for nearly one-fourth of all COPD cases, and thus airflow limitation in never-smokers needs further evaluation. Our study aims to elucidate the clinical and physiological aspects of COPD in nonsmokers and to compare smokers and nonsmokers with COPD. MATERIALS AND METHODS: A total of 200 naïve sequential patients with COPD were recruited. The severity of airflow limitation in COPD patients was defined as per Global Initiative for COPD (GOLD) 2019 criteria, and the severity of breathlessness was assessed by the modified Medical Research Council (MRC) dyspnea scale. Data was collected using a patient pro forma, including risk factors for COPD and detailed clinical history. Phenotypic differences along with biomass exposure between never-smokers and smokers were analyzed. RESULTS: Compared to smokers, never-smokers presented at a younger age (55.69 ± 11.5 years; p < 0.001), with a longer duration of dyspnea (5.05 ± 4.96 vs 7.35 ± 6.98 years, p < 0.01). Chest radiographs revealed hyperinflation in a higher number of smokers as compared to never-smokers (82.9 vs 64.6%, p < 0.05). On spirometry evaluation, smokers were found to have significantly poorer lung function [forced expiratory volume in first second (FEV1) 40.36 ± 17.76%; forced vital capacity (FVC): 58.16 ± 17.02%] as compared to never-smokers (FEV1: 47.1 ± 16.47%; FVC: 67.38 ± 17.02%) with p < 0.05. With respect to severity at presentation, most (45.8%) never-smokers presented with stage 2 COPD as compared to the majority of smokers (46.7%) who presented with stage 3 COPD (p-value of <0.05). Absolute eosinophil count (AEC) and eosinophil proportion in total leucocyte count (TLC) was significantly higher in never-smokers as compared to the smokers (232 ± 204.2 vs 309 ± 238.8, p < 0.05). Risk factor analysis showed mean biomass exposure index was significantly higher in never-smokers as compared to smokers (56.02 vs 6.28; p-value of <0.001). CONCLUSION: Compared to smokers, COPD in never-smokers presents at a younger age, with a longer duration of dyspnea and higher eosinophil count. Biomass exposure is one of the major contributors to etiologies for COPD in nonsmokers.

Genetic analysis for semen quality traits in buffalo bulls.

This study was attempted to estimate the genetic parameters of semen quality traits in buffalo bulls. The study data consisted of 10975 ejaculates from 45 Murrah buffalo bulls (aged 24-72 months) used for breeding program during year 2010 to 2020. Semen quality traits (ejaculate volume, concentration of sperm, mass activity, initial and post-thaw motility, number of sperms per ejaculate, motile sperm number and discard rates) were studied. It was observed that average ejaculate volume was 2.82 ± 1.45 mL with mean concentration of 1040.12 ± 523.26 million/mL. Higher heritability was observed for number of sperms per ejaculate, number of motile sperm and sperm concentration. Significant phenotypic correlation was obtained between volume and number of sperms per ejaculate as well as volume and number of motile sperms. Likewise, significant phenotypic correlation was evident between sperm concentration with sperm number per ejaculate. Highest phenotypic correlation was obtained between sperm count per ejaculate and motile sperm count. Estimated genetic trends showed significant change in volume and motile sperm number. In conclusion, this study ascertains that genetic parameters of semen traits can be considered during the selection of buffalo bulls in breeding program.

Essential Role of NLRP3 Inflammasome in Mediating IL-1ß Production and the Pathobiology of Staphylococcus aureus Endophthalmitis.

Staphylococcal endophthalmitis is one of the leading causes of blindness following ocular surgery and trauma. Dysregulated inflammation during bacterial endophthalmitis causes host-induced inflammatory damage and vision loss if it remains unchecked. Emerging evidence indicates that inflammasome plays a critical role in regulating innate immunity in various infectious and inflammatory diseases. However, the role of the inflammasome in endophthalmitis remains elusive. Here, using a mouse model of Staphylococcus (S) aureus endophthalmitis, we show that NLRP3/ASC/Caspase-1 signaling regulates IL-1ß production in endophthalmitis. We also show that S. aureus and its cell wall components and toxins induce the activation of the NLRP3 inflammasome complex in mouse eyes. Moreover, we found that both infiltrating neutrophils and retinal microglia contribute toward NLRP3 activation and IL-1ß production in S. aureus-infected eyes. Furthermore, our data using NLRP3-/- and IL-1ß-/- mice revealed that NLRP3 and IL-1ß deficiency leads to increased intraocular bacterial burden and retinal tissue damage. Altogether, our study demonstrated an essential role of NLRP3 inflammasome activation in regulating innate immune responses in bacterial endophthalmitis.

Genomic selection for spot blotch in bread wheat breeding panels, full-sibs and half-sibs and index-based selection for spot blotch, heading and plant height.

KEY MESSAGE: Genomic selection is a promising tool to select for spot blotch resistance and index-based selection can simultaneously select for spot blotch resistance, heading and plant height. A major biotic stress challenging bread wheat production in regions characterized by humid and warm weather is spot blotch caused by the fungus Bipolaris sorokiniana. Since genomic selection (GS) is a promising selection tool, we evaluated its potential for spot blotch in seven breeding panels comprising 6736 advanced lines from the International Maize and Wheat Improvement Center. Our results indicated moderately high mean genomic prediction accuracies of 0.53 and 0.40 within and across breeding panels, respectively which were on average 177.6% and 60.4% higher than the mean accuracies from fixed effects models using selected spot blotch loci. Genomic prediction was also evaluated in full-sibs and half-sibs panels and sibs were predicted with the highest mean accuracy (0.63) from a composite training population with random full-sibs and half-sibs. The mean accuracies when full-sibs were predicted from other full-sibs within families and when full-sibs panels were predicted from other half-sibs panels were 0.47 and 0.44, respectively. Comparison of GS with phenotypic selection (PS) of the top 10% of resistant lines suggested that GS could be an ideal tool to discard susceptible lines, as greater than 90% of the susceptible lines discarded by PS were also discarded by GS. We have also reported the evaluation of selection indices to simultaneously select non-late and non-tall genotypes with low spot blotch phenotypic values and genomic-estimated breeding values. Overall, this study demonstrates the potential of integrating GS and index-based selection for improving spot blotch resistance in bread wheat.