A novel copy number variant in the murine Cdh23 gene gives rise to profound deafness and vestibular dysfunction.

Hearing loss is the most common congenital sensory deficit worldwide and exhibits high genetic heterogeneity, making molecular diagnoses elusive for most individuals. Detecting novel mutations that contribute to hearing loss is crucial to providing accurate personalized diagnoses, tailored interventions, and improving prognosis. Copy number variants (CNVs) are structural mutations that are understudied, potential contributors to hearing loss. Here, we present the Abnormal Wobbly Gait (AWG) mouse, the first documented mutant exhibiting waltzer-like locomotor dysfunction, hyperactivity, circling behaviour, and profound deafness caused by a spontaneous CNV deletion in cadherin 23 (Cdh23). We were unable to identify the causative mutation through a conventional whole-genome sequencing (WGS) and variant detection pipeline, but instead found a linked variant in hexokinase 1 (Hk1) that was insufficient to recapitulate the AWG phenotype when introduced into C57BL/6J mice using CRISPR-Cas9. Investigating nearby deafness-associated genes revealed a pronounced downregulation of Cdh23 mRNA and a complete absence of full-length CDH23 protein, which is critical for the development and maintenance of inner ear hair cells, in whole head extracts from AWG neonates. Manual inspection of WGS read depth plots of the Cdh23 locus revealed a putative 10.4 kb genomic deletion of exons 11 and 12 that was validated by PCR and Sanger sequencing. This study underscores the imperative to refine variant detection strategies to permit identification of pathogenic CNVs easily missed by conventional variant calling to enhance diagnostic precision and ultimately improve clinical outcomes for individuals with genetically heterogenous disorders such as hearing loss.

Biochar Production and Characteristics, Its Impacts on Soil Health, Crop Production, and Yield Enhancement: A Review.

Rapid urban expansion and a booming population are placing immense pressure on our agricultural systems, leading to detrimental impacts on soil fertility and overall health. Due to the extensive use of agrochemicals in agriculture, the necessity to meet the expanding demand for food has also resulted in unsustainable farming practices. Around the world, biochar, a multipurpose carbonaceous material, is being used to concurrently solve issues with enhancing soil fertility, plant growth, and development under both normal and stressful circumstances. It improves water retention, fosters nutrient absorption, and promotes microbial activity, creating a fertile environment that supports sustainable and resilient agriculture. Additionally, biochar acts as a carbon sink, contributing to long-term carbon sequestration and mitigating climate change impacts. The major benefit of biochar is that it helps the adsorption process with its highly porous structures and different functional groups. Understanding the elements involved in biochar formation that determine its characteristics and adsorptive capacity is necessary to assure the viability of biochar in terms of plant productivity and soil health, particularly biological activity in soil. This paper focuses on the development, composition, and effects of biochar on soil fertility and health, and crop productivity.

Effect of academic stress, educational environment on academic performance & quality of life of medical & dental students; gauging the understanding of health care professionals on factors affecting stress: A mixed method study.

INTRODUCTION: Throughout their academic careers, medical and dental students face challenges that cause varying levels of stress, affecting their academic performance and quality of life (QoL). Our study aims to ascertain the effect of academic stress and the educational environment on the QoL and academic performance of medical and dental students, encompassing the perspectives of both students and healthcare professionals. METHODS: A mixed-method research was conducted from February to May 2022, comprising students from a medical and dental college in Pakistan. During Phase 1, the students participated in the cross-sectional survey and completed the WHO Quality of Life Scale (WHOQOL-BREF), Academic Stress Scale, and Dundee Ready Educational Environment Measure (DREEM) Inventory questionnaires. Academic performance was evaluated through last year's annual assessment results of the students. During Phase 2 of the study, interviews with healthcare professionals who had experience as the students' counsellors were conducted. RESULTS: The mean age of the sample (n = 440) was 22.24 ±1.4 years. The Cronbach Alpha reliability of the DREEM inventory was 0.877, that of the Academic Stress Scale was 0.939 and the WHOQOL scale was 0.895. More than half of the students (n = 230, 52.3%) reported better QoL and the majority perceived a positive educational environment (n = 323, 73.4%) and higher academic stress (n = 225, 51.1%). Males had significantly more academic stress (p<0.05). Those who perceived a positive educational environment and better QoL had better academic performance (p<0.05). Academic performance was positively and significantly correlated with QoL and academic stress (p = 0.000). In qualitative analysis, 112 codes were generated which converged into 5 themes: challenging educational environment, psychological need and support, individual differences, relationship and family life, and adjustment issues. CONCLUSION: Medical and dental students encounter a myriad of challenges, along with significant academic stress, which detrimentally affects their academic performance, despite perceiving a positive educational environment. Conversely, a better QoL is associated with improved academic performance.

Nitrogenous Fertilizer Coated With Zinc Improves the Productivity and Grain Quality of Rice Grown Under Anaerobic Conditions.

An ample quantity of water and sufficient nutrients are required for economical rice production to meet the challenges of ever-increasing food demand. Currently, slow-release nitrogenous fertilizers for efficient inputs utilization and maximum economic yield of field crops are in the limelight for researchers and farmers. In this study, we evaluated the comparative efficacy of conventional urea and coated urea (zinc and neem) on rice grown under aerobic and anaerobic regimes in greenhouse conditions. For the aerobic regime, field capacity was maintained at 80-100% to keep the soil aerated. On the other hand, for the anaerobic regime, pots were covered with a polythene sheet throughout the experimentation to create flooded conditions. All forms of urea, conventional and coated (zinc and neem), improved plant growth, gas exchange, yield, yield contributing parameters, and quality characteristics of rice crop. However, better performance in all attributes was found in the case of zinc-coated urea. Gas exchange attributes (photosynthetic rate, 30%, and stomatal conductance 24%), yield parameters like plant height (29%), tillers per plant (38%), spikelets per spike (31%), grains per panicle (42%), total biomass (53%), and grain yield (45%) were recorded to be maximum in rice plants treated with zinc-coated urea. The highest grain and straw nitrogen contents, grain protein contents, and grain water absorption ratio were also found in plants with zinc-coated urea applications. In irrigation practices, the anaerobic regime was found to be more responsive compared to the aerobic regime regarding rice growth, productivity, and quality traits. Thus, to enhance the productivity and quality of rice grown in anaerobic conditions, zinc-coated urea is best suited as it is more responsive when compared to other forms of urea.

Foliar application of mepiquat chloride and nitrogen improves yield and fiber quality traits of cotton (Gossypium hirsutum L.).

Cotton (Gossypium hirsutum L.) is one of the most important cash crops primarily grown for fiber. It is a perennial crop with indeterminate growth pattern. Nitrogen (N) is extremely important for vegetative growth as balanced N-nutrition improves photosynthesis, resulting in better vegetative growth. Excessive N-supply results in more vegetative growth, which increases the incidence of insect pest and diseases' infestation, pollute surface and ground water, delays maturity and produces low crop yield with poor quality. The use of plant growth regulators (PGRs) is an emerging option to control excessive vegetative growth. The PGRs help in improving plant architecture, boll retention, boll opening, yield and quality by altering growth and physiological processes such as photosynthesis, assimilate partitioning and nutrients dynamic inside the plant body. Mepiquat chloride (1,1-dimethylpiperidinum chloride) is globally used PGR for canopy development and control of excessive vegetative growth in cotton. This study investigated the effect of mepiquat chloride (MC) and N application on yield and yield components of transgenic cotton variety 'BT-FSH-326'. Two N rates (0, 198 kg ha-1) and five MC rates (0, 30,60, 90 and 120 g ha-1) were included in the study. Results revealed that MC and N application improved boll weight, number of bolls per plant, and seed cotton and lint yields. The highest seed cotton and lint yields (3595 kg ha-1 and 1701 kg ha-1, respectively) were observed under foliar application of 198 kg ha-1 N and 120 g ha-1 MC. Fiber length, fiber strength, micronaire and uniformity were significantly improved with foliar application of MC and N. In conclusion, foliar application of MC and N could be helpful in improving yield and fiber quality of cotton.

Foliar application of potassium and moringa leaf extract improves growth, physiology and productivity of kabuli chickpea grown under varying sowing regimes.

Chickpea (Cicer arietinum L.) is of prime importance because of vital source of protein as major food legume. Globally, it is cultivated on large area to meet dietary requirements of humans. Climatic extremes (erratic rainfall, extreme high and low temperature) are key restrains for its production. Optimum sowing time is considered as an important factor to address climatic variations and to attain maximum yield. Foliar application of potassium (K) has also been reported to increase resistance against abiotic stresses. Similarly, exogenous application of plant based growth substances (bio-stimulants) like moringa leaf extract (MLE) are extensively used to enhance productivity of field crops. Therefore, current study was planned to evaluate the impact of foliar applied K and MLE on growth, physiology and productivity of kabuli chickpea grown under varying sowing dates. There were two sowing dates (normal sown; November 15 and late sown; December 15, 2020). Experiment was comprised of treatments i.e. control, water spray, foliar application of K at 1%, foliar application of MLE at 3% and combined application of K and MLE. Foliar applied K and MLE significantly improved physiological, biochemical and yield attributes of kabuli chickpea cultivated under normal and late sown conditions. Increase in growth and yield attributes like plant height, number of nodules per plant, nodules dry weight, branches and pods per plant, 100- grain weight, biological and grain yield were recorded in case of combined foliar application of K and MLE in normal and late sown chickpea. Maximum improvement in gas exchange attributes (stomatal conductance and transpiration rate), chlorophyll contents, antioxidants (catalase, superoxide dismutase and ascorbate peroxidase) and osmolytes (proline) were recorded with combined application of K and MLE in both sowing dates. Thus, combined applied K and MLE can be used to enhance productivity of kabuli chickpea.

Combined application of zinc and silicon alleviates terminal drought stress in wheat by triggering morpho-physiological and antioxidants defense mechanisms.

Wheat is an important global staple food crop; however, its productivity is severely hampered by changing climate. Erratic rain patterns cause terminal drought stress, which affect reproductive development and crop yield. This study investigates the potential and zinc (Zn) and silicon (Si) to ameliorate terminal drought stress in wheat and associated mechanisms. Two different drought stress levels, i.e., control [80% water holding capacity (WHC) was maintained] and terminal drought stress (40% WHC maintained from BBCH growth stage 49 to 83) combined with five foliar-applied Zn-Si combinations (i.e., control, water spray, 4 mM Zn, 40 mM Si, 4 mM Zn + 40 mM Si applied 7 days after the initiation of drought stress). Results revealed that application of Zn and Si improved chlorophyll and relative water contents under well-watered conditions and terminal drought stress. Foliar application of Si and Zn had significant effect on antioxidant defense mechanism, proline and soluble protein, which showed that application of Si and Zn ameliorated the effects of terminal drought stress mainly by regulating antioxidant defense mechanism, and production of proline and soluble proteins. Combined application of Zn and Si resulted in the highest improvement in growth and antioxidant defense. The application of Zn and Si improved yield and related traits, both under well-watered conditions and terminal drought stress. The highest yield and related traits were recorded for combined application of Zn and Si. For grain and biological yield differences among sole and combined Zn-Si application were statistically non-significant (p>0.05). In conclusion, combined application of Zn-Si ameliorated the adverse effects of terminal drought stress by improving yield through regulating antioxidant mechanism and production of proline and soluble proteins. Results provide valuable insights for further cross talk between Zn-Si regulatory pathways to enhance grain biofortification.

Optimizing sowing date for peanut genotypes in arid and semi-arid subtropical regions.

Peanut (Arachis hypogea L.) is an important nut crop extensively grown in rainfed regions of Pakistan. The crop requires low inputs; thus, could grow successfully under diverse environmental conditions. Due to pegging ability, peanut grows aggressively in sandy and sandy-loam soils. However, it has not introduced to Thal region of southern Punjab, Pakistan. A two-year field experiment was conducted to optimize sowing dates for two peanut genotypes ('BARI-2016' and 'NO-334') in Thal region (Layyah). Similarly, a yield trial was conducted at Chakwal where both genotypes are extensively grown. Five sowing dates (10th April, 1st May, 20th May, 10th June and 30th June) were included in the study. The highest seed yield was obtained with early sown crop (10th April) during both years. Pod formation reduced with increasing atmospheric temperature and no pods were formed on the plants sown on 30th June. Decreased pod formation seemed a major reason for low yield in late-sown crop. The highest yield was observed for the crop sown on 10th April, which was decreased by 40% for the crop sown on 1st May. Genotype 'BARI-2016' performed better for seed yield at both locations compared with 'NO-334'. The results suggested that genotype 'BARI-2016' is more adaptive to arid and semi-arid condition under rainfed or irrigated conditions. Sowing peanut at optimum time would increase seed yield in arid and semi-arid regions. Nonetheless, 'BARI-2016' can be grown under rainfed and irrigated conditions successfully.

Geospatial analysis of distribution of community pharmacies and other health care facilities providing minor ailments services in Malaysia.

BACKGROUND: Minor ailments are defined as common, self-limiting, or uncomplicated conditions that may be diagnosed and managed without a medical intervention. Previous studies reported that pharmacists were able to help patients self-manage minor ailments that led to a reduction of health care burden in other facilities. Nevertheless, public access to community pharmacy and other health care facilities offering services for minor ailments has not yet been explored in Malaysia. Hence, this study aims to determine population access to the above-mentioned services. METHOD: According to the reported practice address in 2018, the spatial distribution of health care facilities was mapped and explored using the GIS mapping techniques. The density of health care facilities was analyzed using thematic maps with hot spot analysis. Population to facility ratio was calculated using the projection of the population growth based on 2010 census data, which was the latest available in the year of analysis. RESULTS: The study included geographical mapping of 7051 general practitioner clinics (GPC), 3084 community pharmacies (CP), 139 public general hospitals (GHs) and 990 public primary health clinics (PHC). The health care facilities were found to be highly dense in urban areas than in the rural ones. There were six districts that had no CP, 2 had no GPC, and 11 did not have both. The overall ratio of GPC, CP, GH, and PHC to the population was 1:4228, 1:10,200, 1:223,619 and 1:31,397, respectively. Should the coverage for minor ailment services in public health care clinics be extended to community pharmacies, the ratio of facilities to population for each district would be better with 1:4000-8000. CONCLUSIONS: The distribution of health care facilities for minor ailment management in Malaysia is relatively good. However, if the scheme for minor ailments were available to community pharmacies, then the patients' access to minor ailments services would be further improved.

Sonoanatomy of female reproductive organ of Sunda porcupine (Hystrix javanica).

The conventional anatomical study of specimens requires cutting processes which destruct the limited specimens. A non-destructive method, namely an ultrasonography, can be used to assess the anatomical organ information of those specimens. The aim of this research is to analyse the macroanatomy of the female reproductive organ in the Sunda porcupine (Hystrix javanica), using ultrasonographical imaging. In this study, four formaldehyde-fixed reproductive organ specimens of the Sunda porcupine were used. A 10-12 MHz linear ultrasound transducer was utilized to provide an imaging format of both longitudinal and transversal views. Photographic images were then used as comparison with a sonographic image. The results show that the ultrasound image of the Sunda porcupine reproductive organ soft tissue was hypoechoic, the lumen and antrum follicles were anechoic, while atretic follicles and the mons pubis were hyperechoic. Generally, the size of the organ was not significantly different between photographical and ultrasonographical imaging (p > .05). In conclusion, ultrasound images can be utilized for anatomical studies of the Sunda porcupine reproductive organs without destructing the specimen.

Extracellular matrix composition of different spleen compartments of fruit bats.

The distribution and composition of extracellular matrix (ECM) of the spleen in two species of fruit bats, namely Cynopterus titthaecheilus and Rousettus leschenaultii, were examined by histochemistry and immunohistochemistry. Reticular fibres accompanied by laminin were identified to make up the splenic stromal network. Types I and III collagen were identified in various spleen compartments with varying intensities. Thin and short elastin fibres were scattered in several parts of the spleen. Visualization of the ECM of the spleen can better demonstrate spleen compartmentalization. The alleged vascular space structure in the fruit bats spleen was the sinus structure that was strengthened by the presence of reticular fibres that limit the sinus basement membrane. The present study identified periellipsoidal lymphoid sheath (PELS)-like structure in fruit bats spleen that had never been identified in mammals before. In addition to describing the structure, this study highlighted the variations in ECM composition of the spleen between species that can provide new insight into the phylogenetic study of spleen morphology.

A comparative genomics approach revealed evolutionary dynamics of microsatellite imperfection and conservation in genus Gossypium.

BACKGROUND: Ongoing molecular processes in a cell could target microsatellites, a kind of repetitive DNA, owing to length variations and motif imperfection. Mutational mechanisms underlying such kind of genetic variations have been extensively investigated in diverse organisms. However, obscure impact of ploidization, an evolutionary process of genome content duplication prevails mostly in plants, on non-coding DNA is poorly understood. RESULTS: Genome sequences of diversely originated plant species were examined for genome-wide motif imperfection pattern, and various analytical tools were employed to canvass characteristic relationships among repeat density, imperfection and length of microsatellites. Moreover, comparative genomics approach aided in exploration of microsatellites conservation footprints in Gossypium evolution. Based on our results, motif imperfection in repeat length was found intricately related to genomic abundance of imperfect microsatellites among 13 genomes. Microsatellite decay estimation depicted slower decay of long motif repeats which led to predominant abundance of 5-nt repeat motif in Gossypium species. Short motif repeats exhibited rapid decay through the evolution of Gossypium lineage ensuing drastic decrease of 2-nt repeats, of which, "AT" motif type dilapidated in cultivated tetraploids of cotton. CONCLUSION: The outcome could be a directive to explore comparative evolutionary footprints of simple non-coding genetic elements i.e., repeat elements, through the evolution of genus-specific characteristics in cotton genomes.

Influence of leaf vein density and thickness on hydraulic conductance and photosynthesis in rice (Oryza sativa L.) during water stress.

The leaf venation architecture is an ideal, highly structured and efficient irrigation system in plant leaves. Leaf vein density (LVD) and vein thickness are the two major properties of this system. Leaf laminae carry out photosynthesis to harvest the maximum biological yield. It is still unknown whether the LVD and/or leaf vein thickness determines the plant hydraulic conductance (Kplant) and leaf photosynthetic rate (A). To investigate this topic, the current study was conducted with two varieties under three PEG-induced water deficit stress (PEG-IWDS) levels. The results showed that PEG-IWDS significantly decreased A, stomatal conductance (gs), and Kplant in both cultivars, though the IR-64 strain showed more severe decreases than the Hanyou-3 strain. PEG-IWDS significantly decreased the major vein thickness, while it had no significant effect on LVD. A, gs and Kplant were positively correlated with each other, and they were negatively correlated with LVD. A, gs and Kplant were positively correlated with the inter-vein distance and major vein thickness. Therefore, the decreased photosynthesis and hydraulic conductance in rice plants under water deficit conditions are related to the decrease in the major vein thickness.