Effect of Pulmonary Hypertension on Survival Outcomes in Patients With Transcatheter Aortic Valve Replacement: A Systematic Review and Meta-Analysis.

The aim of this meta-analysis was to determine the effect of pulmonary hypertension (PH) on survival in patients undergoing transcatheter aortic valve replacement (TAVR). The present study was conducted according to the guidelines of Preferred Reporting of Systematic Review and Meta-Analysis (PRISMA). We conducted a comprehensive search of electronic databases including PubMed/MEDLINE, Embase, Cochrane Library, and Web of Science from January 1, 2015, to March 10, 2024. Outcomes assessed in this meta-analysis included early and late all-cause mortality and cardiovascular mortality. Total 15 studies were integrated into the pooled analysis to assess the impact of PH on outcomes among patients undergoing TAVR, comprising a total sample size of 35,732 individuals. The pooled prevalence of PH stood at 52.57% (n=18,767). Predominantly, the studies were conducted in the United States (n=6), followed by Germany (n=3), with one study each from Japan, Italy, Switzerland, Brazil, Poland, and Australia. Pooled analysis showed that risk of short-term mortality was greater in patients with PH compared to patients without PH (risk ratio (RR): 1.46, 95% CI: 1.19 to 1.80). Risk of long-term mortality was greater in patients with PH (RR: 1.42, 95% CI: 1.29 to 1.55). Risk of cardiovascular mortality was also greater in patients with PH compared to patients without PH (RR: 1.66, 95% CI: 1.36 to 2.02). We advocate for further research to address gaps in understanding different types of PH and their impacts on mortality and cardiovascular outcomes.

Cerebroprotective Potential of Andrographolide Nanoparticles: In silico and In vivo Investigations.

Ischemic stroke remains the leading cause of death and disability, while the main mechanisms of dominant neurological damage in stroke contain oxidative stress and inflammation. Docking studies revealed a binding energy of - 6.1 kcal/mol for AG, while the co-crystallized ligand (CCl) exhibited a binding energy of - 7.3 kcal/mol with NOS. AG demonstrated favourable hydrogen bond interactions with amino acids ASN A:354 and ARG A:388 and hydrophobic interactions with GLU A:377. Molecular dynamics simulations throughout 100 ns indicated a binding affinity of - 27.65±2.88 kcal/mol for AG, compared to - 18.01±4.02 kcal/mol for CCl. These findings suggest that AG possesses a superior binding affinity for NOS compared to CCl, thus complementing the stability of NOS at the docked site.AG has limited applications owing to its low bioavailability, poor water solubility, and high chemical and metabolic instability.The fabrication method was employed in the preparation of AGNP, SEM analysis confirmed spherical shape with size in 19.4±5 nm and investigated the neuroprotective effect in cerebral stroke rats induced by 30 min of carotid artery occlusion followed by 4 hr reperfusion, evaluated by infarction size, ROS/RNS via GSH, MPO, NO estimationand AchE activity, and monitoring EEG function. Cortex and hippocampal histology were compared between groups. AGNP treatment significantly decreased Infarction size and increased GSH levels (p<0.01**), decreased MPO (p<0.01**), NO (p<0.01**), AchE (p<0.01**), restored to normal EEG amplitude, minimizing unsynchronized polyspikes and histological data revealed that increased pyramidal cell layer thickness and decreased apoptotic neurons in hippocampus, cortex appeared normal neurons with central large vesicular nuclei, containing one or more nucleoli in compared to AG treatment. Based on brain biochemical, histopathology reports AGNP exhibited significant cerebroprotective activity compared to AG on ischemic rats.

Community perspective and healthcare assessment in malaria endemic states of India: a cross-sectional study protocol.

INTRODUCTION: India's contribution to the malaria burden was highest in South-East Asia Region in 2021, accounting for 79% of the estimated malaria cases and 83% of malaria-related deaths. Intensified Malaria Control Programme supported by Global Funds to Fight against AIDS, Tuberculosis and Malaria has deployed crucial interventions to reduce the overall burden of malaria in India. Evaluation of utilisation of malaria elimination interventions by the community and assessment of the healthcare system is underway in eleven high malaria endemic states in India. Health system preparedness for malaria elimination, logistics, and supply chain management of diagnostic kits and anti-malarial drugs in addition to the knowledge, attitude and practice of the healthcare workers is also being assessed. METHODS AND ANALYSIS: The study is being undertaken in 11 malaria endemic states with a variable annual parasite incidence of malaria. In total, 47 districts (administrative unit of malaria control operations) covering 37 976 households are to be interviewed and assessed. We present here the protocol following which the study is being undertaken at the behest and approval of Ministry of Health and Family Welfare in India. ETHICS AND DISSEMINATION: No patients were involved in the study. Study findings will be shared with Institutional ethics board of National Institute for Malaria Research New Delhi (NIMR) in a timely, comprehensive, accurate, unbiased, unambiguous and transparent manner and to the National Vector-borne Disease (Malaria) Control Programme officers and the Community public who participated. Important findings will be communicated through community outreach meetings which are existing in the Health system. Results will be informed to study participants via local fieldwork supervised by District Malaria Officers. Also findings will be published in reputed journals based on Indian Council of Medical Research (ICMR) publication policy.The ICMR-NIMR ethics committee approved the study via letter No. NIMR/ECM/2023/Feb/14 dated 24 April 2023 for version 5. All standard ethical practices will be followed.

A safe, cost-effective, and high-throughput SARS-CoV-2 antigen capture ELISA suitable for large-scale screening in low-resource settings.

Diagnostics employing multiple modalities have been essential for controlling and managing COVID-19, caused by SARS-CoV-2. However, scaling up Reverse Transcription-Quantitative Polymerase Chain Reaction (RT-qPCR), the gold standard for SARS-CoV-2 detection, remains challenging in low and middle-income countries. Cost-effective and high-throughput alternatives like enzyme-linked immunosorbent assay (ELISA) could address this issue. We developed an in-house SARS-CoV-2 nucleocapsid capture ELISA, and validated on 271 nasopharyngeal swab samples from humans (n = 252), bovines (n = 10), and dogs (n = 9). This ELISA has a detection limit of 195 pg/100 µL of nucleocapsid protein and does not cross-react with related coronaviruses, ensuring high specificity to SARS-CoV-2. Diagnostic performance was evaluated using receiver operating characteristic curve analysis, showing a diagnostic sensitivity of 67.78 % and specificity of 100 %. Sensitivity improved to 74.32 % when excluding positive clinical samples with RT-qPCR Ct values > 25. Furthermore, inter-rater reliability analysis demonstrated substantial agreement (κ values = 0.73-0.80) with the VIRALDTECT II Multiplex RT-qPCR kit and perfect agreement with the CoVeasy™ COVID-19 rapid antigen self-test (κ values = 0.89-0.93). Our findings demonstrated that the in-house nucleocapsid capture ELISA is suitable for SARS-CoV-2 testing in humans and animals, meeting the necessary sensitivity and specificity thresholds for cost-effective, large-scale screening.

Exploring Seaweed-Associated Marine Microbes: Growth Impacts and Enzymatic Potential for Sustainable Resource Utilization.

Seaweed, a valuable marine resource widely cultivated worldwide, can be vulnerable to stress and microbiome alterations, resulting in the decay of seaweeds and substantial economic losses. To investigate the seaweed-microbiome interaction, our study aimed to isolate marine bacteria and fungi that can cause Ice-Ice disease and evaluate their enzymatic characteristics for potential application in bioethanol production from seaweed biomass. Three red seaweed species (Gracilaria edulis, Kappaphycus alvarezii, and Eucheuma cottonii) were obtained for our study and placed in separate culture tanks. Among the 18 isolated marine microbial species, 12 tested positive for agar and carrageenan activity: six exhibited both activities, three displayed only agar activity, and three only carrageenan activity. DNA sequencing of the positive microbes identified ten bacteria and two yeast species. The 3,5-Dinitrosalicylic acid (DNSA) assay results revealed that the identified bacterial Caldibacillus kokeshiiformis strain FJAT-47861 exhibited the highest carrageenase activity (0.76 units/ml), while the yeast Pichia fermentans strain PM79 demonstrated the highest agarase activity (0.52 units/ml). Notably, Pichia fermentans strain PM79 exhibited the highest overall agarase and carrageenase activity, averaging 0.63 units/ml. The average carrageenase activity of all six positive microbes was 1.5 times higher than their agarase activity. These findings suggest that the 12 isolated microbes hold potential for bioethanol production from macroalgae, as their agarase and carrageenase activity indicates their ability to break down seaweed cell wall carbohydrates, causing ice-ice disease. Moreover, these results provide exciting prospects for harnessing the bioconversion capabilities of these microbes, paving the way for sustainable and efficient bioethanol production from seaweed resources. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-024-01205-w.

Harnessing Raman spectroscopy for the analysis of plant diversity.

Here, we explore the application of Raman spectroscopy for the assessment of plant biodiversity. Raman spectra from 11 vascular plant species commonly found in forest ecosystems, specifically angiosperms (both monocots and eudicots) and pteridophytes (ferns), were acquired in vivo and in situ using a Raman leaf-clip. We achieved an overall accuracy of 91% for correct classification of a species within a plant group and identified lignin Raman spectral features as a useful discriminator for classification. The results demonstrate the potential of Raman spectroscopy in contributing to plant biodiversity assessment.

Recent Advances in Direct Regioselective C-H Chlorination at Aromatic and Aliphatic Positions.

Direct installation of key functionalities in a molecule through C-H bond activation is one of the thrust areas as well as challenging task in organic synthesis. Particularly, introduction of chlorine in a molecule imparts additional benefits for further functionalizations as well as improves the electronic behaviour such as lipophilicity and polarity towards drug development process. The chlorinated molecules have also been established as efficient biologically relevant scaffolds. Current manuscript has been focused on the direct installation of the chlorine atom at various aromatic and aliphatic positions to produce functional molecules. The key highlight of the manuscript belongs to the site selectivity (regioselectivity) for the installation of chlorine functionality. Manuscript describes the advanced methods developed for the direct C-H chlorination reactions and further simplified for the chlorination reactions at various positions including aromatic (o-, m-, and p-), benzylic, heteroaromatic, and aliphatic positions. Directing groups (DGs) and the coordination with the catalyst is the key for the enhancement of regioselectivities during direct C-H chlorination reactions.

Selenium Nanoparticles as Neuroprotective Agents: Insights into Molecular Mechanisms for Parkinson's Disease Treatment.

Oxidative stress and the accumulation of misfolded proteins in the brain are the main causes of Parkinson's disease (PD). Several nanoparticles have been used as therapeutics for PD. Despite their therapeutic potential, these nanoparticles induce multiple stresses upon entry. Selenium (Se), an essential nutrient in the human body, helps in DNA formation, stress control, and cell protection from damage and infections. It can also regulate thyroid hormone metabolism, reduce brain damage, boost immunity, and promote reproductive health. Selenium nanoparticles (Se-NPs), a bioactive substance, have been employed as treatments in several disciplines, particularly as antioxidants. Se-NP, whether functionalized or not, can protect mitochondria by enhancing levels of reactive oxygen species (ROS) scavenging enzymes in the brain. They can also promote dopamine synthesis. By inhibiting the aggregation of tau, α-synuclein, and/or Aß, they can reduce the cellular toxicities. The ability of the blood-brain barrier to absorb Se-NPs which maintain a healthy microenvironment is essential for brain homeostasis. This review focuses on stress-induced neurodegeneration and its critical control using Se-NP. Due to its ability to inhibit cellular stress and the pathophysiologies of PD, Se-NP is a promising neuroprotector with its anti-inflammatory, non-toxic, and antimicrobial properties.

Structural diversification of fungal cell wall in response to the stress signaling and remodeling during fungal pathogenesis.

Fungi are one of the most diverse organisms found in our surroundings. The heterotrophic lifestyle of fungi and the ever-changing external environmental factors pose numerous challenges for their survival. Despite all adversities, fungi continuously develop new survival strategies to secure nutrition and space from their host. During host-pathogen interaction, filamentous phytopathogens in particular, effectively infect their hosts by maintaining polarised growth at the tips of hyphae. The fungal cell wall, being the prime component of host contact, plays a crucial role in fortifying the intracellular environment against the harsh external environment. Structurally, the fungal cell wall is a highly dynamic yet rigid component, responsible for maintaining cellular morphology. Filamentous pathogens actively maintain their dynamic cell wall to compensate rapid growth on the host. Additionally, they secrete effectors to dampen the sophisticated mechanisms of plant defense and initiate various downstream signaling cascades to repair the damage inflicted by the host. Thus, the fungal cell wall serves as a key modulator of fungal pathogenicity. The fungal cell wall with their associated signaling mechanisms emerge as intriguing targets for host immunity. This review comprehensively examines and summarizes the multifaceted findings of various research groups regarding the dynamics of the cell wall in filamentous fungal pathogens during host invasion.

Large Hematoma Following Erector Spinae Plane Block: A Case Report.

The ultrasound-guided erector spinae plane (ESP) block is an emerging fascial plane block, first described in 2016 for treating thoracic neuropathic pain. Since its introduction, it has been incorporated into multiple surgical procedures and has demonstrated proven benefits such as postoperative analgesia and reduction in opioid consumption. Being a superficial plane block, it avoids complications such as pneumothorax and hematoma, making it a safe mode of analgesia. We report a rare case of hematoma formation following ESP block in a patient who underwent mitral valve repair under cardiopulmonary bypass.

Reproductive and child health transition among selected empowered action groups states of India: A district-level analysis.

BACKGROUND: Health is an inseparable part of life and central to all life supporting systems. The reproductive and child health shares a major portion of public health cases that is crucial for socio-economic development. Studies on reproductive and child health have traditionally been focused on demographic aspects using socio-economic parameters. Given the emphasis of Sustainable Development Goal (SDG)-3 on health and well-being, it is imperative to understand the geo-spatial dimension with the visible transition of key health indicators of fertility, maternal and infant/child health in the high burdened districts within these high focus Empowered Action Group (EAG) states of Rajasthan, Madhya Pradesh, Uttar Pradesh and Bihar that make up nearly 40% of India's population with relatively laggard health status. METHODOLOGY: This paper aims to understand the status and trend of key reproductive and child health indicators and vital statistics based on the recent representative demographic surveys. We intend to undertake a district level spatio-temporal analysis by developing District Composite Health Profile (DCHP) using Composite Index Method on selected 13 equally weighted key reproductive and child health indicators. The study has been carried out using data from National Family Health Survey-4 (2015-16) and National Family Health Survey-5 (2019-21) survey rounds. We employed geo-spatial techniques i.e. Moran's-I, and univariate LISA to comprehend the geographical clustering of high and low health burden districts and their heterogeneities at the district level. RESULTS/CONCLUSIONS: The study highlights emerging inter-districts, and inter-state disparities over survey periods. With consistent improvement in the selected EAG states over time, the overall reproductive and child health status through DCHP along with each indicator was relatively better in the states of Rajasthan and worse in Bihar. Districts along the Terai belt in Uttar Pradesh and Bihar consistently performed sluggish during survey rounds. The geo-spatial clustering follows the political boundary of states, albeit with intra-state variations. Monitoring of key health indicators using composite index method provides a useful leverage for identifying priority districts/regions for universal health access that should also consider geographical space as an important policy dimension.

Time to implement tailored interventions in Chhattisgarh, east-central India to reach malaria elimination.

BACKGROUND OBJECTIVES: Despite significant progress in malaria control throughout India, Chhattisgarh state continues to be a significant contributor to both malaria morbidity and mortality. This study aims to identify key factors associated with malaria endemicity, with a goal of focusing on these factors for malaria elimination by 2030. METHODS: We employed an analysis and narrative review methodology to summarize the existing evidence on malaria epidemiology in Chhattisgarh. Data encompassing environmental conditions, dominant malaria vectors and their distribution, and the impact of previous interventions on malaria control, were extracted from published literature using PubMed and Google Scholar. This information was subsequently correlated with malaria incidence data using appropriate statistical and geographical methods. RESULTS: Much of the malaria burden in Chhattisgarh state is concentrated in a few specific districts. The primary malaria vectors in these regions are Anopheles culicifacies and An. fluviatilis. High transmission areas are found in tribal belts which are challenging to access and are characterized by densely forested areas that provide a conducive habitat for malaria vectors. INTERPRETATION CONCLUSION: Conducive environmental conditions characterized by high forest cover, community behavior, and insurgency, contribute to high malaria endemicity in the area. Challenges include insecticide resistance in malaria vectors and asymptomatic malaria. Allocating additional resources to high-endemic districts is crucial. Innovative and focused malaria control programs of the country, such as DAMAN and Malaria Mukt Abhiyan, hold immense importance.

Biomass Derived Biofluorescent Carbon Dots for Energy Applications: Current Progress and Prospects.

Biomass resources are often disposed of inefficiently and it causes environmental degradation. These wastes can be turned into bio-products using effective conversion techniques. The synthesis of high-value bio-products from biomass adheres to the principles of a sustainable circular economy in a variety of industries, including agriculture. Recently, fluorescent carbon dots (C-dots) derived from biowastes have emerged as a breakthrough in the field, showcasing outstanding fluorescence properties and biocompatibility. The C-dots exhibit unique quantum confinement properties due to their small size, contributing to their exceptional fluorescence. The significance of their fluorescent properties lies in their versatile applications, particularly in bio-imaging and energy devices. Their rapid and straight-forward production using green/chemical precursors has further accelerated their adoption in diverse applications. The use of green precursors for C-dot not only addresses the biomass disposal issue through a scientific approach, but also establishes a path for a circular economy. This approach not only minimizes biowaste, which also harnesses the potential of fluorescent C-dots to contribute to sustainable practices in agriculture. This review explores recent developments and challenges in synthesizing high-quality C-dots from agro-residues, shedding light on their crucial role in advancing technologies for a cleaner and more sustainable future.

Oxime-functionalized anti-insecticide fabric reduces insecticide exposure through dermal and nasal routes, and prevents insecticide-induced neuromuscular-dysfunction and mortality.

Farmers from South Asian countries spray insecticides without protective gear, which leads to insecticide exposure through dermal and nasal routes. Acetylcholinesterase plays a crucial role in controlling neuromuscular function. Organophosphate and carbamate insecticides inhibit acetylcholinesterase, which leads to severe neuronal/cognitive dysfunction, breathing disorders, loss of endurance, and death. To address this issue, an Oxime-fabric is developed by covalently attaching silyl-pralidoxime to the cellulose of the fabric. The Oxime-fabric, when stitched as a bodysuit and facemask, efficiently deactivates insecticides (organophosphates and carbamates) upon contact, preventing exposure. The Oxime-fabric prevents insecticide-induced neuronal damage, neuro-muscular dysfunction, and loss of endurance. Furthermore, we observe a 100% survival rate in rats when repeatedly exposed to organophosphate-insecticide through the Oxime-fabric, while no survival is seen when organophosphate-insecticide applied directly or through normal fabric. The Oxime-fabric is washable and reusable for at least 50 cycles, providing an affordable solution to prevent insecticide-induced toxicity and lethality among farmers.

Harnessing the innate immune system by revolutionizing macrophage-mediated cancer immunotherapy.

Immunotherapy is a promising and safer alternative to conventional cancer therapies. It involves adaptive T-cell therapy, cancer vaccines, monoclonal antibodies, immune checkpoint blockade (ICB), and chimeric antigen receptor (CAR) based therapies. However, most of these modalities encounter restrictions in solid tumours owing to a dense, highly hypoxic and immune-suppressive microenvironment as well as the heterogeneity of tumour antigens. The elevated intra-tumoural pressure and mutational rates within fastgrowing solid tumours present challenges in efficient drug targeting and delivery. The tumour microenvironment is a dynamic niche infiltrated by a variety of immune cells, most of which are macrophages. Since they form a part of the innate immune system, targeting macrophages has become a plausible immunotherapeutic approach. In this review, we discuss several versatile approaches (both at pre-clinical and clinical stages) such as the direct killing of tumour-associated macrophages, reprogramming pro-tumour macrophages to anti-tumour phenotypes, inhibition of macrophage recruitment into the tumour microenvironment, novel CAR macrophages, and genetically engineered macrophages that have been devised thus far. These strategies comprise a strong and adaptable macrophage-toolkit in the ongoing fight against cancer and by understanding their significance, we may unlock the full potential of these immune cells in cancer therapy.

Physical rehabilitation program for cardiorespiratory health and quality of life among breast cancer survivors in UAE: protocol for a randomized control trial.

BACKGROUND: Cancer is a medical condition where some cells of the body reproduce uncontrollably and metastasize to other parts of the body. The burden of the disease is significantly high both at the global and national levels. In UAE, cancer was found to be the third leading cause of death. Breast cancer has been ranked first due to its prevalence, incidence, and mortality in UAE. Breast cancer survivors have significantly poor cardiovascular tolerance which affects their quality of life (QoL), even after the carcinoma has been treated or removed. Thus, the protocol aims to analyze the changes in cardiovascular endurance and QoL domains for breast cancer survivors in the United Arab Emirates using a long-term 2-month physical rehabilitation. METHODS: A total of 60 breast cancer survivors would be included in the study using a randomized controlled allocation of a 2-month physical rehabilitation intervention program with 3 months of follow-up. The intervention would target the cardiovascular endurance component of the participants to improve their physical well-being and quality of life ultimately. DISCUSSION: The findings of the study would have high clinical significance among breast cancer survivors in the UAE. The proposed physical rehabilitation program could be beneficial in improving cardiovascular endurance and thereby reduce the risk of mortality among breast cancer survivors. In addition, the physiological benefits of the exercise program could improve their quality-of-life domains including physical, mental, and social well-being. On a larger view, it could also help to reduce the economic burden on the health system due to associated complications. TRIAL REGISTRATION: ClinicalTrials.gov NCT06013527. Registered on 28 August 2023.

Machine learning analysis of thermophysical and thermohydraulic properties in ethylene glycol- and glycerol-based SiO2 nanofluids.

The study investigates the heat transfer and friction factor properties of ethylene glycol and glycerol-based silicon dioxide nanofluids flowing in a circular tube under continuous heat flux circumstances. This study tackles the important requirement for effective thermal management in areas such as electronics cooling, the automobile industry, and renewable energy systems. Previous research has encountered difficulties in enhancing thermal performance while handling the increased friction factor associated with nanofluids. This study conducted experiments in the Reynolds number range of 1300 to 21,000 with particle volume concentrations of up to 1.0%. Nanofluids exhibited superior heat transfer coefficients and friction factor values than the base liquid values. The highest enhancement in heat transfer was 5.4% and 8.3% for glycerol and ethylene glycol -based silicon dioxide Nanofluid with a relative friction factor penalty of ∼30% and 75%, respectively. To model and predict the complicated, nonlinear experimental data, five machine learning approaches were used: linear regression, random forest, extreme gradient boosting, adaptive boosting, and decision tree. Among them, the decision tree-based model performed well with few errors, while the random forest and extreme gradient boosting models were also highly accurate. The findings indicate that these advanced machine learning models can accurately anticipate the thermal performance of nanofluids, providing a dependable tool for improving their use in a variety of thermal systems. This study's findings help to design more effective cooling solutions and improve the sustainability of energy systems.

Maternal TGF-ß ligand Panda breaks the radial symmetry of the sea urchin embryo by antagonizing the Nodal type II receptor ACVRII.

In the highly regulative embryo of the sea urchin Paracentrotus lividus, establishment of the dorsal-ventral (D/V) axis critically depends on the zygotic expression of the TGF-ß nodal in the ventral ectoderm. nodal expression is first induced ubiquitously in the 32-cell embryo and becomes progressively restricted to the presumptive ventral ectoderm by the early blastula stage. This early spatial restriction of nodal expression is independent of Lefty, and instead relies on the activity of Panda, a maternally expressed TGF-ß ligand related to Lefty and Inhibins, which is required maternally for D/V axis specification. However, the mechanism by which Panda restricts the early nodal expression has remained enigmatic and it is not known if Panda works like a BMP ligand by opposing Nodal and antagonizing Smad2/3 signaling, or if it works like Lefty by sequestering an essential component of the Nodal signaling pathway. In this study, we report that Panda functions as an antagonist of the TGF-ß type II receptor ACVRII (Activin receptor type II), which is the only type II receptor for Nodal signaling in the sea urchin and is also a type II receptor for BMP ligands. Inhibiting translation of acvrII mRNA disrupted D/V patterning across all 3 germ layers and caused acvrII morphants to develop with a typical Nodal loss-of-function phenotype. In contrast, embryos overexpressing acvrII displayed strong ectopic Smad1/5/8 signaling at blastula stages and developed as dorsalized larvae, a phenotype very similar to that caused by over activation of BMP signaling. Remarkably, embryos co-injected with acvrII mRNA and panda mRNA did not show ectopic Smad1/5/8 signaling and developed with a largely normal dorsal-ventral polarity. Furthermore, using an axis induction assay, we found that Panda blocks the ability of ACVRII to orient the D/V axis when overexpressed locally. Using co-immunoprecipitation, we showed that Panda physically interacts with ACVRII, as well as with the Nodal co-receptor Cripto, and with TBR3 (Betaglycan), which is a non-signaling receptor for Inhibins in mammals. At the molecular level, we have traced back the antagonistic activity of Panda to the presence of a single proline residue, conserved with all the Lefty factors, in the ACVRII binding motif of Panda, instead of a serine as in most of TGF-ß ligands. Conversion of this proline to a serine converted Panda from an antagonist that opposed Nodal signaling and promoted dorsalization to an agonist that promoted Nodal signaling and triggered ventralization when overexpressed. Finally, using phylogenomics, we analyzed the emergence of the agonist and antagonist form of Panda in the course of evolution. Our data are consistent with the idea that the presence of a serine at that position, like in most TGF-ß, was the ancestral condition and that the initial function of Panda was possibly in promoting and not in antagonizing Nodal signaling. These results highlight the existence of key functional and structural elements conserved between Panda and Lefty, allow to draw an intriguing parallel between sea urchin Panda and mammalian Inhibin α and raise the unexpected possibility that the original function of Panda may have been in activation of the Nodal pathway rather than in its inhibition.

Characterizing genetic diversity of Sclerotium rolfsii isolates by biomapping of mycelial compatibility groupings and multilocus sequence analysis.

Genetic diversity in Sclerotium rolfsii is useful for understanding its population structure, identifying different mycelial compatibility groups (MCGs), and developing targeted strategies for disease management in affected crops. In our study, a comprehensive genetic analysis was conducted on 50 isolates of S. rolfsii, collected from various geographic regions and host plants. Two specific genes, TEF1α and RPB2, were utilized to assess the genetic diversity and relationships among these isolates. Notably, out of 1225 pairings examined, only 154 exhibited a compatible reaction, while the majority displayed antagonistic reactions, resulting in the formation of a barrier zone. The isolates were grouped into 10 distinct MCGs. These MCGs were further characterized using genetic sequencing. TEF1α sequences distinguished the isolates into 17 distinct clusters, and RPB2 sequences classified them into 20 clusters. Some MCGs shared identical gene sequences within each gene, while others exhibited unique sequences. Intriguingly, when both TEF1α and RPB2 sequences were combined, all 10 MCGs were effectively differentiated, even those that appeared identical with single-gene analysis. This combined approach provided a comprehensive understanding of the genetic diversity and relationships among the S. rolfsii isolates, allowing for precise discrimination between different MCGs. The results shed light on the population structure and genetic variability within this plant pathogenic fungus, providing valuable insights for disease management and control strategies. This study highlights the significance of comprehending the varied virulence characteristics within S. rolfsii isolates, categorizing them into specific virulence groups based on disease severity index (DSI) values. The association with MCGs provides additional insights into the genetic underpinnings of virulence in this pathogen. Furthermore, the identification of geographical patterns in virulence implies the influence of region-specific factors, with potential implications for disease control and crop protection strategies.Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author 1 Given name: [G. M. Sandeep] Last name [Kumar]. Author 2 Given name: [Praveen Kumar] Last name [Singh]. Also, kindly confirm the details in the metadata are correct.I confirm that the given names are accurate and presented in the correct sequence.