Porcine circovirus 2d associated with stillborn mummified foetus of pig

Recurrent occurrence of stillborn piglets was noticed along with live births during farrowing in pigs in an organized pig farm of Uttar Pradesh. On detailed post mortem examination, externally, the foetus was found to be partially dehydrated and dark brown in colour with shrunken eyes. Internally, visceral organs including lungs, heart, kidneys, liver, spleen and intestine were partially dehydrated and dark brown in colour. Upon molecular investigation, the pooled tissue samples were found positive for porcine circovirus 2 (PCV2) infection using PCR technique and further confirmed the PCV2d genotype by DNA sequencing. Other most possible infections including porcine parvoviral infection (PPV), PCV3 and porcine respiratory and reproductive syndrome virus infection (PRRS) were found negative using PCR and RT-PCR techniques, respectively. This result is suggestive of role of PCV2d as a possible etiological agent to cause stillbirth and mummification of porcine foetuses

EFFECT OF SUPPLEMENTATION OF LEUKEMIA INHIBITORY FACTOR ON IN VITRO DEVELOPMENT OF BUFFALO EMBRYOS

ABSTRAC

The central role of IL-33/IL-1RL1 pathway in asthma:From pathogenesis to intervention

Interleukin-33 (IL-33), a member of the IL-1 family, and its cognate receptor, Interleukin-1 receptor like-1 (IL-1RL1 or ST2), are susceptibility genes for childhood asthma. In response to cellular damage, IL-33 is released from barrier tissues as an & lsquo;alarmin & rsquo; to activate the innate immune response. IL-33 drives type 2 responses by inducing signalling through its receptor IL-1RL1 in several immune and structural cells, thereby leading to type 2 cytokine and chemokine production. IL-1RL1 gene transcript encodes different isoforms generated through alternative splicing. Its soluble isoform, IL-1RL1-a or sST2, acts as a decoy receptor by sequestering IL-33, thereby inhibiting IL1RL1-b/IL-33 signalling. IL-33 and its receptor IL-1RL1 are therefore considered as putative biomarkers or targets for pharmacological intervention in asthma. This review will provide an overview of the genetics and biology of the IL-33/IL-1RL1 pathway in the context of asthma pathogenesis. It will discuss the potential and complexities of targeting the cytokine or its receptor, how genetics or biomarkers may inform precision medicine for asthma targeting this pathway, and the possible positioning of therapeutics targeting IL-33 or its receptor in the expanding landscape of novel biologicals applied in asthma management. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/)

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death

Role of Mitofusin 2 in the Renal Stress Response

The role of mitofusin 2 (MFN2), a key regulator of mitochondrial morphology and function in the renal stress response is unknown. To assess its role, the MFN2 floxed gene was conditionally deleted in the kidney of mice (MFN2 cKO) by Pax2 promoter driven Cre expression (Pax2Cre). MFN2 cKO caused severe mitochondrial fragmentation in renal epithelial cells that are critical for normal kidney tubular function. However, despite a small (20%) decrease in nephron number, newborn cKO pups had organ or tubular function that did not differ from littermate Cre-negative pups. MFN2 deficiency in proximal tubule epithelial cells in primary culture induced mitochondrial fragmentation but did not significantly alter ATP turnover, maximal mitochondrial oxidative reserve capacity, or the low level of oxygen consumption during cyanide exposure. MFN2 deficiency also did not increase apoptosis of tubule epithelial cells under non-stress conditions. In contrast, metabolic stress caused by ATP depletion exacerbated mitochondrial outer membrane injury and increased apoptosis by 80% in MFN2 deficient vs. control cells. Despite similar stress-induced Bax 6A7 epitope exposure in MFN2 deficient and control cells, MFN2 deficiency significantly increased mitochondrial Bax accumulation and was associated with greater release of both apoptosis inducing factor and cytochrome c. In conclusion, MFN2 deficiency in the kidney causes mitochondrial fragmentation but does not affect kidney or tubular function during development or under non-stress conditions. However, MFN2 deficiency exacerbates renal epithelial cell injury by promoting Bax-mediated mitochondrial outer membrane injury and apoptosis

Efficient Elimination of Cancer Cells by Deoxyglucose-ABT-263/737 Combination Therapy

As single agents, ABT-263 and ABT-737 (ABT), molecular antagonists of the Bcl-2 family, bind tightly to Bcl-2, Bcl-xL and Bcl-w, but not to Mcl-1, and induce apoptosis only in limited cell types. The compound 2-deoxyglucose (2DG), in contrast, partially blocks glycolysis, slowing cell growth but rarely causing cell death. Injected into an animal, 2DG accumulates predominantly in tumors but does not harm other tissues. However, when cells that were highly resistant to ABT were pre-treated with 2DG for 3 hours, ABT became a potent inducer of apoptosis, rapidly releasing cytochrome c from the mitochondria and activating caspases at submicromolar concentrations in a Bak/Bax-dependent manner. Bak is normally sequestered in complexes with Mcl-1 and Bcl-xL. 2DG primes cells by interfering with Bak-Mcl-1 association, making it easier for ABT to dissociate Bak from Bcl-xL, freeing Bak to induce apoptosis. A highly active glucose transporter and Bid, as an agent of the mitochondrial apoptotic signal amplification loop, are necessary for efficient apoptosis induction in this system. This combination treatment of cancer-bearing mice was very effective against tumor xenograft from hormone-independent highly metastasized chemo-resistant human prostate cancer cells, suggesting that the combination treatment may provide a safe and effective alternative to genotoxin-based cancer therapies

Mechanistic framework to link root growth models with weather and soil physical properties, including example applications to soybean growth in Brazil

Background and aimsRoot elongation is generally limited by a combination of mechanical impedance and water stress in most arable soils. However, dynamic changes of soil penetration resistance with soil water content are rarely included in models for predicting root growth. Better modelling frameworks are needed to understand root growth interactions between plant genotype, soil management, and climate. Aim of paper is to describe a new model of root elongation in relation to soil physical characteristics like penetration resistance, matric potential, and hypoxia.MethodsA new diagrammatic framework is proposed to illustrate the interaction between root elongation, soil management, and climatic conditions. The new model was written in Matlab®, using the root architecture model RootBox and a model that solves the 1D Richards equations for water flux in soil. Inputs: root architectural parameters for Soybean; soil hydraulic properties; root water uptake function in relation to matric flux potential; root elongation rate as a function of soil physical characteristics. Simulation scenarios: (a) compact soil layer at 16 to 20 cm; (b) test against a field experiment in Brazil during contrasting drought and normal rainfall seasons.Results(a) Soil compaction substantially slowed root growth into and below the compact layer. (b) Simulated root length density was very similar to field measurements, which was influenced greatly by drought. The main factor slowing root elongation in the simulations was evaluated using a stress reduction function.ConclusionThe proposed framework offers a way to explore the interaction between soil physical properties, weather and root growth. It may be applied to most root elongation models, and offers the potential to evaluate likely factors limiting root growth in different soils and tillage regimes

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field