Suppressive might of a few: T follicular regulatory cells impede auto-reactivity despite being outnumbered in the germinal centres.

The selection of high-affinity B cells and the production of high-affinity antibodies are mediated by T follicular helper cells (Tfhs) within germinal centres (GCs). Therein, somatic hypermutation and selection enhance B cell affinity but risk the emergence of self-reactive B cell clones. Despite being outnumbered compared to their helper counterpart, the ablation of T follicular regulatory cells (Tfrs) results in enhanced dissemination of self-reactive antibody-secreting cells (ASCs).

Dynamics and future prediction of LULC on Pare River basin of Arunachal Pradesh using machine learning techniques.

Anthropogenic disturbances caused by increasing population densities are a significant concern as they accelerate climate change. Thus, regular monitoring of land use/land cover (LULC) is essential to mitigate these effects. Pare River basin of Arunachala Pradesh situated in the foothills of Eastern Himalayas was selected for this study.

Amount of antigen, T follicular helper cells and affinity of founder cells shape the diversity of germinal center B cells: A computational study.

A variety of B cell clones seed the germinal centers, where a selection stringency expands the fitter clones to generate higher affinity antibodies. However, recent experiments suggest that germinal centers often retain a diverse set of B cell clones with a range of affinities and concurrently carry out affinity maturation. Amid a tendency to flourish germinal centers with fitter clones, how several B cell clones with differing affinities can be concurrently selected remains poorly understood.

Tingible body macrophages arise from lymph node-resident precursors and uptake B cells by dendrites.

Antibody affinity maturation depends on the formation of germinal centers (GCs) in lymph nodes. This process generates a massive number of apoptotic B cells, which are removed by a specialized subset of phagocytes, known as tingible body macrophages (TBMs). Although defects in these cells are associated with pathological conditions, the identity of their precursors and the dynamics of dying GC B cell disposal remained unknown.

mutation yields supercompetitive B cells primed for malignant transformation.

Multicellular life requires altruistic cooperation between cells. The adaptive immune system is a notable exception, wherein germinal center B cells compete vigorously for limiting positive selection signals. Studying primary human lymphomas and developing new mouse models, we found that mutations affecting disrupt a critical immune gatekeeper mechanism that strictly limits B cell fitness during antibody affinity maturation.

Impact of COVID-19 on ports, multimodal logistics and transport sector in India: Responses and policy imperatives.

The COVID-19 pandemic spread rapidly in 2020 and led to full or partial lockdowns worldwide. The restrictions led to most economies contracting in the April-June quarter of 2020. As per the IMF World Economic Outlook of June 2020, the global economy was expected to contract by 4.

Testing and isolation to prevent overloaded healthcare facilities and reduce death rates in the SARS-CoV-2 pandemic in Italy.

Background: During the first wave of COVID-19, hospital and intensive care unit beds got overwhelmed in Italy leading to an increased death burden. Based on data from Italian regions, we disentangled the impact of various factors contributing to the bottleneck situation of healthcare facilities, not well addressed in classical SEIR-like models. A particular emphasis was set on the undetected fraction (dark figure), on the dynamically changing hospital capacity, and on different testing, contact tracing, quarantine strategies.

Sepsis induces interleukin 6, gp130/JAK2/STAT3, and muscle wasting.

Background: Sepsis and inflammation can cause intensive care unit-acquired weakness (ICUAW). Increased interleukin-6 (IL-6) plasma levels are a risk factor for ICUAW. IL-6 signalling involves the glycoprotein 130 (gp130) receptor and the JAK/STAT-pathway, but its role in sepsis-induced muscle wasting is uncertain.

Membrane composition and lipid to protein ratio modulate amyloid kinetics of yeast prion protein.

Understanding of prion aggregation in a membrane environment may help to ameliorate neurodegenerative complications caused by the amyloid forms of prions. Here, we investigated the membrane binding-induced aggregation of yeast prion protein Sup35. Using the combination of fluorescence correlation spectroscopy (FCS) at single molecule resolution and other biophysical studies, we establish that lipid composition and lipid/protein ratio are key modulators of the aggregation kinetics of Sup35.

Development of the reproduction number from coronavirus SARS-CoV-2 case data in Germany and implications for political measures.

Background: SARS-CoV-2 has induced a worldwide pandemic and subsequent non-pharmaceutical interventions (NPIs) to control the spread of the virus. As in many countries, the SARS-CoV-2 pandemic in Germany has led to a consecutive roll-out of different NPIs. As these NPIs have (largely unknown) adverse effects, targeting them precisely and monitoring their effectiveness are essential.

Genomic Landscape and Targeted Treatment of Gallbladder Cancer: Results of a First Ongoing Prospective Study.

 Prognosis of gallbladder cancer (GBC) has not changed in the past 20 years. Comprehensive genomic profiling (CGP) carries potential to determine the actionability for multiple targets, including , , , , , and . This study evaluates the role of CGP and targeted therapies.

Osmolytes ameliorate the effects of stress in the absence of the heat shock protein Hsp104 in Saccharomyces cerevisiae.

Aggregation of the prion protein has strong implications in the human prion disease. Sup35p is a yeast prion, and has been used as a model protein to study the disease mechanism. We have studied the pattern of Sup35p aggregation inside live yeast cells under stress, by using confocal microscopy, fluorescence activated cell sorting and western blotting.

Lineage space and the propensity of bacterial cells to undergo growth transitions.

The molecular makeup of the offspring of a dividing cell gradually becomes phenotypically decorrelated from the parent cell by noise and regulatory mechanisms that amplify phenotypic heterogeneity. Such regulatory mechanisms form networks that contain thresholds between phenotypes. Populations of cells can be poised near the threshold so that a subset of the population probabilistically undergoes the phenotypic transition.

WITHDRAWN: Curcumin shifts RAS-induced pro-proliferative MEK/ERK-signaling toward pro-apoptotic p38MAPK/JNK1-signaling, triggering p53 activation and apoptosis.

This article has been withdrawn by the authors. A mistake was made during the preparation of Fig 1C, NKE panel. The Western blot data shown for p-ERK1/2 and actin are not from this set, but rather a similar set of data from a different experiment.

Role of functionality in two-component signal transduction: a stochastic study.

We present a stochastic formalism for signal transduction processes in a bacterial two-component system. Using elementary mass action kinetics, the proposed model takes care of signal transduction in terms of a phosphotransfer mechanism between the cognate partners of a two-component system, viz., the sensor kinase and the response regulator.

Analysis of DevR regulated genes in Mycobacterium tuberculosis.

The DevRS two component system of Mycobacterium tuberculosis is responsible for its dormancy in host and becomes operative under hypoxic condition. It is experimentally known that phosphorylated DevR controls the expression of several downstream genes in a complex manner. In the present work we propose a theoretical model to show role of binding sites in DevR mediated gene expression.

Quantification of noise in bifunctionality-induced post-translational modification.

We present a generic analytical scheme for the quantification of fluctuations due to bifunctionality-induced signal transduction within the members of a bacterial two-component system. The proposed model takes into account post-translational modifications in terms of elementary phosphotransfer kinetics. Sources of fluctuations due to autophosphorylation, kinase, and phosphatase activity of the sensor kinase have been considered in the model via Langevin equations, which are then solved within the framework of linear noise approximation.

Positive feedback and temperature mediated molecular switch controls differential gene regulation in Bordetella pertussis.

Based on the phosphorelay kinetics operative within BvgAS two component system we propose a mathematical framework for signal transduction and gene regulation of phenotypic phases in Bordetella pertussis. The proposed model identifies a novel mechanism of transcriptional interference between two promoters present in the bvg locus. To understand the system behavior under elevated temperature, the developed model has been studied in two different ways.