Molecular mechanisms regulating T helper 2 cell differentiation and function.

T helper 2 (TH2) cells orchestrate type 2 immunity during protective antihelminth immunity and help restore tissue homoeostasis. Their misdirected activities against innocuous substances also underlie atopic diseases, such as asthma and allergy. Recent technological advances are uncovering novel insights into the molecular mechanisms governing TH2 cell differentiation and function.

Recipient tissue microenvironment determines developmental path of intestinal innate lymphoid progenitors.

Innate lymphoid cells (ILCs) are critical in maintaining tissue homeostasis, and during infection and inflammation. Here we identify, by using combinatorial reporter mice, a rare ILC progenitor (ILCP) population, resident to the small intestinal lamina propria (siLP) in adult mice. Transfer of siLP-ILCP into recipients generates group 1 ILCs (including ILC1 and NK cells), ILC2s and ILC3s within the intestinal microenvironment, but almost exclusively group 1 ILCs in the liver, lung and spleen. Single cell gene expression analysis and high dimensional spectral cytometry analysis of the siLP-ILCPs and ILC progeny indicate that the phenotype of the group 1 ILC progeny is also influenced by the tissue microenvironment. Thus, a local pool of siLP-ILCP can contribute to pan-ILC generation in the intestinal microenvironment but has more restricted potential in other tissues, with a greater propensity than bone marrow-derived ILCPs to favour ILC1 and ILC3 production. Therefore, ILCP potential is influenced by both tissue of origin and the microenvironment during development. This may provide additional flexibility during the tuning of immune reactions.

Structural brain preservation: a potential bridge to future medical technologies.

When faced with the prospect of death, some people would prefer a form of long-term preservation that may allow them to be restored to healthy life in the future, if technology ever develops to the point that this is feasible and humane. Some believe that we may have the capacity to perform this type of experimental preservation today-although it has never been proven-using contemporary methods to preserve the structure of the brain. The idea is that the morphomolecular organization of the brain encodes the information required for psychological properties such as personality and long-term memories. If these structures in the brain can be maintained intact over time, this could theoretically provide a bridge to access restorative technologies in the future. To consider this hypothesis, we first describe possible metrics that can be used to assess structural brain preservation quality. We next explore several possible methods to preserve structural information in the brain, including the traditional cryonics method of cryopreservation, as well as aldehyde-stabilized cryopreservation and fluid preservation. We focus in-depth on fluid preservation, which relies on aldehyde fixation to induce chemical gel formation in a wide set of biomolecules and appears to be a cost-effective method. We describe two theoretical recovery technologies, alongside several of the ethical and legal complexities of brain preservation, all of which will require a prudent approach. We believe contemporary structural brain preservation methods have a non-negligible chance of allowing successful restoration in the future and that this deserves serious research efforts by the scientific community.

Presence of emerging organic contaminants and microbial indicators in surface water and groundwater in urban India.

This study presents a first combined assessment of emerging organic contaminants (EOC) and antimicrobial resistance (AMR) indicators in the South Indian city of Bengaluru from multiple sources, addressing a knowledge gap on EOCs and AMR occurrences and relationships in different water sources in urban India. A unique approach in this study was to combine the detection of EOCs with an assessment of the AMR-indicating class 1 integron-integrase gene, intI1. Twenty-five samples collected from groundwater, local surface waters, and tap water imported from the Cauvery Basin were screened for 1499 EOCs. A total of 125 EOCs were detected at concentrations per compound of up to 314 µg/L. Concentrations for a range of contaminants were higher than those previously detected in Indian groundwaters. High concentrations of Per- and polyfluoroalkyl substances (PFAS) were detected with up to 1.8 µg/L in surface water and up to 0.9 µg/L in groundwater. Calculated risk quotients indicated potential AMR development caused by high concentrations of azithromycin, fluconazole, and sulfanilamide in surface waters that have little protection against sewage inflows. Surface waters that have recently undergone environmental restoration (e.g., removing silted bottom layers and enhancing protection against encroachments and sewage inflows) had lower EOC detections and risk of AMR development. Specific EOC detections, e.g., the ubiquitous detection of the sweetener sucralose (in use since ∼2000), indicated recent groundwater recharge and a contribution of imported Cauvery River water for recharge. This study highlights the need for monitoring and water protection, the role of EOCs as potential drivers of AMR, and the success of surface water protection measures to improve freshwater quality.

Biostasis: A Roadmap for Research in Preservation and Potential Revival of Humans.

Human biostasis, the preservation of a human when all other contemporary options for extension of quality life are exhausted, offers the speculative potential for survival via continuation of life in the future. While provably reversible preservation, also known as suspended animation, is not yet possible for humans, the primary justification for contemporary biostasis is the preservation of the brain, which is broadly considered the seat of memories, personality, and identity. By preserving the information contained within the brain's structures, it may be possible to resuscitate a healthy whole individual using advanced future technologies. There are numerous challenges in biostasis, including inadequacies in current preservation techniques, methods to evaluate the quality of preservation, and potential future revival technologies. In this report, we describe a roadmap that attempts to delineate research directions that could improve the field of biostasis, focusing on optimizing preservation protocols and establishing metrics for querying preservation quality, as well as pre- and post-cardiac arrest factors, stabilization strategies, and methods for long-term preservation. We acknowledge the highly theoretical nature of future revival technologies and the importance of achieving high-fidelity brain preservation to maximize the potential of future repair technologies. We plan to update the research roadmap biennially. Our goal is to encourage multidisciplinary communication and collaboration in this field.

Association of bradykinin receptor 2 (BDKRB2) variants with physical performance and muscle mass: Findings from the LACE sarcopenia trial.

INTRODUCTION: Understanding genetic contributors to sarcopenia (age-related loss of muscle strength and mass) is key to finding effective therapies. Variants of the bradykinin receptor 2 (BDKRB2) have been linked to athletic and muscle performance. The rs1799722-9 and rs5810761 T alleles have been shown to be overrepresented in endurance athletes, possibly due to increased transcriptional rates of the receptor. These variants have been rarely studied in older people or people with sarcopenia. METHODS: We performed a post hoc sub-study of the Leucine and ACE (LACE) inhibitor trial, which enrolled 145 participants aged ≥70 years with low grip strength and low gait speed. Participants' blood samples were genotyped for rs179972 using TaqMan and rs5810761 by amplification through Hotstar Taq. Genotypes were compared with outcomes of physical performance and body composition measures. RESULTS: Data from 136 individuals were included in the analysis. For rs1799722 the genotype frequency (TT: 17, CC: 48, CT: 71) remained in Hardy-Weinberg Equilibrium (HWE p = 0.248). There was no difference between the genotypes for six-Minute Walk Distance (6MWD) or Short Physical Performance Battery (SPPB). Men with the TT genotype had a significantly greater 6MWD than other genotypes (TT 400m vs CT 310m vs CC 314m, p = 0.027), and greater leg muscle mass (TT 17.59kg vs CT 15.04kg vs CC 15.65kg, p = 0.007). For rs5810761, the genotype frequency (-9-9: 31, +9+9: 43, -9+9: 60) remained in HWE (p = 0.269). The +9+9 genotype was associated with a significant change in SPPB score at 12 months (-9-9 0 vs -9+9 0 vs +9+9-1, p<0.001), suggesting an improvement. In men, the -9-9 genotype was associated with lower arm fat (-9-9 2.39kg vs -9+9 2.72kg vs +9+9 2.76kg, p = 0.019). CONCLUSION: In men, the rs1799722 TT genotype was associated with longer 6MWD and greater leg muscle mass, while the rs5810761 -9-9 genotype was associated with lower arm fat mass.

ILC2-derived LIF licences progress from tissue to systemic immunity.

Migration and homing of immune cells are critical for immune surveillance. Trafficking is mediated by combinations of adhesion and chemokine receptors that guide immune cells, in response to chemokine signals, to specific locations within tissues and the lymphatic system to support tissue-localized immune reactions and systemic immunity1,2. Here we show that disruption of leukaemia inhibitory factor (LIF) production from group 2 innate lymphoid cells (ILC2s) prevents immune cells leaving the lungs to migrate to the lymph nodes (LNs). In the absence of LIF, viral infection leads to plasmacytoid dendritic cells (pDCs) becoming retained in the lungs where they improve tissue-localized, antiviral immunity, whereas chronic pulmonary allergen challenge leads to marked immune cell accumulation and the formation of tertiary lymphoid structures in the lung. In both cases immune cells fail to migrate to the lymphatics, leading to highly compromised LN reactions. Mechanistically, ILC2-derived LIF induces the production of the chemokine CCL21 from lymphatic endothelial cells lining the pulmonary lymphatic vessels, thus licensing the homing of CCR7+ immune cells (including dendritic cells) to LNs. Consequently, ILC2-derived LIF dictates the egress of immune cells from the lungs to regulate tissue-localized versus systemic immunity and the balance between allergen and viral responsiveness in the lungs.

Agricultural extension service, technology adoption, and production risk nexus: Evidence from Bangladesh.

Rice production is inherently risky and volatile, and farmers in Bangladesh face a wide range of risks, including weather, pest and disease attacks, interruptions to input supply, and market-associated risks. Moreover, poor farm households often perceive risks in adopting new technology, even though it could improve productivity and food security. Such households are thus caught in a "risk-induced trap" that precludes them from realizing the benefits of technological innovation. Extension service is one way to help farmers improve risk management skills and escape risk-induced traps, but there is limited empirical analysis of its impact in Bangladesh. The objective of the study is to measure the nexus between agricultural extension services, technology adoption, and production risks as well as women empowerment in agriculture index. IFPRI utilized stratified random sampling to determine the 5603 households in 2018 (which is nationally called the BIHS-2018 dataset) from rural and pre-urban areas of Bangladesh. Out of these 5603 households, 2663 households were specifically selected for the study related to rice farming to achieve the main objective of the study. Focusing on rice farming, a moment-based Poisson regression model is estimated with 2SLS and identifies risks associated with key technologies and potential productivity and risk-reducing effects. The results revealed that wealthier households are more likely to adopt technology for minimizing production risk and women's empowerment which can positively affect productivity by mitigating risk. The result revealed a positive and significant difference in WEAI between the AES participant and non-participant group. We find that engagement in agricultural extension services was associated with technology adoption and production risk reduction. The agricultural extension services increased, technology adoption by 4.2 % and decreased production risk by 2.4 %. Based on the findings, it is concluded that more comprehensive extension services can enhance rice production and ameliorate farmers' risk in rice production to some extent.

The impact of COVID-19 on livelihood assets: a case study of high-value crop farmers in North-West Bangladesh.

The COVID-19 pandemic has had a catastrophic impact on public health, extending to the food system and people's livelihoods worldwide, including Bangladesh. This study aimed to ascertain the COVID-19 pandemic impacts on livelihood assets in the North-Western areas (Rajshahi and Rangpur) of Bangladesh. Primary data were collected from 320 farmers engaged in high-value agriculture using a multistage sampling method. The data were analysed using first-order structural equation modelling. The findings reveal a significant impact (p < 0.01) of the pandemic on all livelihood assets in Bangladesh. Notably, human assets exhibited the highest impact, with a coefficient of 0.740, followed sequentially by financial (0.709), social (0.684), natural (0.600), physical (0.542), and psychological (0.537) assets. Government-imposed lockdowns and mobility restrictions were identified as the major causes of the pandemic's negative effects on livelihoods, which included lost income, rising food prices, decreased purchasing power, inadequate access to food and medical supplies, increased social insecurity, and a rise in depression, worry, and anxiety among farmers. The effects of COVID-19 and associated policy measures on the livelihoods of high-value crop farmers have reversed substantial economic and nutritional advances gained over the previous decade. This study suggests attention to the sustainable livelihoods of farmers through direct cash transfer and input incentive programs to minimize their vulnerability to a pandemic like COVID-19 or any other crisis in the future.

Cross-talk between ILC2 and Gata3high Tregs locally constrains adaptive type 2 immunity.

Regulatory T cells (Tregs) control adaptive immunity and restrain type 2 inflammation in allergic disease. Interleukin-33 promotes the expansion of tissue-resident Tregs and group 2 innate lymphoid cells (ILC2s); however, how Tregs locally coordinate their function within the inflammatory niche is not understood. Here, we show that ILC2s are critical orchestrators of Treg function. Using spatial, cellular, and molecular profiling of the type 2 inflamed niche, we found that ILC2s and Tregs engage in a direct (OX40L-OX40) and chemotaxis-dependent (CCL1-CCR8) cellular dialogue that enforces the local accumulation of Gata3high Tregs, which are transcriptionally and functionally adapted to the type 2 environment. Genetic interruption of ILC2-Treg communication resulted in uncontrolled type 2 lung inflammation after allergen exposure. Mechanistically, we found that Gata3high Tregs can modulate the local bioavailability of the costimulatory molecule OX40L, which subsequently controlled effector memory T helper 2 cell numbers. Hence, ILC2-Treg interactions represent a critical feedback mechanism to control adaptive type 2 immunity.

Gender differences in job satisfaction among gig workers in Bangladesh.

The gig economy (temporary, contract, and freelance online jobs rather than permanent positions) is a component of the fourth industrial revolution and preview of future work. The rise of digital platforms has increased career opportunities and income potential, particularly for women. Yet, the sex-disaggregated evidence regarding platform usage, employment characteristics, and working motivations and satisfaction remains untapped. Using data from a quantitative survey of Bangladeshi gig workers (242 men and 201 women) conducted in 2022, this paper addresses these gaps between male and female workers. The gig economy appears to be gender-segregated across digital platform usages and working categories. Women tend to prioritize digital work options for managing multiple responsibilities, while men are often driven by the potential for higher income. This study conceptually utilized the two-factor theory and empirically ordered a probit model to identify gender differences in job satisfaction. Job satisfaction was significantly increased by work-life balance, monthly income, and social-media connection, while an increase in working hours, complexity in payment systems, and unstable networks all led to a decrease in job satisfaction. The findings have implications for the future growth of the gig economy, provide new insights into gender differences in job satisfaction, and underscore the need for gender-sensitive policies in the online labor market.

Mef2d potentiates type-2 immune responses and allergic lung inflammation.

Innate lymphoid cells (ILCs) and adaptive T lymphocytes promote tissue homeostasis and protective immune responses. Their production depends on the transcription factor GATA3, which is further elevated specifically in ILC2s and T helper 2 cells to drive type-2 immunity during tissue repair, allergic disorders, and anti-helminth immunity. The control of this crucial up-regulation is poorly understood. Using CRISPR screens in ILCs we identified previously unappreciated myocyte-specific enhancer factor 2d (Mef2d)-mediated regulation of GATA3-dependent type-2 lymphocyte differentiation. Mef2d-deletion from ILC2s and/or T cells specifically protected against an allergen lung challenge. Mef2d repressed Regnase-1 endonuclease expression to enhance IL-33 receptor production and IL-33 signaling and acted downstream of calcium-mediated signaling to translocate NFAT1 to the nucleus to promote type-2 cytokine-mediated immunity.

Does rural transformation affect rural income inequality? Insights from cross-district panel data analysis in Bangladesh.

Rural transformation plays a crucial role in enhancing the income and employment prospects of the rural labor force. We investigate the effects of rural transformation on rural income inequality at the district level in Bangladesh using data from five years of nationally representative Household Income and Expenditure Surveys. The Gini coefficient is used to measure rural income inequality. In contrast, the share of high-value agricultural outputs and the share of rural non-farm employment are used as indicators of rural transformation. We find that rural income inequality is positively associated with the share of high-value agricultural outputs and the share of rural non-farm employment. The non-linear regression result shows an inverted U-shaped relationship between rural transformation and income inequality, which indicates that income inequality initially increases with rural transformation but decreases in the long run. Additionally, we find that rural income inequality is positively correlated with the proportion of household education expenditures, agricultural rental activity, and the share of remittances. This study also reveals that income inequality in rural areas of Bangladesh has a significant negative correlation with the government's social safety net program.

Fluid preservation in brain banking: a review.

Fluid preservation is nearly universally used in brain banking to store fixed tissue specimens for future research applications. However, the effects of long-term immersion on neural circuitry and biomolecules are not well characterized. As a result, there is a need to synthesize studies investigating fluid preservation of brain tissue. We searched PubMed and other databases to identify studies measuring the effects of fluid preservation in nervous system tissue. We categorized studies based on the fluid preservative used: formaldehyde solutions, buffer solutions, alcohol solutions, storage after tissue clearing, and cryoprotectant solutions. We identified 91 studies containing 197 independent observations of the effects of long-term storage on cellular morphology. Most studies did not report any significant alterations due to long-term storage. When present, the most frequent alteration was decreased antigenicity, commonly attributed to progressive crosslinking by aldehydes that renders biomolecules increasingly inaccessible over time. To build a mechanistic understanding, we discuss biochemical aspects of long-term fluid preservation. A subset of lipids appears to be chemical altered or extracted over time due to incomplete retention in the crosslinked gel. Alternative storage fluids mitigate the problem of antigen masking but have not been extensively characterized and may have other downsides. We also compare fluid preservation to cryopreservation, paraffin embedding, and resin embedding. Overall, existing evidence suggests that fluid preservation provides maintenance of neural architecture for decades, including precise structural details. However, to avoid the well-established problem of overfixation caused by storage in high concentration formaldehyde solutions, fluid preservation procedures can use an initial fixation step followed by an alternative long-term storage fluid. Further research is warranted on optimizing protocols and characterizing the generalizability of the storage artifacts that have been identified.

"Right Into the Center": A Semantic Analysis of Direction in Operating Room Instruction.

OBJECTIVE: In our previous work, teaching surgeons used potentially ambiguous language in the OR 12.3 times per minute. Our objectives were to examine ambiguous examples featuring Directional Frame of Reference (DFoR), which involves instructions containing directional terms like "up" or "left," and to uncover what contributes to understanding or misunderstanding of such instruction. DESIGN: We videorecorded the critical moments of 6 surgeries, as chosen by the surgeons. With a semanticist, we applied constructs from formal semantics to choose potentially ambiguous DFoR terms commonly flagged in our previous work. We separately interviewed attending and resident surgeons, asking each to describe the meaning of those DFoR terms while they viewed case recordings alongside transcripts. We compared their responses, analyzing them for agreement in direction. We performed thematic analysis on case and interview transcripts for themes related to DFoR. SETTING: Midwestern academic university teaching hospital. PARTICIPANTS: Six attending and 6 resident surgeons. RESULTS: Attending and resident surgeons disagreed on direction in 9 of the 26 (34.6%) DFoR examples. Misunderstanding arose from using linear direction to describe three-dimensional space, e.g., "up" for anterior/cephalad/right. It also arose when combining degree modifiers with DfoR, e.g., "we're far enough back" combines the ambiguities of "back" (DfoR) and "far enough" (degree modifier). Use of axial parts (noun-like directional terms), e.g., "bottom," and confusing "left" for "right" also provoked misunderstanding. Misunderstanding was associated with lack of experience and mitigated by pointing with a finger or instrument, concurrent with speech. CONCLUSIONS: Use of ambiguous language with DFoR incurs a high potential for misunderstanding, especially with novice surgeons. We recommend avoiding linear directions and axial parts, and instead physically pointing to represent complex 3D directions. Degree modifiers can be replaced with exact distances e.g., replace "little more anterior" with "1 centimeter anterior," and semaphores can be used to clarify direction.

Identification of influential weather parameters and seasonal drought prediction in Bangladesh using machine learning algorithm.

Droughts pose a severe environmental risk in countries that rely heavily on agriculture, resulting in heightened levels of concern regarding food security and livelihood enhancement. Bangladesh is highly susceptible to environmental hazards, with droughts further exacerbating the precarious situation for its 170 million inhabitants. Therefore, we are endeavouring to highlight the identification of the relative importance of climatic attributes and the estimation of the seasonal intensity and frequency of droughts in Bangladesh. With a period of forty years (1981-2020) of weather data, sophisticated machine learning (ML) methods were employed to classify 35 agroclimatic regions into dry or wet conditions using nine weather parameters, as determined by the Standardized Precipitation Evapotranspiration Index (SPEI). Out of 24 ML algorithms, the four best ML methods, ranger, bagEarth, support vector machine, and random forest (RF) have been identified for the prediction of multi-scale drought indices. The RF classifier and the Boruta algorithms shows that water balance, precipitation, maximum and minimum temperature have a higher influence on drought intensity and occurrence across Bangladesh. The trend of spatio-temporal analysis indicates, drought intensity has decreased over time, but return time has increased. There was significant variation in changing the spatial nature of drought intensity. Spatially, the drought intensity shifted from the northern to central and southern zones of Bangladesh, which had an adverse impact on crop production and the livelihood of rural and urban households. So, this precise study has important implications for the understanding of drought prediction and how to best mitigate its impacts. Additionally, the study emphasizes the need for better collaboration between relevant stakeholders, such as policymakers, researchers, communities, and local actors, to develop effective adaptation strategies and increase monitoring of weather conditions for the meticulous management of droughts in Bangladesh.

Spatial proteomics of hippocampal subfield-specific pathology in Alzheimer's disease and primary age-related tauopathy.

INTRODUCTION: Alzheimer's disease (AD) and primary age-related tauopathy (PART) both harbor 3R/4R hyperphosphorylated-tau (p-tau)-positive neurofibrillary tangles (NFTs) but differ in the spatial p-tau development in the hippocampus. METHODS: Using Nanostring GeoMx Digital Spatial Profiling, we compared protein expression within hippocampal subregions in NFT-bearing and non-NFT-bearing neurons in AD (n = 7) and PART (n = 7) subjects. RESULTS: Proteomic measures of synaptic health were inversely correlated with the subregional p-tau burden in AD and PART, and there were numerous differences in proteins involved in proteostasis, amyloid beta (Aß) processing, inflammation, microglia, oxidative stress, and neuronal/synaptic health between AD and PART and between definite PART and possible PART. DISCUSSION: These results suggest subfield-specific proteome differences that may explain some of the differences in Aß and p-tau distribution and apparent pathogenicity. In addition, hippocampal neurons in possible PART may have more in common with AD than with definite PART, highlighting the importance of Aß in the pathologic process. HIGHLIGHTS: Synaptic health is inversely correlated with local p-tau burden. The proteome of NFT- and non-NFT-bearing neurons is influenced by the presence of Aß in the hippocampus. Neurons in possible PART cases share more proteomic similarities with neurons in ADNC than they do with neurons in definite PART cases.

Cooperation of ILC2s and TH2 cells in the expulsion of intestinal helminth parasites.

Type 2 immune responses form a critical defence against enteric worm infections. In recent years, mouse models have revealed shared and unique functions for group 2 innate lymphoid cells and T helper 2 cells in type 2 immune response to intestinal helminths. Both cell types use similar innate effector functions at the site of infection, whereas each population has distinct roles during different stages of infection. In this Perspective, we review the underlying mechanisms used by group 2 innate lymphoid cells and T helper 2 cells to cooperate with each other and suggest an overarching model of the interplay between these cell types over the course of a helminth infection.

The alarmin IL33 orchestrates type 2 immune-mediated control of thymus regeneration.

As the primary site of T-cell development, the thymus dictates immune competency of the host. The rates of thymus function are not constant, and thymus regeneration is essential to restore new T-cell production following tissue damage from environmental factors and therapeutic interventions. Here, we show the alarmin interleukin (IL) 33 is a product of Sca1+ thymic mesenchyme both necessary and sufficient for thymus regeneration via a type 2 innate immune network. IL33 stimulates expansion of IL5-producing type 2 innate lymphoid cells (ILC2), which triggers a cellular switch in the intrathymic availability of IL4. This enables eosinophil production of IL4 to re-establish thymic mesenchyme prior to recovery of thymopoiesis-inducing epithelial compartments. Collectively, we identify a positive feedback mechanism of type 2 innate immunity that regulates the recovery of thymus function following tissue injury.