The NF-κB Factor Relish maintains blood progenitor homeostasis in the developing Drosophila lymph gland.

Post-larval hematopoiesis in Drosophila largely depends upon the stockpile of progenitors present in the blood-forming organ/lymph gland of the larvae. During larval stages, the lymph gland progenitors gradually accumulate reactive oxygen species (ROS), which is essential to prime them for differentiation. Studies have shown that ROS triggers the activation of JNK (c-Jun Kinase), which upregulates fatty acid oxidation (FAO) to facilitate progenitor differentiation. Intriguingly, despite having ROS, the entire progenitor pool does not differentiate simultaneously in the late larval stages. Using expression analyses, genetic manipulation and pharmacological approaches, we found that the Drosophila NF-κB transcription factor Relish (Rel) shields the progenitor pool from the metabolic pathway that inducts them into the differentiation program by curtailing the activation of JNK. Although ROS serves as the metabolic signal for progenitor differentiation, the input from ROS is monitored by the developmental signal TAK1, which is regulated by Relish. This developmental circuit ensures that the stockpile of ROS-primed progenitors is not exhausted entirely. Our study sheds light on how, during development, integrating NF-κB-like factors with metabolic pathways seem crucial to regulating cell fate transition during development.

Terminology and methods used to differentiate injury intent of hospital burn patients in South Asia: Results from a systematic scoping review.

INTRODUCTION: A key component in the classification of all injury types is to differentiate whether the injury was deliberately inflicted and by whom, commonly known as "intent" in the surveillance literature. These data guide patient care and inform surveillance strategies. South Asia is believed to have the greatest number of intentional burn injuries, but national surveillance data is not disaggregated by injury intent. Scientific literature can be used for injury surveillance where national data collection does not exist. In order to synthesise research findings, it is essential to assess the potential impact of misclassification bias. We therefore conducted a systematic scoping review to understand terminology and methods used to differentiate injury intent of hospital burn patients in South Asia. METHODS: We followed the methods in our registered protocol (https://doi.org/10.17605/OSF.IO/DCYNQ). Studies met defined population, concept, context, and study design criteria. The databases Embase, MEDLINE, CINAHL, PsycInfo, and PakMediNet were searched. Two reviewers independently screened results. Data were extracted in a standardised manner and verified. The rigour of the method used to differentiate injury intent was appraised. RESULTS: 1435 articles were screened. Of these, 89 met our inclusion criteria. Most articles were from India and Pakistan, and used an observational study design. There were 14 stem terms used in the articles. The most common was "cause". There were 40 classifier terms. The most common were "accident", "suicide", and "homicide". Few articles defined these terms. The method used to differentiate injury intent was only described explicitly in 17% of articles and the rigour of the methods used were low. Where methods of differentiation were described, they appear to be based on patient or family report rather than multidisciplinary assessment. CONCLUSION: The heterogeneity in terms, lack of definitions, and limited investigation of injury intent means this variable is likely to be prone to misclassification bias. We strongly recommend that the global burn community unites to develop a common data element, including definitions and methods of assessment, for the concept of burn injury intent to enable more reliable data collection practices and interstudy comparisons.

Terminology and methods used to differentiate injury intent of hospital burn patients in South Asia: a systematic scoping review protocol.

BACKGROUND: The greatest proportion of burn injuries globally occur in South Asia, where there are also high numbers of intentional burns. Burn injury prevention efforts are hampered by poor surveillance data on injury intent. There is a plethora of local routinely collected data in the research literature from South Asia that could be used for epidemiological purposes, but it is not known whether the definitions and methods of differentiation of injury intent are sufficiently homogenous to allow valid study comparisons. METHODS: We will conduct a systematic scoping review to understand terminology and methods used to differentiate injury intent of hospital burn patients in South Asia. The objectives of the study are to: determine the breadth of terminology and common terms used for burn injury intent; to determine if definitions are comparable across studies where the same term is used; and to appraise the rigour of methods used to differentiate burn injury intent and suitability for comparison across studies. The databases Embase, MEDLINE, CINAHL, PsycINFO, and PakMediNet will be searched. Screening and data extraction will be completed independently by two reviewers. To be included, the article must be as follows: peer reviewed, primary research, study cutaneous burns, based on hospital patients from a country in South Asia, and use intent terminology or discuss a method of differentiation of injury intent. Results will be restricted to English language studies. No date restrictions will be applied. A plain language summary and terminology section are included for non-specialist readers. DISCUSSION: Results will be used to inform stakeholder work to develop standardised terminology and methods for burn injury intent in South Asia. They will be published open access in peer-reviewed journals wherever possible. SYSTEMATIC REVIEW REGISTRATION: This review has been registered with the Open Science Framework ( https://doi.org/10.17605/OSF.IO/DCYNQ ).

A Scoping Review of Gender Differences in Suicide in India.

Introduction: Much of the published literature on suicide comes from high income countries. In countries such as India, female suicide rates exceed the global suicide rate and suicide rates found in their male counterparts. Results from previous studies indicate that factors related to suicide among men and women in India are different from those seen in high-income countries. To date, no reviews have considered the relationship between gender and suicide in India. Therefore, the aim of this scoping review is to provide a comprehensive understanding of existing literature reporting gender differences in suicide rates, methods, risk factors and antecedent factors in India by reviewing published studies. Method: A scoping review was conducted to map the existing literature on gender differences in suicide in India. To identify peer-reviewed publications, online databases PsycINFO and Embase were searched. The search terms were [suicid* AND India*]. The searches took place in November 2020 and May 2021, with no language restrictions. Articles published from 2014 onwards from India were included. Reference lists of selected studies were searched for studies that could meet the inclusion criteria. Results: This review identified 17 studies that met the inclusion criteria. The ratio between women and men who die by suicide in India is much lower than in high-income countries. Hanging was found to be a more commonly used method of suicide among both men and women, in comparison to high-income countries where hanging is more common among men. This review also identified several gaps in the literature. There were few studies that examined suicide among transgender Indians. There was limited literature on gender differences in risk and protective factors for suicide. Limitations such as the omission of a lack of gender-based analyses in several studies and under-reporting of suicide rates were identified. Conclusion: Understanding suicide within the context of individual countries is essential in designing culture-appropriate suicide prevention strategies. This review identified an urgent need to establish and evaluate suicide surveillance systems in India. Furthermore, additional research is warranted to understand suicide among individuals who identify outside the gender binary, and gender-specific risk and protective factors.

Combination of Immunofluorescence and Quantitative Fluorescence In-situ Hybridization for Analysing Differential Gene Expression in the Niche Cells of the Drosophila Lymph Gland.

The Drosophila larval haematopoietic organ or lymph gland consists of multiple cell types arranged in zones. The smallest stem cell compartment consists of 40-45 cells that constitute the haematopoietic niche. In order to analyse the haematopoietic niche, it needs to be labelled with a specific antibody to differentiate it from the other cell types. To characterise a phenotype, it is often necessary to investigate the expression of a gene in a particular stem cell compartment within the lymph gland. In such a situation, in-situ hybridization is performed, as it indicates the localization of gene expression. Although chromogenic in-situ hybridization enables us to compare the signal and tissue morphology simultaneously, it fails to harness the information related to the degree of gene expression. Dual immunofluorescence and in-situ hybridization (IF-FISH) serves as the powerful technique that helps to visualize both protein and mRNA expression within the same cell type. This technique also provides reliable quantification regarding mRNA expression levels. When dealing with a few cells within the organ, like the niche of the larval lymph gland, fluorescently labelled riboprobes allows us to localize and assess the magnitude of gene expression within the niche cells, which are also immunolabelled with a niche-specific marker, to distinguish them from the adjoining cell types.

Relish plays a dynamic role in the niche to modulate Drosophila blood progenitor homeostasis in development and infection.

Immune challenges demand the gearing up of basal hematopoiesis to combat infection. Little is known about how during development, this switch is achieved to take care of the insult. Here, we show that the hematopoietic niche of the larval lymph gland of Drosophila senses immune challenge and reacts to it quickly through the nuclear factor-κB (NF-κB), Relish, a component of the immune deficiency (Imd) pathway. During development, Relish is triggered by ecdysone signaling in the hematopoietic niche to maintain the blood progenitors. Loss of Relish causes an alteration in the cytoskeletal architecture of the niche cells in a Jun Kinase-dependent manner, resulting in the trapping of Hh implicated in progenitor maintenance. Notably, during infection, downregulation of Relish in the niche tilts the maintenance program toward precocious differentiation, thereby bolstering the cellular arm of the immune response.

Dpp dependent Hematopoietic stem cells give rise to Hh dependent blood progenitors in larval lymph gland of Drosophila.

Drosophila hematopoiesis bears striking resemblance with that of vertebrates, both in the context of distinct phases and the signaling molecules. Even though, there has been no evidence of Hematopoietic stem cells (HSCs) in Drosophila, the larval lymph gland with its Hedgehog dependent progenitors served as an invertebrate model of progenitor biology. Employing lineage-tracing analyses, we have now identified Notch expressing HSCs in the first instar larval lymph gland. Our studies clearly establish the hierarchical relationship between Notch expressing HSCs and the previously described Domeless expressing progenitors. These HSCs require Decapentapelagic (Dpp) signal from the hematopoietic niche for their maintenance in an identical manner to vertebrate aorta-gonadal-mesonephros (AGM) HSCs. Thus, this study not only extends the conservation across these divergent taxa, but also provides a new model that can be exploited to gain better insight into the AGM related Hematopoietic stem cells (HSCs).