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Lysosomes coordinate cellular metabolism and growth upon sensing of essential nutrients, including cholesterol. Through bioinformatic analysis of lysosomal proteomes, we identified lysosomal cholesterol signaling (LYCHOS, previously annotated as G protein-coupled receptor 155), a multidomain transmembrane protein that enables cholesterol-dependent activation of the master growth regulator, the protein kinase mechanistic target of rapamycin complex 1 (mTORC1). Cholesterol bound to the amino-terminal permease-like region of LYCHOS, and mutating this site impaired mTORC1 activation. At high cholesterol concentrations, LYCHOS bound to the GATOR1 complex, a guanosine triphosphatase (GTPase)-activating protein for the Rag GTPases, through a conserved cytoplasm-facing loop. By sequestering GATOR1, LYCHOS promotes cholesterol- and Rag-dependent recruitment of mTORC1 to lysosomes. Thus, LYCHOS functions in a lysosomal pathway for cholesterol sensing and couples cholesterol concentrations to mTORC1-dependent anabolic signaling.

BackgroundSpatial compartmentalization of metabolic pathways within membrane-separated organelles is key to the ability of eukaryotic cells to precisely regulate their biochemical functions. Membrane-bound organelles such as mitochondria, endoplasmic reticulum (ER) and lysosomes enable the concentration of metabolic precursors within optimized chemical environments, greatly accelerating the efficiency of both anabolic and catabolic reactions, enabling division of labor and optimal utilization of resources. However, metabolic compartmentalization also poses a challenge to cells because it creates spatial discontinuities that must be bridged for reaction cascades to be connected and completed. To do so, cells employ different methods to coordinate metabolic fluxes occurring in different organelles, such as membrane-localized transporters to facilitate regulated metabolite exchange between mitochondria and lysosomes, non-vesicular transport pathways via physical contact sites connecting the ER with both mitochondria and lysosomes, as well as localized regulatory signaling processes that coordinately regulate the activity of all these organelles.Scope of reviewThis review covers how cells use membrane transporters, membrane contact sites, and localized signaling pathways to mediate inter-organelle communication and coordinate metabolism. We also describe how disruption of inter-organelle communication is an emerging driver in a multitude of diseases, from cancer to neurodegeneration.Major conclusionsEffective communication among organelles is essential to cellular health and function. Identifying the major molecular players involved in mediating metabolic coordination between organelles will further our understanding of cellular metabolism in health and lead us to design better therapeutics against dysregulated metabolism in disease.

The industrial Internet of Things (IIoT) is prominently emerging in applications of large-scale and wide-area applications, such as oilfield management, smart grid management, real-time equipment monitoring, and integration of traffic management systems for smart cities. Relying on short-range wireless technologies (e.g., WirelessHART and ISA100.11a), traditional wireless solutions for industrial automation find it challenging to support the expansive scale of today's IIoT. To address this limitation, we propose to adopt LoRaWAN, a prominent low-power wide-area network technology, for industrial automation. LoRaWAN for industrial automation poses some unique challenges. The fundamental building blocks of any industrial automation system are feedback control loops that largely rely on real-time communication. LoRaWAN traditionally adopts a simple protocol based on ALOHA with no collision avoidance or Listen Before Talk with Clear Channel Assessment and Random Backoff mechanisms to minimize energy consumption, which are less suitable for real-time communication. Existing real-time protocols for short-range technologies cannot be applied to a LoRaWAN network due to its unique characteristics such as asymmetry between downlink and the uplink spectrum, predefined modes (or classes) of operation, and concurrent reception through orthogonal spreading factors. In this paper, we address these challenges and propose RTPL- a Real-Time communication Protocol for LoRaWAN networks. RTPL is a low-overhead and conflict-free communication protocol allowing autonomous real-time communication of low-energy devices and exploits LoRa's capability of parallel communication. We implement our approach on LoRa devices and evaluate through both physical experiments and extensive simulations. All results show that RTPL achieves on average 75% improvement in real-time performance without sacrificing throughput or energy compared to traditional LoRaWAN. [ABSTRACT FROM AUTHOR]

Summary The 19th ISCB Student Council Symposium (SCS2023) organized by ISCB-SC adopted a hybrid format for the first time, allowing participants to engage in-person in Lyon, France, and virtually via an interactive online platform. The symposium prioritized inclusivity, featuring on-site sessions, poster presentations, and social activities for in-person attendees, while virtual participants accessed live sessions, interactive Q&A, and a virtual exhibit hall. Attendee statistics revealed a global reach, with Europe as the major contributor. SCS2023's success in bridging in-person and virtual experiences sets a precedent for future events in Computational Biology and Bioinformatics. Availability and Implementation The details of the symposium, speaker information, schedules, and accepted abstracts, are available in the program booklet (https://doi.org/10.5281/zenodo.8173977). For organizers interested in adopting a similar hybrid model, it would be beneficial to have access to details regarding the online platform used, the types of sessions offered, and the challenges faced. Future iterations of SCS can address these aspects to further enhance accessibility and inclusivity. [ABSTRACT FROM AUTHOR]

Background: Deliberate self-poisoning (DSP) is one of the leading causes of mortality and morbidity in India. Drug overdose is one of the most common methods for the same and is a growing public health concern globally. It is important to know the spectrum of drugs used for the same and to identify any specific groups at risk. Methodology: This retrospective cohort study included patients presenting with medication drug overdose to the emergency department (ED) from January 2017 to December 2018. Patient data were obtained from the ED triage registry software and clinical workstation. Following this, their hospital outcome was determined. Results: During the study period, 1802 patients presented with DSP among which drug overdose comprised 27.6% (498/1802). The mean age was 32.8 years (SD-12.6) with a higher incidence in the age group comprising young adults (16–30 years, 52%), majority being females (68%). The most commonly consumed drugs belonged to the drug class of benzodiazepines (22%), NSAIDs (19.2%), antihistamines (15%), antidepressants (12%), and antipsychotics (10.2%). The mortality rate was 0.2%. Conclusion: Benzodiazepines were the most commonly consumed class of drugs used for DSP, followed closely by NSAIDs. Drug overdose showed a higher incidence in the age group of highly productive young adults. The incidence exhibited a seasonal pattern with peak in April and May. Although the mortality rate following drug overdose remains low, drug overdose is a commonly used method for DSP and continues to be a growing public health concern. [ABSTRACT FROM AUTHOR]