Integrated stress response signaling acts as a metabolic sensor in fat tissues to regulate oocyte maturation and ovulation.

Reproduction is an energy-intensive process requiring systemic coordination. However, the inter-organ signaling mechanisms that relay nutrient status to modulate reproductive output are poorly understood. Here, we use Drosophila melanogaster as a model to establish the integrated stress response (ISR) transcription factor, Atf4, as a fat tissue metabolic sensor that instructs oogenesis. We demonstrate that Atf4 regulates lipase activity to mediate yolk lipoprotein synthesis in the fat body. Depletion of Atf4 in the fat body also blunts oogenesis recovery after amino acid deprivation and re-feeding, suggestive of a nutrient-sensing role for Atf4. We also discovered that Atf4 promotes secretion of a fat-body-derived neuropeptide, CNMamide, which modulates neural circuits that promote egg-laying behavior (ovulation). Thus, we posit that ISR signaling in fat tissue acts as a "metabolic sensor" that instructs female reproduction-directly by impacting yolk lipoprotein production and follicle maturation and systemically by regulating ovulation.

Integrated Stress Response signaling acts as a metabolic sensor in fat tissues to regulate oocyte maturation and ovulation.

Reproduction is an energy-intensive process requiring systemic coordination. However, the inter-organ signaling mechanisms that relay nutrient status to modulate reproductive output are poorly understood. Here, we use Drosophila melanogaster as a model to establish the Integrated Stress response (ISR) transcription factor, Atf4, as a fat tissue metabolic sensor which instructs oogenesis. We demonstrate that Atf4 regulates the lipase Brummer to mediate yolk lipoprotein synthesis in the fat body. Depletion of Atf4 in the fat body also blunts oogenesis recovery after amino acid deprivation and re-feeding, suggestive of a nutrient sensing role for Atf4. We also discovered that Atf4 promotes secretion of a fat body-derived neuropeptide, CNMamide, which modulates neural circuits that promote egg-laying behavior (ovulation). Thus, we posit that ISR signaling in fat tissue acts as a "metabolic sensor" that instructs female reproduction: directly, by impacting yolk lipoprotein production and follicle maturation, and systemically, by regulating ovulation.

Building resilient and responsive research collaborations to tackle antimicrobial resistance-Lessons learnt from India, South Africa, and UK.

Research, collaboration, and knowledge exchange are critical to global efforts to tackle antimicrobial resistance (AMR). Different healthcare economies are faced with different challenges in implementing effective strategies to address AMR. Building effective capacity for research to inform AMR-related strategies and policies is recognised as an important contributor to success. Interdisciplinary, intersector, as well as international collaborations are needed to span global to local efforts to tackle AMR. The development of reciprocal, long-term partnerships between collaborators in high-income and in low- and middle-income countries (LMICs) needs to be built on principles of capacity building. Using case studies spanning local and international research collaborations to codesign, implement, and evaluate strategies to tackle AMR, we have evaluated and build upon the ESSENCE criteria for capacity building in LMICs. The first case study describes the local codesign and implementation of antimicrobial stewardship (AMS) in the state of Kerala in India. The second case study describes an international research collaboration investigating AMR surgical patient pathways in India, the UK, and South Africa. We describe the steps undertaken to develop robust, agile, and flexible AMS research and implementation teams. Notably, investing in capacity building ensured that the programmes described in these case studies were sustained through the current severe acute respiratory syndrome coronavirus pandemic. Describing the strategies adopted by a local and an international collaboration to tackle AMR, we provide a model for capacity building in LMICs that can support sustainable and agile AMS programmes.

Mid IR hollow core fiber gas laser emitting at 4.6 µm.

Emission at 4.6 µm was observed from an N2O filled hollow core fiber laser. 8-ns pump pulses at 1.517 µm excited a vibrational overtone resulting in lasing on an R and P branch fundamental transition from the upper pump state. At optimum gas pressure of 80 Torr, photon conversion efficiency of 9% and slope efficiency of 3% were observed from a mirrorless laser. The laser threshold occurred at absorbed pump energy of 150 nJ in a 45-cm long fiber with 85 µm core diameter. The observed dependence of the laser output on gas pressure was shown to be a result of line broadening and relaxation rates.