Re-Patterning Sleep Architecture in Drosophila through Gustatory Perception and Nutritional Quality

Organisms perceive changes in their dietary environment and enact a suite of behavioral and metabolic adaptations that can impact motivational behavior, disease resistance, and longevity. However, the precise nature and mechanism of these dietary responses is not known. We have uncovered a novel link between dietary factors and sleep behavior in Drosophila melanogaster. Dietary sugar rapidly altered sleep behavior by modulating the number of sleep episodes during both the light and dark phase of the circadian period, independent of an intact circadian rhythm and without affecting total sleep, latency to sleep, or waking activity. The effect of sugar on sleep episode number was consistent with a change in arousal threshold for waking. Dietary protein had no significant effect on sleep or wakefulness. Gustatory perception of sugar was necessary and sufficient to increase the number of sleep episodes, and this effect was blocked by activation of bitter-sensing neurons. Further addition of sugar to the diet blocked the effects of sweet gustatory perception through a gustatory-independent mechanism. However, gustatory perception was not required for diet-induced fat accumulation, indicating that sleep and energy storage are mechanistically separable. We propose a two-component model where gustatory and metabolic cues interact to regulate sleep architecture in response to the quantity of sugar available from dietary sources. Reduced arousal threshold in response to low dietary availability may have evolved to provide increased responsiveness to cues associated with alternative nutrient-dense feeding sites. These results provide evidence that gustatory perception can alter arousal thresholds for sleep behavior in response to dietary cues and provide a mechanism by which organisms tune their behavior and physiology to environmental cues

Identifying the research, advocacy, policy and implementation needs for the prevention and management of respiratory syncytial virus lower respiratory tract infection in low- and middle-income countries

Introduction: The high burden of respiratory syncytial virus (RSV) infection in young children disproportionately occurs in low- and middle-income countries (LMICs). The PROUD (Preventing RespiratOry syncytial virUs in unDerdeveloped countries) Taskforce of 24 RSV worldwide experts assessed key needs for RSV prevention in LMICs, including vaccine and newer preventive measures. Methods: A global, survey-based study was undertaken in 2021. An online questionnaire was developed following three meetings of the Taskforce panellists wherein factors related to RSV infection, its prevention and management were identified using iterative questioning. Each factor was scored, by non-panellists interested in RSV, on a scale of zero (very-low-relevance) to 100 (very-high-relevance) within two scenarios: (1) Current and (2) Future expectations for RSV management. Results: Ninety questionnaires were completed: 70 by respondents (71.4% physicians; 27.1% researchers/scientists) from 16 LMICs and 20 from nine high-income (HI) countries (90.0% physicians; 5.0% researchers/scientists), as a reference group. Within LMICs, RSV awareness was perceived to be low, and management was not prioritised. Of the 100 factors scored, those related to improved diagnosis particularly access to affordable point-of-care diagnostics, disease burden data generation, clinical and general education, prompt access to new interventions, and engagement with policymakers/payers were identified of paramount importance. There was a strong need for clinical education and local data generation in the lowest economies, whereas upper-middle income countries were more closely aligned with HI countries in terms of current RSV service provision. Conclusion: Seven key actions for improving RSV prevention and management in LMICs are proposed

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Bertha M. Ryan (interviewed by Jennifer B. Krishnan)

Interview conducted with an MIT alumna as part of the Margaret MacVicar Memorial AMITA (Association of MIT Alumnae) Oral History Project. The purpose of the project is to document the life histories of women graduates of the Massachusetts Institute of Technology

Neighborhood location and nutritional resources as a risk factor for congenital heart disease in the fetus

BACKGROUND: Congenital heart disease (CHD) is the most common birth defect, influenced by maternal health, environmental conditions, and genetics. Maternal health and nutrition, particularly maternal diabetes, is a modifiable risk factor for development of CHD in the fetus. However, the importance of food access during pregnancy on the development of CHD remains unknown. The objective of this study was to investigate the association between maternal neighborhood characteristics, particularly food access, and occurrence of prenatally diagnosed CHD. METHODS: A retrospective case series studied maternal-fetal dyads with prenatally diagnosed CHD between 2019 and 2021 in Washington, DC. Moran\u27s I of maternal addresses evaluated geographic clustering of disease. Negative binomial regression assessed association between census tract demographics and population-adjusted CHD rate. RESULTS: A total of 307 dyads were analyzed. Global Moran\u27s I showed significant CHD clustering (p-value = .004). However, degree of clustering was not clinically meaningful. After adjusting for neighborhood socioeconomic status, residing in food deserts was not a predictor for CHD. However, neighborhoods with a higher percentage of households receiving Supplemental Nutrition Assistance Program (SNAP) benefits were associated with higher rates of conotruncal heart defects (Incident Rate Ratio [IRR] = 1.04, CI = 1.01-1.08) and aggregate CHD (IRR = 1.03, CI = 1.01-1.05). CONCLUSIONS: Neighborhood location and food access were not associated with CHD. However, increased enrollment in SNAP was associated with higher rates of CHD. The association between CHD and SNAP benefits warrants further exploration. Understanding food access and maternal nutrition may illuminate disparities in the burden of CHD

Recent Progress on Ligand-Protected Metal Nanoclusters in Photocatalysis

The reckless use of non-replenishable fuels by the growing population for energy and the resultant incessant emissions of hazardous gases and waste products into the atmosphere have insisted that scientists fabricate materials capable of managing these global threats at once. In recent studies, photocatalysis has been employed to focus on utilizing renewable solar energy to initiate chemical processes with the aid of semiconductors and highly selective catalysts. A wide range of nanoparticles has showcased promising photocatalytic properties. Metal nanoclusters (MNCs) with sizes below 2 nm, stabilized by ligands, show discrete energy levels and exhibit unique optoelectronic properties, which are vital to photocatalysis. In this review, we intend to compile information on the synthesis, true nature, and stability of the MNCs decorated with ligands and the varying photocatalytic efficiency of metal NCs concerning changes in the aforementioned domains. The review discusses the photocatalytic activity of atomically precise ligand-protected MNCs and their hybrids in the domain of energy conversion processes such as the photodegradation of dyes, the oxygen evolution reaction (ORR), the hydrogen evolution reaction (HER), and the CO2 reduction reaction (CO2RR)

Gender-related barriers and delays in accessing tuberculosis diagnostic and treatment services: a systematic review of qualitative studies. Tuberc Res Treat.

Background. Tuberculosis (TB) remains a significant global public health problem with known gender-related (male versus female) disparities. We reviewed the qualitative evidence (written/spoken narrative) for gender-related differences limiting TB service access from symptom onset to treatment initiation. Methods. Following a systematic process, we searched 12 electronic databases, included qualitative studies that assessed gender differences in accessing TB diagnostic and treatment services, abstracted data, and assessed study validity. Using a modified &quot;inductive coding&quot; system, we synthesized emergent themes within defined barriers and delays limiting access at the individual and provider/system levels and examined gender-related differences. Results. Among 13,448 studies, 28 studies were included. All were conducted in developing countries and assessed individual-level barriers; 11 (39%) assessed provider/system-level barriers, 18 (64%) surveyed persons with suspected or diagnosed TB, and 7 (25%) exclusively surveyed randomly sampled community members or health care workers. Each barrier affected both genders but had gendervariable nature and impact reflecting sociodemographic themes. Women experienced financial and physical dependence, lower general literacy, and household stigma, whereas men faced work-related financial and physical barriers and community-based stigma. Conclusions. In developing countries, barriers limiting access to TB care have context-specific gender-related differences that can inform integrated interventions to optimize TB services