Progress made in malaria control during the past decade has prompted increasing global dialogue on malaria elimination and eradication. The product development pipeline for malaria has never been ...stronger, with promising new tools to detect, treat, and prevent malaria, including innovative diagnostics, medicines, vaccines, vector control products, and improved mechanisms for surveillance and response. There are at least 25 projects in the global malaria vaccine pipeline, as well as 47 medicines and 13 vector control products. In addition, there are several next-generation diagnostic tools and reference methods currently in development, with many expected to be introduced in the next decade. The development and adoption of these tools, bolstered by strategies that ensure rapid uptake in target populations, intensified mechanisms for information management, surveillance, and response, and continued financial and political commitment are all essential to achieving global eradication.
Objective
In contrast to intentionally restricting energy intake, restricting the eating window may be an option for treating obesity. By comparing time‐restricted eating (TRE) with an unrestricted ...(non‐TRE) control, it was hypothesized that TRE facilitates weight loss, alters body composition, and improves metabolic measures.
Methods
Participants (17 women and 3 men; mean SD: 45.5 12.1 years; BMI 34.1 7.5 kg/m2) with a prolonged eating window (15.4 0.9 hours) were randomized to TRE (n = 11: 8‐hour window, unrestricted eating within window) versus non‐TRE (n = 9: unrestricted eating) for 12 weeks. Weight, body composition (dual x‐ray absorptiometry), lipids, blood pressure, 2‐hour oral glucose tolerance, 2‐week continuous glucose monitoring, and 2‐week physical activity (actigraphy assessed) were measured during the pre‐ and end‐intervention periods.
Results
The TRE group significantly reduced the eating window (end‐intervention window: 9.9 2.0 hours) compared with the non‐TRE group (end‐intervention window: 15.1 1.1 hours) (P < 0.01). Compared with non‐TRE, TRE decreased the number of eating occasions, weight, lean mass, and visceral fat (all P ≤ 0.05). Compared with preintervention measures, the TRE group reduced the number of eating occasions (−21.9% 30.1%) and reduced weight (−3.7% 1.8%), fat mass (−4% 2.9%), lean mass (−3.0% 2.7%), and visceral fat (−11.1% 13.4%) (all P ≤ 0.05). Physical activity and metabolic measures remained unchanged.
Conclusions
In the setting of a randomized trial, TRE presents a simplified view of food intake that reduces weight.
Arginine methyltransferases critically regulate cellular homeostasis by modulating the functional outcome of their substrates. The protein arginine methyltransferase 5 (PRMT5) is an enzyme involved ...in growth and survival pathways promoting tumorigenesis. However, little is known about the biologic function of PRMT5 and its therapeutic potential in multiple myeloma (MM). In the present study, we identified and validated PRMT5 as a new therapeutic target in MM. PRMT5 is overexpressed in patient MM cells and associated with decreased progression-free survival and overall survival. Either genetic knockdown or pharmacological inhibition of PRMT5 with the inhibitor EPZ015666 significantly inhibited growth of both cell lines and patient MM cells. Furthermore, PRMT5 inhibition abrogated NF-κB signaling. Interestingly, mass spectrometry identified a tripartite motif-containing protein 21 TRIM21 as a new PRMT5-partner, and we delineated a TRIM21-dependent mechanism of NF-κB inhibition. Importantly, oral administration of EPZ015666 significantly decreased MM growth in a humanized murine model of MM. These data both demonstrate the oncogenic role and prognostic relevance of PRMT5 in MM pathogenesis, and provide the rationale for novel therapies targeting PRMT5 to improve patient outcome.
Non-nutritive sweeteners like sucralose are consumed by billions of people. While animal and human studies have demonstrated a link between synthetic sweetener consumption and metabolic ...dysregulation, the mechanisms responsible remain unknown. Here we use a diet supplemented with sucralose to investigate the long-term effects of sweet/energy imbalance. In flies, chronic sweet/energy imbalance promoted hyperactivity, insomnia, glucose intolerance, enhanced sweet taste perception, and a sustained increase in food and calories consumed, effects that are reversed upon sucralose removal. Mechanistically, this response was mapped to the ancient insulin, catecholamine, and NPF/NPY systems and the energy sensor AMPK, which together comprise a novel neuronal starvation response pathway. Interestingly, chronic sweet/energy imbalance promoted increased food intake in mammals as well, and this also occurs through an NPY-dependent mechanism. Together, our data show that chronic consumption of a sweet/energy imbalanced diet triggers a conserved neuronal fasting response and increases the motivation to eat.
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•Chronic sucralose diet triggers increased food intake•Dietary sucralose creates a sweet/energy imbalance•Sweet/energy imbalance activates a conserved neuronal starvation response•Sucralose effect on feeding is conserved from flies to mammals
Wang et al. show that chronic consumption of the synthetic sweetener sucralose causes increased food intake in the fruit fly. This effect involves a neuronal starvation pathway, and a similar effect was observed in mice. These findings suggest that disrupting the sweet/energy balance of food may have unanticipated consequences.
Glaucomatous neurodegeneration, a blinding disease affecting millions worldwide, has a need for the exploration of new and effective therapies. Previously, the glucagon-like peptide-1 receptor ...(GLP-1R) agonist NLY01 was shown to reduce microglia/macrophage activation, rescuing retinal ganglion cells after IOP elevation in an animal model of glaucoma. GLP-1R agonist use is also associated with a reduced risk for glaucoma in patients with diabetes. In this study, we demonstrate that several commercially available GLP-1R agonists, administered either systemically or topically, hold protective potential in a mouse model of hypertensive glaucoma. Further, the resulting neuroprotection likely occurs through the same pathways previously shown for NLY01. This work contributes to a growing body of evidence suggesting that GLP-1R agonists represent a viable therapeutic option for glaucoma.
Multilevel Organisation of Animal Sociality Grueter, Cyril C.; Qi, Xiaoguang; Zinner, Dietmar ...
Trends in ecology & evolution,
September 2020, 2020-09-00, 20200901, Volume:
35, Issue:
9
Journal Article
Peer reviewed
Open access
Multilevel societies (MLSs), stable nuclear social units within a larger collective encompassing multiple nested social levels, occur in several mammalian lineages. Their architectural complexity and ...size impose specific demands on their members requiring adaptive solutions in multiple domains. The functional significance of MLSs lies in their members being equipped to reap the benefits of multiple group sizes. Here, we propose a unifying terminology and operational definition of MLS. To identify new avenues for integrative research, we synthesise current literature on the selective pressures underlying the evolution of MLSs and their implications for cognition, intersexual conflict, and sexual selection. Mapping the drivers and consequences of MLS provides a reference point for the social evolution of many taxa, including our own species.
There has been growing recognition of the multilevel nature of many animal social systems but little effort to operationalise it by integrating findings across species.How members of social units in MLSs interact and how dispersal shapes the kinship structure across multiple levels of society is of paramount importance for a holistic understanding of the evolution of sociality.MLSs may offer a flexible solution to a set of socioecological challenges at multiple levels.Whether the structural complexity of MLSs has knock-on consequences for sexual selection, cognition, cultural transmission, and disease dynamics remain important avenues for future research.Understanding the evolution and functional significance of animal MLSs will prove valuable for reconstructing the pillars of human sociality.
Recently a dark matter-electron (DM-electron) paradigm has drawn much attention. Models beyond the standard halo model describing DM accelerated by high energy celestial bodies are under intense ...examination as well. In this Letter, a velocity components analysis (VCA) method dedicated to swift analysis of accelerated DM-electron interactions via semiconductor detectors is proposed and the first HPGe detector-based accelerated DM-electron analysis is realized. Utilizing the method, the first germanium based constraint on sub-GeV solar reflected DM-electron interaction is presented with the 205.4 kg·day dataset from the CDEX-10 experiment. In the heavy mediator scenario, our result excels in the mass range of 5-15 keV/c^{2}, achieving a 3 orders of magnitude improvement comparing with previous semiconductor experiments. In the light mediator scenario, the strongest laboratory constraint for DM lighter than 0.1 MeV/c^{2} is presented. The result proves the feasibility and demonstrates the vast potential of the VCA technique in future accelerated DM-electron analyses with semiconductor detectors.
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