Millions of people in the United States consume dietary supplements hoping to maintain or improve their health; however, extensive research has failed to demonstrate the efficacy of numerous ...supplements in disease prevention. In addition, concerns about the safety of routine and high-dose supplementation have been raised. The Food and Drug Administration regulates dietary supplement quality, safety, and labeling, and the Federal Trade Commission monitors advertisements and marketing; still, vast enforcement challenges remain, and optimal governmental oversight has not been achieved. If the composition and quality of ingredients cannot be reliably ensured, the validity of research on dietary supplements is questionable. Moreover, the health of the US public is put at risk.
Women and underrepresented minoritized (URM) persons remain marginalized in physical science, technology, engineering, and math (pSTEM). Relative to non-URM men, URM women may experience a double ...disadvantage based on their gender and race whereby they observe few same-gender and few same-race role models in pSTEM while additionally internalizing stereotypes linking pSTEM with non-URM men. Our hypothesized model was partly supported in a sample of undergraduates (N = 1,068; 68% women, 44% URM). First, perceiving same-gender or same-race pSTEM role models predicted lower explicit stereotypes among women and URM individuals regarding gender and race, respectively. Second, explicit and implicit associations linking pSTEM with men and White/Asian persons predicted (a) lower pSTEM identity among women and URM students and (b) higher identity among men and non-URM students. Finally, both implicit and explicit pSTEM identity positively predicted expectancy–value beliefs.
Periodontitis is a biofilm-induced inflammatory disease characterized by dysbiosis of the commensal periodontal microbiota. It is unclear how natural regulation of inflammation affects the ...periodontal biofilm. Promoters of active resolution of inflammation, including resolvin E1 (RvE1), effectively treat inflammatory periodontitis in animal models. The goals of this study were 1) to compare periodontal tissue gene expression in different clinical conditions, 2) to determine the impact of local inflammation on the composition of subgingival bacteria, and 3) to understand how inflammation impacts these changes. Two clinically relevant experiments were performed in rats: prevention and treatment of ligature-induced periodontitis with RvE1 topical treatment. The gingival transcriptome was evaluated by RNA sequencing of mRNA. The composition of the subgingival microbiota was characterized by 16S rDNA sequencing. Periodontitis was assessed by bone morphometric measurements and histomorphometry of block sections. H&E and tartrate-resistant acid phosphatase staining were used to characterize and quantify inflammatory changes. RvE1 treatment prevented bone loss in ligature-induced periodontitis. Osteoclast density and inflammatory cell infiltration in the RvE1 groups were lower than those in the placebo group. RvE1 treatment reduced expression of inflammation-related genes, returning the expression profile to one more similar to health. Treatment of established periodontitis with RvE1 reversed bone loss, reversed inflammatory gene expression, and reduced osteoclast density. Assessment of the rat subgingival microbiota after RvE1 treatment revealed marked changes in both prevention and treatment experiments. The data suggest that modulation of local inflammation has a major role in shaping the composition of the subgingival microbiota.
Despite the promise that molecular data would provide a seemingly unlimited source of independent characters, many plant phylogenetic studies are still based on only two regions, the plastid genome ...and nuclear ribosomal DNA (nrDNA). Their popularity can be explained by high-copy numbers and universal polymerase chain reaction (PCR) primers that make their sequences easily amplified and converted into parallel datasets. Unfortunately, their utility is limited by linked loci and limited characters resulting in low confidence in the accuracy of phylogenetic estimates, especially when rapid radiations occur. In another contribution on anchored phylogenomics in angiosperms, we presented flowering plant-specific anchored enrichment probes for hundreds of conserved nuclear genes and demonstrated their use at the level of all angiosperms. In this contribution, we focus on a common problem in phylogenetic reconstructions below the family level: Weak or unresolved backbone due to rapid radiations (≤10 million years) followed by long divergence, using the Cariceae–Dulichieae–Scirpeae (CDS, Cyperaceae) clade as a test case. By comparing our nuclear matrix of 461 genes to a typical Sanger-sequence dataset consisting of a few plastid genes (matK, ndhF) and an nrDNA marker (ETS), we demonstrate that our nuclear data is fully compatible with the Sanger dataset and resolves short backbone internodes with high support in both concatenated and coalescence-based analyses. In addition, we show that nuclear gene tree incongruence is inversely proportional to phylogenetic information content, indicating that incongruence is mostly due to gene tree estimation error. This suggests that large numbers of conserved nuclear loci could produce more accurate trees than sampling rapidly evolving regions prone to saturation and long-branch attraction. The robust phylogenetic estimates obtained here, and high congruence with previous morphological and molecular analyses, are strong evidence for a complete tribal revision of CDS clade. The anchored hybrid enrichment probes used in this study should be similarly effective in other flowering plant groups.
Delineation of functional synaptic connections is fundamental to understanding sensory processing. Olfactory signals are synaptically processed initially in the olfactory bulb (OB) where neural ...circuits are formed among inhibitory interneurons and the output neurons mitral cells (MCs) and tufted cells (TCs). TCs function in parallel with but differently from MCs and are further classified into multiple subpopulations based on their anatomic and functional heterogeneities. Here, we combined optogenetics with electrophysiology to characterize the synaptic transmission from a subpopulation of TCs, which exclusively express the neuropeptide cholecystokinin (CCK), to two groups of spatially segregated GABAergic interneurons, granule cells (GCs) and glomerular interneurons in mice of both sexes with four major findings. First, CCKergic TCs receive direct input from the olfactory sensory neurons (OSNs). This monosynaptic transmission exhibits high fidelity in response to repetitive OSN input. Second, CCKergic TCs drive GCs through two functionally distinct types of monosynaptic connections: (1) dendrodendritic synapses onto GC distal dendrites via their lateral dendrites in the superficial external plexiform layer (EPL); (2) axodendritic synapses onto GC proximal dendrites via their axon collaterals or terminals in the internal plexiform layer (IPL) on both sides of each bulb. Third, CCKergic TCs monosynaptically excite two subpopulations of inhibitory glomerular interneurons via dendrodendritic synapses. Finally, sniff-like patterned activation of CCKergic TCs induces robust frequency-dependent depression of the dendrodendritic synapses but facilitation of the axodendritic synapses. These results demonstrated important roles of the CCKergic TCs in olfactory processing by orchestrating OB inhibitory activities.
Neuronal morphology and organization in the olfactory bulb (OB) have been extensively studied, however, the functional operation of neuronal interactions is not fully understood. We combined optogenetic and electrophysiological approaches to investigate the functional operation of synaptic connections between a specific population of excitatory output neuron and inhibitory interneurons in the OB. We found that these output neurons formed distinct types of synapses with two populations of spatially segregated interneurons. The functional characteristics of these synapses vary significantly depending on the presynaptic compartments so that these output neurons can dynamically rebalance inhibitory feedback or feedforward to other neurons types in the OB in response to dynamic rhythmic inputs.
The megadiverse genus Carex (c. 2000 species, Cyperaceae) has a nearly cosmopolitan distribution, displaying an inverted latitudinal richness gradient with higher species diversity in cold‐temperate ...areas of the Northern Hemisphere. Despite great expansion in our knowledge of the phylogenetic history of the genus and many molecular studies focusing on the biogeography of particular groups during the last few decades, a global analysis of Carex biogeography and diversification is still lacking. For this purpose, we built the hitherto most comprehensive Carex‐dated phylogeny based on three markers (ETS–ITS–matK), using a previous phylogenomic Hyb‐Seq framework, and a sampling of two‐thirds of its species and all recognized sections. Ancestral area reconstruction, biogeographic stochastic mapping, and diversification rate analyses were conducted to elucidate macroevolutionary biogeographic and diversification patterns. Our results reveal that Carex originated in the late Eocene in E Asia, where it probably remained until the synchronous diversification of its main subgeneric lineages during the late Oligocene. E Asia is supported as the cradle of Carex diversification, as well as a “museum” of extant species diversity. Subsequent “out‐of‐Asia” colonization patterns feature multiple asymmetric dispersals clustered toward present times among the Northern Hemisphere regions, with major regions acting both as source and sink (especially Asia and North America), as well as several independent colonization events of the Southern Hemisphere. We detected 13 notable diversification rate shifts during the last 10 My, including remarkable radiations in North America and New Zealand, which occurred concurrently with the late Neogene global cooling, which suggests that diversification involved the colonization of new areas and expansion into novel areas of niche space.
Inherited retinal degeneration (RD) constitutes a heterogeneous group of genetic retinal degenerative disorders. The molecular mechanisms underlying RD encompass a diverse spectrum of cellular ...signaling, with the unfolded protein response (UPR) identified as a common signaling pathway chronically activated in degenerating retinas. TRIB3 has been recognized as a key mediator of the PERK UPR arm, influencing various metabolic pathways, such as insulin signaling, lipid metabolism, and glucose homeostasis, by acting as an AKT pseudokinase that prevents the activation of the AKT → mTOR axis. This study aimed to develop a gene-independent approach targeting the UPR TRIB3 mediator previously tested by our group using a genetic approach in mice with RD. The goal was to validate a therapeutic approach targeting TRIB3 interactomes through the pharmacological targeting of EGFR-TRIB3 and delivering cell-penetrating peptides targeting TRIB3 → AKT. The study employed rd10 and P23H RHO mice, with afatinib treatment conducted in p15 rd10 mice through daily intraperitoneal injections. P15 P23H RHO mice received intraocular injections of cell-penetrating peptides twice at a 2-week interval. Our study revealed that both strategies successfully targeted TRIB3 interactomes, leading to an improvement in scotopic A- and B-wave ERG recordings. Additionally, the afatinib-treated mice manifested enhanced photopic ERG amplitudes accompanied by a delay in photoreceptor cell loss. The treated rd10 retinas also showed increased PDE6β and RHO staining, along with an elevation in total PDE activity in the retinas. Consequently, our study demonstrated the feasibility of a gene-independent strategy to target common signaling in degenerating retinas by employing a TRIB3-based therapeutic approach that delays retinal function and photoreceptor cell loss in two RD models.
Objective To assess the association between off-hour (weekends and nights) presentation, door to balloon times, and mortality in patients with acute myocardial infarction.Data sources Medline ...in-process and other non-indexed citations, Medline, Embase, Cochrane Database of Systematic Reviews, and Scopus through April 2013.Study selection Any study that evaluated the association between time of presentation to a healthcare facility and mortality or door to balloon times among patients with acute myocardial infarction was included.Data extraction Studies’ characteristics and outcomes data were extracted. Quality of studies was assessed with the Newcastle-Ottawa scale. A random effect meta-analysis model was applied. Heterogeneity was assessed using the Q statistic and I2.Results 48 studies with fair quality, enrolling 1 896 859 patients, were included in the meta-analysis. 36 studies reported mortality outcomes for 1 892 424 patients with acute myocardial infarction, and 30 studies reported door to balloon times for 70 534 patients with ST elevation myocardial infarction (STEMI). Off-hour presentation for patients with acute myocardial infarction was associated with higher short term mortality (odds ratio 1.06, 95% confidence interval 1.04 to 1.09). Patients with STEMI presenting during off-hours were less likely to receive percutaneous coronary intervention within 90 minutes (odds ratio 0.40, 0.35 to 0.45) and had longer door to balloon time by 14.8 (95% confidence interval 10.7 to 19.0) minutes. A diagnosis of STEMI and countries outside North America were associated with larger increase in mortality during off-hours. Differences in mortality between off-hours and regular hours have increased in recent years. Analyses were associated with statistical heterogeneity.Conclusion This systematic review suggests that patients with acute myocardial infarction presenting during off-hours have higher mortality, and patients with STEMI have longer door to balloon times. Clinical performance measures may need to account for differences arising from time of presentation to a healthcare facility.
Research suggests that anxiety disorders tend to temporally precede depressive disorders, a finding potentially relevant to understanding comorbidity. The current study used diary methods to ...determine whether daily anxious mood also temporally precedes daily depressed mood. 55 participants with generalized anxiety disorder (GAD) and history of depressive symptoms completed a 21-day daily diary tracking anxious and depressed mood. Daily anxious and depressed moods were concurrently associated. Daily anxious mood predicted later depressed mood at a variety of time lags, with significance peaking at a two-day lag. Depressed mood generally did not predict later anxious mood. Results suggest that the temporal antecedence of anxiety over depression extends to daily symptoms in GAD. Implications for the refinement of comorbidity models, including causal theories, are discussed.
► Studies suggest that anxiety disorders tend to temporally precede depression. ► Temporal associations between symptoms within disorders remain unclear. ► We explore sequencing of daily symptoms within generalized anxiety disorder. ► Anxious mood strongly predicted later depressed mood, but not vice versa. ► Anxious mood was most strongly predictive of depressed mood at a two-day lag.
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