Molecular Mechanisms Regulating GRF Activity in Plant Growth, Development, and Environmental Responses.

Plants rely on complex regulatory mechanisms to ensure proper growth and development. As sessile organisms, these mechanisms must be flexible enough to adapt to changes in the environment. The GROWTH-REGULATING FACTORs (GRFs) are plant-specific transcription factors that act as a central hub controlling plant growth and development, offering promising biotechnological applications to enhance plant performance. Here, we analyze the complex molecular mechanisms that regulate GRF activity, and how their natural and synthetic variants can impact on plant growth and development. We describe the biological roles of the GRFs and examine how they regulate gene expression and contribute to the control of organ growth and the plant's response to a changing environment. This review focuses on the premise that unlocking their full biotechnological potential requires a thorough understanding of the various regulatory layers governing GRF activity, the functional divergence among GRF family members and the gene networks that they regulate.

Themes and Topics on Diversity, Equity, and Inclusion in JMIR Dermatology Publications.

Publications dealing with topics considered to be pertinent to diversity, equity, and inclusion are increasing. Due to the increasing trend, dermatology journals have started to implement ways to evaluate and understand these publications. Here, we discuss a keyword approach to identify and then categorize these publications. Keywords identified 43 manuscripts. Two reviewers screened the articles' titles and abstracts, and recommended a full manuscript review for 24 publications. Through the scope of definitions from the National Institutes of Health, an editorial board member performed a full-text review and assigned a primary theme to the publications. Themes included equity (n=20) and diversity/inclusion (n=4). Topics were racial/ethnic differences in care delivery or society (n=17), incomplete understanding of gender and sex (n=3), gender identity (n=2), socioeconomic class and its impact on health (n=1), care for rural underserved communities (n=1), and religion (n=1). The results of this review demonstrate a predominance of equity-related publications, particularly emphasizing racial/ethnic differences in health care delivery, in the publications identified in JMIR Dermatology. Future research can focus on creating a review aid to assist editorial board members when providing feedback to manuscripts, refining the keywords, and using thematic analysis methodology to evaluate large sets of publications.

Pharmacological and genetic increases in liver NADPH levels ameliorate NASH progression in female mice.

Non-alcoholic steatohepatitis (NASH) is one of the fastest growing liver diseases worldwide, and oxidative stress is one of NASH main key drivers. Nicotinamide adenine dinucleotide phosphate (NADPH) is the ultimate donor of reductive power to a number of antioxidant defences. Here, we explored the potential of increasing NADPH levels to prevent NASH progression. We used nicotinamide riboside (NR) supplementation or a G6PD-tg mouse line harbouring an additional copy of the human G6PD gene. In a NASH mouse model induced by feeding mice a methionine-choline deficient (MCD) diet for three weeks, both tools increased the hepatic levels of NADPH and ameliorated the NASH phenotype induced by the MCD intervention, but only in female mice. Boosting NADPH levels in females increased the liver expression of the antioxidant genes Gsta3, Sod1 and Txnrd1 in NR-treated mice, or of Gsr for G6PD-tg mice. Both strategies significantly reduced hepatic lipid peroxidation. NR-treated female mice showed a reduction of steatosis accompanied by a drop of the hepatic triglyceride levels, that was not observed in G6PD-tg mice. NR-treated mice tended to reduce their lobular inflammation, showed a reduction of the NK cell population and diminished transcription of the damage marker Lcn2. G6PD-tg female mice exhibited a reduction of their lobular inflammation and hepatocyte ballooning induced by the MCD diet, that was related to a reduction of the monocyte-derived macrophage population and the Tnfa, Ccl2 and Lcn2 gene expression. As conclusion, boosting hepatic NADPH levels attenuated the oxidative lipid damage and the exhausted antioxidant gene expression specifically in female mice in two different models of NASH, preventing the progression of the inflammatory process and hepatic injury.

New Insights into Nutrition and Gut-Liver Axis: A Focus on Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver disease and represents a public health issue in Western industrialized countries [...].

Diversity, Equity, and Inclusion of Dermatology Journals and Their Editorial Board Members.

Dermatology as a whole suffers from minority underrepresentation. We conducted a search of the top 60 dermatology journals for mention of their approach to increasing diversity, equity, and inclusion (DEI) within their publication through editorial board members or peer-review processes. Of those 60, only 5 had DEI statements or editorial board members dedicated to increasing DEI. There are publications with checklists and frameworks for increasing DEI within the literature. We propose that more journals implement these resources within their peer-review process to increase diversity within their publication.

Cultural Competence and Humility.

The increasing diversification of the United States has led to more racially and ethnically discordant visits between health care providers and patients; this is especially true in dermatology due to the lack of diversity in the field. Diversifying the health care workforce has been shown to reduce health care disparities and is an ongoing goal of dermatology. Improving cultural competence and humility among physicians is an important part of addressing health care inequities. This article reviews cultural competence, cultural humility, and practices dermatologists can incorporate to address this challenge.

Occam's Razor and Prehospital Documentation: When the Simpler Solution Resulted in Better Documentation.

INTRODUCTION: The Tactical Combat Casualty Care (TCCC) card has undergone several changes since its first introduction in 1996. In 2013, updates to the card included more data points to increase prehospital documentation quality and enable performance improvement. This study reviews the proportions of data collected before and after the implementation of the new TCCC card. METHODS: This is a secondary analysis of a previously described dataset from the Department of Defense Trauma Registry (DODTR) focused on prehospital medical care. In this sub-analysis, we defined the pre-implementation period as 2009-2013 followed by a 1-year run-in with the post-implementation period as 2015-2019. Our primary outcome was documentation of a pulse rate and our secondary outcomes included documentation of other vital signs. We used multivariable logistic regression models to adjust for confounders. RESULTS: There were 18,182 encounters that met inclusion for this analysis-14,711 before and 3,471 after the update. Across all vital signs, there was a peak around 2012-2013 with a drop noted in 2015. Comparing the preimplementation and post-implementation groups, there were higher proportions with documentation of a pulse rate (62% versus 49%), respirations (51% versus 45%), systolic pressure (53% versus 46%), diastolic pressure (49% versus 41%), oxygen saturation (55% versus 46%), and pain score (27% versus 19%, all p is less than 0.001) in the pre-implementation group. When adjusting for injury severity score (ISS), casualty category, and year of injury, the odds ratio of documentation of a pulse after implementation was 0.01 (95% CI: 0.00-0.01). When adjusting for ISS and casualty category, the odds ratio was 0.64 (95% CI: 0.60-0.70). When adjusting for ISS only, the odds ratio was 0.58 (95% CI: 0.54-0.63). CONCLUSIONS: Implementation of the new TCCC card resulted in overall lower documentation proportions which persisted after adjusting for measurable confounders.

BfmRS encodes a regulatory system involved in light signal transduction modulating motility and desiccation tolerance in the human pathogen Acinetobacter baumannii.

We have previously shown that Acinetobacter baumannii as well as other relevant clinical bacterial pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa, perceive and respond to light at 37 °C, the normal temperature in mammal hosts. In this work, we present evidence indicating that the two-component system BfmRS transduces a light signal in A. baumannii at this temperature, showing selective involvement of the BfmR and BfmS components depending on the specific cellular process. In fact, both BfmR and BfmS participate in modulation of motility by light, while only BfmR is involved in light regulation of desiccation tolerance in this microorganism. Neither BfmR nor BfmS contain a photoreceptor domain and then most likely, the system is sensing light indirectly. Intriguingly, this system inhibits blsA expression at 37 °C, suggesting antagonistic functioning of both signaling systems. Furthermore, we present evidence indicating that the phosphorylatable form of BfmR represses motility. Overall, we provide experimental evidence on a new biological function of this multifaceted system that broadens our understanding of A. baumannii's physiology and responses to light.

SCARECROW-LIKE28 modulates organ growth in Arabidopsis by controlling mitotic cell cycle exit, endoreplication, and cell expansion dynamics.

The processes that contribute to plant organ morphogenesis are spatial-temporally organized. Within the meristem, mitosis produces new cells that subsequently engage in cell expansion and differentiation programs. The latter is frequently accompanied by endoreplication, being an alternative cell cycle that replicates the DNA without nuclear division, causing a stepwise increase in somatic ploidy. Here, we show that the Arabidopsis SCL28 transcription factor promotes organ growth by modulating cell expansion dynamics in both root and leaf cells. Gene expression studies indicated that SCL28 regulates members of the SIAMESE/SIAMESE-RELATED (SIM/SMR) family, encoding cyclin-dependent kinase inhibitors with a role in promoting mitotic cell cycle (MCC) exit and endoreplication, both in response to developmental and environmental cues. Consistent with this role, mutants in SCL28 displayed reduced endoreplication, both in roots and leaves. We also found evidence indicating that SCL28 co-expresses with and regulates genes related to the biogenesis, assembly, and remodeling of the cytoskeleton and cell wall. Our results suggest that SCL28 controls, not only cell proliferation as reported previously but also cell expansion and differentiation by promoting MCC exit and endoreplication and by modulating aspects of the biogenesis, assembly, and remodeling of the cytoskeleton and cell wall.

Changes in actigraphy metrics associated with PROMIS measures after orthopaedic surgery.

AIM: This study examined the feasibility of integrating actigraphy devices into orthopaedic surgical settings to assess the concurrent validity between objective actigraphy data and PROMIS measures. Additionally, the association between changes in actigraphy data and longitudinal changes in PROMIS measures was examined. METHODS: Data were collected from 17 participants using actigraphy devices the week prior to and after orthopaedic surgery from 02/2019 to 03/2020. Participants completed PROMIS measures (Physical Function, Sleep Disturbance, Pain Interference) preoperatively and up to 6 months postoperatively. Nonparametric correlations (rs ) assessed for concurrent validity. Linear mixed-effects models examined the association between changes in actigraphy data and PROMIS measures. RESULTS: Prolonged wake after sleep onset was associated with increased sleep disturbances (rs = 0.49; p = 0.045) and pain interference (rs = 0.51; p = 0.04). Changes in pain interference were correlated with increased awakenings (rs = 0.54; p = 0.03). Increased wake after sleep onset was associated with worsening sleep disturbance (ß = 0.12; p = 0.01) and pain interference scores over the postoperative period (ß = 0.12; p = 0.02). CONCLUSIONS: This study is among the first to examine changes in objective actigraphy data and longitudinal PROMIS measures following orthopaedic surgery and illustrates the feasibility of incorporating actigraphy into surgical settings to evaluate postoperative recovery.

Acidogenic and aciduric properties of Streptococcus mutans serotype c according to its genomic variability.

Streptococcus mutans (S. mutans) has a wide genetic diversity that contributes to its phenotypic heterogeneity, and may be related to attributes associated with acidogenicity and aciduricity. The aim of this study was to evaluate the acidogenic and aciduric properties of S. mutans serotype c isolates from saliva of schoolchildren according to the genomic variability. S. mutans isolates were identified by polymerase chain reaction. Fifty S. mutans serotype c isolates were genotyped by pulsed field gel electrophoresis and tested for their ability to produce and resist acid. Three specific genotypes were identified in the caries-active group and only one in the caries-free group. Although isolates were similarly acidogenic, an exclusive caries-active genotype had the greatest glycolytic activity. In contrast, isolates exhibited variable aciduricity, and three caries-active genotypes were the least aciduric. We concluded that there is genetic variability within serotype c. Acid production was similar regardless of the caries status but correlated with the number of genotypes. In addition, resistance to acid could be an important characteristic for the establishment and colonisation of specific genotypes in children with caries. However, it is important to evaluate children's intrinsic characteristics and other phenotypic properties to explain the physiopathological behaviour of the different genotypes.

Differential Influence of Soluble Dietary Fibres on Intestinal and Hepatic Carbohydrate Response.

Refined foods are commonly depleted in certain bioactive components that are abundant in 'natural' (plant) foods. Identification and addition of these 'missing' bioactives in the diet is, therefore, necessary to counteract the deleterious impact of convenience food. In this study, multiomics approaches were employed to assess the addition of the popular supplementary soluble dietary fibers inulin and psyllium, both in isolation and in combination with a refined animal feed. A 16S rRNA sequencing and 1H NMR metabolomic investigation revealed that, whilst inulin mediated an increase in Bifidobacteria, psyllium elicited a broader microbial shift, with Parasutterella and Akkermansia being increased and Enterorhabdus and Odoribacter decreased. Interestingly, the combination diet benefited from both inulin and psyllium related microbial changes. Psyllium mediated microbial changes correlated with a reduction of glucose (R -0.67, -0.73, respectively, p < 0.05) and type 2 diabetes associated metabolites: 3-methyl-2-oxovaleric acid (R -0.72, -0.78, respectively, p < 0.05), and citrulline (R -0.77, -0.71, respectively, p < 0.05). This was in line with intestinal and hepatic carbohydrate response (e.g., Slc2a2, Slc2a5, Khk and Fbp1) and hepatic lipogenesis (e.g., Srebf1 and Fasn), which were significantly reduced under psyllium addition. Although established in the liver, the intestinal response associated with psyllium was absent in the combination diet, placing greater significance upon the established microbial, and subsequent metabolomic, shift. Our results therefore highlight the heterogeneity that exists between distinct dietary fibers in the context of carbohydrate uptake and metabolism, and supports psyllium containing combination diets, for their ability to negate the impact of a refined diet.

Regulation of blood-brain barrier integrity by microbiome-associated methylamines and cognition by trimethylamine N-oxide.

BACKGROUND: Communication between the gut microbiota and the brain is primarily mediated via soluble microbe-derived metabolites, but the details of this pathway remain poorly defined. Methylamines produced by microbial metabolism of dietary choline and L-carnitine have received attention due to their proposed association with vascular disease, but their effects upon the cerebrovascular circulation have hitherto not been studied. RESULTS: Here, we use an integrated in vitro/in vivo approach to show that physiologically relevant concentrations of the dietary methylamine trimethylamine N-oxide (TMAO) enhanced blood-brain barrier (BBB) integrity and protected it from inflammatory insult, acting through the tight junction regulator annexin A1. In contrast, the TMAO precursor trimethylamine (TMA) impaired BBB function and disrupted tight junction integrity. Moreover, we show that long-term exposure to TMAO protects murine cognitive function from inflammatory challenge, acting to limit astrocyte and microglial reactivity in a brain region-specific manner. CONCLUSION: Our findings demonstrate the mechanisms through which microbiome-associated methylamines directly interact with the mammalian BBB, with consequences for cerebrovascular and cognitive function. Video abstract.

The Arabidopsis GRAS-type SCL28 transcription factor controls the mitotic cell cycle and division plane orientation.

Gene expression is reconfigured rapidly during the cell cycle to execute the cellular functions specific to each phase. Studies conducted with synchronized plant cell suspension cultures have identified hundreds of genes with periodic expression patterns across the phases of the cell cycle, but these results may differ from expression occurring in the context of intact organs. Here, we describe the use of fluorescence-activated cell sorting to analyze the gene expression profile of G2/M cells in the growing root. To this end, we isolated cells expressing the early mitosis cell cycle marker CYCLINB1;1-GFP from Arabidopsis root tips. Transcriptome analysis of these cells allowed identification of hundreds of genes whose expression is reduced or enriched in G2/M cells, including many not previously reported from cell suspension cultures. From this dataset, we identified SCL28, a transcription factor belonging to the GRAS family, whose messenger RNA accumulates to the highest levels in G2/M and is regulated by MYB3R transcription factors. Functional analysis indicates that SCL28 promotes progression through G2/M and modulates the selection of cell division planes.

Electronic Wave-Packets in Integer Quantum Hall Edge Channels: Relaxation and Dissipative Effects.

We theoretically investigate the evolution of the peak height of energy-resolved electronic wave-packets ballistically propagating along integer quantum Hall edge channels at filling factor equal to two. This is ultimately related to the elastic scattering amplitude for the fermionic excitations evaluated at different injection energies. We investigate this quantity assuming a short-range capacitive coupling between the edges. Moreover, we also phenomenologically take into account the possibility of energy dissipation towards additional degrees of freedom-both linear and quadratic-in the injection energy. Through a comparison with recent experimental data, we rule out the non-dissipative case as well as a quadratic dependence of the dissipation, indicating a linear energy loss rate as the best candidate for describing the behavior of the quasi-particle peak at short enough propagation lengths.