Global patterns and drivers of leaf photosynthetic capacity : the relative importance of environmental factors and evolutionary history

Altres ajuts: Fundación Ramon Areces grant CIVP20A6621Aim: understanding the considerable variability and drivers of global leaf photosynthetic capacity [indicated by the maximum carboxylation rate standardized to 25°C (Vc,max25)] is an essential step for accurate modelling of terrestrial plant photosynthesis and carbon uptake under climate change. Although current environmental conditions have often been connected with empirical and theoretical models to explain global Vc,max25 variability through acclimatization and adaptation, long-term evolutionary history has largely been neglected, but might also explicitly play a role in shaping the Vc,max25 variability. - Location: global - Time period: contemporary - Major taxa studied: terrestrial plants. - Methods: we compiled a geographically comprehensive global dataset of Vc,max25 for C3 plants (n = 6917 observations from 2157 species and 425 sites covering all major biomes world-wide), explored the biogeographical and phylogenetic patterns of Vc,max25, and quantified the relative importance of current environmental factors and evolutionary history in driving global Vc,max25 variability. - Results: we found that Vc,max25 differed across different biomes, with higher mean values in relatively drier regions, and across different life-forms, with higher mean values in non-woody relative to woody plants and in legumes relative to non-leguminous plants. The values of Vc,max25 displayed a significant phylogenetic signal and diverged in a contrasting manner across phylogenetic groups, with a significant trend along the evolutionary axis towards a higher Vc,max25 in more modern clades. A Bayesian phylogenetic linear mixed model revealed that evolutionary history (indicated by phylogeny and species) explained nearly 3-fold more of the variation in global Vc,max25 than present-day environment (53 vs. 18%). - Main conclusions: these findings contribute to a comprehensive assessment of the patterns and drivers of global Vc,max25 variability, highlighting the importance of evolutionary history in driving global Vc,max25 variability, hence terrestrial plant photosynthesis

Pediatric multiple sclerosis: update on diagnostic criteria, imaging, histopathology and treatment choices

Pediatric multiple sclerosis (MS) represents less than 5% of the MS population, but patients with pediatric-onset disease reach permanent disability at a younger age than adult onset patients. Accurate diagnosis at presentation and optimal long-term treatment is vital to mitigate ongoing neuroinflammation and irreversible neurodegeneration. However, it may be difficult to early differentiate pediatric MS from acute disseminated encephalomyelitis (ADEM) and neuromyelitis optica spectrum disorders (NMOSD) as they often have atypical presentation that differs from that of adult-onset MS. The purpose of this review is to summarize the updated views on diagnostic criteria, imaging, histopathology and treatment choices

A multimodal cell census and atlas of the mammalian primary motor cortex

ABSTRACT We report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex (MOp or M1) as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties, and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Together, our results advance the collective knowledge and understanding of brain cell type organization: First, our study reveals a unified molecular genetic landscape of cortical cell types that congruently integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a unified taxonomy of transcriptomic types and their hierarchical organization that are conserved from mouse to marmoset and human. Third, cross-modal analysis provides compelling evidence for the epigenomic, transcriptomic, and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types and subtypes. Fourth, in situ single-cell transcriptomics provides a spatially-resolved cell type atlas of the motor cortex. Fifth, integrated transcriptomic, epigenomic and anatomical analyses reveal the correspondence between neural circuits and transcriptomic cell types. We further present an extensive genetic toolset for targeting and fate mapping glutamatergic projection neuron types toward linking their developmental trajectory to their circuit function. Together, our results establish a unified and mechanistic framework of neuronal cell type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties

Disparities in healthcare providers’ interpretations and implementations of ACIP’s meningococcal vaccine recommendations

Invasive meningococcal disease (IMD) caused by the bacteria Neisseria meningitidis is rare but potentially fatal. For healthy adolescents, the US Advisory Committee on Immunization Practices (ACIP) recommends routine vaccination with MenACWY and recommends MenB vaccination under shared clinical decision-making (previously “Category B”). The recommendation for MenB vaccination was the first category B recommendation in adolescents, and it is unclear how healthcare providers (HCPs) implement these guidelines. This 2017 web-based survey of US HCPs explored characteristics associated with prescribing or receiving MenB and MenACWY vaccines, HCP knowledge of vaccine recommendations, and real-world practice patterns. Of 529 respondents, 436 prescribed MenB vaccines to their eligible adolescent/young adult patients and 93 prescribed MenACWY vaccines only. MenB vaccine prescribers were more likely to be pediatricians compared with MenACWY vaccine only prescribers, and patients who received MenB vaccines were more likely to be non-Hispanic whites living in shared spaces (eg, college dormitories) than those not receiving the vaccine. Seventy-seven percent of HCPs indicated that they prescribe MenACWY vaccines consistently with ACIP recommendations (to all members of an age group), whereas only 7% indicated that they prescribe MenB vaccines consistently with ACIP recommendations (individual clinical decision making). Patient-related factors, disease-related factors, and guidelines all influenced HCP decisions to prescribe meningococcal vaccines. Providing HCPs with clear guidance on how to initiate discussion of MenB vaccines with patients and their caregivers may aid in fully protecting US adolescents against meningococcal disease caused by 5 of the disease-causing serogroups

Real-world experience of women using extended-cycle vs monthly-cycle combined oral contraception in the United States: the National Health and Wellness Survey

Abstract Background The real-world experience of women receiving extended-cycle combined oral contraception (COC) versus monthly-cycle COC has not been reported. Methods Data were from the United States 2013 National Health and Wellness Survey. Eligible women (18–50 years old, premenopausal, without hysterectomy) currently using extended-cycle COC (3 months between periods) were compared with women using monthly-cycle COC. Treatment satisfaction (1 “extremely dissatisfied” to 7 “extremely satisfied”), adherence (8-item Morisky Medication Adherence Scale©), menstrual cycle-related symptoms, health-related quality of life (HRQOL) and health state utilities (Medical Outcomes Short Form Survey-36v2®), depression (9-item Patient Health Questionnaire), sleep difficulties, Work Productivity and Activity Impairment-General Health, and healthcare resource use were assessed using one-way analyses of variance, chi-square tests, and generalized linear models (adjusted for covariates). Results Participants included 260 (6.7%) women using extended-cycle and 3616 (93.3%) using monthly-cycle COC. Women using extended-cycle COC reported significantly higher treatment satisfaction (P = 0.001) and adherence (P = 0.04) and reduced heavy menstrual bleeding (P = 0.029). A non-significant tendency toward reduced menstrual pain (39.5% versus 47.3%) and menstrual cycle-related symptoms (40.0% versus 48.7%) was found in women using extended-cycle versus monthly-cycle COC. Significantly more women using extended-cycle COC reported health-related diagnoses, indicating preferential prescription for extended-cycle COC among women reporting more health problems. Consistent with this poorer health, more women using extended-cycle COC reported fatigue, headache, and activity impairment (P values < 0.05). There were no other significant differences between groups. Conclusions This real-world observational study supports extended-cycle COC as a valuable treatment option with high satisfaction, high adherence, and reduced heavy menstrual bleeding

Treatment Dosing Patterns and Clinical Outcomes for Patients with Type 2 Diabetes Starting or Switching to Treatment with Insulin Glargine (300 Units per Milliliter) in a Real-World Setting: A Retrospective Observational Study

<p><strong>Article full text</strong></p> <p><br> The full text of this article can be found <a href="https://link.springer.com/article/10.1007/s12325-017-0651-3"><b>here</b>.</a><br> <br> <strong>Provide enhanced digital features for this article</strong><br> If you are an author of this publication and would like to provide additional enhanced digital features for your article then please contact <u>[email protected]</u>.<br> <br> The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.<br> <br> Other enhanced features include, but are not limited to:<br> • Slide decks<br> • Videos and animations<br> • Audio abstracts<br> • Audio slides<u></u></p

Young adult and middle age mortality in Butajira demographic surveillance site, Ethiopia : lifestyle, gender and household economy

Background Public health research characterising the course of life through the middle age in developing societies is scarce. The aim of this study is to explore patterns of adult (15–64 years) mortality in an Ethiopian population over time, by gender, urban or rural lifestyle, causes of death and in relation to household economic status and decision-making. Methods The study was conducted in Butajira Demographic Surveillance Site (DSS) in south-central Ethiopia among adults 15–64 years old. Cohort analysis of surveillance data was conducted for the years 1987–2004 complemented by a prospective case-referent (case control) study over two years. Rate ratios were computed to assess the relationships between mortality and background variables using a Poisson regression model. In the case-referent component, odds ratios (95% confidence intervals) were used to assess the effect of certain risk factors that were not included in the surveillance system. Results A total of 367 940 person years were observed in a period of 18 years, in which 2 860 deaths occurred. One hundred sixty two cases and 486 matched for age, sex and place of residence controls were included in the case referent (case control) study. Only a modest downward trend in adult mortality was seen over the 18 year period. Rural lifestyle carried a significant survival disadvantage [mortality rate ratio 1.62 (95% CI 1.44 to 1.82), adjusted for gender, period and age group], while the overall effects of gender were negligible. Communicable disease mortality was appreciably higher in rural areas [rate ratio 2.05 (95% CI 1.73 to 2.44), adjusted for gender, age group and period]. Higher mortality was associated with a lack of literacy in a household, poor economic status and lack of women's decision making. Conclusion A complex pattern of adult mortality prevails, still influenced by war, famine and communicable diseases. Individual factors such as a lack of education, low economic status and social disadvantage all contribute to increased risks of mortality.This study was financially supported by SAREC (Swedish Agency for Research Co-operation with Developing Countries).</p

Dependence of Tumor Cell Lines and Patient-Derived Tumors on the NAD Salvage Pathway Renders Them Sensitive to NAMPT Inhibition with GNE-618

Nicotinamide adenine dinucleotide (NAD) is a critical metabolite that is required for a range of cellular reactions. A key enzyme in the NAD salvage pathway is nicotinamide phosphoribosyl transferase (NAMPT), and here, we describe GNE-618, an NAMPT inhibitor that depletes NAD and induces cell death in vitro and in vivo. While cells proficient for nicotinic acid phosphoribosyl transferase (NAPRT1) can be protected from NAMPT inhibition as they convert nicotinic acid (NA) to NAD independent of the salvage pathway, this protection only occurs if NA is added before NAD depletion. We also demonstrate that tumor cells are unable to generate NAD by de novo synthesis as they lack expression of key enzymes in this pathway, thus providing a mechanistic rationale for the reliance of tumor cells on the NAD salvage pathway. Identifying tumors that are sensitive to NAMPT inhibition is one potential way to enhance the therapeutic effectiveness of an NAMPT inhibitor, and here, we show that NAMPT, but not NAPRT1, mRNA and protein levels inversely correlate with sensitivity to GNE-618 across a panel of 53 non-small cell lung carcinoma cell lines. Finally, we demonstrate that GNE-618 reduced tumor growth in a patient-derived model, which is thought to more closely represent heterogeneous primary patient tumors. Thus, we show that dependence of tumor cells on the NAD salvage pathway renders them sensitive to GNE-618 in vitro and in vivo, and our data support further evaluation of the use of NAMPT mRNA and protein levels as predictors of overall sensitivity