NITROGEN DYNAMICS IN THE RUMEN AND ABOMASUM OF SHEEP DETERMINED WITH 15 N-LABELLED AMMONIA OR 15 N-LABELLED DUCKWEED

An experiment was carried out to investigate the dynamics of nitrogen (N) in the rumen and abomasum of rumen and abomasum-cannulated sheep using 15 N dilution techniques. The 15 N tracer was administered into the rumen as 15 N-ammonia or 15 N-labelled duckweed and the transfer of the 15 N label to various N pools was followed. Flow of digesta from the rumen into the abomasum was ascertained by double marker technique with cobalt and acid insoluble ash as liquid digesta and particle digesta marker, respectively. Results showed that the average of rumen water volume was 4.5 l ± SEM 0.57 and the mean water flow through the abomasum (8.6 ± 0.45 l/d) was higher than outflow from the rumen (7.4 ± 0.55 l/d). Nitrogen intake tended to be higher, but total-N passing the abomasum tended to be lower when the sheep were infused by 15 N-ammonia than when they were ingesting 15 N-duckweed. The ammonia concentration in abomasal digesta was about 93 mg N/kg and non ammonia N (NAN) was about 1.58 g N/kg. The rates of flow of total-N as ammonia-N and as NAN did not differ (P>0.05) between animals or diets, with means (± SEM) of 57.7 ± 0.96 and 964 ± 2.13 mmol/d (or 0.81 and 13.5 g N/d), respectively. About 34-59% of the dietary N was removed from the rumen as ammonia (absorbed and in digesta). The enrichments of rumen ammonia N appeared to have reached plateau values after about 10 h of 15 N-ammonia infusion. The percentage of bacterial-N derived from ammonia-N (from the period of 15 N-ammonia infusion) was 53.63 % (ratio of plateau enrichments) and thus 37.47% of bacterial-N was derived from NAN sources in the rumen. The total 15 N flow through the abomasum was higher (P<0.001) when 5 N duckweed was given rather than 15 N-ammonia (2.40 0.02 mmol/d). The 15 N in NAN flowing to the abomasum (mmol/d) was also significantly higher (P<0.001) when 15 N-duckweed was given rather than 15 N ammonia, with means of 0.00, respectively. The flow of 15 N in ammonia, on the other hand, was lower (P<0.01) when sheep ingested 15 N-duckweed than when they were infused with 15 N-ammonia (0.09  0.00v. 0.13  0.09  mmol/d).Damry 1 Keywords : Nitrogen Dynamics, Rumen, Ammonia-N, Bacterial-

Extrapolated longer-term effects of the DAPA-CKD trial: a modelling analysis

Background: The Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial assessed dapagliflozin versus placebo, in addition to standard therapy, in patients with chronic kidney disease (CKD) and albuminuria, and was terminated prematurely due to overwhelming efficacy. The study objective was to model the long-term clinical outcomes of DAPA-CKD beyond the trial follow-up. Methods: A Markov model extrapolated event incidence per 1000 patients and CKD progression rates for patients receiving dapagliflozin or placebo over a 10-year time horizon. We derived treatment-specific CKD stage transition matrices using DAPA-CKD trial data. We extrapolated relevant efficacy endpoints using parametric survival equations for all-cause mortality and generalized estimating equations for recurrent events. Results: When extrapolated over a 10-year period, patients randomized to dapagliflozin spent more time in CKD stages 1–3 and less in stages 4–5 than placebo [0.65 (95% CrI 0.41, 0.90) and –0.23 (95% CrI -0.45, 0.00) years per patient, respectively]. Dapagliflozin prevented an estimated 83 deaths and 51 patients initiating kidney replacement therapy per 1000 patients over 10 years. Predicted rates of hospitalized heart failure and abrupt declines in kidney function were reduced (19 and 39 estimated events per 1000 patients, respectively). Conclusions: Adding dapagliflozin to standard therapeutic management of CKD is expected to have long-term cardiorenal benefit beyond what has been demonstrated in the DAPA-CKD trial, with patients predicted to live longer with fewer complications

Physical activity attenuates the influence of FTO variants on obesity risk: A meta-analysis of 218,166 adults and 19,268 children

Background: The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n = 218,166) and nine studies of children and adolescents (n = 19,268). Methods and Findings: All studies identified to have data on the FTO rs9939609 variant (or any proxy [r2>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTO×PA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A-) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20-1.26), but PA attenuated this effect (pinteraction= 0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio = 1.22/allele, 95% CI 1.19-1.25) than in the inactive group (odds ratio = 1.30/allele, 95% CI 1.24-1.36). No such interaction was found in children and adolescents. Concl

Molecular Features of Cancers Exhibiting Exceptional Responses to Treatment

A small fraction of cancer patients with advanced disease survive significantly longer than patients with clinically comparable tumors. Molecular mechanisms for exceptional responses to therapy have been identified by genomic analysis of tumor biopsies from individual patients. Here, we analyzed tumor biopsies from an unbiased cohort of 111 exceptional responder patients using multiple platforms to profile genetic and epigenetic aberrations as well as the tumor microenvironment. Integrative analysis uncovered plausible mechanisms for the therapeutic response in nearly a quarter of the patients. The mechanisms were assigned to four broad categories—DNA damage response, intracellular signaling, immune engagement, and genetic alterations characteristic of favorable prognosis—with many tumors falling into multiple categories. These analyses revealed synthetic lethal relationships that may be exploited therapeutically and rare genetic lesions that favor therapeutic success, while also providing a wealth of testable hypotheses regarding oncogenic mechanisms that may influence the response to cancer therapy. Profiling multi-platform genomics of 110 cancer patients with an exceptional therapeutic response, Wheeler et al. identify putative molecular mechanisms explaining this survival phenotype in ∼23% of cases. Therapeutic success is related to rare molecular features of responding tumors, exploiting synthetic lethality and oncogene addiction

TRY plant trait database – enhanced coverage and open access

Plant traits—the morphological, anatomical, physiological, biochemical and phenological characteristics of plants—determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits—almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives