Longitudinal association of built environment pattern with DXA-derived body fat in elderly Hong Kong Chinese: A latent profile analysis.

BACKGROUND: One major limitation of prior studies regarding the associations between built environment (BE) and obesity has been the use of anthropometric indices (e.g., body mass index [BMI]) for assessing obesity status, and there has been limited evidence of associations between BE and body fat. This study aimed to explore the longitudinal association between BE and body fat in a cohort of elderly Hong Kong Chinese and examine whether the BE-body fat associations differed by BMI categories. METHODS: Between 2001 and 2003, 3944 participants aged 65-98 years were recruited and followed for a mean of 6.4 years. BE characteristics were assessed via Geographic Information System. Body fat (%) at whole body and regional areas (trunk, limbs, android, and gynoid) were assessed by dual energy X-ray absorptiometry at baseline and three follow-ups. Latent profile analysis was used to derive BE class, and linear mixed-effects models were used to investigate the associations of BE class with changes in body fat. Stratified analyses by BMI categories were also conducted. RESULTS: Three BE classes were identified. Participants in Class 2 (characterized by greater open space and proportion of residential land use) had a slower increase in whole body fat (B = -0.403, 95% confidence interval [CI]: -0.780, -0.014) and limbs fat (-0.471, 95% CI: -0.870, -0.071) compared with participants in Class 1 (characterized by high proportion of commercial land use). There were significant interactions of BE class with BMI, and participants in Class 2 had a slower increase in whole body fat and regional fat compared with participants in Class 1 (B ranging from -0.987 [limbs] to -0.523 [gynoid]) among overweight and obese participants only. CONCLUSIONS: We found that those who resided in the areas characterized by greater open space and proportion of residential land use had a slower body fat increase

Not just passengers, but co-pilots! Non-rhizobial nodule-associated bacteria promote cowpea growth and symbiosis with (brady)rhizobia.

AIMS: To isolate and characterize non-rhizobial nodule-associated bacteria (NAB) from cowpea root-nodules regarding their performance of plant-growth-promoting mechanisms and their ability to enhance cowpea growth and symbiosis when co-inoculated with bradyrhizobia. METHODS AND RESULTS: Sixteen NAB were isolated, identified, and in vitro evaluated for plant growth promotion traits. The ability to promote cowpea growth was analyzed when co-inoculated with Bradyrhizobium pachyrhizi BR 3262 in sterile and non-sterile substrates. The 16S rRNA gene sequences analysis revealed that NAB belonged to the genera Chryseobacterium (4), Bacillus (3), Microbacterium (3), Agrobacterium (1), Escherichia (1), Delftia (1), Pelomonas (1), Sphingomonas (1), and Staphylococcus (1). All strains produced different amounts of auxin siderophores and formed biofilms. Twelve out of the 16 strains carried the nifH, a gene associated with nitrogen fixation. Co-inoculation of NAB (ESA 424 and ESA 29) with Bradyrhizobium pachyrhizi BR 3262 significantly promoted cowpea growth, especially after simultaneous inoculation with the three strains. CONCLUSIONS: NAB are efficient cowpea growth promoters and can improve the efficiency of the symbiosis between cowpea and the N2-fixing microsymbiont B. pachyrhizi BR 3262, mainly under a specific triple microbial association

Reduced metabolic efficiency in sedentary eucaloric conditions predicts greater weight regain in adults with obesity following sustained weight loss.

BACKGROUND: Successful long-term weight loss maintenance after caloric restriction (CR) is rarely achieved. Besides known metabolic, behavioural, and cognitive factors, 24-hour energy expenditure (24hEE) relative to body size (i.e., metabolic efficiency) might influence subsequent weight loss maintenance. METHODS: Eleven participants with obesity (BMI = 39.0 ± 8.7 kg/m2, body fat = 36.1 ± 6.4%) had 24hEE measured in a whole-room indirect calorimeter during eucaloric conditions and weight stability prior to starting a 6-week inpatient CR study (50% of daily energy needs). Twenty-four-hour energy expenditure was adjusted via regression analysis for fat free mass (FFM) and fat mass (FM) by DXA. Body composition was reassessed at the end of CR and after 1-year follow-up. Free-living weight was assessed by monthly weight measurements during 12 months. RESULTS: After 6-week CR, participants lost 8.5 ± 2.7% weight (FFM: -6.3 ± 3.6 kg, FM: -3.4 ± 1.2 kg) but regained 5.1 ± 8.0% 1 year following CR, which was mostly due to FFM regain (+5.7 ± 5.5 kg) and unchanged FM. A relatively higher 24hEE by 100 kcal/day prior to CR was associated with an average greater rate of weight regain by +0.3 kg/month during follow-up and a greater final weight regain by +5.1 kg after 1 year of follow-up. CONCLUSION: These results suggest that reduced metabolic efficiency in 24hEE during eucaloric, sedentary conditions may predict greater weight regain after CR-induced weight loss

Requirement for LIM kinases in acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aggressive disease for which only few targeted therapies are available. Using high-throughput RNA interference (RNAi) screening in AML cell lines, we identified LIM kinase 1 (LIMK1) as a potential novel target for AML treatment. HighLIMK1expression was significantly correlated with shorter survival of AML patients and coincided withFLT3mutations,KMT2Arearrangements, and elevatedHOXgene expression. RNAi- and CRISPR-Cas9-mediated suppression as well as pharmacologic inhibition of LIMK1 and its close homolog LIMK2 reduced colony formation and decreased proliferation due to slowed cell-cycle progression ofKMT2A-rearranged AML cell lines and patient-derived xenograft (PDX) samples. This was accompanied by morphologic changes indicative of myeloid differentiation. Transcriptome analysis showed upregulation of several tumor suppressor genes as well as downregulation of HOXA9 targets and mitosis-associated genes in response to LIMK1 suppression, providing a potential mechanistic basis for the anti-leukemic phenotype. Finally, we observed a reciprocal regulation between LIM kinases (LIMK) and CDK6, a kinase known to be involved in the differentiation block ofKMT2A-rearranged AML, and addition of the CDK6 inhibitor palbociclib further enhanced the anti-proliferative effect of LIMK inhibition. Together, these data suggest that LIMK are promising targets for AML therapy

Radiochirurgie vs. Ganzhirnbestrahlung– mehr Lebensqualität, mehr Leistungsfähigkeit?

Hintergrund: Lebensqualität und Neurokognition rückt zunehmend in den klinischen und wissenschaftlichen Fokus in der Behandlung von Hirnmetastasen. Ziel: Die vorliegende Arbeit basiert auf einer selektiven Literaturrecherche in der Datenbank PubMed zum Thema neurokognitive Veränderungen und Lebensqualität nach zerebraler Radiotherapie. Es wird eine Übersicht über die aktuelle Datenlage gegeben. Ergebnisse und Schlussfolgerung: Die technischen Verbesserungen in der Radioonkologie führen zu schneller und effektiver Hochpräzisionsbestrahlung. Die potenziell geringere intrakranielle Kontrolle nach stereotaktischer Radiochirurgie („stereotactic radiosurgery“, SRS) scheint im Vergleich zur Ganzhirnbestrahlung („whole brain radiation therapy“, WBRT) keinen relevanten Einfluss auf das Überleben zu haben. Daher ist die Erhaltung der Neurokognition und der Lebensqualität zentrales Ziel der Behandlung und Gegenstand der aktuellen Forschung

High-resolution spatiotemporal modeling of daily near-surface air temperature in Germany over the period 2000–2020.

The commonly used weather stations cannot fully capture the spatiotemporal variability of near-surface air temperature (Tair), leading to exposure misclassification and biased health effect estimates. We aimed to improve the spatiotemporal coverage of Tair data in Germany by using multi-stage modeling to estimate daily 1 × 1 km minimum (Tmin), mean (Tmean), maximum (Tmax) Tair and diurnal Tair range during 2000–2020. We used weather station Tair observations, satellite-based land surface temperature (LST), elevation, vegetation and various land use predictors. In the first stage, we built a linear mixed model with daily random intercepts and slopes for LST adjusted for several spatial predictors to estimate Tair from cells with both Tair and LST available. In the second stage, we used this model to predict Tair for cells with only LST available. In the third stage, we regressed the second stage predictions against interpolated Tair values to obtain Tair countrywide. All models achieved high accuracy (0.91 ≤ R2 ≤ 0.98) and low errors (1.03 °C ≤ Root Mean Square Error (RMSE) ≤ 2.02 °C). Validation with external data confirmed the good performance, locally, i.e., in Augsburg for all models (0.74 ≤ R2 ≤ 0.99, 0.87 °C ≤ RMSE ≤ 2.05 °C) and countrywide, for the Tmean model (0.71 ≤ R2 ≤ 0.99, 0.79 °C ≤ RMSE ≤ 1.19 °C). Annual Tmean averages ranged from 8.56 °C to 10.42 °C with the years beyond 2016 being constantly hotter than the 21-year average. The spatial variability within Germany exceeded 15 °C annually on average following patterns including mountains, rivers and urbanization. Using a case study, we showed that modeling leads to broader Tair variability representation for exposure assessment of participants in health cohorts. Our results indicate the proposed models as suitable for estimating nationwide Tair at high resolution. Our product is critical for temperature-based epidemiological studies and is also available for other research purposes

TET1 promotes growth of T-cell acute lymphoblastic leukemia and can be antagonized via PARP inhibition.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological cancer characterized by skewed epigenetic patterns, raising the possibility of therapeutically targeting epigenetic factors in this disease. Here we report that among different cancer types, epigenetic factor TET1 is highly expressed in T-ALL and is crucial for human T-ALL cell growth in vivo. Knockout of TET1 in mice and knockdown in human T cell did not perturb normal T-cell proliferation, indicating that TET1 expression is dispensable for normal T-cell growth. The promotion of leukemic growth by TET1 was dependent on its catalytic property to maintain global 5-hydroxymethylcytosine (5hmC) marks, thereby regulate cell cycle, DNA repair genes, and T-ALL associated oncogenes. Furthermore, overexpression of the Tet1-catalytic domain was sufficient to augment global 5hmC levels and leukemic growth of T-ALL cells in vivo. We demonstrate that PARP enzymes, which are highly expressed in T-ALL patients, participate in establishing H3K4me3 marks at the TET1 promoter and that PARP1 interacts with the TET1 protein. Importantly, the growth related role of TET1 in T-ALL could be antagonized by the clinically approved PARP inhibitor Olaparib, which abrogated TET1 expression, induced loss of 5hmC marks, and antagonized leukemic growth of T-ALL cells, opening a therapeutic avenue for this disease

Bernstein inequality in L^α norms.

The classical Bernstein inequality estimates the derivative of a polynomial at a fixed point with the supremum norm and a factor depending on the point only. Recently, this classical inequality was generalized to arbitrary compact subsets on the real line. That generalization is sharp and naturally introduces potential theoretical quantities. It also gives a hint how a sharp L α Bernstein inequality should look like. In this paper we prove this conjectured Lα Bernstein type inequality and we also prove its sharpness

Condensed tannins as antioxidants that protect poplar against oxidative stress from drought and UV-B.

Condensed tannins (CTs, proanthocyanidins) are widespread polymeric flavan-3-ols known for their ability to bind proteins. In poplar (Populus spp.), leaf condensed tannins are induced by both biotic and abiotic stresses, suggesting diverse biological functions. Here we demonstrate the ability of CTs to function as physiological antioxidants, preventing oxidative and cellular damage in response to drought and UV-B irradiation. Chlorophyll fluorescence was used to monitor photosystem II performance, and both hydrogen peroxide and malondialdehyde content was assayed as a measure of oxidative damage. Transgenic MYB-overexpressing poplar (Populus tremula x tremuloides) with high CT content showed reduced photosystem damage and lower hydrogen peroxide and malondialdehyde content after drought and UV-B stress. This antioxidant effect of CT was observed using two different poplar MYB CT regulators, in multiple independent lines and different genetic backgrounds. Additionally, low-CT MYB134-RNAi transgenic poplars showed enhanced susceptibility to drought-induced oxidative stress. UV-B radiation had different impacts than drought on chlorophyll fluorescence, but all high-CT poplar lines displayed reduced sensitivity to both stresses. Our data indicate that CTs are significant defenses against oxidative stress. The broad distribution of CTs in forest systems which are exposed to diverse abiotic stresses suggests that these compounds have wider functional roles than previously realized. This article is protected by copyright. All rights reserved

Clinical presentation and differential splicing of SRSF2, U2AF1 and SF3B1 mutations in patients with acute myeloid leukemia.

Previous studies demonstrated that splicing factor mutations are recurrent events in hematopoietic malignancies with both clinical and functional implications. However, their aberrant splicing patterns in acute myeloid leukemia remain largely unexplored. In this study, we characterized mutations in SRSF2, U2AF1, and SF3B1, the most commonly mutated splicing factors. In our clinical analysis of 2678 patients, splicing factor mutations showed inferior relapse-free and overall survival, however, these mutations did not represent independent prognostic markers. RNA-sequencing of 246 and independent validation in 177 patients revealed an isoform expression profile which is highly characteristic for each individual mutation, with several isoforms showing a strong dysregulation. By establishing a custom differential splice junction usage pipeline, we accurately detected aberrant splicing in splicing factor mutated samples. A large proportion of differentially used junctions were novel, including several junctions in leukemia-associated genes. In SRSF2(P95H) mutants, we further explored the possibility of a cascading effect through the dysregulation of the splicing pathway. Furthermore, we observed a validated impact on overall survival for two junctions overused in SRSF2(P95H) mutants. We conclude that splicing factor mutations do not represent independent prognostic markers. However, they do have genome-wide consequences on gene splicing leading to dysregulated isoform expression of several genes