A sparse covarying unit that describes healthy and impaired human gut microbiota development

Characterizing the organization of the human gut microbiota is a formidable challenge given the number of possible interactions between its components. Using a statistical approach initially applied to financial markets, we measured temporally conserved covariance among bacterial taxa in the microbiota of healthy members of a Bangladeshi birth cohort sampled from 1 to 60 months of age. The results revealed an ecogroup of 15 covarying bacterial taxa that provide a concise description of microbiota development in healthy children from this and other low-income countries, and a means for monitoring community repair in undernourished children treated with therapeutic foods. Features of ecogroup population dynamics were recapitulated in gnotobiotic piglets as they transitioned from exclusive milk feeding to a fully weaned state consuming a representative Bangladeshi diet

Neoadjuvant Chemotherapy Modulates the Immune Microenvironment in Metastases of Tubo-Ovarian High-Grade Serous Carcinoma

This research was funded by Swiss Cancer League (BIL KLS-2883-02-2012), the European Research Council (ERC322566), Cancer Research UK (A16354), and Barts and The London Charity (467/1307)

Chronic cisplatin treatment promotes enhanced damage repair and tumor progression in a mouse model of lung cancer

Chemotherapy resistance is a major obstacle in cancer treatment, yet the mechanisms of response to specific therapies have been largely unexplored in vivo. Employing genetic, genomic, and imaging approaches, we examined the dynamics of response to a mainstay chemotherapeutic, cisplatin, in multiple mouse models of human non-small-cell lung cancer (NSCLC). We show that lung tumors initially respond to cisplatin by sensing DNA damage, undergoing cell cycle arrest, and inducing apoptosis—leading to a significant reduction in tumor burden. Importantly, we demonstrate that this response does not depend on the tumor suppressor p53 or its transcriptional target, p21. Prolonged cisplatin treatment promotes the emergence of resistant tumors with enhanced repair capacity that are cross-resistant to platinum analogs, exhibit advanced histopathology, and possess an increased frequency of genomic alterations. Cisplatin-resistant tumors express elevated levels of multiple DNA damage repair and cell cycle arrest-related genes, including p53-inducible protein with a death domain (Pidd). We demonstrate a novel role for PIDD as a regulator of chemotherapy response in human lung tumor cells.National Institutes of Health (U.S.) (grant 5-UO1-CA84306)National Cancer Institute (U.S.) (CA034992

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Topological organization of multichromosomal regions by the long intergenic noncoding RNA Firre

RNA, including long noncoding RNA (lncRNA), is known to be an abundant and important structural component of the nuclear matrix. However, the molecular identities, functional roles and localization dynamics of lncRNAs that influence nuclear architecture remain poorly understood. Here, we describe one lncRNA, Firre, that interacts with the nuclear-matrix factor hnRNPU through a 156-bp repeating sequence and localizes across an ~5-Mb domain on the X chromosome. We further observed Firre localization across five distinct trans-chromosomal loci, which reside in spatial proximity to the Firre genomic locus on the X chromosome. Both genetic deletion of the Firre locus and knockdown of hnRNPU resulted in loss of colocalization of these trans-chromosomal interacting loci. Thus, our data suggest a model in which lncRNAs such as Firre can interface with and modulate nuclear architecture across chromosomes

The Design of a Thermoelectric Generator and Its Medical Applications

Growing energy demands are driving people to generate power in every possible way. New energy sources are needed to plug the energy gap. There is a growing interest in distributed energy generation due to its remarkable advantages such as flexibility, reliability, adaptability and minimal transmission losses. Thermoelectric generators (TEGs) are one such distributed power source that relies on thermal energy for electricity generation. The current review focusses on the design and optimization of TEGs to maximize the power output from the available thermal sources. The basic principle of thermoelectricity generation and suitable architecture for specific applications are explained with an overview of materials and manufacturing processes. Various cooling techniques to dissipate heat from the cold side and their influence on overall efficiency are reviewed in this work. Applications of TEGs for powering biomedical sensors have been discussed in detail. Recent advancements in TEGs for various implantable devices and their power requirements are evaluated. The exploitation of TEGs to generate power for wearable sensors has been presented, along with published experimental data. It is envisioned that this study will provide profound knowledge on TEG design for specific applications, which will be helpful for future endeavours

Harnessing Soil Microbes to Improve Plant Phosphate Efficiency in Cropping Systems

Phosphorus is an essential macronutrient required for plant growth and development. It is central to many biological processes, including nucleic acid synthesis, respiration, and enzymatic activity. However, the strong adsorption of phosphorus by minerals in the soil decreases its availability to plants, thus reducing the productivity of agricultural and forestry ecosystems. This has resulted in a complete dependence on non-renewable chemical fertilizers that are environmentally damaging. Alternative strategies must be identified and implemented to help crops acquire phosphorus more sustainably. In this review, we highlight recent advances in our understanding and utilization of soil microbes to both solubilize inorganic phosphate from insoluble forms and allocate it directly to crop plants. Specifically, we focus on arbuscular mycorrhizal fungi, ectomycorrhizal fungi, and phosphate-solubilizing bacteria. Each of these play a major role in natural and agroecosystems, and their use as bioinoculants is an increasing trend in agricultural practices

Controllable and Scalable Engineered Soil Surrogates Utilizing Simulated Soil Organic Matter for the Study of Environmental, Ecological, and Agricultural Processes

Copyright © 2020 American Chemical Society. An entirely new, tunable, and scalable platform (model) approach for the detailed study of important molecular processes that take place in geomacromolecular matrices, such as soils, using block copolymer materials at inorganic interfaces has been developed and applied to gain a molecular-level understanding of environmental pollutant/soil interactions. This approach provides a scalable platform with molecular-level control of the soil organic matter (SOM) chemical composition and structure, allowing one to examine proposed SOM interactions with agricultural chemicals (ACs). Accordingly, a series of engineered soil surrogates (ESSs) utilizing simulated SOM was synthesized, in which multiblock oligomers were tethered to silica particles, creating one-, two-, and three-tiered ESSs, via controlled radical polymerization. Using norflurazon (NOR) as a model AC sorbate for batch mode sorption experiments, it was found that binding interactions with the ESSs are not just organic content-driven but are also dependent on the nature of the chemical structure of an ESS. By a stepwise increase in the polarity of the second and third tiers, it is shown that the ability of the ESS to sorb NOR decreases, pointing to a largely hydrophobic driving force for NOR adsorption to the ESSs. The ESS platform approach also allows for the investigation of other, more nuanced interactions with this study, directly showing that hydrogen bonding, electrostatic interactions, conformation, and π-stacking strongly influence NOR binding. This approach can also be applied to a range of other environmentally and agriculturally important issues, such as soil remediation, microbial community dynamics and evolution, nutrient cycling, and carbon sequestration, where soil variability between replicate samples has limited research advances