Search

Summary: During mammalian embryogenesis, changes in morphology and gene expression are concurrent with epigenomic reprogramming. Using human embryonic stem cells representing the preimplantation blastocyst (naive) and postimplantation epiblast (primed), our data in 2iL/I/F naive cells demonstrate that a substantial portion of known human enhancers are premarked by H3K4me1, providing an enhanced open chromatin state in naive pluripotency. The 2iL/I/F enhancer repertoire occupies 9% of the genome, three times that of primed cells, and can exist in broad chromatin domains over 50 kb. Enhancer chromatin states are largely poised. Seventy-seven percent of 2iL/I/F enhancers are decommissioned in a stepwise manner as cells become primed. While primed topologically associating domains are largely unaltered upon differentiation, naive 2iL/I/F domains expand across primed boundaries, affecting three-dimensional genome architecture. Differential topologically associating domain edges coincide with 2iL/I/F H3K4me1 enrichment. Our results suggest that naive-derived 2iL/I/F cells have a unique chromatin landscape, which may reflect early embryogenesis. : Human ESCs grown in 2iL/I/F are useful for studying the transition from naive to primed pluripotency. Battle et al. show that the naive epigenome is globally enhanced for H3K4me1. Many of the H3K4me1 regions are putative enhancers and are lost, or decommissioned, during the transition to primed. Differential topologically associating domains (TADs) exist between states and contain H3K4me1 enrichment at TAD boundaries. Keywords: enhancers, 3D genome architecture, naive hESCs, embryogenesis

Introduction Intact epithelial-immune barriers play a critical role in maintaining a physical defense between external environmental antigens and the internal immune system. In allergy, epithelial barriers are often dysfunctional, contributing [...], Epithelial barrier dysfunction is a significant factor in many allergic diseases, including eosinophilic esophagitis (EoE). Infiltrating leukocytes and tissue adaptations increase metabolic demands and decrease oxygen availability at barrier surfaces. Understanding of how these processes impact barrier is limited, particularly in allergy. Here, we identified a regulatory axis whereby the oxygen-sensing transcription factor HIF-1[alpha] orchestrated epithelial barrier integrity, selectively controlling tight junction CLDN1 (claudin-1). Prolonged experimental hypoxia or HIF1A knockdown suppressed HIF-1[alpha]-dependent claudin-1 expression and epithelial barrier function, as documented in 3D organotypic epithelial cultures. L2-IL[5.SUP.OXA] mice with EoE-relevant allergic inflammation displayed localized eosinophil oxygen metabolism, tissue hypoxia, and impaired claudin-1 barrier via repression of HIF-1[alpha]/claudin-1 signaling, which was restored by transgenic expression of esophageal epithelial-targeted stabilized HIF-1[alpha]. EoE patient biopsy analysis identified a repressed HIF-1[alpha]/claudin-1 axis, which was restored via pharmacologic HIF-1[alpha] stabilization ex vivo. Collectively, these studies reveal HIF-1[alpha]'s critical role in maintaining barrier and highlight the HIF-1[alpha]/claudin-1 axis as a potential therapeutic target for EoE.

Abstract The study of whether life exists, is extinct, or not depends on various sophisticated experimental studies, as many different signatures of life can be used. The experimental procedures that can be performed to identify life can be further restricted by time, resources, and mobility constraints. Therefore, any research analyzing the presence of extraterrestrial life must be precise and unambiguous. This research focuses on the objective of the extraterrestrial life detection domain and seeks to provide an efficient protocol that can produce life detection decisions based on empirical data obtained through chemical analysis under time and resource-constrained conditions. While the majority of existing frameworks in this field are designed to identify biomolecules, our goal is to accomplish the same with minimal operational expense and mission complexity. We argue that the thoughtful integration of multiple biomolecular detections with lesser complexity and a robust framework can improve overall mission performance by satisfying the necessary time and resource constraints. In this study, a rapid multiple biomolecules-based life detection protocol (MBLDP-R) from soil samples is developed from scratch and embedded in an operational scientific rover subsystem targeted for planetary analysis missions. The study uses artificial biomolecule samples and simulated extraterrestrial environments to illustrate the suggested protocol’s end-to-end process. First, we list a few significant biomolecules, including lipids, proteins, carbohydrates, nucleic acids, ammonia, and pigments. Then, a weighted qualitative test scoring is applied to sort out the best test method for the finally selected biomolecules which are used as operational analogue to showcase the protocol’s in-situ analysis and decision-making capabilities. Based on the suitable biomolecules, a scientific exploration subsystem is developed, and the implemented protocol is built to perform onboard sample analysis. Evaluation results show that: (1) the proposed MBLDP-R protocol could effectively predict the classes with an average f1-score of 98.65% (macro) and 90.00% (micro), (2) the area under the Receiver Operating Characteristics (AUC-ROC) curve shows the sample categories to be correctly predicted 92% of the time (97% for Extant, 88% for Extinct, and 92% in the case of NPL), and (3) the protocol is time-efficient with an average completion time of 17.60 min, demonstrating the protocol’s rapid nature in detecting biosignatures in soil samples. The research outcome yields useful additional data for related future studies, particularly in the design of scientific frameworks for mission-specific requirements with limited resources while also serving as a reference point for constraint evaluation methods for similar systems.

The present study was designed to evaluate the use of estrus synchronization and fixedtime artificial insemination (FTAI) after synchronization of ovulation in the bovine Lidia cattle called 'Brava dos Açores'. For such purpose, a total of 70 females was submitted to FTAI after a CIDR®-Cosynch synchronization protocol, in which on Day 0, a progesterone-impregnated internal controlled release drug (CIDR®) was inserted intravaginally, and GnRH was administered intramuscularly. After 5 or 7 days, respectively for heifers or cows, PGF2a was administered and the CIDR® removed, being the artificial insemination performed after 60 hours only once using straws containing 50 million mL of spermatozoa per straw. Before starting synchronization, all animals were vaccinated against several diseases, and only females negative for IBR/BVD, Trichomoniasis, Brucellosis, Leucosis and Campylobacteriosis were selected to be used in the experiment. Pregnancy diagnoses were performed, by ultrasonography. During the experiment, females took a routine course, to reduce the stress during the different procedures such as to place and remove the implants and the artificial insemination, because as they are known to be quite nervous, it can seriously impair seriously the results. In general, 64% of the cows became pregnant vs 40% for heifers, which can be considered satisfactory considering the nature of inseminated cattle. It can be, thus, concluded that the animal's correct management, as well as the use of the presented protocols are fundamental to achieve the success of this technique, so that the use of these protocols and animal's management when inseminating this type of animals is strongly recommended. [ABSTRACT FROM AUTHOR]

Abstract Coffin-Lowry Syndrome (CLS) is a rare X-linked genetic disorder characterized by growth delays, facial dysmorphisms, and intellectual disabilities. Currently, there are limited published case reports regarding the anesthetic management of patients with CLS. Managing anesthesia for CLS patients can be complex due to difficult airway management. In this case report, we present a patient with CLS who underwent surgical intervention, highlighting the anesthetic considerations encountered throughout the perioperative period. We aim to summarize the difficulties involved in anesthetic management of rare conditions like CLS to improve clinical outcomes for affected individuals.

One of the most perplexing discoveries from COVID-19 pandemic was the office building overall energy consumption failing to appreciably drop once staff began working from home. Also, we are witnessing an exponential growing of Internet of Things (IoT) ecosystem but most of them have been implemented for personal usage rather in an enterprise environment. The big challenge in installing a large-scale IoT ecosystem at enterprise level resides on costs, the selection of proper devices, and the management of these devices and users. NOSIoT NFC-based solution consists of a simple mobile application that will read an NFC tag in a specific workstation. The communication and management are performed through Home Assistant. All the information is stored into a database to calculate the energy consumed by each workstation. The solution provides an innovative approach for enterprise level, delivering a low-cost end-to-end flow with high flexibility, and easy "Tap&Go". This allows companies to be more climate-friendly and positively contribute for green buildings. [ABSTRACT FROM AUTHOR]