Clinical and functional analyses of the novel STAR c.558C>A in a patient with classic lipoid congenital adrenal hyperplasia

Objective: Congenital lipid adrenal hyperplasia (LCAH) is the most serious type of congenital adrenal hyperplasia and is caused by steroid-based acute regulatory (STAR) protein mutations. Herein, we report compound heterozygous mutations c.558C>A (p.S186 R) and c.772C>T (p.Q258*) in a newborn 46 XY patient diagnosed with classic LCAH and explore their clinical and functional characteristics.Methods: Peripheral blood samples were collected from LCAH patient and their families. The pathogenic variant identified by whole-exome sequencing was further confirmed by Sanger sequencing and pedigree verification. The functional consequence and ability to convert cholesterol into progesterone of the identified STAR Q258* and S186 R mutations were analyzed by cell transfection and in vitro assays.Results: The proband was presented with severe glucocorticoid and mineralocorticoid deficiency, high adrenocorticotropic hormone, and enlarged adrenals. Heterozygous mutations p. S186 R and p. Q258* in the STAR gene were identified in the patient, and her parents were carriers, which is consistent with an autosomal recessive disorder. The STAR p. Q258* mutation has been reported and generates a truncated protein. The p. S186 R mutation is a novel variant that disrupts STAR. The residual STAR activities of p. S186R, p. Q258*, and p. S186R/p.Q258* were 13.9%, 7.3%, and 11.2%, respectively, of the wild-type, proving the main negative effects of the mutant proteins.Conclusion: Our findings reveal the molecular mechanisms underlying LCAH pathogenesis, further expanding the genotype and clinical spectrum of LCAH

Bacterial community assembly driven by temporal succession rather than spatial heterogeneity in Lake Bosten: a large lake suffering from eutrophication and salinization

Oligosaline lakes in arid and semi-arid regions play a crucial role in providing essential water resources for local populations. However, limited research exists on the impact of the environment on bacterial community structure in these lakes, co-occurrence patterns and the mechanisms governing bacterial community assembly. This study aims to address this knowledge gap by examining samples collected from five areas of Lake Bosten over four seasons. Using the 16S rRNA gene sequencing method, we identified a total of 510 to 1,005 operational taxonomic units (OTUs) belonging to 37 phyla and 359 genera in Lake Bosten. The major bacterial phyla were Proteobacteria (46.5%), Actinobacteria (25.9%), Bacteroidetes (13.2%), and Cyanobacteria (5.7%), while the major genera were hgcI_clade (12.9%), Limnohabitans (6.2%), and Polynucleobacter (4.7%). Water temperature emerged as the primary driver of these community structure variations on global level. However, when considering only seasonal variations, pH and nitrate were identified as key factors influencing bacterial community structures. Summer differed from other seasons in aspects of seasonal symbiotic patterns of bacterial communities, community assembly and function are different from other seasons. There were notable variations in bacterial community structures between winter and summer. Deterministic processes dominated community assembly, but there was an increase in the proportion of stochastic processes during summer. In summer, the functions related to photosynthesis, nitrogen fixation, and decomposition of organic matter showed higher abundance. Our findings shed light on the response of bacterial communities to environmental changes and the underlying mechanisms of community assembly in oligosaline lakes in arid regions

Primary motor hand area corticospinal excitability indicates overall functional recovery after spinal cord injury

BackgroundAfter spinal cord injury (SCI), the excitability of the primary motor cortex (M1) lower extremity area decreases or disappears. A recent study reported that the M1 hand area of the SCI patient encodes the activity information of both the upper and lower extremities. However, the characteristics of the M1 hand area corticospinal excitability (CSE) changes after SCI and its correlation with extremities motor function are still unknown.MethodsA retrospective study was conducted on the data of 347 SCI patients and 80 healthy controls on motor evoked potentials (MEP, reflection of CSE), extremity motor function, and activities of daily living (ADL) ability. Correlation analysis and multiple linear regression analysis were conducted to analyze the relationship between the degree of MEP hemispheric conversion and extremity motor function/ADL ability.ResultsThe CSE of the dominant hemisphere M1 hand area decreased in SCI patients. In 0–6 m, AIS A grade, or non-cervical injury SCI patients, the degree of M1 hand area MEP hemispheric conversion was positively correlated with total motor score, lower extremity motor score (LEMS), and ADL ability. Multiple linear regression analysis further confirmed the contribution of MEP hemispheric conversion degree in ADL changes as an independent factor.ConclusionThe closer the degree of M1 hand area MEP hemispheric conversion is to that of healthy controls, the better the extremity motor function/ADL ability patients achieve. Based on the law of this phenomenon, targeted intervention to regulate the excitability of bilateral M1 hand areas might be a novel strategy for SCI overall functional recovery

Anomalous structural evolution and glassy lattice in mixed-halide hybrid perovskites

Hybrid halide perovskites have emerged as highly promising photovoltaic materials because of their exceptional optoelectronic properties, which are often optimized via compositional engineering like mixing halides. It is well established that hybrid perovskites undergo a series of structural phase transitions as temperature varies. In this work, the authors find that phase transitions are substantially suppressed in mixed-halide hybrid perovskite single crystals of MAPbI3-xBrx (MA = CH3NH3+ and x = 1 or 2) using a complementary suite of diffraction and spectroscopic techniques. Furthermore, as a general behavior, multiple crystallographic phases coexist in mixed-halide perovskites over a wide temperature range, and a slightly distorted monoclinic phase, hitherto unreported for hybrid perovskites, is dominant at temperatures above 100 K. The anomalous structural evolution is correlated with the glassy behavior of organic cations and optical phonons in mixed-halide perovskites. This work demonstrates the complex interplay between composition engineering and lattice dynamics in hybrid perovskites, shedding new light on their unique properties.Peer ReviewedPostprint (published version

BRIT1/MCPH1 links chromatin remodelling to DNA damage response

To detect and repair damaged DNA, DNA damage response proteins need to overcome the barrier of condensed chromatin to gain access to DNA lesions1. ATP-dependent chromatin remodeling is one of the fundamental mechanisms used by cells to relax chromatin in DNA repair2–3. However, the mechanism mediating their recruitment to DNA lesions remains largely unknown. BRIT1 (also known as MCPH1) is an early DNA damage response protein that is mutated in human primary microcephaly4–8. We report here a previously unknown function of BRIT1 as a regulator of ATP-dependent chromatin remodeling complex SWI/SNF in DNA repair. Upon DNA damage, BRIT1 increases its interaction with SWI/SNF through the ATM/ATR-dependent phosphorylation on the BAF170 subunit. This increase of binding affinity provides a means by which SWI/SNF can be specifically recruited to and maintained at DNA lesions. Loss of BRIT1 causes impaired chromatin relaxation owing to reduced association of SWI/SNF with chromatin. This explains the decreased recruitment of repair proteins to DNA lesions and reduced efficiency of repair in BRIT1-deficient cells, resulting in impaired survival from DNA damage. Our findings, therefore, identify BRIT1 as a key molecule that links chromatin remodeling with DNA damage response in the control of DNA repair, and its dysfunction contributes to human disease