Investigating TNNC1 gene inheritance and clinical outcomes through a comprehensive familial study.

Hypertrophic cardiomyopathy (HCM) and restrictive cardiomyopathy (RCM) have significant phenotypic overlap and a similar genetic background, both caused mainly by variants in sarcomeric genes. HCM is the most common cardiomyopathy, while RCM is a rare and often underdiagnosed heart condition, with a poor prognosis. This study focuses on a large family with four infants diagnosed with fatal RCM associated with biventricular hypertrophy.

A dataset of community perspectives on living conditions and disaster risk management in informal settlements: A case study in KwaZulu-Natal Province, South Africa.

This article describes a dataset of community perspectives on living conditions and disaster risk management in Khan Road, a non-serviced informal settlement, located in Pietermaritzburg, the capital of KwaZulu-Natal province in South Africa. The data were collected by local community researchers via a structured questionnaire of 159 informal dwellers conducted between August and September 2022, using mobile phones via KoboToolbox. The dataset was analysed using exploratory data analysis (EDA) techniques.

Discovery of novel methionine adenosyltransferase 2A (MAT2A) allosteric inhibitors by structure-based virtual screening.

Methionine adenosyltransferase 2A (MAT2A) has been indicated as a drug target for oncology indications. Clinical trials with MAT2A inhibitors are currently on-going. Here, a structure-based virtual screening campaign was performed on the commercially available chemical space which yielded two novel MAT2A-inhibitor chemical series.

Feasibility and Clinical Value of Intraprocedural Doppler Ultrasonography Blood Flow Parameters During Peripheral Endovascular Procedures for Limb Salvage: A Pilot Study.

Purpose: To investigate whether Doppler ultrasound (DUS) blood flow parameters could serve as quantifiable functional endpoints of peripheral endovascular arterial procedures for chronic limb-threatening ischemia (CLTI), influencing wound healing.

Methods: This is a prospective single-center study investigating intraprocedural DUS parameters (pulsatility index [PI] and pedal acceleration time [PAT]) in quantifying immediate hemodynamic alterations in consecutive CLTI patients with wound, ischemia, and foot infection wound class ≥1 undergoing endovascular interventions. Primary endpoints were feasibility of preendovascular and postendovascular treatment measurements of PI/PAT, quantification of immediate PI/PAT modifications of the posterior and anterior foot circulation following revascularization, the correlation between PI and PAT, and 6-month complete wound healing.

Creation and evaluation of a participatory child abuse and neglect workshop for medical students.

Background: Since child abuse and neglect (CAN) is prevalent worldwide, medical students should acquire basic knowledge, skills, and confidence in identifying and addressing CAN. Although significant educational efforts have been previously described, none has focused on using participatory methods to teach medical students CAN.

Purpose: To: 1) develop a participatory educational workshop in CAN for medical students, 2) gather, train, and establish a peer-to-peer teaching group, and 3) assess the effectiveness of the workshop in gain of knowledge and improvement of self-confidence for participants.

MYO10-filopodia support basement membranes at pre-invasive tumor boundaries.

Ductal carcinoma in situ (DCIS) is a pre-invasive stage of breast cancer. During invasion, the encapsulating DCIS basement membrane (BM) is compromised, and tumor cells invade the surrounding stroma. The mechanisms that regulate functional epithelial BMs in vivo are poorly understood.

Sustainable Production of Novel Oleogels Valorizing Microbial Oil Rich in Carotenoids Derived from Spent Coffee Grounds.

Sustainable food systems that employ renewable resources without competition with the food chain are drivers for the bioeconomy era. This study reports the valorization of microwave-pretreated spent coffee grounds (SCGs) to produce oleogels rich in bioactive compounds. Microbial oil rich in carotenoids (MOC) was produced under batch fermentation of using SCG enzymatic hydrolysates.

Development of biodegradable films using sunflower protein isolates and bacterial nanocellulose as innovative food packaging materials for fresh fruit preservation.

This study presents the valorization of side streams from the sunflower-based biodiesel industry for the production of bio-based and biodegradable food packaging following circular economy principles. Bacterial cellulose (BC) was produced via fermentation in 6 L static tray bioreactors using nutrient-rich supplements derived from the enzymatic hydrolysis of sunflower meal (SFM) combined with crude glycerol as carbon source. Novel biofilms were produced using either matrices of protein isolates extracted from sunflower meal (SFMPI) alone or SFMPI matrices reinforced with nanocellulose biofillers of commercial or bacterial origin.

Intramuscular Evaluation of Chimeric Locked Nucleic Acid/2'Methyl-Modified Antisense Oligonucleotides for Targeted Exon 23 Skipping in Mdx Mice.

Duchenne muscular dystrophy (DMD) is a fatal disorder characterised by progressive muscle wasting. It is caused by mutations in the dystrophin gene, which disrupt the open reading frame leading to the loss of functional dystrophin protein in muscle fibres. Antisense oligonucleotide (AON)-mediated skipping of the mutated exon, which allows production of a truncated but partially functional dystrophin protein, has been at the forefront of DMD therapeutic research for over two decades.

Circulating tumor necrosis factor-α levels in non-alcoholic fatty liver disease: A systematic review and a meta-analysis.

Background And Aim: To synthesize data on circulating tumor necrosis factor (TNF)-α levels between patients with histologically confirmed non-alcoholic fatty liver disease (NAFLD) (simple steatosis or non-alcoholic fatty liver [NAFL] and/or non-alcoholic steatohepatitis [NASH]) and controls.

Methods: We performed a systematic search in PubMed, Scopus, and Cochrane Library. Fifty-six studies, published between 2003 and 2019, were finally included, reporting data from 5848 individuals (1634 controls and 4214 NAFLD patients).

Effect of Processed Beverage By-Product-Based Diets on Biological Parameters, Conversion Efficiency and Body Composition of (L) (Diptera: Stratiomyidae).

The effect of spent coffee grounds (SCG), brewer's spent grains (BSG) and their mixtures with the addition of brewer's yeast (BY) were tested in two rearing densities of the Black Soldier Fly, (L.). Different treatments were investigated on larval development, survival, yield, protein conversion (PrCR) and bioconversion rate (BCR), substrate mass reduction and body composition of the insect.

Rapid screening on aflatoxins' presence in nuts using diffuse reflectance infrared Fourier transform spectroscopy and chemometrics.

Aflatoxin in pistachios has been analyzed in this work, using Diffuse Reflectance Infrared Spectroscopy (DRIFTS) with chemometrics. Forty-nine Greek pistachio samples of different aflatoxin concentrations were classified into aflatoxin and non-aflatoxin groups using the 3035-2821, 1770-1721, 1570-1481 and 1260-1061 cm spectral regions in Kubelka-Munk conversion and first derivative form. A chemometric model was developed using twenty-eight samples as calibration, 11 as validation and 10 as test set.

Erratum: Integrin Binding Dynamics Modulate Ligand-Specific Mechanosensing in Mammary Gland Fibroblasts.

[This corrects the article DOI: 10.1016/j.isci.

Mechano-responsiveness of fibrillar adhesions on stiffness-gradient gels.

Fibrillar adhesions are important structural and adhesive components in fibroblasts, and are required for fibronectin fibrillogenesis. While nascent and focal adhesions are known to respond to mechanical cues, the mechanoresponsive nature of fibrillar adhesions remains unclear. Here, we used ratiometric analysis of paired adhesion components to determine an appropriate fibrillar adhesion marker.

Study of the Quality Parameters and the Antioxidant Capacity for the FTIR-Chemometric Differentiation of Oils.

The aim of this work was to characterize the pistachio oil of the Greek variety, "Aegina", evaluate its various quality indices, and investigate the potential use of FTIR as a tool to discriminate different oil qualities. For this purpose, the antioxidant capacity, the tocopherol content and the oxidation and degradation of fatty acids, as described by k, Δk, R-values, and free acidity were evaluated using 45 samples from eight different areas of production and two subsequent years of harvesting. The antioxidant capacity was estimated using 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid diammonium salt (ABTS) and 2,2-diphenyl-1-(2,4,6-trinitrophenyl)hydrazine (DPPH) assays, and the tocopherol content was quantified through HPLC analysis.

Integrin Binding Dynamics Modulate Ligand-Specific Mechanosensing in Mammary Gland Fibroblasts.

The link between integrin activity regulation and cellular mechanosensing of tissue rigidity, especially on different extracellular matrix ligands, remains poorly understood. Here, we find that primary mouse mammary gland stromal fibroblasts (MSFs) are able to spread efficiently, generate high forces, and display nuclear YAP on soft collagen-coated substrates, resembling the soft mammary gland tissue. We describe that loss of the integrin inhibitor, SHARPIN, impedes MSF spreading specifically on soft type I collagen but not on fibronectin.

Dual Transcriptional Profile of during Co-Culture with and Aflatoxin B1 Production: A Pathogen-Pathogen Interaction.

The objective of this study was to investigate the effect of growth temperature and co-culture of with on the production of Aflatoxin B1 (AFB1) and the transcriptional profile of associated regulatory and biosynthetic genes. The transcription of virulence- and homeostasis-associated genes of was also assessed. For this purpose, mono- and co-cultures of strain LQC 15257 and strain 18.

SORLA regulates endosomal trafficking and oncogenic fitness of HER2.

The human epidermal growth factor receptor 2 (HER2) is an oncogene targeted by several kinase inhibitors and therapeutic antibodies. While the endosomal trafficking of many other receptor tyrosine kinases is known to regulate their oncogenic signalling, the prevailing view on HER2 is that this receptor is predominantly retained on the cell surface. Here, we find that sortilin-related receptor 1 (SORLA; SORL1) co-precipitates with HER2 in cancer cells and regulates HER2 subcellular distribution by promoting recycling of the endosomal receptor back to the plasma membrane.

Tensins: Bridging AMP-Activated Protein Kinase with Integrin Activation.

Integrin activation is essential for cell adhesion and for connecting the extracellular matrix to the actin cytoskeleton. Thus, inappropriate integrin activation has been linked to several diseases, including cancer. Recent insights demonstrate that the main fibrillar adhesion component tensin maintains β1-integrin active in these mature adhesions.

Reconstitution of a minimal machinery capable of assembling periplasmic type IV pili.

Type IV pili (Tfp), which are key virulence factors in many bacterial pathogens, define a large group of multipurpose filamentous nanomachines widespread in Bacteria and Archaea. Tfp biogenesis is a complex multistep process, which relies on macromolecular assemblies composed of 15 conserved proteins in model gram-negative species. To improve our limited understanding of the molecular mechanisms of filament assembly, we have used a synthetic biology approach to reconstitute, in a nonnative heterologous host, a minimal machinery capable of building Tfp.

AMPK negatively regulates tensin-dependent integrin activity.

Tight regulation of integrin activity is paramount for dynamic cellular functions such as cell matrix adhesion and mechanotransduction. Integrin activation is achieved through intracellular interactions at the integrin cytoplasmic tails and through integrin-ligand binding. In this study, we identify the metabolic sensor AMP-activated protein kinase (AMPK) as a β1-integrin inhibitor in fibroblasts.

SHANK proteins limit integrin activation by directly interacting with Rap1 and R-Ras.

SHANK3, a synaptic scaffold protein and actin regulator, is widely expressed outside of the central nervous system with predominantly unknown function. Solving the structure of the SHANK3 N-terminal region revealed that the SPN domain is an unexpected Ras-association domain with high affinity for GTP-bound Ras and Rap G-proteins. The role of Rap1 in integrin activation is well established but the mechanisms to antagonize it remain largely unknown.

SHARPIN regulates collagen architecture and ductal outgrowth in the developing mouse mammary gland.

SHARPIN is a widely expressed multifunctional protein implicated in cancer, inflammation, linear ubiquitination and integrin activity inhibition; however, its contribution to epithelial homeostasis remains poorly understood. Here, we examined the role of SHARPIN in mammary gland development, a process strongly regulated by epithelial-stromal interactions. Mice lacking SHARPIN expression in all cells (Sharpin), and mice with a stromal (S100a4-Cre) deletion of Sharpin, have reduced mammary ductal outgrowth during puberty.

L-type calcium channels regulate filopodia stability and cancer cell invasion downstream of integrin signalling.

Mounting in vitro, in vivo and clinical evidence suggest an important role for filopodia in driving cancer cell invasion. Using a high-throughput microscopic-based drug screen, we identify FDA-approved calcium channel blockers (CCBs) as potent inhibitors of filopodia formation in cancer cells. Unexpectedly, we discover that L-type calcium channels are functional and frequently expressed in cancer cells suggesting a previously unappreciated role for these channels during tumorigenesis.

Normal stroma suppresses cancer cell proliferation via mechanosensitive regulation of JMJD1a-mediated transcription.

Tissue homeostasis is dependent on the controlled localization of specific cell types and the correct composition of the extracellular stroma. While the role of the cancer stroma in tumour progression has been well characterized, the specific contribution of the matrix itself is unknown. Furthermore, the mechanisms enabling normal-not cancer-stroma to provide tumour-suppressive signals and act as an antitumorigenic barrier are poorly understood.