Ptbp2 re-expression rescues axon growth defects in Smn-deficient motoneurons.

Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by mutations or deletions in the survival motoneuron 1 () gene, resulting in deficiency of the SMN protein that is essential for motoneuron function. Smn depletion in mice disturbs axonal RNA transport and translation, thereby contributing to axon growth impairment, muscle denervation, and motoneuron degeneration. However, the mechanisms whereby Smn loss causes axonal defects remain unclear.

C9orf72 gene repeat expansion phenotype profile of motor neurone disease in Portugal.

Background: C9orf72 gene repeat expansion (C9RE) is the most frequent gene variant associated with amyotrophic lateral sclerosis (ALS). We aimed to study the phenotype of motor neurone disease (MND) patients with C9RE in a Portuguese cohort.

Methods: Demographical and clinical data of MND patients with (C9RE+) and without C9RE were compared.

Immune responses to central nervous system directed adeno-associated virus gene therapy: Does direct CNS delivery make a difference?

Adeno-associated virus (AAV) mediated gene therapy is a leading gene delivery platform with potential to transform the landscape of treatment for neurological disorders. While AAV is deemed non-immunogenic compared to other viral vectors, adverse immune reactions have been observed in the clinic, raising concerns. As the central nervous system (CNS) has a tightly regulated immune system, characterized by a degree of tolerance, it has been considered a unique target for AAV gene therapy.

Diet and physical exercise in elderly people with obesity: The state of the art.

Obesity is a disease that is assuming pandemic proportions in recent decades. With the advancement of medicine and increased access to care, average survival has increased, resulting in a larger number of elderly people. As a result, the amount of elderly people living with obesity is increasing, and the morbidity and impact of obesity on ageing implies severe limitations for these people.

Genotyping sequence-resolved copy-number variations using pangenomes reveals paralog-specific global diversity and expression divergence of duplicated genes.

Copy-number variable (CNV) genes are important in evolution and disease, yet sequence variation in CNV genes is a blindspot for large-scale studies. We present a method, ctyper, that leverages pangenomes to produce copy-number maps with allele-specific sequences containing locally phased variants of CNV genes from NGS reads. We extensively characterized accuracy and efficiency on a database of 3,351 CNV genes including , , and as well as 212 non-CNV medically-relevant challenging genes.

Sarcopenia may predict recurrence in patients with head and neck cancer.

Background: Malnutrition is a major consequence of head and neck cancer (HNC), often leading to decreased skeletal muscle mass and impacting survival. The goal of this study is to determine the effect of sarcopenia, as defined by skeletal muscle index (SMI), on survival in patients with HNC.

Methods: This is a retrospective review of patients with HNC treated with surgery and/or radiation at a single tertiary care institute.

[Blood flow restriction training (BFRT) in patients before and after total knee arthroplasty].

Background: In healthy individuals, blood flow restriction training (BFRT) has shown positive effects on muscle mass, strength, fatigue resistance, as well as tendon and bone metabolism. BFRT reduces blood flow in the extremities using inflatable cuffs, creating local muscular hypoxia, which produces an anabolic metabolic environment. This promotes significant muscular and cardiovascular adaptations even at low mechanical training loads.

Role of senataxin in R-loop-mediated neurodegeneration.

Senataxin is an RNA:DNA helicase that plays an important role in the resolution of RNA:DNA hybrids (R-loops) formed during transcription. R-loops are involved in the regulation of biological processes such as immunoglobulin class switching, gene expression and DNA repair. Excessive accumulation of R-loops results in DNA damage and loss of genomic integrity.

The prognostic value of pre-treatment sarcopenia in overall survival in head and neck cancer patients: a systematic review.

The aim of this study was to determine the prognostic value of pre-treatment sarcopenia, defined radiologically (cervical (C3) or lumbar (L3) region), in adult head and neck cancer (HNC) patients undergoing treatment with curative intent. A systematic search of the PubMed and Scopus databases was performed up to March 2024. Inclusion criteria were adult patients with locally advanced HNC, sarcopenia defined radiologically at the C3 and/or L3 level, and patients receiving primary treatment with curative intent.

Sarcopenia as a Predictive Factor for Carboplatin Toxicity in Patients with Advanced Non-Small Cell Lung Cancer.

Sarcopenia in cancer patients often negatively impacts various outcomes. Carboplatin, a first-line chemotherapy for non-small cell lung cancer (NSCLC), is dosed based on body weight, which doesn't account for sarcopenia. This study evaluated the association between sarcopenia and carboplatin-related toxicity in NSCLC patients.

RBP4 promotes denervation-induced muscle atrophy through STRA6-dependent pathway.

Backgrounds: Fat infiltration of skeletal muscle has been recognized as a common feature of many degenerative muscle disorders. Retinol binding protein 4 (RBP4) is an adipokine that has been demonstrated to be correlated with the presence and severity of sarcopenia in the elderly. However, the exact role and the underlying mechanism of RBP4 in muscle atrophy remains unclear.

Thyroid dysgenesis associated with dwarfism, osteoporosis and spontaneous fractures in a goat.

An 11-month-old female Saanen goat, weighing 12.7 kg, was taken to the Veterinary Hospital of the Federal University of Minas Gerais because of sternal recumbency. On clinical examination, the animal was much smaller than expected and had hair similar to that of puppies and areas of hyperpigmentation on the head and dorsocervical and dorsothoracic cranial regions.

Causal Relationship Between Gut Microbiota, Metabolites, and Sarcopenia: A Mendelian Randomization Study.

Background: Gut microbiota imbalance and sarcopenia are frequently observed in older adults. Gut microbiota and their metabolites are considered risk factors contributing to the heightened risk of sarcopenia, but whether these associations are causal remains unclear.

Methods: We conducted linkage disequilibrium score regression and 2-sample Mendelian randomization (MR) methods with single-nucleotide polymorphisms sourced from large-scale genome-wide association studies as instrumental variables to examine the causal associations linking gut microbiota with their metabolites to the sarcopenia.

Association between sleep duration and possible sarcopenia in middle-aged and elderly Chinese individuals: evidence from the China health and retirement longitudinal study.

Background: Sarcopenia is a common cause of disability in the aging population, and managing sarcopenia is an important step in building intrinsic capacity and promoting healthy aging. A growing body of evidence suggests that sleep deprivation may be a mediator of the development of sarcopenia. The purpose of this study was to explore the longitudinal association between sleep duration and possible sarcopenia using data from a national sample.

miR-196a in the carcinogenesis and other disorders with an especial focus on its biomarker capacity.

miR-196a has important roles in the pathoetiology of different disorders ranging from non-malignant to malignant ones. This miRNA is transcribed from two genomic loci, namely HOXC and HOXB on human chromosomes 12 and 17, respectively. The current study aims to summarize the role of miR-196a in different disorders.

A Nomogram Including Sarcopenia for Predicting Progression-Free Survival in Patients with Localized Papillary Renal Cell Carcinoma: A Retrospective Cohort Study.

Background: Because of to the removal of subclassification of papillary renal cell carcinoma (pRCC), the survival prognostification of localized pRCC after surgical treatment became inadequate. Sarcopenia was widely evaluated and proved to be a predictive factor for prognosis in RCC patients. Therefore, we comprehensively investigated the survival prediction of the body composition parameters for localized pRCC.

Sarcopenic obesity predicts short- and long-term outcomes after neoadjuvant chemotherapy and surgery for gastric cancer.

Background: Sarcopenic obesity (SO) affects outcomes in various malignancies. However, its clinical significance in patients undergoing neoadjuvant chemotherapy (NAC) for locally advanced gastric cancer (LAGC) remains unclear. This study investigated the impact of pre- and post-NAC SO on postoperative morbidity and survival.

Truncated variants of MAGEL2 are involved in the etiologies of the Schaaf-Yang and Prader-Willi syndromes.

The neurodevelopmental disorders Prader-Willi syndrome (PWS) and Schaaf-Yang syndrome (SYS) both arise from genomic alterations within human chromosome 15q11-q13. A deletion of the SNORD116 cluster, encoding small nucleolar RNAs, or frameshift mutations within MAGEL2 result in closely related phenotypes in individuals with PWS or SYS, respectively. By investigation of their subcellular localization, we observed that in contrast to a predominant cytoplasmic localization of wild-type (WT) MAGEL2, a truncated MAGEL2 mutant was evenly distributed between the cytoplasm and the nucleus.

Chaperoning the chaperones: Proteomic analysis of the SMN complex reveals conserved and etiologic connections to the proteostasis network.

Molecular chaperones and co-chaperones are highly conserved cellular components that perform variety of duties related to the proper three-dimensional folding of the proteome. The web of factors that carries out this essential task is called the proteostasis network (PN). Ribonucleoproteins (RNPs) represent an underexplored area in terms of the connections they make with the PN.

Unilateral hindlimb ischaemia-induced systemic inflammation is associated with non-ischaemic skeletal muscle inflammation.

Skeletal muscle atrophy and dysfunction commonly accompany cardiovascular diseases such as peripheral arterial disease and may be partially attributable to systemic inflammation. We sought to determine whether acute systemic inflammation in a model of hindlimb ischaemia (HLI) could affect skeletal muscle macrophage infiltration, fibre size, or capillarization, independent of the ischaemia. Eight-week-old C57BL/6 male mice underwent either Sham or HLI surgery, and were killed 1, 3, or 7 days post-surgery.

Spinal cord neurone loss and foot placement changes in a rat knock-in model of amyotrophic lateral sclerosis Type 8.

Amyotrophic lateral sclerosis is an age-dependent cell type-selective degenerative disease. Genetic studies indicate that amyotrophic lateral sclerosis is part of a spectrum of disorders, ranging from spinal muscular atrophy to frontotemporal dementia that share common pathological mechanisms. Amyotrophic lateral sclerosis Type 8 is a familial disease caused by mis-sense mutations in .

Effects of essential amino acid (EAA) and glutamine supplementation on skeletal muscle wasting in acute, subacute, and postacute conditions.

Under optimal physiological conditions, muscle mass maintenance is ensured by dietary protein, which balances the amino acid loss during the post-absorption period and preserves the body's protein homeostasis. Conversely, in critical clinical conditions (acute, subacute or postacute), particularly those related to hypomobility or immobility, combined with malnutrition, and local/systemic inflammation, the loss of muscle mass and strength can be quantitatively significant. A decline of more than 1% in muscle mass and of more than 3% in muscle strength has been registered in subjects with aged 20-37 yr after just five days of bed rest, similarly to those observed during one year of age-related decline in individuals over the age of 50.