Acostaali0668

Aging, the greatest risk factor for Alzheimer's disease (AD), may lead to the accumulation of somatic mutations in neurons. We investigated whether somatic mutations, specifically in longer genes, are implicated in AD etiology. First, we modeled the theoretical likelihood of genes being affected by aging-induced somatic mutations, dependent on their length. We then tested this model and found that long genes are indeed more affected by somatic mutations and that their expression is more frequently reduced in AD brains. Furthermore, using gene-set enrichment analysis, we investigated the potential consequences of such long gene disruption. We found that long genes are involved in synaptic adhesion and other synaptic pathways that are predicted to be inhibited in the brains of AD patients. Taken together, our findings indicate that long gene-dependent synaptic impairment may contribute to AD pathogenesis.Long winters led to a one-crop-a-year cultivation system until the winter wheat Dongnongdongmai 1 (Dn1) was successfully cultivated in northeast China. This crop variety is resistant to extremely low temperatures (-35 °C). To better understand the adaptability of winter wheat Dn1 to low temperatures, gas chromatography time-of-flight mass spectrometry (GC-TOF/MS) and metabolomics analysis was conducted on the tillering nodes of winter wheat during the overwintering period. Enzyme-regulating genes of the metabolic products were also quantitatively analysed. The metabolomic results for the tillering nodes in the overwintering period showed that disaccharides had a strong protective effect on winter wheat Dn1. Amino acid metabolism (i.e. proline, alanine and GABA) changed significantly throughout the whole wintering process, whereas organic fatty acid metabolism changed significantly only in the late stage of overwintering. This result indicates that the metabolites used by winter wheat Dn1 differ in different overwintering stages. The relationship between field temperature and metabolite changes in winter wheat Dn1 during overwintering periods is discussed, and disaccharides were identified as the osmotic stress regulators for winter wheat Dn1 during the overwintering process, as well as maintenance of the carbon and nitrogen balance by monosaccharides, amino acids and lipids for cold resistance.There is wide variability in the propensity of somatic cells to reprogram into pluripotency in response to the Yamanaka factors. How to segregate these variabilities to enrich for cells of specific traits that reprogram efficiently remains challenging. Here we report that the variability in reprogramming propensity is associated with the activity of the MKL1/SRF transcription factor and concurs with small cell size as well as rapid cell cycle. Reprogramming progressive cells can be prospectively identified by their low activity of a widely used synthetic promoter, CAG. CAGlow cells arise and expand during cell cycle acceleration in the early reprogramming culture of both mouse and human fibroblasts. Our work illustrates a molecular scenario underlying the distinct reprogramming propensities and demonstrates a convenient practical approach for their enrichment.

While prospective clinical studies on immunotherapy in epidermal growth factor receptor (EGFR) mutant non-small-cell lung cancer (NSCLC) with acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) are ongoing, this study aimed to investigate the outcomes of immunotherapy combinations in such a population in a real-world setting.

The clinical data of pretreated EGFR-mutated NSCLC patients who acquired EGFR-TKI resistance and received immunotherapy were retrospectively analyzed in this study. Tanespimycin inhibitor Progression-free survival (PFS) was assessed using the Kaplan-Meier log-rank test, and univariate and multivariate analysis were performed.

A total of 31 patients were analyzed in this study. A total of 25 (80.6%) patients received combination immunotherapy. In the univariate analysis, patients who received combination immunotherapy seemingly acquired longer PFS than those who received monotherapy, although there was no significant difference (3.42 months vs. 1.61; P = 0.078; hazard ratio (HR) 0.43, 95% CI 0.1ds Patients without liver metastasis and with prior antiangiogenic drugs obtained more benefit from immunotherapy in this setting.

Significant study findings Immunotherapy-based combination therapies are better choices than single-agent regimens in heavily treated EGFR-mutant NSCLC patients. What this study adds Patients without liver metastasis and with prior antiangiogenic drugs obtained more benefit from immunotherapy in this setting.

Self-regulatory behaviour change techniques (BCTs) appear less effective in promoting physical activity amongst older than younger adults. This study aimed to identify reasons for this by examining how participants of different ages understand, experience, and use these BCTs.

Twelve participants (aged 39-75) in a walking intervention study were interviewed twice immediately post-intervention and 3 months later to examine understanding and enactment of self-regulation BCTs. Thematic analysis was used, organised using the framework approach.

Participants acknowledged the importance of setting realistic goals and found pedometers useful. In older adults, the use of goal setting was influenced by previous experience in work settings of this BCT. Occupational status appeared to influence the participants' responses to action planning, irrespective of age, with retired participants preferring not to restrict themselves to specific times. Self-monitoring with diaries appeared to be more useful in assisting the memory of older adults. For most BCTs, differences in understanding and enactment were apparent according to participant age.

Problems with using self-regulation BCTs were apparent, which appeared more common with older adults. Occupational status, cognitive status, or a perceived lack of value of physical activity or of some BCTs are all promising explanations that warrant further investigation.

Problems with using self-regulation BCTs were apparent, which appeared more common with older adults. Occupational status, cognitive status, or a perceived lack of value of physical activity or of some BCTs are all promising explanations that warrant further investigation.