Direct structural analysis of a single acyl carrier protein domain in fatty acid synthase from the fungus Saccharomyces cerevisiae.

Acyl carrier protein (ACP) is the work horse of polyketide (PKS) and fatty acid synthases (FAS) and acts as a substrate shuttling domain in these mega enzymes. In fungi, FAS forms a 2.6 MDa symmetric assembly with six identical copies of FAS1 and FAS2 polypeptides.

Human Alzheimer's disease reactive astrocytes exhibit a loss of homeostastic gene expression.

Astrocytes are one of the brain's major cell types and are responsible for maintaining neuronal homeostasis via regulating the extracellular environment, providing metabolic support, and modulating synaptic activity. In neurodegenerative diseases, such as Alzheimer's disease, astrocytes can take on a hypertrophic appearance. These reactive astrocytes are canonically associated with increases in cytoskeletal proteins, such as glial fibrillary acidic protein and vimentin.

Atomic model for core modifying region of human fatty acid synthase in complex with Denifanstat.

Fatty acid synthase (FASN) catalyzes the de novo synthesis of palmitate, a 16-carbon chain fatty acid that is the primary precursor of lipid metabolism and an important intracellular signaling molecule. FASN is an attractive drug target in diabetes, cancer, fatty liver diseases, and viral infections. Here, we develop an engineered full-length human FASN (hFASN) that enables isolation of the condensing and modifying regions of the protein post-translation.

An integrated virtual pathology education platform developed using Microsoft Power Apps and Microsoft Teams.

The transition towards digital pathology and an extensive selection of video conferencing platforms have helped provide continuity to education even during the COVID-19 pandemic. Innovative approaches for pathology education, will likely persist beyond the pandemic, as they have powerful didactic potential. While there is a wide selection of software for use as educational tools, an environment to access all resources with ease is clearly lacking.

Targeting STAT5 Signaling Overcomes Resistance to IDH Inhibitors in Acute Myeloid Leukemia through Suppression of Stemness.

Unlabelled: Mutant isocitrate dehydrogenase 1 (IDH1) and IDH2 block the differentiation of acute myeloid leukemia (AML) cells through production of R-2-hydroxyglutarate (R-2-HG). IDH inhibitors can induce differentiation of AML cells by lowering R-2-HG but have limited clinical efficacy as single agents. Here, we performed a genome-wide CRISPR knockout screen in an Idh1-mutated hematopoietic progenitor cell line to identify genes that increased the differentiation response to ivosidenib, an IDH1 inhibitor.

SARS-CoV-2 impairs interferon production via NSP2-induced repression of mRNA translation.

Viruses evade the innate immune response by suppressing the production or activity of cytokines such as type I interferons (IFNs). Here we report the discovery of a mechanism by which the SARS-CoV-2 virus coopts an intrinsic cellular machinery to suppress the production of the key immunostimulatory cytokine IFN-β. We reveal that the SARS-CoV-2 encoded nonstructural protein 2 (NSP2) directly interacts with the cellular GIGYF2 protein.

Structural Characterization of Endogenous Tuberous Sclerosis Protein Complex Revealed Potential Polymeric Assembly.

Tuberous sclerosis protein complex (pTSC) nucleates a proteinaceous signaling hub that integrates information about the internal and external energy status of the cell in the regulation of growth and energy consumption. Biochemical and cryo-electron microscopy studies of recombinant pTSC have revealed its structure and stoichiometry and hinted at the possibility that the complex may form large oligomers. Here, we have partially purified endogenous pTSC from fasted mammalian brains of rat and pig by leveraging a recombinant antigen binding fragment (F) specific for the TSC2 subunit of pTSC.

ADNC-RS, a clinical-genetic risk score, predicts Alzheimer's pathology in autopsy-confirmed Parkinson's disease and Dementia with Lewy bodies.

Growing evidence suggests overlap between Alzheimer's disease (AD) and Parkinson's disease (PD) pathophysiology in a subset of patients. Indeed, 50-80% of autopsy cases with a primary clinicopathological diagnosis of Lewy body disease (LBD)-most commonly manifesting during life as PD-have concomitant amyloid-beta and tau pathology, the defining pathologies of AD. Here we evaluated common genetic variants in genome-wide association with AD as predictors of concomitant AD pathology in the brains of people with a primary clinicopathological diagnosis of PD or Dementia with Lewy Bodies (DLB), diseases both characterized by neuronal Lewy bodies.

Translational control in the tumor microenvironment promotes lung metastasis: Phosphorylation of eIF4E in neutrophils.

The translation of mRNAs into proteins serves as a critical regulatory event in gene expression. In the context of cancer, deregulated translation is a hallmark of transformation, promoting the proliferation, survival, and metastatic capabilities of cancer cells. The best-studied factor involved in the translational control of cancer is the eukaryotic translation initiation factor 4E (eIF4E).

Evaluation of a multidisciplinary rehabilitation programme for elderly patients with hip fracture: A prospective cohort study.

Objective: To investigate the effectiveness and cost of an 18-month multi-disciplinary Comprehensive Fragility Fracture Management Program (CFFMP) for fragility hip fracture patients.

Design: Prospective cohort study.

Patients: Elderly patients with hip fracture were recruited at their first postoperative follow-up in 2 district hospitals.

Neuropsychological Profile and Dementia Symptom Recognition in Help-Seekers in a Community Early-Detection Program in Hong Kong.

Objectives: To examine the neuropsychological and clinical profile of help-seekers in an early-detection community dementia program and to explore any relationship between profiles and time to seek help.

Design: Cross-sectional.

Setting: Early-detection community dementia program.

Development of Six Arts, a Culturally Appropriate Multimodal Nonpharmacological Intervention in Dementia.

Purpose: There is accumulating evidence for the efficacy of nonpharmacological multimodal stimulation interventions in maintaining cognition and improving quality of life in people with mild-to-moderate dementia. However, the complex nature of these interventions limits their application in practice and research. We report here the design and development of a culturally appropriate framework, the Six Arts, to guide delivery of multimodal interventions in a Chinese community.

A case of young-onset dementia.

Dementia is a major worldwide public health concern in view of the global ageing phenomenon. Dementia usually occurs in old age. However, if the symptoms occur in young patients, the diagnosis can be challenging.

Effect of early pulmonary rehabilitation on health care utilization and health status in patients hospitalized with acute exacerbations of COPD.

Background And Objective: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) incur heavy utilization of health-care resources for patients who require hospitalization. We evaluated whether an early outpatient pulmonary rehabilitation programme (PRP) after hospitalization for AECOPD could reduce acute health-care utilization over the succeeding year.

Methods: Sixty patients admitted with AECOPD were randomized to either PRP or usual care (UC).

Tuberculin skin test reaction and body mass index in old age home residents in Hong Kong.

Objectives: To study the relationship between body mass index (BMI) and tuberculin skin test (TST) reaction in predicting the development of active tuberculosis (TB).

Design: A follow-up study.

Setting: Old age homes.

Prevalence of tuberculous infection and active tuberculosis in old age homes in Hong Kong.

Objectives: To assess the prevalence of tuberculous infection and active tuberculosis (TB) in old age homes in Hong Kong and to determine whether there is institutional transmission in these homes.

Design: Cross-sectional.

Setting: Old age homes.