SMCHD1 genetic variants in type 2 facioscapulohumeral dystrophy and challenges in predicting pathogenicity and disease penetrance.

The molecular diagnosis of type 1 facioscapulohumeral muscular dystrophy (FSHD1) relies on the detection of a shortened D4Z4 array at the 4q35 locus. Until recently, the diagnosis of FSHD2 relied solely on the absence of a shortened D4Z4 allele in clinically affected patients. It is now established that most FSHD2 cases carry a heterozygous variant in the SMCHD1 gene.

Factors associated with attitudes toward death and dying in the second half of life: A scoping review.

How we think and feel about death and dying affects how we live our lives and our opportunities for healthy aging. This scoping review, using the PRISMA guidelines and drawing on the World Health Organizations public health framework for healthy aging, examined the personal, health and environmental factors associated with attitudes toward death and dying in persons 50 years and older. Most of the 74 eligible studies focused only on negative attitudes to death and few studies investigated the comprehensive range of factors that influence attitudes to death and dying.

Systematic review on attitudes towards death and dying in adults 50 years and older living in countries with community transmission of COVID-19.

Background: The COVID-19 pandemic has underscored older adults' vulnerability to severe illness or death. Increased public awareness of mortality, with daily reminders of preventive measures, spurred interest in understanding the impact on death-related thoughts. This systematic review analyses existing literature on death attitudes among individuals aged 50 and older during the COVID-19 pandemic and focuses on associated factors.

Chronic exercise effects on overall depression severity and distinct depressive symptoms in older adults: A protocol of a systematic and meta-analytic review.

Introduction: There is high evidence that chronic exercise benefits overall depression severity in older adults. However, late-life depression is characterized by considerable heterogeneity in clinical manifestation emphasizing the need for more individualized exercise intervention programs. Therefore, the objective of the proposed review is to investigate the effects of chronic exercise on overall depression severity and on different symptoms of depression in randomized controlled trials (RCTs) including older adults with a mean age of at least 60 years, and by considering the moderating effects of intervention characteristics and individual characteristics.

Effects of chronic physical exercise on executive functions and episodic memory in clinical and healthy older adult populations: a systematic review and meta-analysis protocol.

Background: Executive functions (EFs) and episodic memory are fundamental components of cognition that deteriorate with age and are crucial for independent living. While numerous reviews have explored the effect of exercise on these components in old age, these reviews screened and analyzed selected older adult populations, or specific exercise modes, thus providing only limited answers to the fundamental question on the effect of exercise on cognition in old age. This article describes the protocol for a systematic review and multilevel meta-analytic study aiming at evaluating the effectiveness of different types of chronic exercise in improving and/or maintaining EFs and long-term episodic memory in older adults.

Subnational inequalities in years of life lost and associations with socioeconomic factors in pre-pandemic Europe, 2009-19: an ecological study.

Background: Health inequalities have been associated with shorter lifespans. We aimed to investigate subnational geographical inequalities in all-cause years of life lost (YLLs) and the association between YLLs and socioeconomic factors, such as household income, risk of poverty, and educational attainment, in countries within the European Economic Area (EEA) before the COVID-19 pandemic.

Methods: In this ecological study, we extracted demographic and socioeconomic data from Eurostat for 1390 small regions and 285 basic regions for 32 countries in the EEA, which was complemented by a time-trend analysis of subnational regions within the EEA.

Longitudinal associations between sensory and cognitive functioning in adults 60 years or older in Sweden and Denmark.

Background: The objective of this study is to explore the bidirectional, longitudinal associations between self-reported sensory functions (hearing/vision) and cognitive functioning among older adults in Sweden and Denmark during the period 2004-2017.

Methods: The study is based on data from The Survey of Health, Ageing and Retirement in Europe and consists of 3164 persons aged 60 to 93 years. Within-person associations between sensory and cognitive functions were estimated using random intercept cross-lagged panel models.

Human septins organize as octamer-based filaments and mediate actin-membrane anchoring in cells.

Septins are cytoskeletal proteins conserved from algae and protists to mammals. A unique feature of septins is their presence as heteromeric complexes that polymerize into filaments in solution and on lipid membranes. Although animal septins associate extensively with actin-based structures in cells, whether septins organize as filaments in cells and if septin organization impacts septin function is not known.

Why Are Old-Age Disabilities Decreasing in Sweden and Denmark? Evidence on the Contribution of Cognition, Education, and Sensory Functions.

Objectives: Improvements in educational attainment, cognitive and sensory functions, and a decline in the prevalence of disabilities have been observed in older adults in Sweden and Denmark. In the present study, it was investigated whether better cognition, higher educational attainment, and improved sensory function among older adults aged 60 and older in these countries have contributed to decreasing rates of old-age disabilities.

Methods: The analyses were based on repeated cross-sectional data from the Survey of Health, Ageing, and Retirement in Europe for the 2004-2017 period.

Septin-microtubule association via a motif unique to isoform 1 of septin 9 tunes stress fibers.

Septins, a family of GTP-binding proteins that assemble into higher order structures, interface with the membrane, actin filaments and microtubules, and are thus important regulators of cytoarchitecture. Septin 9 (SEPT9), which is frequently overexpressed in tumors and mutated in hereditary neuralgic amyotrophy (HNA), mediates the binding of septins to microtubules, but the molecular determinants of this interaction remained uncertain. We demonstrate that a short microtubule-associated protein (MAP)-like motif unique to SEPT9 isoform 1 (SEPT9_i1) drives septin octamer-microtubule interaction in cells and in vitro reconstitutions.

iASPP contributes to cell cortex rigidity, mitotic cell rounding, and spindle positioning.

iASPP is a protein mostly known as an inhibitor of p53 pro-apoptotic activity and a predicted regulatory subunit of the PP1 phosphatase, which is often overexpressed in tumors. We report that iASPP associates with the microtubule plus-end binding protein EB1, a central regulator of microtubule dynamics, via an SxIP motif. iASPP silencing or mutation of the SxIP motif led to defective microtubule capture at the cortex of mitotic cells, leading to abnormal positioning of the mitotic spindle.

Structural and dynamic characterization of the C-terminal tail of ErbB2: Disordered but not random.

ErbB2 (or HER2) is a receptor tyrosine kinase overexpressed in some breast cancers and associated with poor prognosis. Treatments targeting the receptor extracellular and kinase domains have greatly improved disease outcome in the last 20 years. In parallel, the structures of these domains have been described, enabling better mechanistic understanding of the receptor function and targeted inhibition.

EB1 Restricts Breast Cancer Cell Invadopodia Formation and Matrix Proteolysis via FAK.

Regulation of microtubule dynamics by plus-end tracking proteins (+TIPs) plays an essential role in cancer cell migration. However, the role of +TIPs in cancer cell invasion has been poorly addressed. Invadopodia, actin-rich protrusions specialized in extracellular matrix degradation, are essential for cancer cell invasion and metastasis, the leading cause of death in breast cancer.

COVID-19: Opportunities for interdisciplinary research to improve care for older people in Sweden.

The emergence of COVID-19 has changed the world as we know it, arguably none more so than for older people. In Sweden, the majority of COVID-19-related fatalities have been among people aged ⩾70 years, many of whom were receiving health and social care services. The pandemic has illuminated aspects within the care continuum requiring evaluative research, such as decision-making processes, the structure and organisation of care, and interventions within the complex public-health system.

A proximity-labeling proteomic approach to investigate invadopodia molecular landscape in breast cancer cells.

Metastatic progression is the leading cause of mortality in breast cancer. Invasive tumor cells develop invadopodia to travel through basement membranes and the interstitial matrix. Substantial efforts have been made to characterize invadopodia molecular composition.

The role of APC-mediated actin assembly in microtubule capture and focal adhesion turnover.

Focal adhesion (FA) turnover depends on microtubules and actin. Microtubule ends are captured at FAs, where they induce rapid FA disassembly. However, actin's roles are less clear.

Memo1-Mediated Tiling of Radial Glial Cells Facilitates Cerebral Cortical Development.

Polarized, non-overlapping, regularly spaced, tiled organization of radial glial cells (RGCs) serves as a framework to generate and organize cortical neuronal columns, layers, and circuitry. Here, we show that mediator of cell motility 1 (Memo1) is a critical determinant of radial glial tiling during neocortical development. Memo1 deletion or knockdown leads to hyperbranching of RGC basal processes and disrupted RGC tiling, resulting in aberrant radial unit assembly and neuronal layering.

EB1-binding-myomegalin protein complex promotes centrosomal microtubules functions.

Control of microtubule dynamics underlies several fundamental processes such as cell polarity, cell division, and cell motility. To gain insights into the mechanisms that control microtubule dynamics during cell motility, we investigated the interactome of the microtubule plus-end-binding protein end-binding 1 (EB1). Via molecular mapping and cross-linking mass spectrometry we identified and characterized a large complex associating a specific isoform of myomegalin termed "SMYLE" (for short myomegalin-like EB1 binding protein), the PKA scaffolding protein AKAP9, and the pericentrosomal protein CDK5RAP2.

Syntenin mediates SRC function in exosomal cell-to-cell communication.

The cytoplasmic tyrosine kinase SRC controls cell growth, proliferation, adhesion, and motility. The current view is that SRC acts primarily downstream of cell-surface receptors to control intracellular signaling cascades. Here we reveal that SRC functions in cell-to-cell communication by controlling the biogenesis and the activity of exosomes.

H, C and N assignments of the C-terminal intrinsically disordered cytosolic fragment of the receptor tyrosine kinase ErbB2.

ErbB2 (or HER2) is a receptor tyrosine kinase that is involved in signaling pathways controlling cell division, motility and apoptosis. Though important in development and cell growth homeostasis, this protein, when overexpressed, participates in triggering aggressive HER2+ breast cancers. It is composed of an extracellular part and a transmembrane domain, both important for activation by dimerization, and a cytosolic tyrosine kinase, which activates its intrinsically disordered C-terminal end (CtErbB2).

Adenomatous polyposis coli nucleates actin assembly to drive cell migration and microtubule-induced focal adhesion turnover.

Cell motility depends on tight coordination between the microtubule (MT) and actin cytoskeletons, but the mechanisms underlying this MT-actin cross talk have remained poorly understood. Here, we show that the tumor suppressor protein adenomatous polyposis coli (APC), which is a known MT-associated protein, directly nucleates actin assembly to promote directed cell migration. By changing only two residues in APC, we generated a separation-of-function mutant, APC (m4), that abolishes actin nucleation activity without affecting MT interactions.