Effect of genetic and vascular risk factors on rates of cognitive decline in early-onset and late-onset Alzheimer's disease.

Background: Although previous studies have shown that cognitive decline in Alzheimer's disease (AD) is associated with various risk factors, they primarily focused on late-onset AD (LOAD).

Objective: We aim to evaluate the differential impact of risk factors on the cognitive decline between early-onset AD (EOAD, onset < 65 years) and LOAD (onset 65 years) and explore the longitudinal effect of Apolipoprotein E allele 4 ( ε4) on cortical atrophy in both cohorts.

Methods: Using data from 212 EOAD and 1101 LOAD participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI), we conducted multivariable mixed-effect models to evaluate the impact of ε4, education, hypertension, diabetes, dyslipidemia, and body mass index on cognitive performance.

Effects of Aging on the Immune and Periosteal Response to Fracture in Mice.

Aging predisposes individuals to reduced bone mass and fragility fractures, which are costly and linked to high mortality. Understanding how aging affects fracture healing is essential for developing therapies to enhance bone regeneration in older adults. During the inflammatory phase of fracture healing, immune cells are recruited to the injury site as periosteal skeletal stem/progenitor cells (pSSPCs) rapidly proliferate and differentiate into osteochondral lineages, allowing for fibrocartilaginous callus formation and complete bone healing.

Improved Methodology for Studying Postnatal Osteogenesis via Intramembranous Ossification in a Murine Bone Marrow Injury Model.

Long bone injuries heal through either endochondral or intramembranous bone formation pathways. Unlike the endochondral pathway that requires a cartilage template, the process of intramembranous ossification involves the direct conversion of skeletal stem and progenitor cells (SSPCs) into bone-forming osteoblasts. There are limited surgical methods to model this process in experimental mice.

Development of Biodegradable Bioplastics with Sericin and Gelatin from Silk Cocoons and Fish Waste.

The bioplastics sector promotes environmentally friendly means of cutting down on the usage of fossil fuels, plastic waste, and environmental pollution. Plastic contamination has detrimental effects on both ecological systems and the global food supply. The approach we present here to resolve this issue involves the integration of sericin and gelatin, obtained from cocoon and fish waste, respectively, with nano-reinforced cellulose crystals, to develop a biodegradable and compostable plastic material.

Signaling pathways associated with Lgr6 to regulate osteogenesis.

Fracture management largely relies on the bone's inherent healing capabilities and, when necessary, surgical intervention. Currently, there are limited osteoinductive therapies to promote healing, making targeting skeletal stem/progenitor cells (SSPCs) a promising avenue for therapeutic development. A limiting factor for this approach is our incomplete understanding of the molecular mechanisms governing SSPCs' behavior.

Hypersonic flow study in a pneumatically operated academic shock tunnel.

A hypersonic shock tunnel is a primary tool used for basic experimental research and may be used in engineering and university courses to study compressible flows involving shock waves. In the present study, a pneumatically operated shock tunnel is demonstrated for hypersonic flow studies. The high-pressure nitrogen gas is used to drive a pneumatic cylinder, which is used to burst the thin metal diaphragms.

Wnt-associated adult stem cell marker Lgr6 is required for osteogenesis and fracture healing.

Despite the remarkable regenerative capacity of skeletal tissues, nonunion of bone and failure of fractures to heal properly presents a significant clinical concern. Stem and progenitor cells are present in bone and become activated following injury; thus, elucidating mechanisms that promote adult stem cell-mediated healing is important. Wnt-associated adult stem marker Lgr6 is implicated in the regeneration of tissues with well-defined stem cell niches in stem cell-reliant organs.

PDGF inhibits BMP2-induced bone healing.

Bone regeneration depends on a pool of bone/cartilage stem/progenitor cells and signaling mechanisms regulating their differentiation. Using in vitro approach, we have shown that PDGF signaling through PDGFRβ inhibits BMP2-induced osteogenesis, and significantly attenuates expression of BMP2 target genes. We evaluated outcomes of treatment with two anabolic agents, PDGF and BMP2 using different bone healing models.

APOE ε4 carrier status and sex differentiate rates of cognitive decline in early- and late-onset Alzheimer's disease.

Background: We studied the effect of apolipoprotein E (APOE) ε4 status and sex on rates of cognitive decline in early- (EO) and late- (LO) onset Alzheimer's disease (AD).

Method: We ran mixed-effects models with longitudinal cognitive measures as dependent variables, and sex, APOE ε4 carrier status, and interaction terms as predictor variables in 998 EOAD and 2562 LOAD participants from the National Alzheimer's Coordinating Center.

Results: APOE ε4 carriers showed accelerated cognitive decline relative to non-carriers in both EOAD and LOAD, although the patterns of specific cognitive domains that were affected differed.

Associations between Cortical Thickness and Metamemory in Alzheimer's Disease.

Metacognitive deficits affect Alzheimer's disease (AD) patient safety and increase caregiver burden. The brain areas that support metacognition are not well understood. 112 participants from the Imaging and Genetic Biomarkers for AD (ImaGene) study underwent comprehensive cognitive testing and brain magnetic resonance imaging.

Interactions of B-lymphocytes and bone cells in health and disease.

Bone remodeling occurs through the interactions of three major cell lineages, osteoblasts, which mediate bone formation, osteocytes, which derive from osteoblasts, sense mechanical force and direct bone turnover, and osteoclasts, which mediate bone resorption. However, multiple additional cell types within the bone marrow, including macrophages, T lymphocytes and B lymphocytes influence the process. The bone marrow microenvironment, which is supported, in part, by bone cells, forms a nurturing network for B lymphopoiesis.

Predicting the Emergence of Major Neurocognitive Disorder Within Three Months After a Stroke.

Neurocognitive disorder (NCD) is common after stroke, with major NCD appearing in about 10% of survivors of a first-ever stroke. We aimed to classify clinical- and imaging factors related to rapid development of major NCD 3 months after a stroke, so as to examine the optimal composition of factors for predicting rapid development of the disorder. We hypothesized that the prediction would mainly be driven by neurodegenerative as opposed to vascular brain changes.

Iontophoresis mediated localized delivery of liposomal gold nanoparticles for photothermal and photodynamic therapy of acne.

Acne is one of the common dermatological skin inflammatory conditions. The current therapeutic modalities for the treatment of acne include the administration of antibiotics and anti-inflammatory agents. The rising instance of antibiotic resistance in acne strains has led to the exploration of alternative therapeutic modalities.

Diabetes impairs periosteal progenitor regenerative potential.

Diabetics are at increased risk for fracture, and experience severely impaired skeletal healing characterized by delayed union or nonunion of the bone. The periosteum harbors osteochondral progenitors that can differentiate into chondrocytes and osteoblasts, and this connective tissue layer is required for efficient fracture healing. While bone marrow-derived stromal cells have been studied extensively in the context of diabetic skeletal repair and osteogenesis, the effect of diabetes on the periosteum and its ability to contribute to bone regeneration has not yet been explicitly evaluated.

LGRs in Skeletal Tissues: An Emerging Role for Wnt-Associated Adult Stem Cell Markers in Bone.

Leucine-rich repeat-containing G protein-coupled receptors (LGRs) are adult stem cell markers that have been described across various stem cell niches, and expression of LGRs and their corresponding ligands (R-spondins) has now been reported in multiple bone-specific cell types. The skeleton harbors elusive somatic stem cell populations that are exceedingly compartment-specific and under tight regulation from various signaling pathways. Skeletal progenitors give rise to multiple tissues during development and during regenerative processes of bone, requiring postnatal endochondral and intramembranous ossification.

Investigating global gene expression changes in a murine model of cherubism.

Cherubism is a rare genetic disorder caused primarily by mutations in SH3BP2 resulting in excessive bone resorption and fibrous tissue overgrowth in the lower portions of the face. Bone marrow derived cell cultures derived from a murine model of cherubism display poor osteogenesis and spontaneous osteoclast formation. To develop a deeper understanding for the potential underlying mechanisms contributing to these phenotypes in mice, we compared global gene expression changes in hematopoietic and mesenchymal cell populations between cherubism and wild type mice.

A PDGFRβ-PI3K signaling axis mediates periosteal cell activation during fracture healing.

Insufficient and delayed fracture healing remain significant public health problems with limited therapeutic options. Phosphoinositide 3-kinase (PI3K) signaling, a major pathway involved in regulation of fracture healing, promotes proliferation, migration, and differentiation of osteoprogenitors. We have recently reported that knock-in mice with a global increase in PI3K signaling (gCblYF) show enhanced femoral fracture healing characterized by an extraordinary periosteal response to injury.

Cbl-PI3K interaction regulates Cathepsin K secretion in osteoclasts.

Effective bone resorption by osteoclasts is critical for balanced bone remodeling. We have previously reported that mice harboring a substitution mutation of tyrosine 737 to phenylalanine in the adapter protein Cbl (Cbl, YF) have increased bone volume partly due to decreased osteoclast-mediated bone resorption. The Cbl mutation abrogates interaction between Cbl and the p85 subunit of PI3K.

PDGF Modulates BMP2-Induced Osteogenesis in Periosteal Progenitor Cells.

BMPs are used in various clinical applications to promote bone formation. The limited success of the BMPs in clinical settings and supraphysiological doses required for their effects prompted us to evaluate the influence of other signaling molecules, specifically platelet-derived growth factor (PDGF) on BMP2-induced osteogenesis. Periosteal cells make a major contribution to fracture healing.

Protease-Activated Receptor 1 Deletion Causes Enhanced Osteoclastogenesis in Response to Inflammatory Signals through a Notch2-Dependent Mechanism.

We found that protease-activated receptor 1 (PAR1) was transiently induced in cultured osteoclast precursor cells. Therefore, we examined the bone phenotype and response to resorptive stimuli of PAR1-deficient (knockout [KO]) mice. Bones and bone marrow-derived cells from PAR1 KO and wild-type (WT) mice were assessed using microcomputed tomography, histomorphometry, in vitro cultures, and RT-PCR.

PI3K activation increases SDF-1 production and number of osteoclast precursors, and enhances SDF-1-mediated osteoclast precursor migration.

Our previous studies showed that in a mouse model in which PI3K-AKT activation was increased (YF mice), osteoclast numbers and levels of SDF-1, a chemokine, were augmented. The purpose of this study was to delineate the role of PI3K activation in regulating SDF-1 production and examine whether SDF-1 can stimulate differentiation and/or migration of osteoclast precursors. Using flow cytometric analysis, we demonstrated that compared to wild type mice, bone marrow of YF mice had increased numbers of CXCL12 abundant reticular (CAR) cells, that are a major cell type responsible for producing SDF-1.

Induction of the Hajdu-Cheney Syndrome Mutation in CD19 B Cells in Mice Alters B-Cell Allocation but Not Skeletal Homeostasis.

Mice harboring Notch2 mutations replicating Hajdu-Cheney syndrome (Notch2) have osteopenia and exhibit an increase in splenic marginal zone B cells with a decrease in follicular B cells. Whether the altered B-cell allocation is responsible for the osteopenia of Notch2 mutants is unknown. To determine the effect of NOTCH2 activation in B cells on splenic B-cell allocation and skeletal phenotype, a conditional-by-inversion (COIN) Hajdu-Cheney syndrome allele of Notch2 (Notch2) was used.

A novel role for cathepsin K in periosteal osteoclast precursors during fracture repair.

Osteoporosis management is currently centered around bisphosphonates, which inhibit osteoclast (OC) bone resorption but do not affect bone formation. This reduces fracture risk, but fails to restore healthy bone remodeling. Studies in animal models showed that cathepsin K (CatK) inhibition by genetic deletion or chemical inhibitors maintained bone formation while abrogating resorption during bone remodeling and stimulated periosteal bone modeling.