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Healthcare providers perspectives on HIV-NCD integration to Meet the needs of older adults living with HIV

3 months 2 weeks ago
CONCLUSION: The findings of this study highlight healthcare providers' perceived facilitators and barriers to the integration of NCD care into HIV care platforms. The insights gained from this study hold the potential to inform tailored interventions, policy decisions, and capacity-building initiatives aimed at fostering successful integration and improving overall health care delivery to meet the needs of OALWH in resource-constrained settings.
Jepchirchir Kiplagat

Transferrin receptor-targeted anti-amyloid antibody enhances brain delivery and mitigates ARIA

3 months 2 weeks ago
Amyloid-related imaging abnormalities (ARIA), side effects of anti-amyloid drugs seen in magnetic resonance imaging of the brain, are a major safety concern in patients with Alzheimer's disease. We developed an antibody transport vehicle (ATV) targeting transferrin receptor (TfR) for brain delivery of anti-amyloid-β protein (anti-Aβ) using asymmetrical Fc mutations (ATV^(cisLALA)) that mitigates TfR-related liabilities and retains effector function when bound to Aβ. Administration of...
Michelle E Pizzo

Reduction of TRAF3 by heterozygosity or aging impacts B cell function

3 months 2 weeks ago
TNF receptor-associated factor 3 (TRAF3) is a signaling adaptor protein that is ubiquitously expressed but has highly distinct cell type-specific functions. TRAF3 plays critical roles in restraint of B lymphocyte activation, differentiation, and homeostatic survival. Consistent with such roles, loss-of-function mutations in TRAF3 have long been found in various human B cell malignancies. Mice lacking TRAF3 specifically in B cells have autoimmune manifestations, lymphadenopathy, and increased...
Emma L Hornick

Protracted circum-continent subduction: A mechanism for craton destruction and a rationale for craton longevity

3 months 2 weeks ago
The evolution of continents is shaped by the growth and destruction of long-lived cratons, which serve as their stable cores. Processes for craton destruction are controversial because most invoked mechanisms occur frequently throughout Earth history, making the preservation of cratons for billions of years problematic. Here, we address this issue by presenting a crustal-scale analytical signal-amplitude model obtained from high-resolution airborne and shipborne magnetic data across cratons...
Xi Xu

Hypoxia ameliorates neurodegeneration and movement disorder in a mouse model of Parkinson's disease

3 months 2 weeks ago
Parkinson's disease (PD) is characterized by inclusions of α-synuclein (α-syn) and mitochondrial dysfunction in dopaminergic (DA) neurons of the substantia nigra pars compacta (SNpc). Patients with PD anecdotally experience symptom improvement at high altitude; chronic hypoxia prevents the development of Leigh-like brain disease in mice with mitochondrial complex I deficiency. Here we report that intrastriatal injection of α-syn preformed fibrils (PFFs) in mice resulted in neurodegeneration and...
Eizo Marutani

The intricate link between circadian rhythms and aging: can resetting our circadian clock hold the key to longevity?

3 months 2 weeks ago
The desire to increase life expectancy, coupled with the decline in biological functions that occurs as we age, represents one of the most significant challenges facing our society. Age-related declines in biological functions contribute to frailty and morbidity, demanding innovative strategies to promote healthy aging. The circadian clock, which controls daily physiological processes, is intricately linked to aging and overall health. Circadian disruptions can lead to metabolic dysfunction,...
Najm Ul Hassan

The senescence-inhibitory p53 isoform delta133p53alpha: enhancing cancer immunotherapy and exploring novel therapeutic approaches for senescence-associated diseases

3 months 2 weeks ago
Δ133p53α is a naturally occurring isoform of the tumor suppressor protein p53. Δ133p53α functions as a physiological dominant-negative inhibitor of the full-length p53 protein (commonly referred to as p53). Δ133p53α preferentially inhibits p53-mediated cellular senescence, while it does not inhibit, or may even promote, p53-mediated DNA repair. Owing to this selective inhibitory activity that preserves genome stability, Δ133p53α represents a promising target for enhancement in the prevention and...
Shinji Nakamichi

Mitochondrial dysfunction in peripheral mononuclear blood cells (PBMC) of individuals with mild cognitive impairment

3 months 2 weeks ago
Mitochondrial dysfunction is a hallmark of aging and many age-related neurodegenerative diseases. Mild cognitive impairment (MCI) refers to a clinical condition characterized by noticeable cognitive decline that exceeds normal age-related changes but does not significantly interfere with daily functioning. MCI is often considered an early stage of neurodegenerative conditions, including Alzheimer's disease. We therefore investigated the relationship between mitochondrial function in peripheral...
Fabian Dieter

Tau and tauopathies across primate species: implications for modeling neurodegenerative disorders

3 months 2 weeks ago
Tauopathies are neurodegenerative disorders characterized by the abnormal accumulation and aggregation of hyperphosphorylated tau protein. They can be primary or secondary depending on whether tau inclusions are the predominant pathology (e.g.: frontotemporal dementia related to tau) or are found with other proteinopathies (e.g.: Alzheimer's disease), respectively. Currently, there are no effective treatments to prevent or slow down progressive tau accumulation. Animal models play a critical...
Julia C Colwell

Neuropeptide Y mRNA expression in the aging inferior colliculus of fischer brown norway rats

3 months 2 weeks ago
INTRODUCTION: A major contributor to age-related hearing loss is the decline of GABAergic inhibition, particularly in the inferior colliculus (IC), which is the midbrain hub of the central auditory system. The initial loss of inhibition is thought to be a compensatory mechanism in response to decreased peripheral excitation. However, the downregulation of inhibition in the IC persists with age and leads to functional disruptions and central neural gain. Neuropeptide Y (NPY) is co-expressed by a...
Laila S Almassri

Vulnerability of long-range inputome of basal forebrain in normal aging mice

3 months 2 weeks ago
INTRODUCTION: As the human undergoes the process of aging, it becomes evident that the elderly population exhibits age-related cognitive decline. The basal forebrain (BF) has been shown to have complex connections with the hippocampus (Hip) and medial prefrontal cortex (mPFC) through circuits, and is involved in cognitive functions. However, which circuit is most vulnerable during normal aging remains unclear.
Tingting Sun

Beyond the left cerebral hemisphere: bilateral language lateralization in healthy aging and its clinical implications

3 months 2 weeks ago
CONCLUSION: Among healthy older adults, SP and PP recruit bilateral language-related brain regions, potentially reflecting compensatory mechanisms associated with normal aging. Notably, the IFG pars orbitalis may play a distinct role in supporting phonological fluency, despite not being a region traditionally linked to PP. Further research is needed to clarify the contribution of this region to phonological performance among aging adults.
David Toloza-Ramirez