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The complex life of the oil industry veteran who proposed the Gaia hypothesis
Twenty years of Addgene
Lowlands: where science meets music
I track the movements of the mysterious storm bird
Type of hormone therapy may determine whether trans men continue to menstruate
Study finds those using gel or cream were 10 times more likely to continue to menstruate after their treatment
Company misled investors on possible Alzheimer’s drug, SEC charges
Agency fines Cassava $40 million, and two of its employees lesser amounts, over research on simufilam
Epg5 links proteotoxic stress due to defective autophagic clearance and epileptogenesis in <em>Drosophila</em> and Vici syndrome patients
Epilepsy is a common neurological condition that arises from dysfunctional neuronal circuit control due to either acquired or innate disorders. Autophagy is an essential neuronal housekeeping mechanism, which causes severe proteotoxic stress when impaired. Autophagy impairment has been associated to epileptogenesis through a variety of molecular mechanisms. Vici Syndrome (VS) is the paradigmatic congenital autophagy disorder in humans due to recessive variants in the ectopic P-granules autophagy...
Epg5 links proteotoxic stress due to defective autophagic clearance and epileptogenesis in <em>Drosophila</em> and vici syndrome patients
Epilepsy is a common neurological condition that arises from dysfunctional neuronal circuit control due to either acquired or innate disorders. Autophagy is an essential neuronal housekeeping mechanism, which causes severe proteotoxic stress when impaired. Autophagy impairment has been associated to epileptogenesis through a variety of molecular mechanisms. Vici Syndrome (VS) is the paradigmatic congenital autophagy disorder in humans due to recessive variants in the ectopic P-granules autophagy...
Circulating small non-coding RNA profiling for identification of older adults with low muscle strength and physical performance: A preliminary study
CONCLUSION: The expression of circulating small ncRNAs were comprehensively characterized, revealing distinct signatures in older adults with both low muscle strength and physical performance compared to normal individuals. Although preliminary, this characterization can advance small ncRNA research on age-related declines in muscle strength and physical performance by providing foundational data for further investigation.
Differences in motor learning-related structural plasticity of layer 2/3 parvalbumin-positive interneurons of the young and aged motor cortex
Changes to neuronal connectivity are believed to be a key factor in cognitive impairments associated with normal aging. Because of its effect on activities of daily living, deficient motor control is a critical type of cognitive decline to understand. Diminished inhibitory networks in the cortex are implicated in such motor control deficits, pointing to the connectivity of inhibitory cortical interneurons as an important area for study. Here, we used chronic two-photon microscopy to track the...
RAB12-LRRK2 complex suppresses primary ciliogenesis and regulates centrosome homeostasis in astrocytes
The leucine-rich repeat kinase 2 (LRRK2) phosphorylates a subset of RAB GTPases, and their phosphorylation levels are elevated by Parkinson's disease (PD)-linked mutations of LRRK2. However, the precise function of the LRRK2-regulated RAB GTPase in the brain remains to be elucidated. Here, we identify RAB12 as a robust LRRK2 substrate in the mouse brain through phosphoproteomics profiling and solve the structure of RAB12-LRRK2 protein complex through Cryo-EM analysis. Mechanistically, RAB12...
Reassessing kinetin's effect on PINK1 and mitophagy
Substantial evidence indicates that a decline in mitochondrial health contributes to the development of Parkinson disease. Accordingly, therapeutic stimulation of mitophagy, the autophagic turnover of dysfunctional mitochondria, is a promising approach to treat Parkinson disease. An attractive target in such a setting is PINK1, a protein kinase that initiates the mitophagy cascade. Previous reports suggest that PINK1 kinase activity can be enhanced by kinetin triphosphate (KTP), an enlarged ATP...
Heart rate variability and autonomic nervous system imbalance: Potential biomarkers and detectable hallmarks of aging and inflammaging
The most cutting-edge issue in the research on aging is the quest for biomarkers that transcend molecular and cellular domains to encompass organismal-level implications. We recently hypothesized the role of Autonomic Nervous System (ANS) imbalance in this context. Studies on ANS functions during aging highlighted an imbalance towards heightened sympathetic nervous system (SNS) activity, instigating a proinflammatory milieu, and attenuated parasympathetic nervous system (PNS) function, which...
Advances in understanding biomarkers and treating neurological diseases - Role of the cerebellar dysfunction and emerging therapies
Cerebellar dysfunction is increasingly recognized as a critical factor in various neurological diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Research has revealed distinct cerebellar atrophy patterns in conditions such as AD and multiple system atrophy, and studies in mice have highlighted its impact on motor control and cognitive functions. Emerging research into autism spectrum disorder (ASD) has identified key targets, such as...
Tiny fish carve out massive breeding colonies containing millions of nests
Study points to “oases of marine life” in need of protection
Spanish university head accused of inflating citations to his own work
Dozens of Springer Nature papers flagged for excessively citing Juan Manuel Corchado
Lost in translation: Inconvenient truths on the utility of mouse models in Alzheimer's disease research
The recent, controversial approval of antibody-based treatments for Alzheimer's disease (AD) is fueling a heated debate on the molecular determinants of this condition. The discussion should also incorporate a critical revision of the limitations of preclinical mouse models in advancing our understanding of AD. We critically discuss the limitations of animal models, stressing the need for careful consideration of how experiments are designed and results interpreted. We identify the shortcomings...
Increased nocturnal urinary cortisol levels in the elderly patients with depression, coexisting major geriatric syndromes and combined pathogenetic mechanisms
CONCLUSION: The depression in elderly patient should be reconsidered as a systemic disease, with coexisting major geriatric syndromes (disability, dementia, frailty) and combined pathogenetic mechanisms (metabolic syndrome, impaired renal function, low-grade inflammation, and allostatic load). Cortisol confirmed its role as principal mediator of the aging process in both dementia and metabolic syndrome.
Systemic dysregulation and molecular insights into poor influenza vaccine response in the aging population
Vaccination-induced protection against influenza is greatly diminished and increasingly heterogeneous with age. We investigated longitudinally (up to five time points) a cohort of 234 vaccinated >65-year-old vaccinees with adjuvanted vaccine FluAd across two independent seasons. System-level analyses of multiomics datasets measuring six modalities and serological data revealed that poor responders lacked time-dependent changes in response to vaccination as observed in responders, suggestive of...
A living organoid biobank of patients with Crohn's disease reveals molecular subtypes for personalized therapeutics
Crohn's disease (CD) is a complex and heterogeneous condition with no perfect preclinical model or cure. To address this, we explore adult stem cell-derived organoids that retain their tissue identity and disease-driving traits. We prospectively create a biobank of CD patient-derived organoid cultures (PDOs) from colonic biopsies of 53 subjects across all clinical subtypes and healthy subjects. Gene expression analyses enabled benchmarking of PDOs as tools for modeling the colonic epithelium in...