Surfacic networks.

Surfacic networks are structures built upon a 2D manifold. Many systems, including transportation networks and various urban networks, fall into this category. The fluctuations of node elevations imply significant deviations from typical plane networks and require specific tools to understand their impact.

RuvBL1/2 reduce toxic dipeptide repeat protein burden in multiple models of C9orf72-ALS/FTD.

A G4C2 hexanucleotide repeat expansion in is the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD). Bidirectional transcription and subsequent repeat-associated non-AUG (RAN) translation of sense and antisense transcripts leads to the formation of five dipeptide repeat (DPR) proteins. These DPRs are toxic in a wide range of cell and animal models.

Highly enriched carbon and oxygen isotopes in carbonate-derived CO at Gale crater, Mars.

Carbonate minerals are of particular interest in paleoenvironmental research as they are an integral part of the carbon and water cycles, both of which are relevant to habitability. Given that these cycles are less constrained on Mars than they are on Earth, the identification of carbonates has been a point of emphasis for rover missions. Here, we present carbon (δC) and oxygen (δO) isotope data from four carbonates encountered by the Curiosity rover within the Gale crater.

Remotely administered non-deceptive placebos reduce COVID-related stress, anxiety, and depression.

Research suggests that placebos administered without deception (i.e. non-deceptive placebos) may provide an effective and low-effort intervention to manage stress and improve mental health.

A systematic review of immunosuppressive protocols used in AAV gene therapy for monogenic disorders.

The emergence of adeno-associated virus (AAV)-based gene therapy has brought hope to patients with severe monogenic disorders. However, immune responses to AAV vectors and transgene products present challenges that require effective immunosuppressive strategies. This systematic review focuses on the immunosuppressive protocols used in 38 clinical trials and 35 real-world studies, considering a range of monogenic diseases, AAV serotypes, and administration routes.

Association between Residential Greenness and Allostatic Load: A Cohort Study.

The association between residential greenness and allostatic load (AL), a marker of composite physiological burden and predictor of chronic disease, remains understudied. This study comprised 212,600 UK Biobank participants recruited over 2007 and 2010 at the baseline. Residential greenness was modeled as the normalized difference vegetation index (NDVI) from high spatial resolution (0.

Ap4b1-knockout mouse model of hereditary spastic paraplegia type 47 displays motor dysfunction, aberrant brain morphology and ATG9A mislocalization.

Mutations in any one of the four subunits (ɛ4, β4, μ4 and σ4) comprising the adaptor protein Complex 4 results in a complex form of hereditary spastic paraplegia, often termed adaptor protein Complex 4 deficiency syndrome. Deficits in adaptor protein Complex 4 complex function have been shown to disrupt intracellular trafficking, resulting in a broad phenotypic spectrum encompassing severe intellectual disability and progressive spastic paraplegia of the lower limbs in patients. Here we report the presence of neuropathological hallmarks of adaptor protein Complex 4 deficiency syndrome in a clustered regularly interspaced short palindromic repeats-mediated -knockout mouse model.

Loss of TMEM106B exacerbates C9ALS/FTD DPR pathology by disrupting autophagosome maturation.

Disruption to protein homeostasis caused by lysosomal dysfunction and associated impairment of autophagy is a prominent pathology in amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). The most common genetic cause of ALS/FTD is a G4C2 hexanucleotide repeat expansion in (C9ALS/FTD). Repeat-associated non-AUG (RAN) translation of G4C2 repeat transcripts gives rise to dipeptide repeat (DPR) proteins that have been shown to be toxic and may contribute to disease etiology.

An interaction between synapsin and C9orf72 regulates excitatory synapses and is impaired in ALS/FTD.

Dysfunction and degeneration of synapses is a common feature of amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). A GGGGCC hexanucleotide repeat expansion in the C9ORF72 gene is the main genetic cause of ALS/FTD (C9ALS/FTD). The repeat expansion leads to reduced expression of the C9orf72 protein.

Organic carbon concentrations in 3.5-billion-year-old lacustrine mudstones of Mars.

The Sample Analysis at Mars instrument stepped combustion experiment on a Yellowknife Bay mudstone at Gale crater, Mars revealed the presence of organic carbon of Martian and meteoritic origins. The combustion experiment was designed to access refractory organic carbon in Mars surface sediments by heating samples in the presence of oxygen to combust carbon to CO. Four steps were performed, two at low temperatures (less than ∼550 °C) and two at high temperatures (up to ∼870 °C).

-derived poly-GA DPRs undergo endocytic uptake in iAstrocytes and spread to motor neurons.

Dipeptide repeat (DPR) proteins are aggregation-prone polypeptides encoded by the pathogenic GGGGCC repeat expansion in the gene, the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. In this study, we focus on the role of poly-GA DPRs in disease spread. We demonstrate that recombinant poly-GA oligomers can directly convert into solid-like aggregates and form characteristic β-sheet fibrils in vitro.

An event-related potential investigation of distanced self-talk: Replication and comparison to detached reappraisal.

Emotion regulation is critical for managing stress, but many regulatory strategies consume high levels of cognitive resources to implement, which are depleted under stress. This raises a conundrum: the tools we have to feel better may be ineffective when they are most needed. Recent event-related potential (ERP) research indicates that distanced self-talk (i.

Resistance training for Black men with depressive symptoms: a pilot randomized controlled trial to assess acceptability, feasibility, and preliminary efficacy.

Background: Depression is under-recognized in Black men, who are less likely to seek or have access to psychiatric treatment. Resistance training (RT; i.e.

SMN-deficient cells exhibit increased ribosomal DNA damage.

Spinal muscular atrophy, the leading genetic cause of infant mortality, is a motor neuron disease caused by low levels of survival motor neuron (SMN) protein. SMN is a multifunctional protein that is implicated in numerous cytoplasmic and nuclear processes. Recently, increasing attention is being paid to the role of SMN in the maintenance of DNA integrity.

SPG15 protein deficits are at the crossroads between lysosomal abnormalities, altered lipid metabolism and synaptic dysfunction.

Hereditary spastic paraplegia type 15 (HSP15) is a neurodegenerative condition caused by the inability to produce SPG15 protein, which leads to lysosomal swelling. However, the link between lysosomal aberrations and neuronal death is poorly explored. To uncover the functional consequences of lysosomal aberrations in disease pathogenesis, we analyze human dermal fibroblasts from HSP15 patients as well as primary cortical neurons derived from an SPG15 knockout (KO) mouse model.

Not Lupus Nephritis but a Rare Case of Drug-Induced Pauci-Immune Glomerulonephritis.

Hydralazine-induced pauci-immune glomerulonephritis is a rare cause of glomerulonephritis. It is an anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis that can be rapidly progressive and potentially life-threatening. However, most cases are found to be asymptomatic, and patients often present with acute renal failure and painless hematuria.

Depleted carbon isotope compositions observed at Gale crater, Mars.

Obtaining carbon isotopic information for organic carbon from Martian sediments has long been a goal of planetary science, as it has the potential to elucidate the origin of such carbon and aspects of Martian carbon cycling. Carbon isotopic values (δC) of the methane released during pyrolysis of 24 powder samples at Gale crater, Mars, show a high degree of variation (-137 ± 8‰ to +22 ± 10‰) when measured by the tunable laser spectrometer portion of the Sample Analysis at Mars instrument suite during evolved gas analysis. Included in these data are 10 measured δC values less than -70‰ found for six different sampling locations, all potentially associated with a possible paleosurface.

Quantifying the embodied carbon saving potential of recycling construction and demolition waste in the Greater Bay Area, China: Status quo and future scenarios.

Comparing with the enduring efforts to reduce carbon emissions in design, construction, and operation stages of a construction project, less attention has been paid to emission abatement potential in the end-of-life stage, particularly by recycling waste generated by construction and demolition (C&D) activities. This research aims to cover this knowledge void by quantifying the embodied carbon saving potential of recycling C&D waste. It does so by adopting a Life Cycle Assessment (LCA) and choosing the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) in South China for a case study.

Comparability of Biologics: Global Principles, Evidentiary Consistency and Unrealized Reliance.

The principles of comparability assessments have been accepted globally as offering sensitive and reliable tools with which to evaluate potential changes to biologics that may arise either through processing changes or through the creation of a copy (biosimilar) by a different sponsor. The comparability approach has evolved through systematic advances in four areas: clear and convergent guidelines for evaluation of potential changes to biologics; risk-based systems of weighting analytical data; progressive improvements in analytical methods; and advanced understanding of post-translational modifications. Routine regulatory expectations for clinical equivalence data are being reevaluated, as they seldom contribute to the assessment of similarity.

Herriott cell spot imaging increases the performance of tunable laser spectrometers.

With the availability of high-power (milliwatts) single-mode tunable laser sources that operate at room temperature across the infrared (IR) region, tunable laser spectrometers have seen an explosion of growth in applications that include commercial, Earth and planetary science, and medical and industrial sensing. While the laser sources themselves have shown steady improvement, the detection architecture of using a single-element detector at one end of a multipass cell has remained unchanged over the last few decades. We present here an innovative new approach using a detector array coupled to an IR-transmissive mirror to image all or part of the multipass spot pattern of the far mirror and record spectra for each pixel.

Reduced Glucose Tolerance and Skeletal Muscle GLUT4 and IRS1 Content in Cyclists Habituated to a Long-Term Low-Carbohydrate, High-Fat Diet.

Very little is known about how long-term (>6 months) adaptation to a low-carbohydrate, high-fat (LCHF) diet affects insulin signaling in healthy, well-trained individuals. This study compared glucose tolerance; skeletal muscle glucose transporter 4 (GLUT4) and insulin receptor substrate 1 (IRS1) content; and muscle enzyme activities representative of the main energy pathways (3-hydroxyacetyl-CoA dehydrogenase, creatine kinase, citrate synthase, lactate dehydrogenase, phosphofructokinase, phosphorylase) in trained cyclists who followed either a long-term LCHF or a mixed-macronutrient (Mixed) diet. On separate days, a 2-hr oral glucose tolerance test was conducted, and muscle samples were obtained from the vastus lateralis of fasted participants.