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A bstract The search for dark matter weakly interacting massive particles with noble liquids has probed masses down and below a GeV/ c 2 . The ultimate limit is represented by the experimental threshold on the energy transfer to the nuclear recoil. Currently, the experimental sensitivity has reached a threshold equivalent to a few ionization electrons. In these conditions, the contribution of a Bremsstrahlung photon or a so-called Migdal electron due to the sudden acceleration of a nucleus after a collision might be sizable. In the present work, we use a Bayesian approach to study how these effects can be exploited in experiments based on liquid argon detectors. In particular, taking inspiration from the DarkSide-50 public spectra, we develop a simulated experiment to show how the Migdal electron and the Bremsstrahlung photon allow to push the experimental sensitivity down to masses of 0.1 GeV /c 2 , extending the search region for dark matter particles of previous results. For these masses we estimate the effect of the Earth shielding that, for strongly interacting dark matter, makes any detector blind. Finally, we show how the sensitivity scales for higher exposure.

Voltage-dependent anion channels (VDACs) are expressed in three isoforms, with common channeling properties and different roles in cell survival. We show that VDAC1 silencing potentiates apoptotic challenges, whereas VDAC2 has the opposite effect. Although all three VDAC isoforms are equivalent in allowing mitochondrial Ca 2+ loading upon agonist stimulation, VDAC1 silencing selectively impairs the transfer of the low-amplitude apoptotic Ca 2+ signals. Co-immunoprecipitation experiments show that VDAC1, but not VDAC2 and VDAC3, forms complexes with IP 3 receptors, an interaction that is further strengthened by apoptotic stimuli. These data highlight a non-redundant molecular route for transferring Ca 2+ signals to mitochondria in apoptosis.

ObjectiveTo determine the frequency and characteristics of brainstem or cerebellar involvement in myelin-oligodendrocyte-glycoprotein-antibody-associated-disorder (MOGAD) versus aquaporin-4-IgG-seropositive-neuromyelitis optica spectrum disorder (AQP4-IgG-NMOSD) and multiple sclerosis (MS).MethodsIn this observational study, we retrospectively identified 185 Mayo Clinic MOGAD patients with: (1) characteristic MOGAD phenotype, (2) MOG-IgG seropositivity by live cell-based assay and (3) MRI lesion(s) of brainstem, cerebellum or both. We compared the symptomatic attacks to AQP4-IgG-NMOSD (n=30) and MS (n=30).ResultsBrainstem or cerebellar involvement occurred in 62/185 (34%) MOGAD patients of which 39/62 (63%) were symptomatic. Ataxia (45%) and diplopia (26%) were common manifestations. The median age in years (range) in MOGAD of 24 (2–65) was younger than MS at 36 (16–65; p=0.046) and AQP4-IgG-NMOSD at 45 (6–72; p=0.006). Isolated attacks involving the brainstem, cerebellum or both were less frequent in MOGAD (9/39 (23%)) than MS (22/30 (73%); p<0.001) but not significantly different from AQP4-IgG-NMOSD (14/30 (47%); p=0.07). Diffuse middle cerebellar peduncle MRI-lesions favoured MOGAD (17/37 (46%)) over MS (3/30 (10%); p=0.001) and AQP4-IgG-NMOSD (3/30 (10%); p=0.001). Diffuse medulla, pons or midbrain MRI lesions occasionally occurred in MOGAD and AQP4-IgG-NMOSD but never in MS. Cerebrospinal fluid (CSF) oligoclonal bands were rare in MOGAD (5/30 (17%)) and AQP4-IgG-NMOSD (2/22 (9%); p=0.68) but common in MS (18/22 (82%); p<0.001). Disability at nadir or recovery did not differ between the groups.ConclusionInvolvement of the brainstem, cerebellum or both is common in MOGAD but usually occurs as a component of a multifocal central nervous system attack rather than in isolation. We identified clinical, CSF and MRI attributes that can help discriminate MOGAD from AQP4-IgG-NMOSD and MS.

Heavy metal levels appear to be associated with low bone mineral density (BMD) and the consequent osteoporosis risk, but the relationship with the disease has not been clearly defined. The altered expression pattern of numerous genes, including detoxifying genes, seems to play a pivotal role in this context, leading to increased susceptibility to several diseases, including osteoporosis. The purpose of this study is to analyse circulating heavy metals levels and the expression of detoxifying genes in osteoporotic patients (OPs, n = 31), compared with healthy subjects (CTRs, n = 32). Heavy metals concentration in plasma samples was determined by Inductively Coupled Plasma Mass Spectrometry (ICP-MS), and the subsequent expression analysis of NAD(P)H quinone dehydrogenase 1 ( NQO1 ), Catalase ( CAT ), and Metallothionein 1E ( MT1E ) genes in Peripheral Blood Mononuclear Cells (PBMCs) was assessed by real-time polymerase chain reaction (qRT-PCR). Copper (Cu), mercury (Hg), molybdenum (Mo) and lead (Pb) were found to be significantly higher in the plasma of OPs compared to CTRs. Analysis of the expression levels of detoxifying genes showed a significant decrease in CAT and MT1E in OP group. In addition, Cu correlated positively with the expression levels of both CAT and MT1E in CTRs group and MT1E in OPs. This study shows an increased circulating concentration of certain metals combined with an altered expression pattern of detoxifying genes in OPs, highlighting a novel aspect to be investigated in order to better characterize the role of metals in the pathogenesis of osteoporosis.

Prostate cancer is a disease with a high incidence and mortality rate in men worldwide. Serum prostate-specific antigens (PSA) are the main circulating biomarker for this disease in clinical practices. In this work, we present a portable and reusable microfluidic device for PSA quantification. This device comprises a polymethyl methacrylate microfluidic platform coupled with electrochemical detection. The platinum working microelectrode was positioned in the outflow region of the microchannel and was modified with carbon nanofibers (CNF)-decorated gold nanoporous (GNP) structures by the dynamic hydrogen bubble template method, through the simultaneous electrodeposition of metal precursors in the presence of CNF. CNF/GNP structures exhibit attractive properties, such as a large surface to volume ratio, which increases the antibody’s immobilization capacity and the electroactive area. CNFs/GNP structures were characterized by scanning electron microscopy, energy dispersive spectrometry, and cyclic voltammetry. Anti-PSA antibodies and HRP were employed for the immune-electrochemical reaction. The detection limit for the device was 5 pg mL−1, with a linear range from 0.01 to 50 ng mL−1. The coefficients of variation within and between assays were lower than 4.40%, and 6.15%, respectively. Additionally, its clinical performance was tested in serum from 30 prostate cancer patients. This novel device was a sensitive, selective, portable, and reusable tool for the serological diagnosis and monitoring of prostate cancer.

Caves formed by sulfuric acid dissolution have been identified worldwide. These caves can host diverse microbial communities that are responsible for speleogenesis and speleothem formation. It is not well understood how microbial communities change in response to surface water entering caves. Illumina 16S rRNA sequencing and bioinformatic tools were used to determine the impact of surface water on the microbial community diversity and function within a spring pool found deep in the Monte Conca Cave system in Sicily, Italy. Sulfur oxidizers comprised more than 90% of the microbial community during the dry season and were replaced by potential anthropogenic contaminants such as Escherichia and Lysinibacillus species after heavy rains. One sampling date appeared to show a transition between the wet and dry seasons when potential anthropogenic contaminants (67.3%), sulfur-oxidizing bacteria (13.6%), and nitrogen-fixing bacteria (6.5%) were all present within the spring pool.

Celiac disease (CD), a human leukocyte antigen-associated disorder, is caused by gluten sensitivity and is characterized by mucosal alterations in the small intestine. Currently, its diagnosis involves the determination of serological markers. The traditional method for clinically determining these markers is the enzyme-linked immunosorbent assay. However, immunosensors offer sensitivity and facilitate the development of miniaturized and portable analytical systems. This work focuses on developing an amperometric immunosensor for the quantification of IgA antibodies against tissue transglutaminase (IgA anti-TGA) in human serum samples, providing information on a critical biomarker for CD diagnosis. The electrochemical device was designed on a polyimide substrate using a novel solid ink of wax and carbon nanofibers (CNFs). The working electrode microzone was defined by incorporating aminofunctionalized TiO2 nanoparticles (TiO2NPs). The interactions and morphology of CNFs/wax and TiO2NPs/CNFs/wax electrodes were assessed through different characterization techniques. Furthermore, the device was electrochemically characterized, demonstrating that the incorporation of CNFs into the wax matrix significantly enhanced its conductivity and increased the active surface area of the electrode, while TiO2NPs contributed to the immunoreaction area. The developed device exhibited remarkable sensitivity, selectivity, and reproducibility. These results indicate that the fabricated device is a robust and reliable tool for the precise serological diagnosis of CD.

Photoreceptor outer segments are surrounded by a carbohydrate-rich matrix, the interphotoreceptor matrix, necessary for physiological retinal function. Few roles for molecules characterizing the interphotoreceptor matrix have been clearly defined. Recent studies have found the presence of nonsense mutations in the interphotoreceptor matrix proteoglycan 2 ( IMPG2) gene in patients affected by retinal dystrophies. IMPG2 encodes for a proteoglycan synthesized by photoreceptors and secreted in the interphotoreceptor matrix. Little is known about the structure and function of this protein, we thus decided to characterize zebrafish impg2 . In zebrafish there are two Impg2 proteins, Impg2a and Impg2b. We generated a phylogenetic tree based on IMPG2 protein sequence similarity among vertebrates, showing a significant similarity between humans and teleosts. The human and zebrafish proteins share conserved domains, as also shown by homology models. Expression analyses of impg2a and impg2b show a continued expression in the photoreceptor layer starting from developmental stages and continuing through adulthood. Between 1 and 6 months post-fertilization, there is a significant shift of Impg2 expression toward the outer segment region, suggesting an increase in secretion. This raises intriguing hypotheses about its possible role(s) during retinal maturation, laying the groundwork for the generation of most needed models for the study of IMPG2-related inherited retinal dystrophies.