Closing the Gap between Observed Low-Mass Galaxy HI Kinematics and CDM Predictions

Testing the standard cosmological model ($\Lambda$CDM) at small scales is challenging. Galaxies that inhabit low-mass dark matter halos provide an ideal test bed for dark matter models by linking observational properties of galaxies at small scales (low mass, low velocity) to low-mass dark matter halos. However, the observed kinematics of these galaxies do not align with the kinematics of the dark matter halos predicted to host them, obscuring our understanding of the low-mass end of the galaxy-halo connection. We use deep HI observations of low-mass galaxies at high spectral resolution in combination with cosmological simulations of dwarf galaxies to better understand the connection between dwarf galaxy kinematics and low-mass halos. Specifically, we use HI line widths to directly compare to the maximum velocities in a dark matter halo, and find that each deeper measurement approaches the expected one-to-one relationship between the observed kinematics and the predicted kinematics in $\Lambda$CDM. We also measure baryonic masses and place these on the Baryonic Tully-Fisher relation (BTFR). Again, our deepest measurements approach the theoretical predictions for the low-mass end of this relation, a significant improvement on similar measurements based on line widths measured at 50\% and 20\% of the peak. Our data also hints at the rollover in the BTFR predicted by hydrodynamical simulations of $\Lambda$CDM for low-mass galaxies.Comment: 13 pages of text, 4 figures, submitted to AAS Journal

Novel agonists for serotonin 5-HT7 receptors reverse metabotropic glutamate receptor-mediated long-term depression in the hippocampus of wild-type and Fmr1 KO mice, a model of Fragile X Syndrome

Serotonin 5-HT7 receptors are expressed in the hippocampus and modulate the excitability of hippocampal neurons. We have previously shown that 5-HT7 receptors modulate glutamate-mediated hippocampal synaptic transmission and long-term synaptic plasticity. In particular, we have shown that activation of 5-HT7 receptors reversed metabotropic glutamate receptor-mediated long-term depression (mGluR-LTD) in wild-type (wt) and in Fmr1 KO mice, a mouse model of Fragile X Syndrome in which mGluR-LTD is abnormally enhanced, suggesting that 5-HT7 receptor agonists might be envisaged as a novel therapeutic strategy for Fragile X Syndrome. In this perspective, we have characterized the basic in vitro pharmacokinetic properties of novel molecules with high binding affinity and selectivity for 5-HT7 receptors and we have tested their effects on synaptic plasticity using patch clamp on acute hippocampal slices. Here we show that LP-211, a high affinity selective agonist of 5-HT7 receptors, reverses mGluR-LTD in wt and Fmr1 KO mice, correcting a synaptic malfunction in the mouse model of Fragile X Syndrome. Among novel putative agonists of 5-HT7 receptors, the compound BA-10 displayed improved affinity and selectivity for 5-HT7 receptors and improved in vitro pharmacokinetic properties with respect to LP-211. BA-10 significantly reversed mGluR-LTD in the CA3-CA1 synapse in wt and Fmr1KO mice, indicating that BA-10 behaved as a highly effective agonist of 5-HT7 receptors and reduced exaggerated mGluR-LTD in a mouse model of Fragile X Syndrome. On the other side, the compounds RA-7 and PM-20, respectively arising from in vivo metabolism of LP-211 and BA-10, had no effect on mGluR-LTD thus did not behave as agonists of 5-HT7 receptors in our conditions. The present results provide information about the structure-activity relationship of novel 5-HT7 receptor agonists and indicate that LP-211 and BA-10 might be used as novel pharmacological tools for the therapy of Fragile X Syndrome

A Census of the Extended Neutral Hydrogen around 18 MHONGOOSE Galaxies

We present the analysis of the diffuse, low column density H I environment of 18 MHONGOOSE galaxies. We obtained deep observations with the Robert C. Byrd Green Bank Telescope and reached down to a 3σ column density detection limit of NHI = 6.3 × 1017 cm-2 over a 20 km s-1 line width. We analyze the environment around these galaxies, with a focus on H I gas that reaches column densities below NHI = 1019 cm-2. We calculate the total amount of H I gas in and around the galaxies, revealing that nearly all of these galaxies contained excess H I outside of their disks. We quantify the amount of diffuse gas in the maps of each galaxy, defined by H I gas with column densities below 1019 cm-2, and find a large spread in percentages of diffuse gas. However, by binning the percentage of diffuse H I into quarters, we find that the bin with the largest number of galaxies is the lowest quartile (0%-25% diffuse H I). We identified several galaxies that may be undergoing gas accretion onto the galaxy disk using multiple methods of analysis, including azimuthally averaging column densities beyond the disk, and identifying structure within our integrated intensity (moment 0) maps. We measured H I mass outside the disks of most of our galaxies, with rising cumulative flux even at large radii. We also find a strong correlation between the fraction of diffuse gas in a galaxy and its baryonic mass, and we test this correlation using both Spearman and Pearson correlation coefficients. We see evidence of a dark matter halo mass threshold of Mhalo ∼ 1011.1 M⊙ in which galaxies with high fractions of diffuse H I all reside below. It is in this regime that cold-mode accretion should dominate. Finally, we suggest a rotation velocity of vrot ∼ 80 km s-1 as an upper threshold to find diffuse-gas-dominated galaxies

Mitochondria-mediated apoptosis of hcc cells triggered by knockdown of glutamate dehydrogenase 1: Perspective for its inhibition through quercetin and permethylated anigopreissin a

Metabolic reprogramming is a hallmark of cancer cells required to ensure high energy needs and the maintenance of redox balance. A relevant metabolic change of cancer cell bioenergetics is the increase in glutamine metabolism. Hepatocellular carcinoma (HCC), one of the most lethal cancer and which requires the continuous development of new therapeutic strategies, shows an up-regulation of human glutamate dehydrogenase 1 (hGDH1). GDH1 function may be relevant in cancer cells (or HCC) to drive the glutamine catabolism from L-glutamate towards the synthesis of α-ketoglutarate (α-KG), thus supplying key tricarboxylic acid cycle (TCA cycle) metabolites. Here, the effects of hGLUD1 gene silencing (siGLUD1) and GDH1 inhibition were evaluated. Our results demonstrate that siGLUD1 in HepG2 cells induces a significant reduction in cell proliferation (58.8% ± 10.63%), a decrease in BCL2 expression levels, mitochondrial mass (75% ± 5.89%), mitochondrial membrane potential (30% ± 7.06%), and a significant increase in mitochondrial superoxide anion (25% ± 6.55%) compared to control/untreated cells. The inhibition strategy leads us to identify two possible inhibitors of hGDH1: quercetin and Permethylated Anigopreissin A (PAA). These findings suggest that hGDH1 could be a potential candidate target to impair the metabolic reprogramming of HCC cells

Detection of the diffuse HI emission in the Circumgalactic Medium of NGC 891 and NGC 4565

We present detections of 21-cm emission from neutral hydrogen (HI) in the circumgalactic medium (CGM) of the local edge-on galaxies NGC 891 and NGC 4565 using the Robert C. Byrd Green Bank Telescope (GBT). With our 5$\sigma$ sensitivity of $8.2 \times 10^{16}$ cm$^{-2}$ calculated over a 20 km s$^{-1}$ channel, we achieve $>5\sigma$ detections out to $90-120$ kpc along the minor axes. The velocity width of the CGM emission is as large as that of the disk $\approx 500$ km s$^{-1}$, indicating the existence of a diffuse component permeating the halo. We compare our GBT measurements with interferometric data from the Westerbork Synthesis Radio Telescope (WSRT). The WSRT maps the HI emission from the disk at high S/N but has limited surface brightness sensitivity at the angular scales probed with the GBT. After convolving the WSRT data to the spatial resolution of the GBT (FWHM = 9.1$'$), we find that the emission detected by the WSRT accounts for $48^{+15}_{-25}$% ($58^{+4}_{-18}$%) of the total flux recovered by the GBT from the CGM of NGC 891(NGC 4565). The existence of significant GBT-only flux suggests the presence of a large amount of diffuse, low column density HI emission in the CGM. For reasonable assumptions, the extended diffuse HI could account for $5.2\pm0.9$% and $2.0\pm0.8$% of the total HI emission of NGC 891 and NGC 4565.Comment: 14 pages, 5 figures, published in Ap

Osteoblasts Display Different Responsiveness to TRAIL-Induced Apoptosis During Their Differentiation Process

Apoptosis can occur throughout the life span of osteoblasts (OBs), beginning from the early stages of differentiation and continuing throughout all stages of their working life. Here, we investigated the effects of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) on normal human OBs showing for the first time that the expression of TRAIL receptors is modulated during OB differentiation. In particular, the TRAIL receptor ratio was in favor of the deaths because of the low expression of DcR2 in undifferentiated OBs, differently it was shifted toward the decoys in differentiated ones. Undifferentiated OBs treated with TRAIL showed reduced cell viability, whereas differentiated OBs displayed TRAIL resistance. The OB sensitiveness to TRAIL was due to the up-regulation of DR5 and the down-regulation of DcR2. The main death receptor involved in TRAIL-reduced OB viability was DR5 as demonstrated by the rescue of cell viability observed in the presence of anti-DR5 neutralizing antibody. Besides the ratio of TRAIL receptors, the sensitivity of undifferentiated OBs to TRAIL-cytotoxic effect was also associated with low mRNA levels of intracellular anti-apoptotic proteins, such as cFLIP, the activation of caspase-8 and -3, as well as the DNA fragmentation. This study suggests that apoptotic effect exerted by TRAIL/TRAIL-receptor system on normal human OB is strictly dependent upon cell differentiation status

Trends in coffee and tea consumption during the covid-19 pandemic

Over the last two years, many countries have enforced confinement to limit both the spread of COVID-19 and the demand for medical care. Confinement has resulted in a disruption of work routines, boredom, depression, and changes in eating habits, among them consumption of coffee and tea. Following six databases, we examined articles tracking consumption of these beverages. Out of 472 articles, including 23 beverage entries, 13 matched our criteria. While no clear trend in coffee consumption during the coronavirus pandemic emerged (7 of 13 studies indicated an increase, accounting for 53.8%), tea consumption clearly increased (70% versus 30%). Considering the global health emergency continuum, more research is needed to better understand the paths underlying food choices and the ways those changes may influence health outcomes, including those related to COVID-19 disease

A family history of type 2 diabetes as a predictor of fatty liver disease in diabetes-free individuals with excessive body weight

Comprehensive screening for non-alcoholic fatty liver disease (NAFLD) may help prompt clinical management of fatty liver disease. A family history, especially of diabetes, has been little studied as a predictor for NAFLD. We characterized the cross-sectional relationship between a family history of type 2 diabetes (FHT2D) and NAFLD probability in 1185 diabetes-free Apulian (Southern-Italy) subjects aged > 20 years with overweight or obesity not receiving any drug or supplementation. Clinical data and routine biochemistry were analysed. NAFLD probability was defined using the fatty liver index (FLI). A first-degree FHT2D was assessed by interviewing subjects and assigning a score of 0, 1, or 2 if none, only one, or both parents were affected by type 2 diabetes mellitus (T2DM). Our study population featured most females (70.9%, N = 840), and 48.4% (N = 574) of the sample had first-degree FHT2D. After dividing the sample by a FHT2D, we found a higher BMI, Waist Circumference (WC), and diastolic blood pressure shared by FHT2D subjects; they also showed altered key markers of glucose homeostasis, higher triglyceride levels, and worse liver function. FLI scores were significantly lower in subjects without a first-degree FHT2D. After running logistic regression models, a FHT2D was significantly associated with the NAFLD probability, even adjusting for major confounders and stratifying by age (under and over 40 years of age). A FHT2D led to an almost twofold higher probability of NAFLD, regardless of confounding factors (OR 2.17, 95% CI 1.63 to 2.89). A first-degree FHT2D acts as an independent determinant of NAFLD in excess weight phenotypes, regardless of the age group (younger or older than 40 years). A NAFLD risk assessment within multidimensional screening might be useful in excess weight subjects reporting FHT2D even in the absence of diabetes

Non alcoholic fatty liver disease is positively associated with increased glycated haemoglobin levels in subjects without diabetes

Screening for non-alcoholic fatty liver disease (NAFLD) is key step for primary management of fatty liver in the clinical setting. Excess weight subjects carry a greater metabolic risk even before exhibiting pathological patterns, including diabetes. We characterized the cross-sectional relationship between routine circulating biomarkers and NAFLD in a large sample of diabetes-free subjects with overweight or obesity, to elucidate any independent relationship. A population sample of 1232 consecutive subjects with a body mass index of at least 25 kg/m2, not receiving any drug or supplemental therapy, was studied. Clinical data and routine biochemistry were analyzed. NAFLD was defined using the validated fatty liver index (FLI), classifying subjects with a score ≥ 60% as at high risk. Due to extreme skewing of variables of interest, resampling matching for age and sex was performed. Our study population was characterized by a majority of females (69.90%) and a prevalence of NAFLD in males (88.90%). As a first step, propensity score matching was explicitly performed to balance the two groups according to the FLI cut-off. Based on the resulting statistical trajectories, corroborated even after data matching, we built two logistic regression models on the matched population (N = 732) to verify any independent association. We found that each unit increase of FT3 implicated a 50% increased risk of NAFLD (OR 1.506, 95%CI 1.064 to 2.131). When including glycated haemoglobin (HbA1c) in the model, free-triiodothyronine (FT3) lost significance (OR 1.557, 95%CI 0.784 to 3.089) while each unit increase in HbA1c (%) indicated a significantly greater NAFLD risk, by almost two-fold (OR 2.32, 95%CI 1.193 to 4.512). Glucose metabolism dominates a key pathway along the hazard trajectories of NAFLD, turned out to be key biomarker in monitoring the risk of fatty liver in diabetes-free overweight subjects. Each unit increase in HbA1c (%) indicated a significantly greater NAFLD risk, by almost two-fold, in our study