Miracle-dz/UniFAR-FTUs huggingface dataset:
Noncoding RNA Gas5 Is a Growth Arrest– and Starvation-Associated Repressor of the Glucocorticoid Receptor

Gas5 is a noncoding RNA that acts as a decoy glucocorticoid response element to inhibit glucocorticoid-mediated transcription. Noncoding RNA Decoys Steroid receptors are transcription factors that are activated by ligand binding, which allows these proteins to bind specific sequences called “response elements” in the promoters of target genes to stimulate transcription. Now, Kino et al. find that a noncoding RNA can also interact with steroid receptors and inhibit their binding to the DNA response elements, thereby repressing steroid receptor activity. The authors found that the noncoding RNA growth arrest–specific 5 (Gas5), which accumulates in cells that have been deprived of nutrients or growth factors, bound to the glucocorticoid receptor and competed with DNA glucocorticoid response elements for binding to the receptor, thereby inhibiting glucocorticoid-mediated transcription. This sensitized cells to undergo apoptosis in response to stress by preventing the glucocorticoid-mediated transcription of antiapoptotic genes. Gas5 also interacted with other steroid receptors and inhibited their transcriptional activity, suggesting that decoy RNA response elements may be a common mechanism for regulating transcription factor activity. The availability of nutrients influences cellular growth and survival by affecting gene transcription. Glucocorticoids also influence gene transcription and have diverse activities on cell growth, energy expenditure, and survival. We found that the growth arrest–specific 5 (Gas5) noncoding RNA, which is abundant in cells whose growth has been arrested because of lack of nutrients or growth factors, sensitized cells to apoptosis by suppressing glucocorticoid-mediated induction of several responsive genes, including the one encoding cellular inhibitor of apoptosis 2. Gas5 bound to the DNA-binding domain of the glucocorticoid receptor (GR) by acting as a decoy glucocorticoid response element (GRE), thus competing with DNA GREs for binding to the GR. We conclude that Gas5 is a “riborepressor” of the GR, influencing cell survival and metabolic activities during starvation by modulating the transcriptional activity of the GR.
Integral field spectroscopy of ionized and molecular gas in cool cluster cores: evidence for cold feedback?

We present VLT-SINFONI K-band integral field spectroscopy of the central galaxies in the cool core clusters A 1664, A2204 and PKS 0745-191, to probe the spatio-kinematic properties of the Paα and ro-vibrational H 2 line emission. In A1664, the two emission-line velocity systems seen in our previous Hα spectroscopy appear in both Paα and H 2 emission, with notable morphological differences. The recession velocity of the red component of Paα increases linearly with decreasing radius, particularly along an 8 kpc filament aligned with the major axis of the underlying galaxy and the cluster X-ray emission. These kinematics are modelled as gravitational free-fall as gas cools rapidly out of the hot phase. In A2204, the gas shows three or four filaments reaching radii of 10 kpc, three of which lie towards 'ghost bubbles' seen in X-ray imaging by Sanders et al. For PKS 0745―191, we confirm the twin-arm morphology in the narrow-band images of Donahue et al.; the Paα kinematics suggest rotational motion about an axis aligned with the kiloparsec-scale radio jet; on nucleus, we find an underlying broad Paα component [full width at half-maximum (FWHM) 1700 km s -1 ] and a secondary H 2 velocity system redshifted by +500 km s -1 . The H 2 v = 1-0 S(3)/Paα ratio is the highest in the most isolated and extended regions where it matches the levels in the NGC 1275 filaments as modelled by Ferland et al. Regions with much lower ratios highlight active star formation and are often kinematically quiescent (FWHM < 200 km s -1 ). Our findings suggest that the three clusters may be captured in different stages of the 'cold feedback' cycle of Pizzolato & Soker, with A1664 in a short-lived phase of extreme cooling and star formation prior to an active galactic nucleus (AGN) heating event; PKS 0745-191 in an outburst state with the AGN accreting from a cool gas disc, and A2204 in a later phase in which cool gas is dragged out of the galaxy by the buoyant rise of old radio bubbles.
Systematic review of the prevalence of nodal metastases and the prognostic utility of sentinel lymph node biopsy in cutaneous squamous cell carcinoma

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer and its incidence is rising. The prognosis is mostly good but patients with high‐risk cSCC have a greater risk of recurrence and death. The aim of the present study was to conduct a systematic review analyzing the prevalence, predictors and prognostic utility of sentinel lymph node (SLN) involvement in cSCC. We performed a published work search in Ovid MEDLINE and reviewed the reference lists of selected studies. Based on the 23 studies included in the systematic review, the proportion of patients with cSCC and positive SLN biopsy findings was 8% (95% confidence interval, 5.1–10.8%; I2= 44.51%). We found no studies reporting on predictors of SLN involvement in cSCC or on the prognostic utility of this finding following adjustment for confounders. The rate of positive SLN in cSCC is less than previously reported. Criteria for recommending SLN biopsy as a staging tool for cSCC vary considerably from study to study, and none of the studies were large enough to reliably identify predictors of SLN positivity. No randomized controlled trials have yet analyzed whether SLN biopsy may improve the prognosis of cSCC. More studies are required on the prognostic value of SLN positivity and the associated risk factors in cSCC.
Testing the Effects of Procedural Justice and Overaccommodation in Traffic Stops

Research shows that perceptions of procedural justice influence people’s trust, confidence, and obligation to obey law and legal authorities as well as their willingness to cooperate with and support legal authorities. Interpersonal interaction styles that are central to procedural justice theory also play a key role in communication accommodation theory (CAT). Based on video clips depicting a police traffic stop, we use a randomized experiment to test the effects of procedural justice and overaccommodation on trust in police, willingness to cooperate with police, and obligation to obey police and the law. The results demonstrate that procedural justice has more powerful effects than overaccommodation on reported trust and confidence in the officer, as well as respondents’ obligation to obey and willingness to cooperate with the officer. Moreover, although procedural justice generated strong effects on encounter-specific attitudes, it did not exert any effect on more general attitudes toward police.
Challenges Facing Early Phase Trials Sponsored by the National Cancer Institute: An Analysis of Corrective Action Plans to Improve Accrual

Accruing patients in a timely manner represents a significant challenge to early phase cancer clinical trials. The NCI Cancer Therapy Evaluation Program analyzed 19 months of corrective action plans (CAP) received for slow-accruing phase I and II trials to identify slow accrual reasons, evaluate whether proposed corrective actions matched these reasons, and assess the CAP impact on trial accrual, duration, and likelihood of meeting primary scientific objectives. Of the 135 CAPs analyzed, 69 were for phase I trials and 66 for phase II trials. Primary reasons cited for slow accrual were safety/toxicity (phase I: 48%), design/protocol concerns (phase I: 42%, phase II: 33%), and eligibility criteria (phase I: 41%, phase II: 35%). The most commonly proposed corrective actions were adding institutions (phase I: 43%, phase II: 85%) and amending the trial to change eligibility or design (phase I: 55%, phase II: 44%). Only 40% of CAPs provided proposed corrective actions that matched the reasons given for slow accrual. Seventy percent of trials were closed to accrual at time of analysis (phase I = 48; phase II = 46). Of these, 67% of phase I and 70% of phase II trials met their primary objectives, but they were active three times longer than projected. Among closed trials, 24% had an accrual rate increase associated with a greater likelihood of meeting their primary scientific objectives. Ultimately, trials receiving CAPs saw improved accrual rates. Future trials may benefit from implementing CAPs early in trial life cycles, but it may be more beneficial to invest in earlier accrual planning. Clin Cancer Res; 22(22); 5408–16. ©2016 AACR. See related commentary by Mileham and Kim, p. 5397
Cutting Edge: Antigen-Specific TGFβ-Induced Regulatory T Cells Suppress Th17-Mediated Autoimmune Disease1

CD4+ T cells from the TCR transgenic TxA23 mouse recognize a peptide from the H/K-ATPase α-chain. When TxA23 CD4+ thymocytes are differentiated into Th1, Th2, and Th17 lines, all three subpopulations induced autoimmune gastritis (AIG) upon transfer into nu/nu recipients. The induction of AIG by naive T cells or by Th1 or Th2 cell lines could be prevented by the cotransfer of polyclonal Foxp3+ T regulatory cells (nTreg), whereas Th17-induced AIG was resistant to suppression. We compared the capacity of different types of Treg to suppress Th17-mediated AIG. Cotransfer of either nTreg or polyclonal TGFβ-induced Treg (iTreg) did not prevent AIG, while cotransfer of TGFβ-induced Ag-specific TxA23 iTreg completely prevented the development of disease. Ag-specific iTreg were able to suppress Th17-mediated disease when injected 6 days after the Th17 effectors. The implications of these results for the use of Treg for the cellular biotherapy of autoimmune disease are discussed.
Mental health of victims of intimate partner violence: results from a national epidemiologic survey.

OBJECTIVE This study assessed the national incidence and mental health correlates of recent intimate partner violence among adults interviewed by the wave 2 National Epidemiologic Survey on Alcohol and Related Conditions. METHODS Data were collected about minor and severe forms of intimate partner violence among adults who reported being married, recently married, or in a romantic relationship in the past 12 months (N=25,626). RESULTS A total of 1,608 individuals reported being victims of intimate partner violence, including 5.8% of men and 5.6% of women. New onset of axis I disorders was significantly more common among victims of intimate partner violence than among nonvictims (22.5% and 9.7%, respectively; OR=2.6) and was related to frequency of violent acts. CONCLUSIONS Intimate partner violence is common, and victimization, especially if recurrent, markedly increases the risk for developing several psychiatric disorders.
Locomotor pattern generation in the spinal cord: Studies in adult lamprey and zebrafish

The overall objective of this thesis is to characterize the mechanisms involved in the generation of locomotor activity in the spinal cord. To this end, we initially used the lamprey spinal cord to determine the transmitter phenotype of commissural interneurons (CINs). In addition, we developed a novel preparation of the brainstem-spinal cord of the adult zebrafish and used it to determine the mechanisms of locomotor pattern generation. The results obtained show: (1) That the left–right alternation is maintained because commissural glycinergic interneurons outnumber the glutamatergic ones. It was also shown that CINs display a graded rostrocaudal distribution and are immunoreactive to both glycine and glutamate. The difference in the proportion of inhibitory and excitatory CINs represents an anatomical substrate that ensures the predominance of alternating activity during locomotion. (2) That adult zebrafish spinal cord can produce locomotor activity and be used to study the organization of the locomotor circuitry. In this study we developed both a semi-intact and an in vitro preparation of the juvenile/adult zebrafish spinal cord that are able to generate a rhythmic motor pattern with characteristics similar to swimming in intact animals. In the in vitro preparation, spinal cord neurons were accessible for patch-clamp recordings to study their pattern of activation during fictive locomotion. (3) That 5-HT is released within the locomotor circuitry and acts as an intrinsic modulator to set the baseline locomotor activity. 5-HT decreases the frequency of the locomotor rhythm by increasing the mid-cycle inhibition and delaying the onset of the following onphase excitation. Thus endogenous 5-HT sets the balance between excitation and inhibition and set the baseline locomotor frequency. (4) That a brief stimulation of descending inputs at a defined region located at the first segments of the spinal cord induces long-lasting coordinated swimming activity. The burst amplitude, frequency and duration of the episode can increase by changing the frequency and strength of the stimulus pulses. The descending inputs seems to act as a switch to turn on the activity of the spinal locomotor network in the caudal spinal cord that relies mostly on iontropic glutamate receptors. In summary, our results provide anatomical evidence underlying the dominance of reciprocal inhibition over excitation during locomotion. We also showed that our newly developed in vitro adult zebrafish spinal cord preparation can be used to study spinal circuitry underlying locomotion.
Synthesis of surfactant-free SnS nanoplates in an aqueous solution

We report a synthetic route to produce surfactant-free SnS nanoplates with the Pbnm crystal structure. The process is quick and environmentally-friendly, accomplished under mild aqueous conditions. The synthesis involves two steps, formation of an intermediate tin oxide hydroxide (Sn6O4(OH)4) gel and its chemical transformation into SnS nanoplates in the presence of a sulfide precursor (Na2S). We found that addition of a small amount of PVP during the chemical transformation results in the formation of cubic SnS with the Cmcm crystal structure. We discuss the development of the crystal structures on the basis of density functional theory (DFT) calculations on the structure–energy relationship of SnS nanostructures. The optical properties of the SnS nanoplates and nanocubes are compared.
Environmental selection during the last ice age on the mother-to-infant transmission of vitamin D and fatty acids through breast milk

Significance The frequency of the human-specific EDAR V370A isoform is highly elevated in North and East Asian populations. The gene is known to have several pleiotropic effects, among which are sweat gland density and ductal branching in the mammary gland. The former has led some geneticists to argue that the near-fixation of this allele was caused by selection for modulation of thermoregulatory sweating. We provide an alternative hypothesis, that selection instead acted on the allele’s effect of increasing ductal branching in the mammary gland, thereby amplifying the transfer of critical nutrients to infants via mother’s milk. This is likely to have occurred during the Last Glacial Maximum when a human population was genetically isolated in the high-latitude environment of the Beringia. Because of the ubiquitous adaptability of our material culture, some human populations have occupied extreme environments that intensified selection on existing genomic variation. By 32,000 years ago, people were living in Arctic Beringia, and during the Last Glacial Maximum (LGM; 28,000–18,000 y ago), they likely persisted in the Beringian refugium. Such high latitudes provide only very low levels of UV radiation, and can thereby lead to dangerously low levels of biosynthesized vitamin D. The physiological effects of vitamin D deficiency range from reduced dietary absorption of calcium to a compromised immune system and modified adipose tissue function. The ectodysplasin A receptor (EDAR) gene has a range of pleiotropic effects, including sweat gland density, incisor shoveling, and mammary gland ductal branching. The frequency of the human-specific EDAR V370A allele appears to be uniquely elevated in North and East Asian and New World populations due to a bout of positive selection likely to have occurred circa 20,000 y ago. The dental pleiotropic effects of this allele suggest an even higher occurrence among indigenous people in the Western Hemisphere before European colonization. We hypothesize that selection on EDAR V370A occurred in the Beringian refugium because it increases mammary ductal branching, and thereby may amplify the transfer of critical nutrients in vitamin D-deficient conditions to infants via mothers’ milk. This hypothesized selective context for EDAR V370A was likely intertwined with selection on the fatty acid desaturase (FADS) gene cluster because it is known to modulate lipid profiles transmitted to milk from a vitamin D-rich diet high in omega-3 fatty acids.
Hypertension and Risk of Renal Cell Carcinoma Among White and Black Americans

Background: Renal cell carcinoma and hypertension (a well-established renal cancer risk factor) are both more frequent among blacks than whites in the United States. The association between hypertension and renal cell carcinoma has not been examined in black Americans. We investigated the hypertension–renal cancer association by race, and we assessed the role of hypertension in the racial disparity of renal cancer incidence. Methods: Participants were enrolled in a population-based case-control study in Detroit and Chicago during 2002–2007 (number of cases: 843 whites, 358 blacks; number of controls: 707 whites, 519 blacks). Participants reported their history of hypertension and antihypertensive drug use. We used unconditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for demographic characteristics, smoking, body mass index, and family history of cancer. Results: Hypertension doubled renal cancer risk (OR = 2.0 [CI = 1.7–2.5]) overall. For whites, the OR was 1.9 (CI = 1.5–2.4), whereas for blacks it was 2.8 (2.1–3.8) (P for interaction = 0.11). ORs increased with time after hypertension diagnosis (P for trend <0.001), reaching 4.1 (CI = 2.3–7.4) for blacks and 2.6 (CI = 1.7–4.1) for whites after 25 years. ORs for poorly controlled hypertension were 4.5 (CI = 2.3–8.8) for blacks and 2.1 (CI = 1.2–3.8) for whites. If these estimates correctly represent causal effects and if, hypothetically, hypertension could be prevented entirely among persons aged 50–79 years, the black/white disparity in renal cancer could be reversed among women and reduced by two-thirds among men. Conclusions: Hypertension is a risk factor for renal cancer among both blacks and whites, and might explain a substantial portion of the racial disparity in renal cancer incidence. Preventing and controlling hypertension might reduce renal cancer incidence, adding to the known benefits of blood pressure control for heart disease and stroke reduction, particularly among blacks.
Role of Interleukin 37 as a Novel Proangiogenic Factor in Juvenile Idiopathic Arthritis

Objective The aim of this study was to investigate interleukin 37 (IL-37) levels in the serum and synovial fluid of patients with juvenile idiopathic arthritis (JIA), its expression in peripheral blood mononuclear cells, and correlation with disease activity and angiogenesis. Methods Seventy JIA patients and 50 control subjects were examined. The Juvenile Arthritis Disease Activity Score in 27 joints (JADAS-27) was calculated. Immunoassays were used to measure the serum and synovial fluid levels of IL-37, vascular endothelial growth factor (VEGF), soluble VEGF receptor 1 (sVEGF-R1), and sVEGF-R2. Relative expression of IL-37 mRNA in peripheral blood mononuclear cells and the power Doppler ultrasound score of the affected joint were measured. Results Patients with JIA were subdivided as 20 systemic-onset, 20 polyarticular, and 30 oligoarticular (10 persistent, 20 extended) cases. Serum levels of IL-37, VEGF, VEGF-R1, and VEGF-R2 and relative IL-37 mRNA expression were significantly higher in JIA patients when compared with the control subjects (p < 0.001). These concentrations were significantly higher in systemic-onset JIA compared with those in polyarticular and oligoarticular JIA, and in polyarticular JIA when compared with oligoarticular JIA (p < 0.001). Serum, synovial, and mRNA expression levels of IL-37 were positively correlated with C-reactive protein, erythrocyte sedimentation rate, Juvenile Arthritis Disease Activity Score in 27 joints, power Doppler ultrasound score (p < 0.001), and the serum and synovial VEGF and VEGF-RI and -R2 levels (p < 0.05). Conclusions Our results demonstrate that IL-37 levels and mRNA expression were significantly increased in JIA patients, and their levels were positively correlated with disease activity and markers of angiogenesis (VEGF and VEGF receptors), suggesting that IL-37 may be correlated with angiogenesis.
Ultrasonographic Characterization of the db/db Mouse: An Animal Model of Metabolic Abnormalities

The availability of an animal model able to reliably mirror organ damage occurring in metabolic diseases is an urgent need. These models, mostly rodents, have not been fully characterized in terms of cardiovascular, renal, and hepatic ultrasound parameters, and only sparse values can be found in literature. Aim of this paper is to provide a detailed, noninvasive description of the heart, vessels, liver, and kidneys of the db/db mouse by ultrasound imaging. Sixteen wild type and thirty-four db/db male mice (11-week-old) were studied. State-of-the-art ultrasound technology was used to acquire images of cardiovascular, renal, and hepatic districts. A set of parameters describing function of the selected organs was evaluated. db/db mice are characterized by systolic and diastolic dysfunction, confirmed by strain analysis. Abdominal aortic and carotid stiffness do not seem to be increased in diabetic rodents; furthermore, they are characterized by a smaller mean diameter for both vessels. Renal microcirculation is significantly compromised, while liver steatosis is only slightly higher in db/db mice than in controls. We offer here for the first time an in vivo detailed ultrasonographic characterization of the db/db mouse, providing a useful tool for a thoughtful choice of the right rodent model for any experimental design.