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Persistent alterations of proopiomelanocortin (Pomc) and mu-opioid receptor (Oprm1) activity and stress responses after alcohol are critically involved in vulnerability to alcohol dependency. Gene transcriptional regulation altered by alcohol may play important roles. Mice with genome-wide deletion of neuronal Pomc enhancer1 (nPE1(-/-)), had hypothalamic-specific partial reductions of beta-endorphin and displayed lower alcohol consumption, compared to wildtype littermates (nPE1(+/+)). We used RNA-Seq to measure steady-state nuclear mRNA transcripts of opioid and stress genes in hypothalamus of nPE1(+/+) and nPE1(-/-) mice after 1-day acute withdrawal from chronic excessive alcohol drinking or after water. nPE1(-/-) had lower basal Pomc and Pdyn (prodynorphin) levels compared to nPE1(+/+), coupled with increased basal Oprm1 and Oprk1 (kappa-opioid receptor) levels, and low alcohol drinking increased Pomc and Pdyn to the basal levels of nPE1(+/+) in the water group, without significant effects on Oprm1 and Oprk1. In nPE1(+/+), excessive alcohol intake increased Pomc and Oprm1, with no effect on Pdyn or Oprk1. For stress genes, nPE1(-/-) had lowered basal Oxt (oxytocin) and Avp (arginine vasopressin) that were restored by low alcohol intake to basal levels of nPE1(+/+). In nPE1(+/+), excessive alcohol intake decreased Oxt and Avpi1 (AVP-induced protein1). Functionally examining the effect of pharmacological blockade of mu-opioid receptor, we found that naltrexone reduced excessive alcohol intake in nPE1(+/+), but not nPE1(-/-). Our results provide evidence relevant to the transcriptional profiling of the critical genes in mouse hypothalamus: enhanced opioid and reduced stress gene transcripts after acute withdrawal from excessive alcohol may contribute to altered reward and stress responses.

Background: The development of imaging-based biomarkers has the potential to overcome major challenges in the accurate and reproducible assessment of disease severity and response to novel therapies in Hidradenitis Suppurativa (HS). Understanding the advantages and limitations of existing non-invasive imaging modalities in dermatological disease will aid in the development of hypotheses and inform the design of future studies. Methods: A scoping review was performed using Medline, Embase, Web of Science Databases and evaluation of "gray literature" until June 30, 2019. Citations were examined according to pre-defined inclusion and exclusion criteria. Citations were reviewed by two independent reviewers. Narrative Synthesis was used to summarize data, structured by imaging modality. Results: Non-invasive imaging modalities, such as ultrasound, MRI, RCM, EIS, OCT, and MIT, were identified. Only ultrasound, MRI and MIT have been used in HS. Image modalities vary in image depth, resolution, cost, accessibility and correlation with known aspects of disease activity in HS. Discussion and Conclusion: The benefits and limitations of each imaging modality are products of cost, accessibility, validity and reliability. An additional hurdle to the development of image-based biomarkers in HS is a lack of established analytical benchmarks that can be correlated with existing biological, inflammatory and clinical parameters. This review has identified potential imaging biomarkers, as well as relevant analytical benchmarks that reflect the presence or absence of disease. Further investigation work is needed to analytically and clinically validate these imaging variables in order to identify potential imaging biomarkers in HS.

Type II CRISPR-Cas systems defend prokaryotes from bacteriophage

Soon after exposure to genotoxic reagents, mammalian cells inhibit transcription to prevent collisions with repair machinery and to mount a proper DNA damage response. However, mechanisms underlying early transcriptional inhibition are poorly understood. In this report, we show that site-specific acetylation of super elongation complex (SEC) subunit AFF1 by p300 reduces its interaction with other SEC components and impairs P-TEFb-mediated C-terminal domain phosphorylation of RNA polymerase II both in vitro and in vivo. Reexpression of wild-type AFF1, but not an acetylation mimic mutant, restores SEC component recruitment and target gene expression in AFF1 knockdown cells. Physiologically, we show that, upon genotoxic exposure, p300-mediated AFF1 acetylation is dynamic and strongly correlated with concomitant global down-regulation of transcription-and that this can be reversed by over-expression of an acetylation-defective AFF1 mutant. Therefore, we describe a mechanism of dynamic transcriptional regulation involving p300-mediated acetylation of a key elongation factor during genotoxic stress.

Monocyte counts are increased during human tuberculosis (TB) but it has not been determined whether Mycobacterium tuberculosis (Mtb) directly regulates myeloid commitment. We demonstrated that exposure to Mtb directs primary human CD34(+) cells to differentiate into monocytes/macrophages. In vitro myeloid conversion did not require type I or type II IFN signaling. In contrast, Mtb enhanced IL-6 responses by CD34(+) cell cultures and IL-6R neutralization inhibited myeloid differentiation and decreased mycobacterial growth in vitro. Integrated systems biology analysis of transcriptomic, proteomic and genomic data of large data sets of healthy controls and TB patients established the existence of a myeloid IL-6/IL6R/CEBP gene module associated with disease severity. Furthermore, genetic and functional analysis revealed the IL6/IL6R/CEBP gene module has undergone recent evolutionary selection, including Neanderthal introgression and human pathogen adaptation, connected to systemic monocyte counts. These results suggest Mtb co-opts an evolutionary recent IFN-IL6-CEBP feed-forward loop, increasing myeloid differentiation linked to severe TB in humans.

The size of oocytes was previously reported to be smaller in obese women with polycystic ovary syndrome (PCOS). In the present prospective cohort study, we sought to determine whether oocyte size and morphology are associated with patient characteristics in non-PCOS women. Oocyte and oolemmal diameter were measured, enlarged perivitelline space (PVS) and ooplasmic granulation were assessed in 308 MII oocytes from 77 IVF/ICSI couples. Statistical analysis was undertaken using SAS version 9.4 (SAS institute Inc., USA). Continuous values are presented as mean SD and compared using a two-sample t test or Mann-Whitney U test as appropriate. Categorical parameters are presented as proportions and compared using a Fisher exact test. Logistic and linear regression models were used to control for the effect of age for categorical and continuous variables respectively. P-value < 0.05 was considered statistically significant. Patients presented with a mean age of 40.3 +/- 5.0 years, had a BMI of 25.1 +/- 6.1 kg/m(2), median AMH levels of 0.6 ng/ml and produced a median of 4 oocytes. Mean total oocyte diameter was 163.2 +/- 7.4 mu m (range 145.8-182.1 mu m), while oolemmal diameter was 109.4 +/- 4.1 mu m (range 98.5-122.3 mu m). After adjusting for age and ovarian reserve increasing BMI was associated with decreased total oocyte diameter (p<0.05). Total oocyte diameter was also inversely associated with AMH levels (p = 0.03) and oocyte yield (p = 0.04). In contrast to total oocyte diameter, oolemmal diameter was not related to patient characteristics. Younger women and those with large oocyte yields demonstrated fewer oocytes with ooplasmic granulation (p<0.05 and p = 0.01). After adjustments for age, ooplasmic granulation was also less frequently observed in oocytes from women with higher AMH (p = 0.03) and increasing BMI (p<0.01). Fertilization was more likely in oocytes with larger oolemmal diameter (p = 0.008). Embryos from oocytes with larger total and ooplasmic diameters were more likely to be transferred or frozen (p = 0.004 and p = 0.01). In non-PCOS infertile women, BMI and ovarian function

Background: Psoriasis is a chronic inflammatory skin disease

Several SQUAMASA PROMOTER BINDING PROTEIN-LIKE (SPL) transcription

Animal hepaciviruses represent promising surrogate models for hepatitis