There is a short gamma-ray burst prompt phase at the beginning of each long one

We compare the prompt intrinsic spectral properties of a sample of short Gamma--ray Burst (GRB) with the first 0.3 seconds (rest frame) of long GRBs observed by Fermi/GBM. We find that short GRBs and the first part of long GRBs lie on the same E_p--E_iso correlation, that is parallel to the relation for the time averaged spectra of long GRBs. Moreover, they are indistinguishable in the E_p--L_iso plane. This suggests that the emission mechanism is the same for short and for the beginning of long events, and both short and long GRBs are very similar phenomena, occurring on different timescales. If the central engine of a long GRB would stop after ~0.3 * (1+z) seconds the resulting event would be spectrally indistinguishable from a short GRB.Comment: 14 pages, 6 figures, MNRAS accepte

Transcription Impacts the Efficiency of mRNA Translation via Co-transcriptional N6-adenosine Methylation

Transcription and translation are two main pillars of gene expression. Due to the different timings, spots of action, and mechanisms of regulation, these processes are mainly regarded as distinct and generally uncoupled, despite serving a common purpose. Here, we sought for a possible connection between transcription and translation. Employing an unbiased screen of multiple human promoters, we identified a positive effect of TATA box on translation and a general coupling between mRNA expression and translational efficiency. Using a CRISPR-Cas9-mediated approach, genome-wide analyses, and in vitro experiments, we show that the rate of transcription regulates the efficiency of translation. Furthermore, we demonstrate that m6A modification of mRNAs is co-transcriptional and depends upon the dynamics of the transcribing RNAPII. Suboptimal transcription rates lead to elevated m6A content, which may result in reduced translation. This study uncovers a general and widespread link between transcription and translation that is governed by epigenetic modification of mRNAs

The role of Isocitrate Lyase (ICL1) in the metabolic adaptation of Candida albicans biofilms

Background A major characteristic of Candida biofilm cells that differentiates them from free-floating cells is their high tolerance to antifungal drugs. This high resistance is attributed to particular biofilm properties, including the accumulation of extrapolymeric substances, morphogenetic switching, and metabolic flexibility. Objectives This study evaluated the roles of metabolic processes (in particular the glyoxylate cycle) on biofilm formation, antifungal drug resistance, morphology, and cell wall components. Methods Growth, adhesion, biofilm formation, and cell wall carbohydrate composition were quantified for isogenic Candida albicans ICL1/ICL1, ICL1/icl1, and icl1/icl1 strains. The morphology and topography of these strains were compared by light microscopy and scanning electron microscopy. FKS1 (glucan synthase), ERG11 (14-α-demethylase), and CDR2 (efflux pump) mRNA levels were quantified using qRT-PCR. Results The ICL1/icl1 and icl1/icl1 strains formed similar biofilms and exhibited analogous drug-tolerance levels to the control ICL1/ICL1 strains. Furthermore, the drug sequestration ability of β-1, 3-glucan, a major carbohydrate component of the extracellular matrix, was not impaired. However, the inactivation of ICL1 did impair morphogenesis. ICL1 deletion also had a considerable effect on the expression of the FKS1, ERG11, and CDR2 genes. FKS1 and ERG11 were upregulated in ICL1/icl1 and icl1/icl1 cells throughout the biofilm developmental stages, and CDR2 was upregulated at the early phase. However, their expression was downregulated compared to the control ICL1/ICL1 strain. Conclusions We conclude that the glyoxylate cycle is not a specific determinant of biofilm drug resistance

In vitro Candida albicans biofilm formation on different titanium surface topographies

Objectives To investigate if differences in titanium implant surface topography influence Candida albicans biofilm formation. Materials and Methods Titanium discs were prepared and characterized using a profilometer: Group A (R a 0.15 µm, smooth), Group B (R a 0.64 µm, minimally rough) and Group C (R a 1.3 µm, moderately rough). Contact angle and surface free energy (SFE) were determined for each group. Non-preconditioned titanium discs were incubated with C. albicans for 24 h. In additional experiments, the titanium discs were initially coated with human saliva, bovine serum albumin or phosphate-buffered saline for 2 h before incubation with C. albicans for 24 h. The amount of fungal biofilm formation was quantified using a colorimetric assay. Results C. albicans biofilm formation was significantly lower (p < 0.05) on the minimally rough titanium surface compared to smooth and moderately rough surfaces. The titanium surface displaying the lowest SFE (Group B) was associated with significantly lower (p < 0.05) C. albicans biofilm formation than the other two groups. Salivary coating resulted in greater adherence of C. albicans with increased surface roughness. Conclusions The minimally rough titanium discs displayed lowest SFE compared to smooth and moderately rough surfaces and showed the least C. albicans biofilm formation. This study demonstrated that C. albicans biofilm formation increased in a SFE-dependent manner. These findings suggest that SFE might be a more explanatory factor for C. albicans biofilm formation on titanium surfaces than roughness. The presence of a pellicle coating may negate the impact of SFE on C. albicans biofilm formation on titanium surfaces

The Rewiring of Ubiquitination Targets in a Pathogenic Yeast Promotes Metabolic Flexibility, Host Colonization and Virulence

Funding: This work was funded by the European Research Council [http://erc.europa.eu/], AJPB (STRIFE Advanced Grant; C-2009-AdG-249793). The work was also supported by: the Wellcome Trust [www.wellcome.ac.uk], AJPB (080088, 097377); the UK Biotechnology and Biological Research Council [www.bbsrc.ac.uk], AJPB (BB/F00513X/1, BB/K017365/1); the CNPq-Brazil [http://cnpq.br], GMA (Science without Borders fellowship 202976/2014-9); and the National Centre for the Replacement, Refinement and Reduction of Animals in Research [www.nc3rs.org.uk], DMM (NC/K000306/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Acknowledgments We thank Dr. Elizabeth Johnson (Mycology Reference Laboratory, Bristol) for providing strains, and the Aberdeen Proteomics facility for the biotyping of S. cerevisiae clinical isolates, and to Euroscarf for providing S. cerevisiae strains and plasmids. We are grateful to our Microscopy Facility in the Institute of Medical Sciences for their expert help with the electron microscopy, and to our friends in the Aberdeen Fungal Group for insightful discussions.Peer reviewedPublisher PD

Training in the Management of Psychobehavioral Conditions: A Needs Assessment Survey of Emergency Medicine Residents

ObjectiveMental health–related ED visits are increasing. Despite this trend, most emergency medicine (EM) residency programs devote little time to psychiatry education. This study aimed to identify EM residents’ perceptions of training needs in emergency psychiatry and self‐confidence in managing patients with psychobehavioral conditions.MethodsA needs assessment survey was distributed to residents at 15 Accreditation Council for Graduate Medical Education–accredited EM programs spanning the U.S. Survey items addressed amount and type of training in psychiatry during residency, perceived training needs in psychiatry, and self‐confidence performing various clinical skills related to emergency psychiatric care. Residents used a 5‐point scale (1 = nothing; 5 = very large amount) to rate their learning needs in a variety of topic areas related to behavioral emergencies (e.g., medically clearing patients, substance use disorders). Using a scale from 0 to 100, residents rated their confidence in their ability to independently perform various clinical skills related to emergency psychiatric care (e.g., differentiating a psychiatric presentation from delirium).ResultsOf the 632 residents invited to participate, 396 (63%) responded. Twelve percent of respondents reported completing a psychiatry rotation during EM residency. One of the 15 participating programs had a required psychiatry rotation. Residents reported that their program used lectures (56%) and/or supervised training in the ED (35%) to teach residents about psychiatric emergencies. Most residents reported minimal involvement in the treatment of patients with psychiatric concerns. The majority of residents (59%) believed that their program should offer more education on managing psychiatric emergencies. Only 14% of residents felt “quite” or “extremely” prepared to treat psychiatric patients. Overall, residents reported the lowest levels of confidence and highest need for more training related to counseling suicidal patients and treating psychiatric issues in special populations (e.g., pregnant women, elderly, and children).ConclusionsMost EM residents desire more training in managing psychiatric emergencies than is currently provided.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152005/1/aet210377-sup-0001-DataSupplementS1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152005/2/aet210377.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152005/3/aet210377_am.pd

Palmitoylethanolamide Counteracts Enteric Inflammation and Bowel Motor Dysfunctions in a Mouse Model of Alzheimer’s Disease

Palmitoylethanolamide (PEA), an endogenous lipid mediator, is emerging as a promising pharmacological agent in multiple neurodegenerative disorders for its anti-inflammatory and neuroprotective properties. However, its effects on enteric inflammation and colonic dysmotility associated with Alzheimer’s disease (AD) are lacking. This study was designed to investigate the beneficial effect of PEA administration in counteracting the enteric inflammation and relieving the bowel motor dysfunctions in an AD mouse model, SAMP8 mice. In addition, the ability of PEA in modulating the activation of enteric glial cells (EGCs), pivotally involved in the pathophysiology of bowel dysfunctions associated with inflammatory conditions, has also been examined. SAMP8 mice at 4 months of age were treated orally with PEA (5&nbsp;mg/kg/day) for 2&nbsp;months. SAMR1 animals were employed as controls. At the end of treatment, parameters dealing with colonic motility, inflammation, barrier integrity and AD protein accumulation were evaluated. The effect of PEA on EGCs was tested in cultured cells treated with lipopolysaccharide (LPS) plus β-amyloid 1–42 (Aβ). SAMP8 treated with PEA displayed: 1) an improvement of in vitro colonic motor activity, citrate synthase activity and intestinal epithelial barrier integrity and 2) a decrease in colonic Aβ and α-synuclein (α-syn) accumulation, S100-β expression as well as enteric IL-1β and circulating LPS levels, as compared with untreated SAMP8 mice. In EGCs, treatment with PEA counteracted the increment of S100-β, TLR-4, NF-κB p65 and IL-1β release induced by LPS and Aβ. These results suggest that PEA, under a condition of cognitive decline, prevents the enteric glial hyperactivation, reduces AD protein accumulation and counteracts the onset and progression of colonic inflammatory condition, as well as relieves intestinal motor dysfunctions and improves the intestinal epithelial barrier integrity. Therefore, PEA represents a viable approach for the management of the enteric inflammation and motor contractile abnormalities associated with AD

Choreography, controversy and child sex abuse: Theoretical reflections on a cultural criminological analysis of dance in a pop music video

This article was inspired by the controversy over claims of ‘pedophilia!!!!’ undertones and the ‘triggering’ of memories of childhood sexual abuse in some viewers by the dance performance featured in the music video for Sia’s ‘Elastic Heart’ (2015). The case is presented for acknowledging the hidden and/or overlooked presence of dance in social scientific theory and cultural studies and how these can enhance and advance cultural criminological research. Examples of how these insights have been used within other disciplinary frameworks to analyse and address child sex crime and sexual trauma are provided, and the argument is made that popular cultural texts such as dance in pop music videos should be regarded as significant in analysing and tracing public perceptions and epistemologies of crimes such as child sex abuse