Improving Serial Imaging Protocols in Spontaneous Intracerebral Hemorrhage

There is no universally agreed upon protocol to image patient presenting with intra-parenchymal hemorrhage of non-traumatic etiology (sICH). At our institution, it is common practice for a patient to have 3 CT’s done within 24 hours. They are often at onset of symptoms or presentation, 6 hours post onset of symptoms, and finally 24 hours post bleed onset. The goal of this project will be to assess the safety and efficacy of obtaining this repeat imaging in our patients in the hopes that limiting unnecessary CT head studies will decrease resource utilization, decrease patient radiation, expedite movement of stable patients out of the ICU and/or disposition

Photo-physics and electronic structure of lateral graphene/MoS2 and metal/MoS2 junctions

Integration of semiconducting transition metal dichalcogenides (TMDs) into functional optoelectronic circuitries requires an understanding of the charge transfer across the interface between the TMD and the contacting material. Here, we use spatially resolved photocurrent microscopy to demonstrate electronic uniformity at the epitaxial graphene/molybdenum disulfide (EG/MoS2) interface. A 10x larger photocurrent is extracted at the EG/MoS2 interface when compared to metal (Ti/Au) /MoS2 interface. This is supported by semi-local density-functional theory (DFT), which predicts the Schottky barrier at the EG/MoS2 interface to be ~2x lower than Ti/MoS2. We provide a direct visualization of a 2D material Schottky barrier through combination of angle resolved photoemission spectroscopy with spatial resolution selected to be ~300 nm (nano-ARPES) and DFT calculations. A bending of ~500 meV over a length scale of ~2-3 micrometer in the valence band maximum of MoS2 is observed via nano-ARPES. We explicate a correlation between experimental demonstration and theoretical predictions of barriers at graphene/TMD interfaces. Spatially resolved photocurrent mapping allows for directly visualizing the uniformity of built-in electric fields at heterostructure interfaces, providing a guide for microscopic engineering of charge transport across heterointerfaces. This simple probe-based technique also speaks directly to the 2D synthesis community to elucidate electronic uniformity at domain boundaries alongside morphological uniformity over large areas

Sporadic ALS is not associated with VAPB gene mutations in Southern Italy

Mutations in the Cu/Zn superoxide dismutase (Sod1) gene have been reported to cause adult-onset autosomal dominant Amyotrophic Lateral Sclerosis (FALS). In sporadic cases (SALS) de novo mutations in the Sod1 gene have occasionally been observed. The recent finding of a mutation in the VAMP/synaptobrevin-associated membrane protein B (VAPB) gene as the cause of amyotrophic lateral sclerosis (ALS8), prompted us to investigate the entire coding region of this gene in SALS patients. One hundred twenty-five unrelated patients with adult-onset ALS and 150 healthy sex-age-matched subjects with the same genetic background were analyzed. Genetic analysis for all exons of the VAPB gene by DHPLC revealed 5 variant profiles in 83 out of 125 SALS patients. Direct sequencing of these PCR products revealed 3 nucleotide substitutions. Two of these were found within intron 3 of the gene, harbouring 4 variant DHPLC profiles. The third nucleotide variation (Asp130Glu) was the only substitution present in the coding region of the VAPB gene, and it occurred within exon 4. It was found in three patients out of 125. The frequency of the detected exon variation in the VAPB gene was not significantly different between patients and controls. In conclusion, our study suggests that VAPB mutations are not a common cause of adult-onset SALS

Spintronics: Fundamentals and applications

Spintronics, or spin electronics, involves the study of active control and manipulation of spin degrees of freedom in solid-state systems. This article reviews the current status of this subject, including both recent advances and well-established results. The primary focus is on the basic physical principles underlying the generation of carrier spin polarization, spin dynamics, and spin-polarized transport in semiconductors and metals. Spin transport differs from charge transport in that spin is a nonconserved quantity in solids due to spin-orbit and hyperfine coupling. The authors discuss in detail spin decoherence mechanisms in metals and semiconductors. Various theories of spin injection and spin-polarized transport are applied to hybrid structures relevant to spin-based devices and fundamental studies of materials properties. Experimental work is reviewed with the emphasis on projected applications, in which external electric and magnetic fields and illumination by light will be used to control spin and charge dynamics to create new functionalities not feasible or ineffective with conventional electronics.Comment: invited review, 36 figures, 900+ references; minor stylistic changes from the published versio

Serotonin and Dopamine Protect from Hypothermia/Rewarming Damage through the CBS/ H2S Pathway

Biogenic amines have been demonstrated to protect cells from apoptotic cell death. Herein we show for the first time that serotonin and dopamine increase H2S production by the endogenous enzyme cystathionine-β-synthase (CBS) and protect cells against hypothermia/rewarming induced reactive oxygen species (ROS) formation and apoptosis. Treatment with both compounds doubled CBS expression through mammalian target of rapamycin (mTOR) and increased H2S production in cultured rat smooth muscle cells. In addition, serotonin and dopamine treatment significantly reduced ROS formation. The beneficial effect of both compounds was minimized by inhibition of their re-uptake and by pharmacological inhibition of CBS or its down-regulation by siRNA. Exogenous administration of H2S and activation of CBS by Prydoxal 5′-phosphate also protected cells from hypothermic damage. Finally, serotonin and dopamine pretreatment of rat lung, kidney, liver and heart prior to 24 h of hypothermia at 3°C followed by 30 min of rewarming at 37°C upregulated the expression of CBS, strongly reduced caspase activity and maintained the physiological pH compared to untreated tissues. Thus, dopamine and serotonin protect cells against hypothermia/rewarming induced damage by increasing H2S production mediated through CBS. Our data identify a novel molecular link between biogenic amines and the H2S pathway, which may profoundly affect our understanding of the biological effects of monoamine neurotransmitters

Low potency toxins reveal dense interaction networks in metabolism

Background The chemicals of metabolism are constructed of a small set of atoms and bonds. This may be because chemical structures outside the chemical space in which life operates are incompatible with biochemistry, or because mechanisms to make or utilize such excluded structures has not evolved. In this paper I address the extent to which biochemistry is restricted to a small fraction of the chemical space of possible chemicals, a restricted subset that I call Biochemical Space. I explore evidence that this restriction is at least in part due to selection again specific structures, and suggest a mechanism by which this occurs. Results Chemicals that contain structures that our outside Biochemical Space (UnBiological groups) are more likely to be toxic to a wide range of organisms, even though they have no specifically toxic groups and no obvious mechanism of toxicity. This correlation of UnBiological with toxicity is stronger for low potency (millimolar) toxins. I relate this to the observation that most chemicals interact with many biological structures at low millimolar toxicity. I hypothesise that life has to select its components not only to have a specific set of functions but also to avoid interactions with all the other components of life that might degrade their function. Conclusions The chemistry of life has to form a dense, self-consistent network of chemical structures, and cannot easily be arbitrarily extended. The toxicity of arbitrary chemicals is a reflection of the disruption to that network occasioned by trying to insert a chemical into it without also selecting all the other components to tolerate that chemical. This suggests new ways to test for the toxicity of chemicals, and that engineering organisms to make high concentrations of materials such as chemical precursors or fuels may require more substantial engineering than just of the synthetic pathways involved

Consensus Report : 2nd European Workshop on Tobacco Use Prevention and Cessation for Oral Health Professionals

Tobacco use has been identified as a major risk factor for oral disorders such as cancer and periodontal disease. Tobacco use cessation (TUC) is associated with the potential for reversal of precancer, enhanced outcomes following periodontal treatment, and better periodontal status compared to patients who continue to smoke. Consequently, helping tobacco users to quit has become a part of both the responsibility of oral health professionals and the general practice of dentistry. TUC should consist of behavioural support, and if accompanied by pharmacotherapy, is more likely to be successful. It is widely accepted that appropriate compensation of TUC counselling would give oral health professionals greater incentives to provide these measures. Therefore, TUC-related compensation should be made accessible to all dental professionals and be in appropriate relation to other therapeutic interventions. International and national associations for oral health professionals are urged to act as advocates to promote population, community and individual initiatives in support of tobacco use prevention and cessation (TUPAC) counselling, including integration in undergraduate and graduate dental curricula. In order to facilitate the adoption of TUPAC strategies by oral health professionals, we propose a level of care model which includes 1) basic care: brief interventions for all patients in the dental practice to identify tobacco users, assess readiness to quit, and request permission to re-address at a subsequent visit, 2) intermediate care: interventions consisting of (brief) motivational interviewing sessions to build on readiness to quit, enlist resources to support change, and to include cessation medications, and 3) advanced care: intensive interventions to develop a detailed quit plan including the use of suitable pharmacotherapy. To ensure that the delivery of effective TUC becomes part of standard care, continuing education courses and updates should be implemented and offered to all oral health professionals on a regular basis

Genetic effects on the timing of parturition and links to fetal birth weight.

This is the final version. Available from Nature Research via the DOI in this record. Data availability: Cohorts should be contacted individually for access to raw genotype and phenotype data, as each cohort has different data access policies. Summary statistics from the meta-analysis, excluding 23andMe, are available at the EGG website (https://egg-consortium.org/), and access to the weights for constructing the polygenic score of gestational duration excluding 23andMe are available at the PGS Catalog (https://www.pgscatalog.org/, score ID: PGS002806). Access to the full set, including 23andMe results, can be obtained after approval from 23andMe is presented to the corresponding author or by completion of a Data Transfer Agreement (https://research.23andme.com/dataset-access/), which exists to protect the privacy of 23andMe participants. Access to the Danish National Birth Cohort (phs000103.v1.p1), Hyperglycemia and Adverse Pregnancy Outcome (phs000096.v4.p1) and Genomic and Proteomic Network (phs000714.v1.p1) individual-level phenotype and genetic data can be obtained through dbGaP Authorized Access portal (https://dbgap.ncbi.nlm.nih.gov/dbgap/aa/wga.cgi?page=login). The informed consent under which the data or samples were collected is the basis for determining the appropriateness of sharing data through unrestricted-access databases or NIH-designated controlled-access data repositories. The summary statistics used in this publication other than the one generated are available at the following links: fetal GWAS of gestational duration (http://egg-consortium.org/gestational-duration-2019.html), fetal and maternal GWAS of birth weight (http://egg-consortium.org/birth-weight-2019.html), miscarriage (http://www.geenivaramu.ee/tools/misc_sumstats.zip), age at first birth, estradiol (women), endometriosis, number of live births and age at menarche (http://www.nealelab.is), age at menopause (https://www.reprogen.org), testosterone (women)58, SHBG, testosterone and CBAT (https://doi.org/10.6084/m9.figshare.c.5304500.v1), pelvic organ prolapse and leiomyoma of the uterus (https://www.finngen.fi/fi), polycystic ovary syndrome (https://www.repository.cam.ac.uk/handle/1810/283491 and https://www.finngen.fi/fi) and pre-eclampsia (European Genome-phenome Archive, https://ega-archive.org, EGAD00010001984). Pan-UK Biobank data are available at https://pan.ukbb.broadinstitute.org/. Precomputed LD scores for European populations (https://data.broadinstitute.org/alkesgroup/LDSCORE/eur_w_ld_chr.tar.bz2) and multi-tissue gene expression precomputed stratified LD scores (https://alkesgroup.broadinstitute.org/LDSCORE/LDSC_SEG_ldscores/Multi_tissue_gene_expr_1000Gv3_ldscores.tgz) are available. eQTL data from GTEx are available at https://gtexportal.org/home/ and from endometrium at http://reproductivegenomics.com.au/shiny/endo_eqtl_rna/. Protein QTL data were obtained from https://www.omicscience.org/apps/pgwas/. Genome Reference Consortium Human Build 37 (hg19) available at https://www.ncbi.nlm.nih.gov/data-hub/genome/GCF_000001405.13/.Code availability: Code for this project has been structured using a Snakemake workflow65 and is available at https://github.com/PerinatalLab/metaGWAS. A public release of it has been deposited in Zenodo (https://doi.org/10.5281/zenodo.7311977).The timing of parturition is crucial for neonatal survival and infant health. Yet, its genetic basis remains largely unresolved. We present a maternal genome-wide meta-analysis of gestational duration (n = 195,555), identifying 22 associated loci (24 independent variants) and an enrichment in genes differentially expressed during labor. A meta-analysis of preterm delivery (18,797 cases, 260,246 controls) revealed six associated loci and large genetic similarities with gestational duration. Analysis of the parental transmitted and nontransmitted alleles (n = 136,833) shows that 15 of the gestational duration genetic variants act through the maternal genome, whereas 7 act both through the maternal and fetal genomes and 2 act only via the fetal genome. Finally, the maternal effects on gestational duration show signs of antagonistic pleiotropy with the fetal effects on birth weight: maternal alleles that increase gestational duration have negative fetal effects on birth weight. The present study provides insights into the genetic effects on the timing of parturition and the complex maternal-fetal relationship between gestational duration and birth weight.Swedish Research CouncilSwedish Research CouncilResearch Council of NorwayResearch Council of NorwayMarch of Dimesunice Kennedy Shriver National Institute Of Child Health & Human Development of the National Institutes of HealthNorwegian Diabetes AssociationNils Normans minnegaveNorwegian Research CouncilMedical Research CouncilBritish Heart FoundationResearch Council of NorwayBritish Heart FoundationDaniel B. Burke Chair for Diabetes Research and NIHCHOPEuropean Regional Development Fund and the programme Mobilitas PlussWellcome Trust and Royal Society Sir Henry Dale FellowshipWellcome TrustOak FoundationFonds de la recherche du Québec en santéUS National Institutes of HealthNovo Nordisk FoundationNovo Nordisk FoundationNovo Nordisk Foundatio

<i>Aspergillus fumigatus</i> FhdA Transcription Factor Is Important for Mitochondrial Activity and Codon Usage Regulation during the Caspofungin Paradoxical Effect

Aspergillus fumigatus is the main etiological agent of aspergillosis. The antifungal drug caspofungin (CSP) can be used against A. fumigatus, and CSP tolerance is observed. We have previously shown that the transcription factor FhdA is important for mitochondrial activity. Here, we show that FhdA regulates genes transcribed by RNA polymerase II and III. FhdA influences the expression of tRNAs that are important for mitochondrial function upon CSP. Our results show a completely novel mechanism that is impacted by CSP