Metabolic characterization of anaerobic fungi provides a path forward for bioprocessing of crude lignocellulose

The conversion of lignocellulose-rich biomass to bio-based chemicals and higher order fuels remains a grand challenge, as single-microbe approaches often cannot drive both deconstruction and chemical production steps. In contrast, consortia based bioprocessing leverages the strengths of different microbes to distribute metabolic loads and achieve process synergy, product diversity, and bolster yields. Here, we describe a biphasic fermentation scheme that combines the lignocellulolytic action of anaerobic fungi isolated from large herbivores with domesticated microbes for bioproduction. When grown in batch culture, anaerobic fungi release excess sugars from both cellulose and crude biomass due to a wealth of highly expressed carbohydrate active enzymes (CAZymes), converting as much as 49% of cellulose to free glucose. This sugar-rich hydrolysate readily supports growth of Saccharomyces cerevisiae, which can be engineered to produce a range of value-added chemicals. Further, construction of metabolic pathways from transcriptomic data reveals that anaerobic fungi do not catabolize all sugars that their enzymes hydrolyze from biomass, leaving other carbohydrates such as galactose, arabinose, and mannose available as nutritional links to other microbes in their consortium. Although basal expression of CAZymes in anaerobic fungi is high, it is drastically amplified by cellobiose breakout products encountered during biomass hydrolysis. Overall, these results suggest that anaerobic fungi provide a nutritional benefit to the rumen microbiome, which can be harnessed to design synthetic microbial communities that compartmentalize biomass degradation and bioproduct formation

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Sociodemographic predictors of latent class membership of problematic and disordered gamblers

This paper reports a series of analyses examining the predictors of gambling subtypes identified from a latent class analysis of problem gambling assessment data, pooled from four health and gambling surveys conducted in Britain between 2007 and 2012. Previous analyses have indicated that gambling assessments have a consistent three class structure showing quantitative and potentially qualitative differences. Bringing this data together is useful for studying more severe problem gamblers, where the small number of respondents has been a chronic limitation of gambling prevalence research. Predictors were drawn from sociodemographic indicators and engagement with other legal addictive behaviours, namely smoking and alcohol consumption. The pooled data was entered into a multinomial logistic regression model in which class membership was regressed along a series of demographic variables and survey year, based on previous analyses of gambling prevalence data. The results identified multiple demographic differences (age, general health, SES, being single, membership of ethnic minority groups) between the non-problem and two classes endorsing some problem gambling indicators. Although these two groups tended to share a sociodemographic profile, the odds of being male, British Asian and a smoker increased between the three groups in line with problem gambling severity. Being widowed was also found to be associated with the most severe gambling class. A number of associations were also observed with other addictive behaviours. However these should be taken as indicative as these were limited subsamples of a single dataset. These findings identify specific groups in which gambling problems are more prevalent, and highlight the importance of the interaction between acute and determinant aspects of impulsivity, suggesting that a more complex account of impulsivity should be considered than is currently present in the gambling literature

Monitoring the Future national survey results on drug use, 1975-2017: Volume I, secondary school students

https://deepblue.lib.umich.edu/bitstream/2027.42/146530/1/Vol 1 2017 FINAL 2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146530/3/license_rdf.rd

Understanding the psychology of mobile gambling: A behavioural synthesis

This manuscript reviews the extant literature on key issues related to mobile gambling and considers whether the potential risks of harm emerging from this platform are driven by pre-existing comorbidities or by psychological processes unique to mobile gambling. We propose an account based on associative learning that suggests this form of gambling is likely to show distinctive features compared with other gambling technologies. Smartphones are a rapidly growing platform on which individuals can gamble using specifically designed applications, adapted websites or text messaging. This review considers how mobile phone use interacts with psychological processes relevant to gambling, the games users are likely to play on smartphones, and the interactions afforded by smartphones. Our interpretation of the evidence is that the schedules of reinforcement found in gambling interact with the ways in which people tend to use smartphones that may expedite the acquisition of maladaptive learned behaviours such as problem gambling. This account is consistent with existing theories and frameworks of problem gambling and has relevance to other forms of mobile phone use

Sociodemographic predictors of latent class membership of problematic and disordered gamblers

This paper reports a series of analyses examining the predictors of gambling subtypes identified from a latent class analysis of problem gambling assessment data, pooled from four health and gambling surveys conducted in Britain between 2007 and 2012. Previous analyses have indicated that gambling assessments have a consistent three class structure showing quantitative and potentially qualitative differences. Bringing this data together is useful for studying more severe problem gamblers, where the small number of respondents has been a chronic limitation of gambling prevalence research. Predictors were drawn from sociodemographic indicators and engagement with other legal addictive behaviours, namely smoking and alcohol consumption. The pooled data was entered into a multinomial logistic regression model in which class membership was regressed along a series of demographic variables and survey year, based on previous analyses of gambling prevalence data. The results identified multiple demographic differences (age, general health, SES, being single, membership of ethnic minority groups) between the non-problem and two classes endorsing some problem gambling indicators. Although these two groups tended to share a sociodemographic profile, the odds of being male, British Asian and a smoker increased between the three groups in line with problem gambling severity. Being widowed was also found to be associated with the most severe gambling class. A number of associations were also observed with other addictive behaviours. However these should be taken as indicative as these were limited subsamples of a single dataset. These findings identify specific groups in which gambling problems are more prevalent, and highlight the importance of the interaction between acute and determinant aspects of impulsivity, suggesting that a more complex account of impulsivity should be considered than is currently present in the gambling literature

Human vestibular schwannoma reduces density of auditory nerve fibers in the osseous spiral lamina

Hearing loss in patients with vestibular schwannoma (VS) is commonly attributed to mechanical compression of the auditory nerve, though recent studies suggest that this retrocochlear pathology may be augmented by cochlear damage. Although VS-associated loss of inner hair cells, outer hair cells, and spiral ganglion cells has been reported, it is unclear to what extent auditory-nerve peripheral axons are damaged in VS patients. Understanding the degree of damage VSs cause to auditory nerve fibers (ANFs) is important for accurately modeling clinical outcomes of cochlear implantation, which is a therapeutic option to rehabilitate hearing in VS-affected ears. A retrospective analysis of human temporal-bone histopathology was performed on archival specimens from the Massachusetts Eye and Ear collection. Seven patients met our inclusion criteria based on the presence of sporadic, unilateral, untreated VS. Tangential sections of five cochlear regions were stained with hematoxylin and eosin, and adjacent sections were stained to visualize myelinated ANFs and efferent fibers. Following confocal microscopy, peripheral axons of ANFs within the osseous spiral lamina were quantified manually, where feasible, and with a "pixel counting " method, applicable to all sections. ANF density was substantially reduced on the VS side compared to the unaffected contralateral side. In the upper basal turn, a significant difference between the VS side and unaffected contralateral side was found using both counting methods, corresponding to the region tuned to 20 0 0 Hz. Even spiral ganglion cells (SGCs) contralateral to VS were affected by the tumor as the majority of contralateral SGC counts were below average for age. This observation provides histological insight into the clinical observation that unilateral vestibular schwannomas pose a long-term risk of progression of hearing loss in the contralateral ear as well. Our pixel counting method for ANF quantification in the osseous spiral lamina is applicable to other pathologies involving sensorineural hearing loss. Future research is needed to classify ANFs into morphological categories, accurately predict their electrical properties, and use this knowledge to inform optimal cochlear implant programming strategies.(C) 2022 Published by Elsevier B.V.Disorders of the head and nec

Monitoring the Future national survey results on drug use, 1975-2017: Overview, key findings on adolescent drug use

https://deepblue.lib.umich.edu/bitstream/2027.42/148123/1/Overview 2018 FINAL print 1-30.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148123/3/license_rd