Specific forms of the lipid ceramide, synthesized by the ceramide synthase enzyme family, are believed to regulate metabolic physiology. Genetic mouse models have established C16 ceramide as a driver ...of insulin resistance in liver and adipose tissue. C18 ceramide, synthesized by ceramide synthase 1 (CerS1), is abundant in skeletal muscle and suggested to promote insulin resistance in humans. We herein describe the first isoform-specific ceramide synthase inhibitor, P053, which inhibits CerS1 with nanomolar potency. Lipidomic profiling shows that P053 is highly selective for CerS1. Daily P053 administration to mice fed a high-fat diet (HFD) increases fatty acid oxidation in skeletal muscle and impedes increases in muscle triglycerides and adiposity, but does not protect against HFD-induced insulin resistance. Our inhibitor therefore allowed us to define a role for CerS1 as an endogenous inhibitor of mitochondrial fatty acid oxidation in muscle and regulator of whole-body adiposity.
We characterized 55 influenza A(H9N2) viruses isolated in Pakistan during 2014-2016 and found that the hemagglutinin gene is of the G1 lineage and that internal genes have differentiated into a ...variety of novel genotypes. Some isolates had up to 4-fold reduction in hemagglutination inhibition titers compared with older viruses. Viruses with hemagglutinin A180T/V substitutions conveyed this antigenic diversity and also caused up to 3,500-fold greater binding to avian-like and >20-fold greater binding to human-like sialic acid receptor analogs. This enhanced binding avidity led to reduced virus replication in primary and continuous cell culture. We confirmed that altered receptor-binding avidity of H9N2 viruses, including enhanced binding to human-like receptors, results in antigenic variation in avian influenza viruses. Consequently, current vaccine formulations might not induce adequate protective immunity in poultry, and emergence of isolates with marked avidity for human-like receptors increases the zoonotic risk.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The varied topography of human skin offers a unique opportunity to study how the body's microenvironments influence the functional and taxonomic composition of microbial communities. Phylogenetic ...marker gene-based studies have identified many bacteria and fungi that colonize distinct skin niches. Here metagenomic analyses of diverse body sites in healthy humans demonstrate that local biogeography and strong individuality define the skin microbiome. We developed a relational analysis of bacterial, fungal and viral communities, which showed not only site specificity but also individual signatures. We further identified strain-level variation of dominant species as heterogeneous and multiphyletic. Reference-free analyses captured the uncharacterized metagenome through the development of a multi-kingdom gene catalogue, which was used to uncover genetic signatures of species lacking reference genomes. This work is foundational for human disease studies investigating inter-kingdom interactions, metabolic changes and strain tracking, and defines the dual influence of biogeography and individuality on microbial composition and function.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objectives
We examine the rational assumption of the interchangeability of legal and illegal monies. Drawing from economics, behavioral economics, and sociology we answer two main research questions: ...(1) Do offenders perceive money earned across various income-generating activities (legal vs. illegal) in the same way? (2) How do consumption patterns (spending and saving) differ across various forms of income-generating activities?
Methods
We use an a priori mixed methods approach with two interrelated studies; a quantitative survey of incarcerated offenders (N = 58) and a qualitative study of semi-structured interviews from four separate previous research projects (N = 107).
Results
We find evidence for the existence of differential consumption patterns based on quantitative and qualitative data from both incarcerated and active offenders regarding their patterns of spending legal and illegal money.
Conclusions
Our findings have implications for choice theories of crime, for public policy approaches to poverty, and crime prevention interventions.
Multiple studies suggest that females are affected by Alzheimer disease (AD) more severely and more frequently than males. Other studies have failed to confirm this and the issue remains ...controversial. Difficulties include differences in study methods and male versus female life expectancy. Another element of uncertainty is that the majority of studies have lacked neuropathological confirmation of the AD diagnosis. We compared clinical and pathological AD severity in 1028 deceased subjects with full neuropathological examinations. The age of dementia onset did not differ by gender but females were more likely to proceed to very severe clinical and pathological disease, with significantly higher proportions having a Mini-Mental State Examination score of 5 or less and Braak stage VI neurofibrillary degeneration. Median neuritic plaque densities were similar in females and males with AD but females had significantly greater tangle density scores. In addition, we found that AD-control brain weight differences were significantly greater for females, even after adjustment for age, disease duration, and comorbid conditions. These findings suggest that when they are affected by AD, females progress more often to severe cognitive dysfunction, due to more severe neurofibrillary degeneration, and greater loss of brain parenchyma.
Feline upper respiratory tract disease (FURTD), often caused by infections etiologies, is a multifactorial syndrome affecting feline populations worldwide. Because of its highly transmissible nature, ...infectious FURTD is most prevalent anywhere cats are housed in groups such as animal shelters, and is associated with negative consequences such as decreasing adoption rates, intensifying care costs, and increasing euthanasia rates. Understanding the etiology and pathophysiology of FURTD is thus essential to best mitigate the negative consequences of this disease. Clinical signs of FURTD include acute respiratory disease, with a small fraction of cats developing chronic sequelae. It is thought that nasal mucosal microbiome changes play an active role in the development of acute clinical signs, but it remains unknown if the microbiome may play a role in the development and progression of chronic clinical disease. To address the knowledge gap surrounding how microbiomes link to chronic FURTD, we asked if microbial community structure of upper respiratory and gut microbiomes differed between cats with chronic FURTD signs and clinically normal cats. We selected 8 households with at least one cat exhibiting chronic clinical FURTD, and simultaneously collected samples from cohabitating clinically normal cats. Microbial community structure was assessed via 16S rDNA sequencing of both gut and nasal microbiome communities. Using a previously described ecophylogenetic method, we identified 136 and 89 microbial features within gut and nasal microbiomes respectively that significantly associated with presence of active FURTD clinical signs in cats with a history of chronic signs. Overall, we find that nasal and gut microbial community members associate with the presence of chronic clinical course, but more research is needed to confirm our observations.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objectives
To determine the prevalence in Australia of multi‐type child maltreatment, defined as two or more maltreatment types (physical abuse, sexual abuse, emotional abuse, neglect, or exposure to ...domestic violence) and to examine its nature, family risk factors, and gender and age cohort differences.
Design
Retrospective cross‐sectional survey using a validated questionnaire.
Setting and participants
Mobile phone random digit‐dial sample of the Australian population aged 16 years and older.
Main outcome measures
National estimates of multi‐type child maltreatment up to age 18 years using the Juvenile Victimisation Questionnaire‐R2: Adapted Version (Australian Child Maltreatment Study).
Results
Of 8503 participants, 62.2% (95% CI, 60.9–63.6%) experienced one or more types of child maltreatment. Prevalence of single‐type maltreatment was 22.8% (95% CI, 21.7–24.0%), whereas 39.4% (95% CI, 38.1–40.7%) of participants reported multi‐type maltreatment and 3.5% (95% CI, 3.0–4.0%) reported all five types. Multi‐type maltreatment was more common for gender diverse participants (66.1% 95% CI, 53.7–78.7%) and women (43.2% 95% CI, 41.3–45.1%) than for men (34.9% 95% CI, 33.0–36.7%). Multi‐type maltreatment prevalence was highest for those aged 25–44 years. Family‐related adverse childhood experiences — especially mental illness and alcohol or substance misuse — increased risk. Exposure to domestic violence was the maltreatment type most often present in multi‐type maltreatment patterns.
Conclusions
Multi‐type child maltreatment is prevalent in Australia and more common in women and gender diverse individuals. Child protection services, health practitioners, and prevention and intervention services must assess and manage multi‐type maltreatment in children and address its health consequences across the lifespan. Public health policy should consider prevention services or strategies that target multi‐type child maltreatment.
We compared data from the National Collegiate Athletic Association (NCAA) Concussion Study (1999-2001) and the NCAA-Department of Defense Concussion Assessment, Research and Education (CARE) ...Consortium (2014-2017) to examine how clinical management, return to play (RTP) and risk of repeat concussion in collegiate football players have changed over the past 15 years.
We analysed data on reported duration of symptoms, symptom-free waiting period (SFWP), RTP and occurrence of within-season repeat concussion in collegiate football players with diagnosed concussion from the NCAA Study (n=184) and CARE (n=701).
CARE athletes had significantly longer symptom duration (CARE median=5.92 days, IQR=3.02-9.98 days; NCAA median=2.00 days, IQR=1.00-4.00 days), SFWP (CARE median=6.00 days, IQR=3.49-9.00 days; NCAA median=0.98 days, IQR=0.00-4.00 days) and RTP (CARE median=12.23 days, IQR=8.04-18.92 days; NCAA median=3.00 days, IQR=1.00-8.00 days) than NCAA Study athletes (all p<0.0001). In CARE, there was only one case of repeat concussion within 10 days of initial injury (3.7% of within-season repeat concussions), whereas 92% of repeat concussions occurred within 10 days in the NCAA Study (p<0.001). The average interval between first and repeat concussion in CARE was 56.41 days, compared with 5.59 days in the NCAA Study (M difference=50.82 days; 95% CI 38.37 to 63.27; p<0.0001).
Our findings indicate that concussion in collegiate football is managed more conservatively than 15 years ago. These changes in clinical management appear to have reduced the risk of repetitive concussion during the critical period of cerebral vulnerability after sport-related concussion (SRC). These data support international guidelines recommending additional time for brain recovery before athletes RTP after SRC.
Jan. 2--Authorities spent the New Year's holiday tracking robbers and a family of potential burglars. One suspect worked as a jailer at the Madison County Jail, Priceville Police Chief Billy Peebles ...said. Morgan County Sheriff's Department Chief Deputy Mike Corley said there were two robberies at Lacey's Spring and an attempted burglary in Priceville over New Year's Eve night and New Year's morning. The burglary led to a foot chase and the arrest of four suspects. The mayhem started Saturday night, New Year's Eve, when a man with a handgun took money from the Food Mart on U.S. 231 at Lacey's Spring, Corley said. Then four individuals allegedly tried to break into an automated teller machine in Priceville, Peebles said. Authorities captured the four, Peebles said, when Priceville Cpl. Rick Williams surprised two men cutting the telephone wire at Regions Bank in Foodland Shopping Center on Alabama 67. Williams was on routine patrol about 3 a.m. when he saw two men dressed in black. "No doubt they were after the ATM cash dispenser at the bank," Peebles said.
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