Integrating Genetics and Neuroimaging to study Subtypes of Binge Drinkers

Risky alcohol use is a major health concern among college students, with 40.1% reporting binge drinking (5 or more drinks in one occasion) and 14.4% reporting heavy drinking (binge drinking on 5 or more occasions) in the past month. Risky alcohol use is thought to be the result of a complex interplay between genes, biological processes, and other phenotypic characteristics. Understanding this complex relationship is further complicated by known phenotypic heterogeneity in the development of alcohol use. Developmental studies have suggested two pathways to risky alcohol use, characterized by externalizing and internalizing characteristics, respectively. However, the underlying biological processes that differentiate these pathways are not fully understood. Neuroimaging studies have assessed reward sensitivity, emotion reactivity, and behavioral inhibition using fMRI and separately demonstrate associations in externalizing and internalizing disorders more broadly. In addition, previous genetic studies have found associations between specific polymorphisms and these externalizing and internalizing subtypes. Therefore, we sought further characterize the biological influences on binge drinking subtypes through the following specific aims: 1) determine the genetic relationship between externalizing and internalizing characteristics in binge drinkers, 2) test whether externalizing and internalizing binge drinkers show differences in brain activation in response to tasks measuring emotion reactivity, reward sensitivity, and behavioral inhibition. In order to achieve these aims, we conducted a series of genetic analyses assessing differences in overall SNP-based heritability and specific associated variants between the externalizing and internalizing subtypes. There were a few variants that reached genome-wide significance, the most notable being a cluster of SNPs associated with internalizing characteristics that were located in the RP3AL gene. In a subset of these binge drinking young adults, brain activation was measured on tasks assessing behavioral inhibition, reward sensitivity, and emotion reactivity. We found some preliminary differences with regard to emotion reactivity, that suggest internalizing binge drinkers are more reactive to faces overall but have blunted reaction to sad faces compared to externalizers. These findings provide an initial step to better understanding the underlying biology between the classic externalizing and internalizing alcohol use subtypes, which has the potential to elucidate new subtype specific targets for prevention and intervention

Editorial: Biofabrication and Biopolymeric Materials Innovation for Musculoskeletal Tissue Engineering cook

The human musculoskeletal system provides form, support, stability, and movement to the body. It is made up of the bones of the skeleton, muscles, cartilage, tendons, ligaments, joints, and other connective tissues. The primary functions of the musculoskeletal system include supporting the body, allowing motion, and protecting vital organs. The skeletal portion of the system serves as the main storage system for calcium and phosphorus and contains critical components of the hematopoietic system (Li and Niu, 2020). Musculoskeletal Disorders (MSDs) include injuries and diseases that primarily affect the movement of the human body. They are characterized by pain and limitations in mobility, dexterity, and overall level of functioning, reducing patients’ ability to work and maintain a good quality of life. A recent analysis of Global Burden of Disease data showed that approximately 1.71 billion people globally have musculoskeletal conditions (Woolf and Pfleger, 2003). MSDs such as osteoarthritis, rheumatoid arthritis, psoriatic arthritis, gout, and ankylosing spondylitis affect joints (McInnes and Schett, 2011; Loeser et al., 2012; Litwic et al., 2013); osteoporosis, osteopenia and associated fragility fractures, as well as traumatic fractures, affect bones (Florencio-Silva et al., 2015); sarcopenia affects muscles, and back and neck pain affect the spine of the human body

Mechanical properties and in vitro modelling of the osteochondral unit

The osteochondral unit (OCU) comprises bone and cartilage, with a gradient interface between hard and soft tissues. Damage and diseases, such as osteoarthritis (OA), cause irreversible changes to the cartilage matrix. Early, clinically silent, matrix changes in OA were compared to healthy, post-mortem cartilage using mechanical and physicochemical techniques. It was found that degradation of matrix components leaves the superficial region susceptible to mechanical damage. Strategies to repair cartilage damage have focused on replication of the extracellular matrix using hydrogel scaffolds. Alginate is commonly used, and its positive effects on chondrocyte phenotype have been attributed to maintenance of a spherical cell morphology. Here, an alginate fluid gel was formed to enable the non-invasive delivery of chondrocytes. It was found, however, that a spherical morphology was insufficient for maintenance of chondrocyte phenotype and geometric confinement of chondrocytes in alginate played a significant role in phenotypic recovery and stability. Fluid gels were then utilised as support matrices for bioprinting of bi-layered structures to recapitulate the OCU. This support matrix could suspend low-viscosity hydrocolloid solutions prior to crosslinking to co-culture chondrocyte and osteoblast populations in spatially defined regions. Distinct chemical and mechanical environments allowed the maintenance of primary cell phenotypes and function

Suspended manufacture of biological structures

We present a novel method of extrusion-based ALM for the production of cell-laden strucutres from low viscosity polymers. The traditional planar print bed is replaced with a bed of micoparticulate fluid gel. During the extrusion process, the fluid gel is displaced whilst providing a support strucutre for the low viscosity material allowing manufacture of relatively complex geometries. The extruded structure can then be easily removed from this self-healing fluid bed. For this study, a bi-layered cell-seeded construct was produced to model the osteochondral junction. Osteochondral plugs were produced by the addition of chondrocytes and osteoblasts to 1.5%w/v gellan and 1.5%w/v gellan-5% nano-hydroxyapatite respectively. The consecutive extrusion of these two solutions into the fluid bed followed by further ionic crosslinking produced the bi-layered construct that was implant into a femoral condyle defect in vitro. Cell viability following extrusion was confirmed using calcein AM/PI live/dead staining showing excellent viability. Constructs were then sectioned, and qRT-PCR was performed, showing a native collagen phenotype across the construct with evidence of matrix markers in the cartilage-like region which were also identified using fluroescent-IHC. Constructs were also tested for their bulk relaxation properties. Addition of nano-hydroxyapatite in the bone-like region resulted in a faster, more elastic relaxation than gellan alone, something that has previously been reported to favour osteogenic differentiation. Please click Additional Files below to see the full abstract

Star Formation, Radio Sources, Cooling X-ray Gas, and Galaxy Interactions in the Brightest Cluster Galaxy in 2A0335+096

We present deep emission-line imaging taken with the SOAR Optical Imaging Camera of the brightest cluster galaxy (BCG) in the nearby (z=0.035) X-ray cluster 2A0335+096. We analyze long-slit optical spectroscopy, archival VLA, Chandra X-ray, and XMM UV data. 2A0335+096 is a bright, cool-core X-ray cluster, once known as a cooling flow. Within the highly disturbed core revealed by Chandra X-ray observations, 2A0335+096 hosts a highly structured optical emission-line system. The redshift of the companion is within 100 km/s of the BCG and has certainly interacted with the BCG, and is likely bound to it. The comparison of optical and radio images shows curved filaments in H-alpha emission surrounding the resolved radio source. The velocity structure of the emission-line bar between the BCG nucleus and the companion galaxy provides strong evidence for an interaction between the two in the last ~50 Myrs. The age of the radio source is similar to the interaction time, so this interaction may have provoked an episode of radio activity. We estimate a star formation rate of >7 solar mass/yr based on the Halpha and archival UV data, a rate similar to, but somewhat lower than, the revised X-ray cooling rate of 10-30 solar masses/year estimated from XMM spectra by Peterson & workers. The Halpha nebula is limited to a region of high X-ray surface brightness and cool X-ray temperature. The detailed structures of H-alpha and X-ray gas differ. The peak of the X-ray emission is not the peak of H-alpha emission, nor does it lie in the BCG. The estimated age of the radio lobes and their interaction with the optical emission-line gas, the estimated timescale for depletion and accumulation of cold gas, and the dynamical time in the system are all similar, suggesting a common trigger mechanism.Comment: Accepted AJ, July 2007 publication. Vol 134, p. 14-2

Patterns of substance use across the first year of college and associated risk factors

Starting college is a major life transition. This study aims to characterize patterns of substance use across a variety of substances across the first year of college and identify associated factors. We used data from the first cohort (N = 2056, 1240 females) of the “Spit for Science” sample, a study of incoming freshmen at a large urban university. Latent transition analysis was applied to alcohol, tobacco, cannabis, and other illicit drug uses measured at the beginning of the fall semester and midway through the spring semester. Covariates across multiple domains – including personality, drinking motivations and expectancy, high school delinquency, peer deviance, stressful events, and symptoms of depression and anxiety – were included to predict the patterns of substance use and transitions between patterns across the first year. At both the fall and spring semesters, we identified three subgroups of participants with patterns of substance use characterized as: (1) use of all four substances; (2) alcohol, tobacco, and cannabis use; and (3) overall low substance use. Patterns of substance use were highly stable across the first year of college: most students maintained their class membership from fall to spring, with just 7% of participants in the initial low substance users transitioning to spring alcohol, tobacco, and cannabis users. Most of the included covariates were predictive of the initial pattern of use, but covariates related to experiences across the first year of college were more predictive of the transition from the low to alcohol, tobacco, and cannabis user groups. Our results suggest that while there is an overall increase in alcohol use across all students, college students largely maintain their patterns of substance use across the first year. Risk factors experienced during the first year may be effective targets for preventing increases in substance use

Prevalence of Nicotine Delivery Systems by Biological Sex in the Spit for Science Study

Nicotine intake usage trends have changed over recent decades given the wide variety of nicotine delivery systems including cigarettes, vaping, hookah, and snubs/chewables. These trends also vary by demographic factors, such as race/ethnicity, sex, and socioeconomic status (SES). For example, studies in rat populations, as well as humans, have found that females tend to be more dependent on nicotine products and have a more difficult time quitting than male rats and humans (Pogun et al., 2017). Also, race/ethnicity may impact the frequency of nicotine usage in different populations; in that non-white Hispanics were more susceptible to smoking through adolescence with a peak at ages 12 and 16; whereas non-Hispanic Asian Americans were less susceptible to smoking at ages 11 and 15 (El-Toukhy et al., 2016). Certain nicotine delivery methods may be more available or perhaps more socially accepted by certain groups of people. While lower SES is associated with more prevalent cigarette advertisements and usage, individuals with a higher SES were associated with an increased prevalence of e-cigarette advertisements, leading to an increased frequency of e-cigarette usage among adolescents (Simon et al., 2018). This project aims to document rates of nicotine use across different nicotine delivery systems in college students by demographic factors. We use the Spit for Science (S4S) database to investigate prevalence rates and study if they differ by sex, race/ethnicity, or SES. It is hypothesized that higher SES individuals will have an increased frequency of use with nicotine products that are non-cigarette based, non-white Hispanics will have greater frequency with nicotine usage, and females within the study sample will display a higher dependency on nicotine products than males. Preliminary analyses reveal that there are more female participants than males throughout the S4S cohorts collected between 2020 and 2022. Across cohorts, prevalence of all nicotine delivery systems differs in female and male participants across all products. Larger differences in prevalence between females and males are observed for cigarettes, smokeless tobacco, and cigars than for products that have been introduced more recently, such as hookah, vaping, and heat-not-burn products. Further analyses will focus on patterns of use in relation to race/ethnicity and SES. Understanding nicotine usage trends within our sample could pave the way for additional research (i.e., genetic studies) and allow for the development of prevention/intervention models tailored to our sample populations.https://scholarscompass.vcu.edu/uresposters/1436/thumbnail.jp

Molecular Genetic Influences on Normative and Problematic Alcohol Use in a Population-Based Sample of College Students

Background: Genetic factors impact alcohol use behaviors and these factors may become increasingly evident during emerging adulthood. Examination of the effects of individual variants as well as aggregate genetic variation can clarify mechanisms underlying risk. Methods: We conducted genome-wide association studies (GWAS) in an ethnically diverse sample of college students for three quantitative outcomes including typical monthly alcohol consumption, alcohol problems, and maximum number of drinks in 24 h. Heritability based on common genetic variants (h2SNP) was assessed. We also evaluated whether risk variants in aggregate were associated with alcohol use outcomes in an independent sample of young adults. Results: Two genome-wide significant markers were observed: rs11201929 in GRID1 for maximum drinks in 24 h, with supportive evidence across all ancestry groups; and rs73317305 in SAMD12 (alcohol problems), tested only in the African ancestry group. The h2SNP estimate was 0.19 (SE = 0.11) for consumption, and was non-significant for other outcomes. Genome-wide polygenic scores were significantly associated with alcohol outcomes in an independent sample. Conclusions: These results robustly identify genetic risk for alcohol use outcomes at the variant level and in aggregate. We confirm prior evidence that genetic variation in GRID1impacts alcohol use, and identify novel loci of interest for multiple alcohol outcomes in emerging adults. These findings indicate that genetic variation influencing normative and problematic alcohol use is, to some extent, convergent across ancestry groups. Studying college populations represents a promising avenue by which to obtain large, diverse samples for gene identification