A Dynamic 6,000-Year Genetic History of Eurasia's Eastern Steppe.

The Eastern Eurasian Steppe was home to historic empires of nomadic pastoralists, including the Xiongnu and the Mongols. However, little is known about the region's population history. Here, we reveal its dynamic genetic history by analyzing new genome-wide data for 214 ancient individuals spanning 6,000 years. We identify a pastoralist expansion into Mongolia ca. 3000 BCE, and by the Late Bronze Age, Mongolian populations were biogeographically structured into three distinct groups, all practicing dairy pastoralism regardless of ancestry. The Xiongnu emerged from the mixing of these populations and those from surrounding regions. By comparison, the Mongols exhibit much higher eastern Eurasian ancestry, resembling present-day Mongolic-speaking populations. Our results illuminate the complex interplay between genetic, sociopolitical, and cultural changes on the Eastern Steppe.

Regulation of planar cell polarity by Smurf ubiquitin ligases.

Planar cell polarity (PCP) is critical for morphogenesis in metazoans. PCP in vertebrates regulates stereocilia alignment in neurosensory cells of the cochlea and closure of the neural tube through convergence and extension movements (CE). Noncanonical Wnt morphogens regulate PCP and CE in vertebrates, but the molecular mechanisms remain unclear. Smurfs are ubiquitin ligases that regulate signaling, cell polarity and motility through spatiotemporally restricted ubiquitination of diverse substrates. Here, we report an unexpected role for Smurfs in controlling PCP and CE. Mice mutant for Smurf1 and Smurf2 display PCP defects in the cochlea and CE defects that include a failure to close the neural tube. Further, we show that Smurfs engage in a noncanonical Wnt signaling pathway that targets the core PCP protein Prickle1 for ubiquitin-mediated degradation. Our work thus uncovers ubiquitin ligases in a mechanistic link between noncanonical Wnt signaling and PCP/CE.

Exploring the Relationships between Sexual Orientation and Gender Identity and Youth Synthetic Cannabinoid Use.

Purpose: Existing studies have identified sexual minorities as being at enhanced risk for reporting synthetic cannabinoid (SC) use. It is unclear whether this association is the result of those that identify as a minority due to sexual orientation being more likely to use SCs, due to those that identify as transgender using SCs more, or both. Deconstructing this relationship will allow for targeted clinical advice and public health campaigns. Methods: Data from the 2015 and 2017 Youth Risk Behavior Study are utilized. In total, 31,279 youth were asked about their gender identity, sexual orientation, and SC use history. Bivariate analyses and logistic regression models were completed to explore relevant associations. Results: Identifying as lesbian, gay, bisexual, or questioning was linked to SC use and continuing SC use. Similarly, identifying as transgender was linked to SC use and continuing use. Regression analyses showed no significant interactive effect; identifying as both LGBQ and transgender does not have a compounding effect on use likelihood. Conclusions: Both sexual orientation and gender identity contribute to the relationship between sexual minority status and SC use noted in extant literature. This relationship is hypothesized to be tied to increased exposure to discrimination, victimization, and social isolation. Thus, efforts to directly counsel LGBTQ patients about the dangers associated with SC use are warranted as well as social policy reforms to better protect and support members of the LGBTQ community.

An Examination of Substance Use Disorder Type, Legal Status of Drug, and Treatment Outcomes.

BACKGROUND: From the anti-tobacco and anti-marijuana campaigns of the twentieth century to the current controversies surrounding vaporizer use and the opioid epidemic, substances and substance use have been at the forefront of cultural, public health, and legal debates for decades. This work explores treatment outcomes among those with substance use disorders (SUD) by 1) comparing legal, semi-legal, and illegal drug types and their impact on treatment outcomes and 2) evaluating the extent that there exist discrepancies between those who need and those who receive treatment. Methods: Binary logistic regression models were employed with data from the 2018 National Survey on Drug Use and Health (NSDUH) to examine the relationship between type of SUD and treatment outcomes. Results: Results indicate that those with SUD to illegal drugs were generally more likely to report a need and receive treatment than those with SUD to a legal drug (alcohol use disorder). Those with SUD to some types of illegal drugs did not report more need, but in some cases reported more treatment. Additionally, analyses indicated that across treatment outcomes, those with marijuana use disorder (semi-legal drug) were less likely to report needing or receiving treatment than those with alcohol use disorder. Conclusions: This research examined the role of drugs' legal status and type of SUD in need for treatment and treatment received. The discrepancy between needing and receiving treatment suggests those with some types of SUDs may be pushed into treatment at higher rates based on the stigma surrounding the substance they use.

The Association Between Social Media Use and Hazardous Alcohol Use Among Youths: A Four-Country Study.

AIMS: To examine the continuing role of daily popular social media use in youth hazardous alcohol consumption in four countries across continents. METHODS: A web-based survey was given to youths aged 15-25 in the USA (n = 1212), South Korea (n = 1192), Finland (n = 1200) and Spain (n = 1212). Hazardous alcohol use (alcohol use disorders identification test-C) was the dependent variable. Main independent variables measured daily use of different social media services. Controls included compulsive Internet use, offline belonging, psychological distress, impulsivity, risk-taking, age and gender. Linear regression models and mediation analyses with bootstrapping were done for each country. RESULTS: Daily use of Facebook and Instagram was associated with higher hazardous alcohol use among youths in Finland, South Korea and Spain. Daily instant messaging was related to higher hazardous alcohol use among South Korean and Finnish youths. Daily YouTube use was associated with higher hazardous alcohol use among youths in South Korea, but lower hazardous alcohol use among youths in the USA and Finland. Daily Twitter use was related to lower hazardous drinking among youths in Finland but higher hazardous drinking among youths in Spain. The mediation analyses revealed that uploading pictures to social media is a possible facilitator of social media-related hazardous alcohol use among youths in the USA and Spain. CONCLUSION: Certain social media platforms might inspire and/or attract hazardously drinking youths, contributing to the growing opportunities for social media interventions.

How Strong is the "Fake ID Effect?" An Examination Using Propensity Score Matching in Two Samples.

BACKGROUND: Underage college students who obtain and use false identification (fake ID) are at risk for negative outcomes. However, it is currently unclear how uniquely the fake ID itself serves as a vehicle to subsequent harm (i.e., the "fake ID effect") over and above general and trait-related risk factors (e.g., deviant peers, low self-control). METHODS: To investigate whether the "fake ID effect" would hold after accounting for phenotypic risk, we utilized propensity score matching (PSM) in a cross-sectional sample of 1,454 students, and a longitudinal replication sample of 3,720 undergraduates. Individuals with a fake ID were matched with individuals without a fake ID, in terms of a number of trait-based and social risk factors. These matched groups were then compared on 5 problematic outcomes (i.e., frequent binge drinking, alcohol-related problems, arrests, marijuana use, and hard drug use). RESULTS: Findings showed that "fake ID effects" were substantially-although not fully-diminished following PSM. The "fake ID effect" remained strongest for alcohol-related arrests. This may relate to issues of enforcement and students' willingness to engage in deviant behavior with a fake ID, or it may be a function of combined processes. CONCLUSIONS: Overall, the findings suggest that interventions should not only be aimed at reducing the fake ID-related alcohol access specifically, but should also be aimed more generally toward at-risk youths' access to alcohol. Future research might examine whether fake IDs have their strongest potency as moderators of the effects of risky traits-such as impulsiveness-on drinking outcomes.

Exploring Butane Hash Oil Use: A Research Note.

The practice of "dabbing" has seen an apparent upswing in popularity in recent months within American drug subcultures. "Dabbing" refers to the use of butane-extracted marijuana products that offer users much higher tetrahydrocannabinol content than flower cannabis through a single dosage process. Though considerably more potent than most marijuana strains in their traditional form, these butane hash oil products and the practice of dabbing are underexplored in the empirical literature, especially in prohibition states. A mixed-methods evaluation of a federally funded treatment program for drug-involved offenders identified a small sample (n = 6) of butane hash oil users and generated focus group interview data on the nature of butane hash oil, the practice of dabbing, and its effects. Findings inform discussion of additional research needed on butane hash oil and its implications for the ongoing marijuana legalization debate, including the diversity of users, routes of administration, and differences between retail/medical and prohibition states.

Misperceptions of peer pill-popping: the prevalence, correlates, and effects of inaccurate assumptions about peer pharmaceutical misuse.

Peer behaviors may significantly influence personal behavior yet individuals may not accurately estimate their peers' actions. Overestimations of peer substance use may encourage initiation or exacerbate extant problems. The present study examines misperceptions of peer pharmaceutical misuse and explores the relationship between reported misuse and perceptions of misuse for four categories of prescription drugs. Data collected from 2,349 college students in the Southeastern United States were analyzed and results indicated that overall perceptions of misuse were significantly higher than actual misuse. These findings suggest that intervention efforts may benefit from addressing misperceptions of pharmaceutical misuse. Study limitations and implications are addressed.

Not-so-clean fun: a profile of bath salt users among a college sample in the United States.

This research examines the characteristics of users of synthetic stimulants marketed as "bath salts." Synthetic stimulants such as MDPV (3,4-Methylenedioxypyrovalerone), Mephedrone (4-Methylmethcathinone), and Methylone (3,4-Methylenedioxymethcathinone) are often contained in products sold at convenience stores and over the Internet in the United States. Despite the recent legal action banning these types of synthetic stimulants, little is known about the characteristics of the users of these substances. This research provides a profile of bath salt users in the United States among an emerging adult population. A self-report survey instrument was administered to 2,349 students at a large university in the southeastern United States. Respondents indicated whether they had used synthetic stimulants and reported demographic characteristics. Results indicated that users of bath salts were more likely to be male, Hispanic or Native American, student athletes, employed, identify as a members of the LGBT community, and users of other substances.

Scoping Literature Review of Disease Modeling of the Opioid Crisis.

Opioid misuse continues to cause significant harm. To investigate current research, we conducted a scoping literature review of disease spread models of opioid misuse from January 2000 to December 2022. In total, 85 studies were identified and examined for the opioids modeled, model type, data sources used and model calibration and validation. Most of the studies (58%, 49) only modeled heroin; the next largest categories were prescription opioids and unspecified opioids which accounted for 9% (8) each. Most models were theoretical compartmental models (57) or applied compartmental models (21). Previously published research was the most used data source (38), and a majority of the model validation involved the researchers setting initial conditions to verify theoretical results (30). To represent typical opioid use more accurately, multiple opioids need to be incorporated into the disease spread models, and applying different modeling techniques may allow other insights into opioid misuse spread.

Cauldrons of Bronze Age nomads reveals 2700 year old yak milk and the deep antiquity of food preparation techniques.

Cauldrons, vessels that are simultaneously common and enigmatic, offer insights into past cultural and social traditions. While assumed to possess a special function, what these cauldrons contained is still largely mysterious. These vessels, such as those made from bronze or copper alloys, function as reservoirs for ancient organics through the antibacterial qualities provided by the metal surfaces. Here we show, through protein analysis, that cauldrons from the Final Bronze Age (ca. 2700 BP) were primarily used to collect blood from ruminants, primarily caprines, likely for the production of sausages in a manner similar to contemporary practices in Mongolia's rural countryside. Our findings present a different function from the recent findings of cooked meat in copper-alloy vessels from the northern Caucasus 2000 years earlier, exposing the diversity in food preparation techniques. Our secondary findings of bovine milk within the cauldron, including peptides specific to Bos mutus, pushes back their regional domestication into the Bronze Age.

Examining the measurement of novel drug perceptions: Salvia divinorum, gender, and peer substance use.

Researchers commonly use a person's perception of the drug use of friends to determine the impact that peers exert on one's own behavior. Recently, there has been concern over this measure's validity. Novel drugs, which are either newly discovered drugs or existing substances only recently used for recreational purposes, may be used so infrequently that people have too few observable opportunities to accurately develop perceptions of their peer's use. Employing survey data collected in 2009 from 2,154 individuals within friendship pairs in the Southeast United States, we explore how gender affects perceptions of the infrequently used, novel drug Salvia divinorum. The study's limitations are noted.

Binge drinking, marijuana use, and friendships: the relationship between similar and dissimilar usage and friendship quality.

While it is commonly understood that the substance use of peers influences an individual's substance use, much less is understood about the interplay between substance use and friendship quality. Using a sample of 2,148 emerging adults nested within 1,074 dyadic friendships, this study separately investigates how concordance and discordance in binge drinking and marijuana use between friends is related to each friend's perceptions of friendship quality. Because "friendship quality" is a complex construct, we employ a measure containing five sub-elements--companionship, a lack of conflict, willingness to help a friend, relationship security, and closeness. Results for both binge drinking and marijuana use reveal that individuals in friendship pairs who are concordant in their substance use perceive significantly higher perceptions of friendship quality than individuals in dyads who are dissimilar in substance use. Specifically, concordant binge drinkers estimate significantly higher levels of companionship, relationship security, and willingness to help their friend than concordant non-users, discordant users, and discordant non-users. However, the highest amount of conflict in friendships is found when both friends engage in binge drinking and marijuana use. Several interpretations of these findings are discussed. Overall, concordance between friends' binge drinking and marijuana use appears to help some elements of friendship quality and harm others.

Genetic population structure of the Xiongnu Empire at imperial and local scales.

The Xiongnu established the first nomadic imperial power, controlling the Eastern Eurasian steppe from ca. 200 BCE to 100 CE. Recent archaeogenetic studies identified extreme levels of genetic diversity across the empire, corroborating historical records of the Xiongnu Empire being multiethnic. However, it has remained unknown how this diversity was structured at the local community level or by sociopolitical status. To address this, we investigated aristocratic and local elite cemeteries at the western frontier of the empire. Analyzing genome-wide data from 18 individuals, we show that genetic diversity within these communities was comparable to the empire as a whole, and that high diversity was also observed within extended families. Genetic heterogeneity was highest among the lowest-status individuals, implying diverse origins, while higher-status individuals harbored less genetic diversity, suggesting that elite status and power was concentrated within specific subsets of the broader Xiongnu population.

Permafrost preservation reveals proteomic evidence for yak milk consumption in the 13th century.

Domesticated yaks endure as iconic symbols of high-altitude frozen landscapes, where herding communities depend on their high-fat milk, transport, dung, and natural fibers. While there is established proteomic evidence for ancient consumption of ruminant and horse milk in the mountains and steppes of northern Eurasia, yak dairy products have yet to be detected. Yak domestication and the species' dispersal from Tibet into the mountainous zones to the north are also poorly resolved due to a paucity of zooarchaeological data. To examine the potential of paleoproteomics to shed light on domesticated yak in Mongolia, we analyzed human dental calculus from Mongol era elite individuals recovered from permafrost burials in Khovsgol province, where people continue to herd yak to this day. We report the first evidence for yak dairy consumption, linked to local resource control. In addition, we confirm a large diversity of recovered whey, curd, tissue, and blood proteins, likely reflecting the excellent preservation conditions found at permafrost sites.

Post-transcriptional regulation of VEGF-A mRNA levels by mitogen-activated protein kinases (MAPKs) during metabolic stress associated with ischaemia/reperfusion.

Angiogenesis is a well-characterised response to the metabolic stresses that occur during ischaemia/reperfusion, but the signalling pathways that regulate it are poorly understood. We tested whether activation of mitogen-activated protein kinases (MAPKs) was involved in regulating the expression of pro-angiogenic growth factors by the metabolic stresses associated with ischaemia/reperfusion in H9c2 rat cardiomyoblasts. Metabolic stress had no effect on vascular endothelial growth factor (VEGF) mRNA levels, but recovery after metabolic inhibition led to a strong induction of VEGF-A mRNA (3.8 ± 0.5-fold at 4 h), a modest rise in VEGF-C mRNA levels (1.7 ± 0.3-fold at 4 h), with no effect on VEGF-B or -D. A VEGF-A promoter reporter construct was unresponsive to metabolic inhibition/recovery and increases in VEGF-A mRNA were not blocked by the transcription inhibitor actinomycin D suggesting that increases in VEGF mRNA were due to enhanced VEGF-A mRNA stability. In addition, studies using reporter constructs demonstrated that regions within the 5' untranslated region (UTR) contributed to enhanced mRNA stability following recovery from metabolic stress. Increases in VEGF-A mRNA were abolished by inhibition of extracellular signal-regulated kinase or c-jun N-terminal kinase MAPKs, suggesting that these kinases may promote angiogenesis in response to metabolic stress during ischaemia/reperfusion by increasing VEGF-A message stability.

Does early drug use-related police contact predict premature mortality and morbidity: A population register-based study.

INTRODUCTION: The aim was to analyse whether age at first drug offense predicts premature mortality and morbidity due to substance use and violence among adolescents and young adults. METHODS: A prospective longitudinal register-linkage study based on a total population sample from Finland including individuals born between 1987 and 1992 and aged 15-25 years during follow-up in 2002-2017 (n = 386 435). Age-specific rates of deaths and health-care admissions (morbidity) during a 5-year follow-up were calculated from the first drug offense. Cox regression models were used to estimate differences in mortality and morbidity at ages 21-25. RESULTS: Of all 15- to 20-year-olds, 1.4% (n = 5540) have had a police contact. The 5-year mortality rates (per 1000 person-years) among those with first drug offense at ages 15-16 was 2.92 [95% confidence interval (CI) 1.56-6.18], and 5.26 (CI 4.00-7.07) and 5.05 (CI 4.06-6.38) at ages 17-18, and 19-20, respectively. The rates of morbidity varied between 61.20 (CI 52.43-71.76) and 87.51 (CI 82.11-93.33). Both mortality and morbidity rates were over 10 times higher than among the general population. In models adjusted for family background, first police contact at an early age (15-16) did not increase the risk of mortality at ages 21-25 compared with first police contact at ages 17-18 (hazard ratio 1.55, CI 0.77-3.09) or 19-20 (hazard ratio 1.52, CI 0.78-2.98). The results were similar for morbidity. DISCUSSION AND CONCLUSIONS: Adolescents with drug-related police contacts have high risk of mortality and morbidity due to substance use and violence regardless of age of first contact.

Sexual Orientation and Synthetic Cannabinoid Use: Examining the Role of Bullying Victimization.

Bullying is a common experience among youths with many adverse consequences. Research indicates that those who identify as lesbian, gay, and bisexual experience bullying at greater levels than heterosexuals. Studies also indicate that sexual minorities are more likely to use alcohol and other drugs, including synthetic cannabinoids (SCs). This paper examines whether the relationship between sexual minority status and SC use is mediated by differential exposure to bullying victimization. Data from the 2015 and 2017 Youth Risk Behavior Study were used. Participants include 30,389 adolescents. Supplemental analyses were conducted with state and district data as those collection efforts incorporated additional bullying measures. Ianobucci's zmediation was used to assess the relationships between sexual orientation, bullying victimization, and SC use. Results confirm the higher prevalence of bullying and SC use among LGBQ students. Multiple forms of bullying victimization (e.g., in-person, online, because of weight/appearance) mediate the relationship between sexual orientation and SC use. The greater prevalence of SC use within the LGBQ population is partially attributed to coping as a result bullying victimization.

Examining Sanction Type and Drug Offender Recidivism: A Register-Based Study in Finland.

Nordic countries incarcerate offenders at much lower rates in comparison with incarceration rates in the United States, and reincarcerate fewer people per capita. Noncustodial alternatives to sanctions, including fines and community service, are used extensively in Finland to reduce negative effects of institutionalization and subsequent disadvantage caused by incarceration. The nature of drug-involved offenders within the Finnish system is reviewed in light of current research about the effectiveness of incarceration and deterrence-based approaches for drug offenders. Employing a 2014 sample from register data (consisting of official government records) of drug offenders in Finland with a 3-year recidivism period, this study utilizes a genetic matching procedure to compare offenders who received fines, conditional sentences (probation), or incarceration. While recognizing that numerous confounding variables affect incarceration, we compare a matched sample of drug offenders and the sanctions they have received from the Finland judicial system to determine whether offenders who initially receive a fine or a conditional sentence reenter the correctional system at different rates than those who are incarcerated. After matching, results found no significant differences between offenders receiving incarceration sentences or those who received noncustodial sentences (fine, or conditional sentence) for general and drug-related recidivism. These results are presented within the context of the Finnish corrections system in order to inform the criminal justice community about culture, incarceration, and process differences that could positively affect working with drug offenders in other localities.

Effects of Autolyzed Yeast Supplementation in a High-Starch Diet on Rumen Health, Apparent Digestibility, and Production Variables of Lactating Holstein Cows.

Fifteen multiparous rumen-cannulated Holstein cows were assigned to one of five treatments in a replicated 5 × 5 Latin square design. The treatments were low-starch (LS) (22.8 ± 1% of dry matter; DM) without autolyzed yeast (AY; LS0, control), high-starch (HS) (31.2 ± 4% of DM) without AY (HS0), and HS with either 15 g (HS15), 30 g (HS30), or 45 g (HS45) of AY supplementation. Cows in HS0 had increased (p < 0.03) dry matter intake (DMI; 24.9 kg/d) and energy-corrected milk (ECM; 34.4 kg/d) compared to cows in LS0 (19.9 and 31.3 kg/d, respectively). There was a tendency for a quadratic treatment effect for feed efficiency (ECM/DMI, p = 0.07) and crude protein (CP) apparent digestibility (AD) (p = 0.09). Cows in HS45 tended (p = 0.09) to have increased DMI (25.6 kg/d) compared to cows in HS0 (24.9 kg/d). Cows in HS0 had greater (p < 0.04) milk protein nitrogen (N; 166 g/d) and microbial N production (161 g/d) than those in LS0 (140 and 138 g/d, respectively). In conclusion, the addition of AY tended to improve DMI, feed efficiency, and CP AD when cows were fed the HS diet.