Duplicate Gene Expression and Possible Mechanisms of Paralog Retention During Bacterial Genome Expansion.

Gene duplication contributes to the evolution of expression and the origin of new genes, but the relative importance of different patterns of duplicate gene expression and mechanisms of retention remains debated and particularly poorly understood in bacteria. Here, we investigated gene expression patterns for two lab strains of the cyanobacterium Acaryochloris marina with expanding genomes that contain about 10-fold more gene duplicates compared with most bacteria. Strikingly, we observed a generally stoichiometric pattern of greater combined duplicate transcript dosage with increased gene copy number, in contrast to the prevalence of expression reduction reported for many eukaryotes. We conclude that increased transcript dosage is likely an important mechanism of initial duplicate retention in these bacteria and may persist over long periods of evolutionary time. However, we also observed that paralog expression can diverge rapidly, including possible functional partitioning, for which different copies were respectively more highly expressed in at least one condition. Divergence may be promoted by the physical separation of most Acaryochloris duplicates on different genetic elements. In addition, expression pattern for ancestrally shared duplicates could differ between strains, emphasizing that duplicate expression fate need not be deterministic. We further observed evidence for context-dependent transcript dosage, where the aggregate expression of duplicates was either greater or lower than their single-copy homolog depending on physiological state. Finally, we illustrate how these different expression patterns of duplicated genes impact Acaryochloris biology for the innovation of a novel light-harvesting apparatus and for the regulation of recA paralogs in response to environmental change.

Developing and implementing survivor-centred approaches for college student-athletes: perspectives from athletic department, Title IX, and campus advocacy personnel.

ABSTRACTBackground: Sexual violence (SV) is a persistent issue on US college campuses, particularly among college student-athletes. Strategies to address SV are urgently needed. Yet, prior research shows that many university practices can be more harmful than helpful to SV survivors and necessitates a reimagination of how institutions support SV survivors. Survivor-centred approaches may be one way to effectively address SV for students, including student-athletes, across college campuses.Objective: This qualitative study explored campus personnel experiences with and perceptions of survivor-centred SV prevention and intervention policies and practices on college campuses and examined how these approaches serve SV survivors, including college student-athletes.Methods: As part of a larger study on campus SV and student-athletes across four institutions, semi-structured interviews with 22 representatives from athletic departments, campus advocacy, and Title IX were conducted. Guided by phenomenology, a thematic analysis approach was used to identify key patterns in survivor-centred SV prevention and intervention policies and practices. Participant demographic data were analysed descriptively.Results: Most participants identified as white (72.2%), heterosexual (63.6%), women (68.2%), and were an average of 41.8 years old (SD = 10.2). The majority were in positions associated with athletic departments (63.6%), and they had been in their role for an average of 5.6 years (SD = 6.6). Through thematic analysis, three main themes were identified: (1) education & accessibility; (2) interpersonal relationships & individual well-being; and (3) campus and societal norms.Conclusions: The findings from this study highlight clear policy and practice recommendations for survivor-centred SV prevention and intervention on college campuses, such as accessible, applicable SV training and the implementation of survivor-centred approaches. Further research is needed to understand existing survivor-centred practices and the facilitators and barriers to their implementation across institutions and within athletic departments.

Sexual violence is a persistent issue on US college campuses, particularly among college student-athletes. Strategies to address SV are urgently needed. Survivor-centred approaches may offer solutions to better serve survivors of sexual violence, including student-athletes.Through interviews with athletic department, Title IX, and campus advocacy personnel, three themes were identified related to developing and implementing survivor-centred approaches: (1) education & accessibility; (2) interpersonal relationships & individual well-being; and (3) campus and societal norms.Further research is needed to understand existing survivor-centred practices and the facilitators and barriers to their implementation across institutions, particularly for college student-athletes.

Cohort Study of Downgraded Misdemeanor Convictions and Subsequent Violent Crime: Differences by Defendant Race and Ethnicity.

Introduction: Criminal convictions may be imperfect markers of criminalized behavior, in part because of criminal legal system processes (e.g., plea bargaining). In this retrospective cohort study of individuals convicted of misdemeanors, authors compared the risk of subsequent criminal charges for a violent crime among those initially charged with a felony with that among those initially charged with only misdemeanors, overall and by defendant race and ethnicity. Methods: The study population included individuals aged ≥18 years who were convicted of a misdemeanor in Washington Superior Courts from January 1, 2015 to December 31, 2019. Those with and without initial felony charges were age/gender matched in a 4:1 ratio. The primary outcome was the first subsequent violent crime charge in Washington Superior Courts through December 31, 2020. Data were analyzed with Fine-Gray hazard models from June 2022 to November 2023. Results: There were 3,841 individuals with initial felony charges and 956 with initial misdemeanor charges only. Median follow-up was 2.4 years for both groups. During follow-up, there were 166 new violent crime charges. In multivariable models, White defendants with initial felony charges had a greater risk of subsequent violent crime charges (subdistribution hazard ratio=2.58; 95% CI=1.24, 5.36) than White defendants with initial misdemeanor charges only. Among Black and Hispanic/Latinx defendants, initial felony versus misdemeanor charges were not associated with subsequent violent crime charges (subdistribution hazard ratio=0.93; 95% CI=0.44, 1.97 among Black defendants; subdistribution hazard ratio=0.49; 95% CI=0.15, 1.57 among Hispanic/Latinx defendants). Conclusions: Findings suggest differential associations between downgrading of felony charges to misdemeanor convictions and future violent crime charges by defendant race and ethnicity, with implications for inequitable collateral consequences of criminal convictions.

Genotype-phenotype correlation in PRKN-associated Parkinson's disease.

Bi-allelic pathogenic variants in PRKN are the most common cause of autosomal recessive Parkinson's disease (PD). 647 patients with PRKN-PD were included in this international study. The pathogenic variants present were characterised and investigated for their effect on phenotype. Clinical features and progression of PRKN-PD was also assessed. Among 133 variants in index cases (n = 582), there were 58 (43.6%) structural variants, 34 (25.6%) missense, 20 (15%) frameshift, 10 splice site (7.5%%), 9 (6.8%) nonsense and 2 (1.5%) indels. The most frequent variant overall was an exon 3 deletion (n = 145, 12.3%), followed by the p.R275W substitution (n = 117, 10%). Exon3, RING0 protein domain and the ubiquitin-like protein domain were mutational hotspots with 31%, 35.4% and 31.7% of index cases presenting mutations in these regions respectively. The presence of a frameshift or structural variant was associated with a 3.4 ± 1.6 years or a 4.7 ± 1.6 years earlier age at onset of PRKN-PD respectively (p < 0.05). Furthermore, variants located in the N-terminus of the protein, a region enriched with frameshift variants, were associated with an earlier age at onset. The phenotype of PRKN-PD was characterised by slow motor progression, preserved cognition, an excellent motor response to levodopa therapy and later development of motor complications compared to early-onset PD. Non-motor symptoms were however common in PRKN-PD. Our findings on the relationship between the type of variant in PRKN and the phenotype of the disease may have implications for both genetic counselling and the design of precision clinical trials.

Provider Perspectives on Addressing Firearm Safety with Older Adults in Primary Care.

OBJECTIVES: Chronic conditions, including mild cognitive impairment and depression, place older adults at high risk of firearm suicide. Approximately 40% of older adults have access to a firearm, and many do not store their firearms safely. However, firearm counseling occurs infrequently in clinical settings. Using by the Ottawa Decision Support Framework (ODSF) to conceptualize the decisional support needed by patients and their providers to facilitate firearm counseling, we explore provider perspectives on desired resources for addressing firearm safety with older adult patients. METHODS: From March - August 2022, we conducted 21 semi-structured interviews with primary care providers caring for older adults. We report deductive concepts as well as emergent themes. RESULTS: Major themes were identified from the three components of the ODSF; decisional needs, decision support and decisional outcomes. Themes included: provider self-efficacy to conduct firearm counseling, clinical workflow considerations, stories for change, patient diagnosis implications, and caregiver involvement. CONCLUSIONS: There is a need for decision aids in the clinical setting that facilitate firearm counseling and promotes shared decision-making about firearm storage. CLINICAL IMPLICATIONS: Implementing a decision aid in the clinical setting can improve provider self-efficacy to conduct firearm counseling and help reduce risk factors associated with firearm-related harm among older adults.

Misclassification of firearm-related violent crime in criminal legal system records: challenges and opportunities.

BACKGROUND: Criminal legal system data are one source for measuring some types of firearm-related harms, including those that do not necessarily result in injury or death, but measurement can be hampered by imprecise criminal code statutes. We quantified the degree of misclassification in Washington state criminal codes for measuring firearm-related crime. FINDINGS: In this study of individuals aged 18 years and older who were convicted of a misdemeanor in Washington Superior Courts from 1/1/2015 through 12/31/2019, we compared firearm-related charges as measured with criminal codes and with manual review of probable cause documents, considered the gold standard. The sample included 5,390 criminal cases. Of these, 77 (1.4%) were firearm-related as measured with criminal codes and 437 (8.1%) were firearm-related as measured via manual record review. In the sample overall, the sensitivity of criminal codes was 17.6% (95% CI 14.2-21.5%), and negative predictive value (NPV) was 93.2% (95% CI 92.5-93.9%). Sensitivity and NPV were higher for cases with exclusively non-violent charges. For all cases and for cases with any violent crime charge, firearm-related crimes described in probable cause documents most often involved explicit verbal threats, firearm possession, and pointing a firearm at or touching a firearm to someone; almost 10% of all cases involved shooting/discharging a firearm. For cases with exclusively non-violent charges, the most common firearm-related crime was unlawful possession. CONCLUSIONS: Criminal records can be used for large-scale policy-relevant studies of firearm-related harms, but this study suggests Washington state criminal codes substantially undercount firearm-related crime, especially firearm-related violent crime.

Behavior Change Techniques Improve Adherence to Physical Activity Recommendations for Adults with Metabolic Syndrome: A Systematic Review.

Background: Exercise and physical activity interventions improve short-term outcomes for people with metabolic syndrome, but long-term improvements are reliant on sustained adherence to lifestyle change for effective management of the syndrome. Effective ways of improving adherence to physical activity and exercise recommendations in this population are unknown. This systematic review aims to determine which interventions enhance adherence to physical activity and/or exercise recommendations for people with metabolic syndrome. Methods: Electronic databases MEDLINE, PubMed, CINAHL, SPORTdiscuss and ProQuest were searched to July 2022. Risk of bias was assessed using the Cochrane risk of bias tool and overall certainty of evidence assessed using the Grading of Recommendation Assessment, Development and Evaluation approach. Results: Four randomized controlled trials with 428 participants (mean age 49-61 years) were included. There was very low certainty evidence from two trials that goal setting interventions may improve adherence to physical activity recommendations over three to six months. There was low certainty evidence from two trials that self-monitoring and feedback interventions increased adherence to physical activity interventions over 12 months for people with metabolic syndrome. Conclusion: Clinicians and researchers may consider using behavior change strategies such as goal setting, monitoring and feedback in interventions for people with metabolic syndrome to increase adherence to physical activity and exercise recommendations over 3 to 12 months, but high-quality evidence is lacking.

Implicit Racial and Gender Bias About Handguns: A New Implicit Association Test.

This study measured implicit and explicit racial bias about women and handguns and addressed important perceptions and stereotypes about gun competence and victimization that vary based on race and gender. We administered a national survey to 1,000 US adults using a new Race-Women-Handguns Implicit Association Test (IAT). Survey weighting was used to generate nationally representative estimates on the prevalence of implicit racial bias about women with handguns. The majority of participants (62.5%) associated Black women with handguns and White women with smartphones (weighted-mean IAT = 0.252; 95% CI [0.227, 0.276]) reflecting an anti-Black bias among US adults that is stereotype consistent associating Black women with handguns and White women with smartphones. The proportion that indicated Black and White women were competent with handguns was low (21.6% and 22.4%, respectively), and the proportion of US adults who indicated Black women are more likely to experience intimate partner violence (range: 19.4%-22.9%) and sexual harassment/assault (range: 11.4%-20.4%) was low compared to the prevalence of both forms of violence US among Black women that may impact the decision to possess a handgun. These findings suggest there is an anti-Black implicit bias about women with handguns (associating Black women with handguns) among US adults and support the need for further research measuring racism in systems and structures that intersect with gun possession.

Trend in Loaded Handgun Carrying Among Adult Handgun Owners in the United States, 2015‒2019.

Objectives. To determine the frequency of loaded handgun carrying among US adult handgun owners overall and by state concealed carry law status. Methods. Using a nationally representative survey of US firearm-owning adults in 2019, we asked handgun owners (n = 2389) about their past-month handgun carrying behavior. Results. A total of 30.3% (95% confidence interval [CI] = 28.0%, 32.6%) of handgun owners carried handguns monthly, of whom 38.1% (95% CI = 33.6%, 42.7%) did so daily. In permitless carry states, 29.7% (95% CI = 25.9%, 33.9%) of handgun owners carried handguns in the past month, compared with 33.1% (95% CI = 29.9%, 36.3%) in shall issue states and 19.7% (95% CI = 14.9%, 25.5%) in may issue states. Of handgun owners without a permit, 7.5% (95% CI = 4.1%, 13.3%) of those in may issue states and 11.5% (95% CI = 8.5%, 15.4%) of those in shall issues states carried handguns in the past month. Conclusions. In 2019, about 16 million US adult handgun owners carried handguns in the past month (up from 9 million in 2015), and approximately 6 million did so daily (twice the 3 million who did so in 2015). Proportionally fewer handgun owners carried handguns in states where issuing authorities had substantial discretion in granting permits. (Am J Public Health. 2022;112(12):1783-1790. https://doi.org/10.2105/AJPH.2022.307094).

Expression of Novel Gene Content Drives Adaptation to Low Iron in the Cyanobacterium Acaryochloris.

Variation in genome content is a potent mechanism of microbial adaptation. The genomes of members of the cyanobacterial genus Acaryochloris vary greatly in gene content as a consequence of the idiosyncratic retention of both recent gene duplicates and plasmid-encoded genes acquired by horizontal transfer. For example, the genome of Acaryochloris strain MBIC11017, which was isolated from an iron-limited environment, is enriched in duplicated and novel genes involved in iron assimilation. Here, we took an integrative approach to characterize the adaptation of Acaryochloris MBIC11017 to low environmental iron availability and the relative contributions of the expression of duplicated versus novel genes. We observed that Acaryochloris MBIC11017 grew faster and to a higher yield in the presence of nanomolar concentrations of iron than did a closely related strain. These differences were associated with both a higher rate of iron assimilation and a greater abundance of iron assimilation transcripts. However, recently duplicated genes contributed little to increased transcript dosage; rather, the maintenance of these duplicates in the MBIC11017 genome is likely due to the sharing of ancestral dosage by expression reduction. Instead, novel, horizontally transferred genes are responsible for the differences in transcript abundance. The study provides insights on the mechanisms of adaptive genome evolution and gene expression in Acaryochloris.

At low concentrations, 3,4-dihydroxyphenylacetic acid (DOPAC) binds non-covalently to alpha-synuclein and prevents its fibrillation.

Several studies have shown that catecholamines can inhibit the fibrillation of alpha-synuclein (alpha-Syn), a small presynaptic protein whose aggregation is believed to be a critical step in the etiology of Parkinson's disease and several other neurodegenerative disorders. However, the mechanism of this inhibition is uncertain. We show here that substoichiometric concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC), a normal product of the metabolism of dopamine, can inhibit the fibrillation of alpha-Syn, due to non-covalent binding of DOPAC to alpha-Syn monomer. Intriguingly, the presence of alpha-Syn accelerates the spontaneous oxidation of DOPAC, and the oxidized form of DOPAC (the quinone) is responsible for the fibrillation inhibition. In addition, the presence of DOPAC leads to the oxidation of the methionine residues of alpha-Syn, probably due to the H(2)O(2) production as a by-product of DOPAC oxidation. The lack of fibrillation results from the formation of stable oligomers, which are very similar to those observed transiently at early stages of the alpha-Syn fibrillation. A possible explanation for this phenomenon is that DOPAC stabilizes the normally transient oligomers and prevents them from subsequent fibril formation. The analysis of the alpha-Syn Y39W variant suggests that DOPAC binds non-covalently to the same N-terminal region of alpha-Syn as lipid vesicles, probably in the vicinity of residue 39. In contrast to the compounds with 1,2-dihydroxyphenyl groups (DOPAC and catechol), their 1,4-dihydroxyphenyl isomers (hydroquinone and homogentisic acid) are able to modify alpha-Syn covalently, probably due to the less steric hindrance in the Michael addition.

The metabolic syndrome, diabetes, and subclinical atherosclerosis assessed by coronary calcium.

OBJECTIVES: We compared the prevalence and extent of coronary artery calcium (CAC) among persons with the metabolic syndrome (MetS), diabetes, and neither condition. BACKGROUND: The prevalence and extent of CAC has not been compared among those with MetS, diabetes, or neither condition. METHODS: Of 1,823 persons (36% female) age 20 to 79 years who had screening for CAC by computed tomography, 279 had MetS, 150 had diabetes, and the remainder (n = 1,394) had neither condition. Metabolic syndrome was defined with >or=3 of the following: body mass index >or=30 kg/m(2); high-density lipoprotein cholesterol <40 mg/dl if male or <50 mg/dl if female; triglycerides >or=150 mg/dl; blood pressure >or=130/85 mm Hg or on treatment; or fasting glucose 110 to 125 mg/dl. The prevalence and odds of any and significant (>or=75th percentile) CAC among these groups and by number of MetS risk factors were determined. RESULTS: Those with neither MetS nor diabetes, MetS, or diabetes had a prevalence of CAC of 53.5%, 58.8%, and 75.3% (p < 0.001), respectively, among men and 37.6%, 50.8%, and 52.6% (p < 0.001), respectively, among women. Coronary artery calcium increased by the number (0 to 5) of MetS risk factors (from 34.0% to 58.3%) (p < 0.001). Forty-one percent of subjects with MetS had either a >20% 10-year risk of CHD or CAC >or=75th percentile for age and gender. Risk factor-adjusted odds for the presence of CAC were 1.40 (95% confidence interval [CI] 1.05 to 1.87) among those with MetS and 1.67 (95% CI 1.12 to 2.50) among those with diabetes, versus those with neither condition. CONCLUSIONS: Those with MetS or diabetes have an increased likelihood of CAC compared with those having neither condition.

The association of hormone replacement therapy and coronary calcium as determined by electron beam tomography.

BACKGROUND: Observational studies have shown that hormone replacement therapy (HRT) is associated with lower coronary heart disease (CHD), and animal studies demonstrate potent antiatherosclerotic estrogen effects. Paradoxically, recent clinical trials have not demonstrated a protective effect. This paradox may be explained by a healthy woman effect bias. Women using HRT have improved health outcomes unrelated to underlying atherosclerotic burden. Examination of the association between coronary calcium (CC), a marker of atherosclerotic plaque burden, and the use of HRT in postmenopausal women may help address this paradox. METHODS: The study population comprised 641 asymptomatic postmenopausal women, 425 (66%) of whom were taking HRT. Data obtained from a self-administered questionnaire and blood samples were analyzed. Electron beam tomography (EBT) for CC was performed on each subject. Analysis of variance (ANOVA) was used to evaluate adjusted means. RESULTS: Independent t tests found that age, low-density lipoproteins (LDL), high-density lipoproteins (HDL), body mass index (BMI), vitamin use, coronary calcium score (CCS), coronary calcified volume (CCV), and the number of coronary calcium lesions (CCL) were significantly different between the HRT group and the non-HRT group. However, after controlling for potential confounders, no significant differences were observed in CCS, CCV, or the number of CCL between the HRT and non-HRT groups. Stratifying by BMI shows that obese/overweight women taking HRT have lower adjusted CCS and fewer CCL than the obese/overweight women not taking HRT. CONCLUSIONS: These findings demonstrate no association between HRT use and CCS, CCV, and CCL after adjusting for measurable confounders in postmenopausal women. Our failure to demonstrate an independent association between HRT use and a marker of atherosclerotic plaque burden suggests that a healthy woman effect may explain the beneficial association between HRT use and CHD in observational studies.