The Membrane QmoABC Complex Interacts Directly with the Dissimilatory Adenosine 5′-Phosphosulfate Reductase in Sulfate Reducing Bacteria

The adenosine 5′-phosphosulfate reductase (AprAB) is the enzyme responsible for the reduction of adenosine 5′-phosphosulfate (APS) to sulfite in the biological process of dissimilatory sulfate reduction, which is carried out by a ubiquitous group of sulfate reducing prokaryotes. The electron donor for AprAB has not been clearly identified, but was proposed to be the QmoABC membrane complex, since an aprBA–qmoABC gene cluster is found in many sulfate reducing and sulfur-oxidizing bacteria. The QmoABC complex is essential for sulfate reduction, but electron transfer between QmoABC and AprAB has not been reported. In this work we provide the first direct evidence that QmoABC and AprAB interact in Desulfovibrio spp., using co-immunoprecipitation, cross-linking Far-Western blot, tag-affinity purification, and surface plasmon resonance studies. This showed that the QmoABC–AprAB complex has a strong steady-state affinity (KD = 90 ± 3 nM), but has a transient character due to a fast dissociation rate. Far-Western blot identified QmoA as the Qmo subunit most involved in the interaction. Nevertheless, electron transfer from menaquinol analogs to APS through anaerobically purified QmoABC and AprAB could not be detected. We propose that this reaction requires the involvement of a third partner to allow electron flow driven by a reverse electron bifurcation process, i.e., electron confurcation. This process is deemed essential to allow coupling of APS reduction to chemiosmotic energy conservation

The Vaginal Microbiome: Disease, Genetics and the Environment

The vagina is an interactive interface between the host and the environment. Its surface is covered by a protective epithelium colonized by bacteria and other microorganisms. The ectocervix is nonsterile, whereas the endocervix and the upper genital tract are assumed to be sterile in healthy women. Therefore, the cervix serves a pivotal role as a gatekeeper to protect the upper genital tract from microbial invasion and subsequent reproductive pathology. Microorganisms that cross this barrier can cause preterm labor, pelvic inflammatory disease, and other gynecologic and reproductive disorders. Homeostasis of the microbiome in the vagina and ectocervix plays a paramount role in reproductive health. Depending on its composition, the microbiome may protect the vagina from infectious or non-infectious diseases, or it may enhance its susceptibility to them. Because of the nature of this organ, and the fact that it is continuously colonized by bacteria from birth to death, it is virtually certain that this rich environment evolved in concert with its microbial flora. Specific interactions dictated by the genetics of both the host and microbes are likely responsible for maintaining both the environment and the microbiome. However, the genetic basis of these interactions in both the host and the bacterial colonizers is currently unknown. _Lactobacillus_ species are associated with vaginal health, but the role of these species in the maintenance of health is not yet well defined. Similarly, other species, including those representing minor components of the overall flora, undoubtedly influence the ability of potential pathogens to thrive and cause disease. Gross alterations in the vaginal microbiome are frequently observed in women with bacterial vaginosis, but the exact etiology of this disorder is still unknown. There are also implications for vaginal flora in non-infectious conditions such as pregnancy, pre-term labor and birth, and possibly fertility and other aspects of women’s health. Conversely, the role of environmental factors in the maintenance of a healthy vaginal microbiome is largely unknown. To explore these issues, we have proposed to address the following questions:

*1.	Do the genes of the host contribute to the composition of the vaginal microbiome?* We hypothesize that genes of both host and bacteria have important impacts on the vaginal microbiome. We are addressing this question by examining the vaginal microbiomes of mono- and dizygotic twin pairs selected from the over 170,000 twin pairs in the Mid-Atlantic Twin Registry (MATR). Subsequent studies, beyond the scope of the current project, may investigate which host genes impact the microbial flora and how they do so.
*2.	What changes in the microbiome are associated with common non-infectious pathological states of the host?* We hypothesize that altered physiological (e.g., pregnancy) and pathologic (e.g., immune suppression) conditions, or environmental exposures (e.g., antibiotics) predictably alter the vaginal microbiome. Conversely, certain vaginal microbiome characteristics are thought to contribute to a woman’s risk for outcomes such as preterm delivery. We are addressing this question by recruiting study participants from the ~40,000 annual clinical visits to women’s clinics of the VCU Health System.
*3.	What changes in the vaginal microbiome are associated with relevant infectious diseases and conditions?* We hypothesize that susceptibility to infectious disease (e.g. HPV, _Chlamydia_ infection, vaginitis, vaginosis, etc.) is impacted by the vaginal microbiome. In turn, these infectious conditions clearly can affect the ability of other bacteria to colonize and cause pathology. Again, we are exploring these issues by recruiting participants from visitors to women’s clinics in the VCU Health System.

Three kinds of sequence data are generated in this project: i) rDNA sequences from vaginal microbes; ii) whole metagenome shotgun sequences from vaginal samples; and iii) whole genome shotgun sequences of bacterial clones selected from vaginal samples. The study includes samples from three vaginal sites: mid-vaginal, cervical, and introital. The data sets also include buccal and perianal samples from all twin participants. Samples from these additional sites are used to test the hypothesis of a per continuum spread of bacteria in relation to vaginal health. An extended set of clinical metadata associated with these sequences are deposited with dbGAP. We have currently collected over 4,400 samples from ~100 twins and over 450 clinical participants. We have analyzed and deposited data for 480 rDNA samples, eight whole metagenome shotgun samples, and over 50 complete bacterial genomes. These data are available to accredited investigators according to NIH and Human Microbiome Project (HMP) guidelines. The bacterial clones are deposited in the Biodefense and Emerging Infections Research Resources Repository ("http://www.beiresources.org/":http://www.beiresources.org/). 

In addition to the extensive sequence data obtained in this study, we are collecting metadata associated with each of the study participants. Thus, participants are asked to complete an extensive health history questionnaire at the time samples are collected. Selected clinical data associated with the visit are also obtained, and relevant information is collected from the medical records when available. This data is maintained securely in a HIPAA-compliant data system as required by VCU’s Institutional Review Board (IRB). The preponderance of these data (i.e., that judged appropriate by NIH staff and VCU’s IRB are deposited at dbGAP ("http://www.ncbi.nlm.nih.gov/gap":http://www.ncbi.nlm.nih.gov/gap). Selected fields of this data have been identified by NIH staff as ‘too sensitive’ and are not available in dbGAP. Individuals requiring access to these data fields are asked to contact the PI of this project or NIH Program Staff. 
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A global collaboration to study intimate partner violence-related head trauma: The ENIGMA consortium IPV working group

Intimate partner violence includes psychological aggression, physical violence, sexual violence, and stalking from a current or former intimate partner. Past research suggests that exposure to intimate partner violence can impact cognitive and psychological functioning, as well as neurological outcomes. These seem to be compounded in those who suffer a brain injury as a result of trauma to the head, neck or body due to physical and/or sexual violence. However, our understanding of the neurobehavioral and neurobiological effects of head trauma in this population is limited due to factors including difficulty in accessing/recruiting participants, heterogeneity of samples, and premorbid and comorbid factors that impact outcomes. Thus, the goal of the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium Intimate Partner Violence Working Group is to develop a global collaboration that includes researchers, clinicians, and other key community stakeholders. Participation in the working group can include collecting harmonized data, providing data for meta- and mega-analysis across sites, or stakeholder insight on key clinical research questions, promoting safety, participant recruitment and referral to support services. Further, to facilitate the mega-analysis of data across sites within the working group, we provide suggestions for behavioral surveys, cognitive tests, neuroimaging parameters, and genetics that could be used by investigators in the early stages of study design. We anticipate that the harmonization of measures across sites within the working group prior to data collection could increase the statistical power in characterizing how intimate partner violence-related head trauma impacts long-term physical, cognitive, and psychological health

STUDI ALTERNATIF PERENCANAAAN SISTEM RANGKA PEMIKUL MOMEN KHUSUS (SRPMK) DENGAN KOLOM BULAT PADA KANTOR PUSAT ESTIKES KEPANJEN MALANG

Kolom merupakam elemen vertikal suatu struktur yang berfungsi menahan beban aksial dan momen sebagai akibat beban gravitasi dan beban lateral yang bekerja pada struktur. Oleh karena itu, kolom memegan penampang penting pada keutuhan struktur, apabila kolom mengalami kegagalan akan berakibat pada keruntuhan struktur bangunan atas gedung. perbedaan kolom bulat dan kolom persegi sangkat mendasar. Jika ditinjau dari tulangan sengkang, kolom bulat perpenampang spiral memiliki jarak sengkang yang berdekatan diabnding dengan kolom dengan kolom persegi yang mempunya bentuk sengkang tunggal dan jarak antara yang relatif besaar. Kolom bulat yang menghasilkan kapsitas penampang, gaya – gaya dalam seperti gaya aksial; gaya geser; gaya momen, dan simpangan (maximum displacement) sehingga dalam skripsi ini untuk mengetahui desain kolom bulat yang efisien dan efikas didalam perencanaan. Hasil yang diperoleh dari perenanaan struktur gedung dengan kolom bulat pada gedung kantor pusat stikes kepanjen malang dengan program bantu STAAD PRO V 8, yang ditinjau dari kapasitas penampang dengan luas mutu beton kolom bulat menghasilkan ØPn (aksial nominal) = 3988,690 kN, ØMn ( Momen nominal ) = 478,812 kNm, Vn (Geser nominal) = 681629,848 N. Sehingga kolom bulat memiliki kapasitas penampang yang lebih besar dan efektif. Ditinjau dari rasio dan gaya-gaya dalam struktur, kolom bulat memiliki gaya aksial = 0,021, kekakuan struktur pada kolom bulat memiliki simpangan (maximum displacements) yang lebih besar dari kolom persegi. Sehingga kekakuan pada kolom bulat lebih tinggi dengan kolom persegi

Behavioral Coping Phenotypes and Associated Psychosocial Outcomes of Pregnant and Postpartum Women During the COVID-19 Pandemic

The impact of COVID-19-related stress on perinatal women is of heightened public health concern given the established intergenerational impact of maternal stress-exposure on infants and fetuses. There is urgent need to characterize the coping styles associated with adverse psychosocial outcomes in perinatal women during the COVID-19 pandemic to help mitigate the potential for lasting sequelae on both mothers and infants. This study uses a data-driven approach to identify the patterns of behavioral coping strategies that associate with maternal psychosocial distress during the COVID-19 pandemic in a large multicenter sample of pregnant women (N = 2876) and postpartum women (N = 1536). Data was collected from 9 states across the United States from March to October 2020. Women reported behaviors they were engaging in to manage pandemic-related stress, symptoms of depression, anxiety and global psychological distress, as well as changes in energy levels, sleep quality and stress levels. Using latent profile analysis, we identified four behavioral phenotypes of coping strategies. Critically, phenotypes with high levels of passive coping strategies (increased screen time, social media, and intake of comfort foods) were associated with elevated symptoms of depression, anxiety, and global psychological distress, as well as worsening stress and energy levels, relative to other coping phenotypes. In contrast, phenotypes with high levels of active coping strategies (social support, and self-care) were associated with greater resiliency relative to other phenotypes. The identification of these widespread coping phenotypes reveals novel behavioral patterns associated with risk and resiliency to pandemic-related stress in perinatal women. These findings may contribute to early identification of women at risk for poor long-term outcomes and indicate malleable targets for interventions aimed at mitigating lasting sequelae on women and children during the COVID-19 pandemic

Household transmission of SARS-CoV-2 in the United States: living density, viral load, and disproportionate impact on communities of color

Households are hotspots for SARS-CoV-2 transmission. In the US, the COVID-19 pandemic has had a disproportionate impact on communities of color. Between April-October 2020, the CO-HOST prospective cohort study enrolled 100 COVID-19 cases and 208 of their household members in North Carolina, including 44% who identified as Hispanic or non-white. Households were enrolled a median of 6 days from symptom onset in the index case. Incident secondary cases within the household were detected by quantitative PCR of weekly nasal swabs (days 7, 14, 21) or by seroconversion at day 28.Excluding 73 household contacts who were PCR-positive at baseline, the secondary attack rate among household contacts was 32% (33/103, 95% CI 22%-44%). The majority of cases occurred by day 7, with later cases confirmed as household-acquired by viral sequencing. Infected persons in the same household had similar nasopharyngeal viral loads (ICC=0.45, 95% CI 0.23-0.62). Households with secondary transmission had index cases with a median viral load that was 1.4 log10 higher than households without transmission (p=0.03) as well as higher living density (>3 persons occupying <6 rooms) (OR 3.3, 95% CI 1.02-10.9). Minority households were more likely to experience high living density and had a higher risk of incident infection than did white households (SAR 51% vs. 19%, p=0.01).Household crowding in the context of high-inoculum infections may amplify the spread of COVID-19, potentially contributing to disproportionate impact on communities of color

High household transmission of SARS-CoV-2 in the United States: living density, viral load, and disproportionate impact on communities of color.

BACKGROUND: Few prospective studies of SARS-CoV-2 transmission within households have been reported from the United States, where COVID-19 cases are the highest in the world and the pandemic has had disproportionate impact on communities of color. METHODS AND FINDINGS: This is a prospective observational study. Between April-October 2020, the UNC CO-HOST study enrolled 102 COVID-positive persons and 213 of their household members across the Piedmont region of North Carolina, including 45% who identified as Hispanic/Latinx or non-white. Households were enrolled a median of 6 days from onset of symptoms in the index case. Secondary cases within the household were detected either by PCR of a nasopharyngeal (NP) swab on study day 1 and weekly nasal swabs (days 7, 14, 21) thereafter, or based on seroconversion by day 28. After excluding household contacts exposed at the same time as the index case, the secondary attack rate (SAR) among susceptible household contacts was 60% (106/176, 95% CI 53%-67%). The majority of secondary cases were already infected at study enrollment (73/106), while 33 were observed during study follow-up. Despite the potential for continuous exposure and sequential transmission over time, 93% (84/90, 95% CI 86%-97%) of PCR-positive secondary cases were detected within 14 days of symptom onset in the index case, while 83% were detected within 10 days. Index cases with high NP viral load (>10^6 viral copies/ul) at enrollment were more likely to transmit virus to household contacts during the study (OR 4.9, 95% CI 1.3-18 p=0.02). Furthermore, NP viral load was correlated within families (ICC=0.44, 95% CI 0.26-0.60), meaning persons in the same household were more likely to have similar viral loads, suggesting an inoculum effect. High household living density was associated with a higher risk of secondary household transmission (OR 5.8, 95% CI 1.3-55) for households with >3 persons occupying <6 rooms (SAR=91%, 95% CI 71-98%). Index cases who self-identified as Hispanic/Latinx or non-white were more likely to experience a high living density and transmit virus to a household member, translating into an SAR in minority households of 70%, versus 52% in white households (p=0.05). CONCLUSIONS: SARS-CoV-2 transmits early and often among household members. Risk for spread and subsequent disease is elevated in high-inoculum households with limited living space. Very high infection rates due to household crowding likely contribute to the increased incidence of SARS-CoV-2 infection and morbidity observed among racial and ethnic minorities in the US. Quarantine for 14 days from symptom onset of the first case in the household is appropriate to prevent onward transmission from the household. Ultimately, primary prevention through equitable distribution of effective vaccines is of paramount importance. AUTHORS SUMMARY: Why was this study done?: Understanding the secondary attack rate and the timing of transmission of SARS-CoV-2 within households is important to determine the role of household transmission in the larger pandemic and to guide public health policies about quarantine.Prospective studies looking at the determinants of household transmission are sparse, particularly studies including substantial racial and ethnic minorities in the United States and studies with adequate follow-up to detect sequential transmission events.Identifying individuals at high risk of transmitting and acquiring SARS-CoV-2 will inform strategies for reducing transmission in the household, or reducing disease in those exposed.What did the researchers do and find?: Between April-November 2020, the UNC CO-HOST study enrolled 102 households across the Piedmont region of North Carolina, including 45% with an index case who identified as racial or ethnic minorities.Overall secondary attack rate was 60% with two-thirds of cases already infected at study enrollment.Despite the potential for sequential transmission in the household, the majority of secondary cases were detected within 10 days of symptom onset of the index case.Viral loads were correlated within families, suggesting an inoculum effect.High viral load in the index case was associated with a greater likelihood of household transmission.Spouses/partners of the COVID-positive index case and household members with obesity were at higher risk of becoming infected.High household living density contributed to an increased risk of household transmission.Racial/ethnic minorities had an increased risk of acquiring SARS-CoV-2 in their households in comparison to members of the majority (white) racial group.What do these findings mean?: Household transmission often occurs quickly after a household member is infected.High viral load increases the risk of transmission.High viral load cases cluster within households - suggesting high viral inoculum in the index case may put the whole household at risk for more severe disease.Increased household density may promote transmission within racial and ethnic minority households.Early at-home point-of-care testing, and ultimately vaccination, is necessary to effectively decrease household transmission

Parental Education and Genetics of BMI from Infancy to Old Age : A Pooled Analysis of 29 Twin Cohorts

Objective The objective of this study was to analyze how parental education modifies the genetic and environmental variances of BMI from infancy to old age in three geographic-cultural regions. Methods A pooled sample of 29 cohorts including 143,499 twin individuals with information on parental education and BMI from age 1 to 79 years (299,201 BMI measures) was analyzed by genetic twin modeling. Results Until 4 years of age, parental education was not consistently associated with BMI. Thereafter, higher parental education level was associated with lower BMI in males and females. Total and additive genetic variances of BMI were smaller in the offspring of highly educated parents than in those whose parents had low education levels. Especially in North American and Australian children, environmental factors shared by co-twins also contributed to the higher BMI variation in the low education level category. In Europe and East Asia, the associations of parental education with mean BMI and BMI variance were weaker than in North America and Australia. Conclusions Lower parental education level is associated with higher mean BMI and larger genetic variance of BMI after early childhood, especially in the obesogenic macro-environment. The interplay among genetic predisposition, childhood social environment, and macro-social context is important for socioeconomic differences in BMI.Peer reviewe