PHOSPHOTRANSACETYLASE AND XYLULOSE 5-PHOSPHATE/FRUCTOSE 6-PHOSPHATE PHOSPHOKETOLASE: TWO EUKARYOTIC PARTNERS OF ACETATE KINASE

Although acetate is a predominant metabolite produced by many eukaryotic microbes, far less attention has been given to acetate metabolism in eukaryotes than in bacteria and archaea. Acetate kinase (Ack), which catalyzes the reversible phosphorylation of acetate from ATP, is a key enzyme in bacterial acetate metabolism. Ack primarily partners with phosphotransacetylase (Pta), which catalyzes the generation of acetyl phosphate from acetyl-CoA, but can also partner with xylulose 5-phosphate/fructose 6-phosphate phosphoketolase (Xfp), which produces acetyl phosphate from either xylulose 5-phosphate or fructose 6-phosphate. The Ack-Pta pathway, found primarily in bacteria, is also present in lower eukaryotes such as the green algae Chlamydomonas reinhardtii and the oomycete, Phytophthora. The Ack-Xfp pathway, which forms a modified pentose phosphoketolase pathway in heterofermentative bacteria, has been found in a number of ascomycete and basidiomycete fungi. Although bacterial and eukaryotic microbes possess these pathways, humans, animals and plants lack these enzymes, making this pathway a potential drug target in eukaryotic pathogens. Two types of Ptas have previously been identified: PtaI and PtaII. PtaII enzymes have an N-terminal regulatory domain that the PtaI enzymes lack. Through sequence analysis, we identified four subtypes, IIa, IIb, IIc, and IId, of the PtaII enzymes based on the presence or absence of two N-terminal subdomains. Here we describe the first biochemical characterization of a eukaryotic Pta, the Phytophthora ramorum Type IIa Pta1 (PrPta1IIa). Although the N-terminus of PrPta1IIa shares only 19% amino acid identity with the N-terminus of the bacterial Escherichia coli and Salmonella enterica PtaIIa enzymes, the effector molecules, ATP, NADH, PEP, and pyruvate, inhibit all three enzymes in the acetyl-CoA-forming direction; whereas, AMP differentially regulates PrPta1IIa compared to SePtaIIa. We hypothesize that Xfp-Ack would function as a modified pentose phosphoketolase pathway to produce acetate and ATP in the opportunistic, fungal pathogen Cryptococcus neoformans, which has two open reading frames, designated as Xfp1 and Xfp2, with sequence identity to Xfp. To investigate the metabolic and physiological role of the Ack-Xfp pathway in C. neoformans, we have generated single XFP1, XFP2 and ACK knockouts, as well as a XFP1/XFP2 double knockout. Our results indicate both Xfp1 and Xfp2 play a role in the survival of C. neoformans within macrophages, and that Ack and Xfp2 most likely partner together under low glucose and possibly low iron environments

Removing Confederate Statues, Now What?: Sustainability and Reimagining Space

Professor tonya thames-taylor, History - Removing Confederate Statues, Now What?: Sustainability and Reimagining Spac

VMAT2-Deficient Mice Display Nigral and Extranigral Pathology and Motor and Nonmotor Symptoms of Parkinson's Disease

Dopamine is transported into synaptic vesicles by the vesicular monoamine transporter (VMAT2; SLC18A2). Disruption of dopamine storage has been hypothesized to damage the dopamine neurons that are lost in Parkinson's disease. By disrupting vesicular storage of dopamine and other monoamines, we have created a progressive mouse model of PD that exhibits catecholamine neuron loss in the substantia nigra pars compacta and locus coeruleus and motor and nonmotor symptoms. With a 95% reduction in VMAT2 expression, VMAT2-deficient animals have decreased motor function, progressive deficits in olfactory discrimination, shorter latency to behavioral signs of sleep, delayed gastric emptying, anxiety-like behaviors at younger ages, and a progressive depressive-like phenotype. Pathologically, the VMAT2-deficient mice display progressive neurodegeneration in the substantia nigra (SNpc), locus coeruleus (LC), and dorsal raphe (DR) coupled with α-synuclein accumulation. Taken together, these studies demonstrate that reduced vesicular storage of monoamines and the resulting disruption of the cytosolic environment may play a role in the pathogenesis of parkinsonian symptoms and neurodegeneration. The multisystem nature of the VMAT2-deficient mice may be useful in developing therapeutic strategies that go beyond the dopamine system

Effect of a bereavement support group on female adolescents’ psychological health: a randomised controlled trial in South Africa

Background Bereavement increases children’s risk for psychological disorders, highlighting the need for effective interventions, especially in areas where orphanhood is common. We aimed to assess the effects of an eight-session support group intervention on the psychological health of bereaved female adolescents in South Africa. Methods This randomised controlled trial enrolled female adolescents at 11 schools in three peri-urban towns of Free State province, South Africa. 453 bereaved ninth-grade students aged 13–17 years who had expressed interest in taking part in the group were randomly assigned (1:1) to receive the intervention or to be waitlisted for programme enrolment after the study period and serve as the control group. The intervention, Abangane (“friends” in isiZulu), is a locally derived, curriculum-based support group focused on coping with loss incorporating indigenous stories and cognitive behavioural therapy components. Weekly group sessions were facilitated by trained social workers or social auxiliary workers from a local non-profit organisation. The primary outcomes included indicators of grief and depression as reported by adolescents and behavioural problems reported by their caregivers. Grief was measured with three scales: the grief subscale of the Core Bereavement Items to assess normative grief; and the Intrusive Grief Thoughts Scale and the Inventory of Complicated Grief–Revised for Children to assess maladaptive grief symptoms in the past 4 weeks. Depression symptoms in the past 7 days were measured with the Center for Epidemiological Studies–Depression Scale for Children. Caregivers completed the Brief Problem Monitor-Parent Form to report on adolescent’s behaviour in the previous 4 weeks. Analysis was intention to treat. This study is registered with ClinicalTrials.gov, number NCT02368808. Findings Between Sept 30, 2014, and Feb 5, 2015, eligible female participants were identified, of whom 226 were assigned to the intervention, Abangane, and 227 were assigned to the waitlisted control group. Analysis included 382 adolescents who completed both surveys (193 participants assigned to Abangane and 189 assigned to waitlist). At follow up, the intervention group had significantly lower scores for primary outcomes, including intrusive grief (p=0·000, Cohen’s d=–0·21), complicated grief (p=0·015, d=–0·14), and depression (p=0·009, d=–0·21) relative to the waitlisted group, while core bereavement scores were similar between groups (p=0·269). Caregivers in the intervention group reported lower levels of behavioural problems among adolescents (p=0·017, d=–0·31). Interpretation Short-term, structured, theory-based support groups with contextually relevant content show promise in mitigating psychological and behavioural problems among bereaved adolescents. Abangane is replicable in resource limited settings, using freely available curriculum materials, existing programme structures, and appropriately trained personnel to implement it

The Impact of a Youth Development Program on Secondary Students’ Career Aspirations

This study’s purpose determined the extent to which adolescents’ participation in a youth development program may be linked to the participants’ post-secondary education and career aspirations. One hundred and seven adolescents, ages 14-19 in grades 8-12 completed Holland’s Vocational Interest Survey and the 4-H Career Decision Survey. Ordinal regression analysis indicated participation in 4-H had a positive impact on career decisions for students who participated in 4-H for two years (p< .038) and six years (p< .001). Significant differences were apparent with 80% of the racial/ethnic groups surveyed concerning a college fair’s impact on career choice and college major determination

Evaluation of the clinical management of HIV-infected patients by private sector doctors in the eThekwini Metro, KwaZulu-Natal.

Background: Although private sector doctors are the backbone of treatment service in many countries, caring for patients with HIV entails a whole new set of challenges and difficulties. The few studies done on the quality of care of HIV patients, in the private sector in developing countries, have highlighted some problems with management. In South Africa, two-thirds of doctors work in the private sector. Though many studies on HIV/AIDS have been undertaken, few have been done in the private sector in terms of the management of this disease. Therefore, a study was undertaken to evaluate the clinical management of HIV-infected patients by private sector doctors. Methods: A descriptive cross-sectional study was undertaken in the eThekwini Metro in KwaZulu-Natal, South Africa, with 190 private sector doctors who, in the first phase of the study, indicated that they manage HIV and AIDS patients and would be willing to participate in the second phase of the study. The HIV guidelines of the Department of Health and Human Services and the South African National Department of Health were used to compare the treatment of HIV patients by these doctors. Results: Eighty-five doctors (54.5%) always measured the CD4 count and viral load levels at diagnosis. Both CD4 counts and viral load were always used by 76 doctors (61.8%) to initiate therapy. Of the doctors, 134 (78.5%) initiated therapy at CD4 count < 200 cells/mm3. The majority of doctors prescribed triple therapy regimens using the 2 NRTI + 1 NNRTI combination. Doctors who utilised CD4 counts tended to also use viral load (VL) to assess effectiveness and change therapy (p < 0.001). At initiation of treatment, 68.5% of the doctors saw their patients monthly and 64.3% saw them every three to six months, when stable. Conclusion: The majority of private sector doctors were compliant with current guidelines for HIV management, hence maintaining an acceptable quality of clinical healthcare

Impact of chronic sexual abuse and depression on inflammation and wound healing in the female reproductive tract of HIV-uninfected and HIV-infected women.

Sexual violence is associated with increased risk of HIV acquisition/transmission in women. Forced sex can result in physical trauma to the reproductive tract as well as severe psychological distress. However, immuno-biological mechanisms linking sexual violence and HIV susceptibility are incompletely understood. Using the Women\u27s Interagency HIV Study repository, a total of 77 women were selected to form 4 groups, stratified by HIV serostatus, in the following categories: 1) no sexual abuse history and low depressive symptom score (below clinically significant cut-off, score

Perceptions of HIV Risk and Explanations of Sexual Risk Behavior Offered by Heterosexual Black Male Barbershop Patrons in Brooklyn, NY

Objective: To describe HIV risk factors among adult heterosexual Black men recruited from four barbershops located in high HIV seroprevalent neighborhoods of Brooklyn, NY. Methods: Data on HIV-risk related behaviors and other characteristics were collected from barbershop clients. All participants (n=60) completed brief risk assessments; and a subset (n=22) also completed focus groups and/or individual interviews. Results: Of the subset of 22 men, 68% were US born, 59% had been in jail/prison, 32% were unemployed; and during the 3 months before the interviews, 68% reported at least two partners and 45% reported unprotected vaginal or anal sex with two or more women. Emergent themes included: 1) the psychological function of multiple partnerships; 2) calculated risk taking regarding condom use; 3) the role of emotional attachment and partner trust in condom use; 4) low perceived HIV risk and community awareness; and 5) lack of relationship between HIV testing and safer sex practices. Conclusions: Interventions among heterosexual Black men should focus not only on increasing HIV awareness and reducing sexual risk, but also on contextual and interpersonal factors that influence sexual risk

Development and formative evaluation of a family-centred adolescent HIV prevention programme in South Africa

Preventing HIV among young people is critical to achieving and sustaining global epidemic control. Evidence from Western settings suggests that family-centred prevention interventions may be associated with greater reductions in risk behaviour than standard adolescent-only models. Despite this, family-centred models for adolescent HIV prevention are nearly non-existent in South Africa − home to more people living with HIV than any other country. This paper describes the development and formative evaluation of one such intervention: an evidence-informed, locally relevant, adolescent prevention intervention engaging caregivers as co-participants. The programme, originally consisting of 19 sessions for caregivers and 14 for adolescents, was piloted with 12 groups of caregiver-adolescent dyads by community-based organizations (CBOs) in KwaZulu-Natal and Gauteng provinces. Literature and expert reviews were employed in the development process, and evaluation methods included analysis of attendance records, session-level fidelity checklists and facilitator feedback forms collected during the programme pilot. Facilitator focus group discussions and an implementer programme workshop were also held. Results highlighted the need to enhance training content related to cognitive behavioural theory and group management techniques, as well as increase the cultural relevance of activities in the curriculum. Participant attendance challenges were also identified, leading to a shortened and simplified session set. Findings overall were used to finalize materials and guidance for a revised 14-week group programme consisting of individual and joint sessions for adolescents and their caregivers, which may be implemented by community-based facilitators in other settings.The United States Agency for International Development (USAID) Southern Africa under the President’s Emergency Plan for AIDS Relief (PEPFAR) through Cooperative Agreement No. AID-674-A-12-00002 awarded to Tulane University.https://www.elsevier.com/locate/evalprogplan2019-06-01hj2018Educational PsychologyPsycholog

Utilization of Alcohol Treatment Among HIV-Positive Women with Hazardous Drinking

Hazardous alcohol consumption has been frequently reported among women with HIV infection and is associated with a variety of negative health consequences. Treatments to reduce alcohol use may bring in health benefits. However, little is known regarding the utilization of alcohol treatment services among HIV+ women with hazardous drinking. Using data from the Women’s Interagency HIV Study (WIHS), this study assessed utilization of any alcohol treatment in the past 6 months and performed multivariable logistic regression to determine correlates of receipt of any alcohol treatment. Among 474 HIV+ women reporting recent hazardous drinking, less than one in five (19%) reported recent utilization of any alcohol treatment. Alcoholics Anonymous (AA) was the most commonly reported (12.9%), followed by inpatient detoxification (9.9%) and outpatient alcohol treatment program (7.0%). Half (51%) receiving any alcohol treatment reported utilization of multiple treatments. Multivariable analyses found alcohol treatment was more often utilized by those who had social support (Odds ratio [OR]=1.68, 95% Confidence Interval [CI]=1.00 to 2.83), fewer economic resources (income $12,000, OR = 3.10, 95% CI=1.53 to 6.27), higher levels of drinking (16–35 drinks/week vs. 12–15 drinks/week, OR=3.02, 95% CI=1.47 to 6.21; 36+ drinks/week vs. 12–15 drinks/week, OR=4.41, 95% CI=2.03 to 9.59), and those who reported any illicit drug use (OR=2.77, 95% CI=1.44 to 5.34). More efforts are needed to enhance the utilization of alcohol treatment. Our findings highlight the unique profile of those who utilized alcohol treatment. Such information is vital to improve treatment delivery to address unmet need in this particular population