Adaptation of the African Couples HIV Testing and Counseling Model for Men who have Sex with Men in the United States: an Application of the ADAPT-ITT Framework

To respond to the need for new HIV prevention services for men who have sex with men (MSM) in the United States, and to respond to new data on the key role of main partnerships in US MSM epidemics, we sought to develop a new service for joint HIV testing of male couples. We used the ADAPT-ITT framework to guide our work. From May 2009 to July 2013, a multiphase process was undertaken to identify an appropriate service as the basis for adaptation, collect data to inform the adaptation, adapt the testing service, develop training materials, test the adapted service, and scale up and evaluate the initial version of the service. We chose to base our adaptation on an African couples HIV testing service that was developed in the 1980s and has been widely disseminated in low- and middle-income countries. Our adaptation was informed by qualitative data collections from MSM and HIV counselors, multiple online surveys of MSM, information gathering from key stakeholders, and theater testing of the adapted service with MSM and HIV counselors. Results of initial testing indicate that the adapted service is highly acceptable to MSM and to HIV counselors, that there are no evident harms (e.g., intimate partner violence, relationship dissolution) associated with the service, and that the service identifies a substantial number of HIV serodiscordant male couples. The story of the development and scale-up of the adapted service illustrates how multiple public and foundation funding sources can collaborate to bring a prevention adaptation from concept to public health application, touching on research, program evaluation, implementation science, and public health program delivery. The result of this process is an adapted couples HIV testing approach, with training materials and handoff from academic partners to public health for assessment of effectiveness and consideration of the potential benefits of implementation; further work is needed to optimally adapt the African couples testing service for use with male–female couples in the United States

Accelerating regional atrophy rates in the progression from normal aging to Alzheimer’s disease

We investigated progression of atrophy in vivo, in Alzheimer’s disease (AD), and mild cognitive impairment (MCI). We included 64 patients with AD, 44 with MCI and 34 controls with serial MRI examinations (interval 1.8 ± 0.7 years). A nonlinear registration algorithm (fluid) was used to calculate atrophy rates in six regions: frontal, medial temporal, temporal (extramedial), parietal, occipital lobes and insular cortex. In MCI, the highest atrophy rate was observed in the medial temporal lobe, comparable with AD. AD patients showed even higher atrophy rates in the extramedial temporal lobe. Additionally, atrophy rates in frontal, parietal and occipital lobes were increased. Cox proportional hazard models showed that all regional atrophy rates predicted conversion to AD. Hazard ratios varied between 2.6 (95% confidence interval (CI) = 1.1–6.2) for occipital atrophy and 15.8 (95% CI = 3.5–71.8) for medial temporal lobe atrophy. In conclusion, atrophy spreads through the brain with development of AD. MCI is marked by temporal lobe atrophy. In AD, atrophy rate in the extramedial temporal lobe was even higher. Moreover, atrophy rates also accelerated in parietal, frontal, insular and occipital lobes. Finally, in nondemented elderly, medial temporal lobe atrophy was most predictive of progression to AD, demonstrating the involvement of this region in the development of AD

Syn-orogenic high-temperature crustal melting: Geochronological and Nd-Sr-Pb isotope constraints from basement-derived granites (Central Damara Orogen, Namibia)

Major and trace element and Nd, Sr and Pb isotope data from c. 550 Ma-old gray granites and c. 510 Ma-old red leucogranites of the high-grade central part of the Damara orogen (Namibia) indicate a dominantly deep crustal origin. Moderately peraluminous gray granites are isotopically evolved (initial epsilon(Nd): C. - 17) and were likely derived from meta-igneous sources with late Archean to Paleoproterozoic crustal residence ages. Based on a comparison with experimental results, the granites were derived by partial melting of a granodioritic biotite gneiss at c. 900-950 degrees C and less than 10 kbar. Slightly peraluminous red leucogranites are also isotopically evolved (initial epsilon(Nd): - 15 to - 18) but have undergone extensive crystal fractionation coupled with minor contamination of mid crustal meta-pelitic material. Major and trace element data do not support closed-system fractional crystallization processes for all samples, however, some chemical features underline the importance of crystal fractionation processes especially for the leucogranites. Isotope data do not support mixing of different crust-derived melts or assimilation of crustal rocks by a mafic magma on a large scale. For the gray granites, unradiogenic Pb isotope compositions with substantial variation in Pb-207/Pb-204 at almost constant (206)pb/(204)pb, strongly negative epsilon(Nd) values and moderately radiogenic Sr isotope compositions argue for an undepleted nature of the source. High Rb/Sr ratios of the red leucogranites permit a comparison with the gray granites but similar initial ENd values indicate that the source of these granites is not fundamentally different to the source of the gray granites. The most acceptable model for both granite types involves partial melting of meta-igneous basement rocks of Archean to Proterozoic age. The consistency of the chemical data with a crustal anatectic origin and the observation that the gray granites intruded before the first peak of high-grade regional metamorphism suggests that they intruded simultaneously with crustal thickening. The red leucogranites are interpreted to be a result of crustal melting during the main peak of regional metamorphism. The heating events that promoted melting of fertile deep-crustal rocks might have been caused by the inferred high heat productivity of heat-producing radioactive elements (Th, U, K) together with crustal thickening during the main periods of orogen

Tactics and Strategic Action

We discuss the dominant approaches to the analysis of social movement tactics and strategies. If there is broad agreement among scholars about their importance to the performance and understanding of collective action, there is considerably less consensus on how best to explain the decisions over tactics and strategy that social movements make, the extent to which decisions reflect individual or group preferences, or the importance that should be accorded to the micro and macro levels of analysis. The debates concerning these questions provide the main focus of our discussion, from contentious politics to actor-centered and interactionist approaches

Microbiome-derived carnitine mimics as previously unknown mediators of gut-brain axis communication

Alterations to the gut microbiome are associated with various neurological diseases, yet evidence of causality and identity of microbiome-derived compounds that mediate gut-brain axis interaction remain elusive. Here, we identify two previously unknown bacterial metabolites 3-methyl-4-(trimethylammonio)butanoate and 4-(trimethylammonio)pentanoate, structural analogs of carnitine that are present in both gut and brain of specific pathogen–free mice but absent in germ-free mice. We demonstrate that these compounds are produced by anaerobic commensal bacteria from the family Lachnospiraceae (Clostridiales) family, colocalize with carnitine in brain white matter, and inhibit carnitine-mediated fatty acid oxidation in a murine cell culture model of central nervous system white matter. This is the first description of direct molecular inter-kingdom exchange between gut prokaryotes and mammalian brain cells, leading to inhibition of brain cell function

A nucleosome assembly protein-like polypeptide binds to chloroplast group II intron RNA in Chlamydomonas reinhardtii

In the unicellular green alga Chlamydomonas reinhardtii, the chloroplast-encoded tscA RNA is part of a tripartite group IIB intron, which is involved in trans-splicing of precursor mRNAs. We have used the yeast three-hybrid system to identify chloroplast group II intron RNA-binding proteins, capable of interacting with the tscA RNA. Of 14 candidate cDNAs, 13 encode identical polypeptides with significant homology to members of the nuclear nucleosome assembly protein (NAP) family. The RNA-binding property of the identified polypeptide was demonstrated by electrophoretic mobility shift assays using different domains of the tripartite group II intron as well as further chloroplast transcripts. Because of its binding to chloroplast RNA it was designated as NAP-like (cNAPL). In silico analysis revealed that the derived polypeptide carries a 46 amino acid chloroplast leader peptide, in contrast to nuclear NAPs. The chloroplast localization of cNAPL was demonstrated by laser scanning confocal fluorescence microscopy using different chimeric cGFP fusion proteins. Phylogenetic analysis shows that no homologues of cNAPL and its related nuclear counterparts are present in prokaryotic genomes. These data indicate that the chloroplast protein described here is a novel member of the NAP family and most probably has not been acquired from a prokaryotic endosymbiont

A nucleosome assembly protein-like polypeptide binds to chloroplast group II intron RNA in Chlamydomonas reinhardtii

In the unicellular green alga Chlamydomonas reinhardtii, the chloroplast-encoded tscA RNA is part of a tripartite group IIB intron, which is involved in trans-splicing of precursor mRNAs. We have used the yeast three-hybrid system to identify chloroplast group II intron RNA-binding proteins, capable of interacting with the tscA RNA. Of 14 candidate cDNAs, 13 encode identical polypeptides with significant homology to members of the nuclear nucleosome assembly protein (NAP) family. The RNA-binding property of the identified polypeptide was demonstrated by electrophoretic mobility shift assays using different domains of the tripartite group II intron as well as further chloroplast transcripts. Because of its binding to chloroplast RNA it was designated as NAP-like (cNAPL). In silico analysis revealed that the derived polypeptide carries a 46 amino acid chloroplast leader peptide, in contrast to nuclear NAPs. The chloroplast localization of cNAPL was demonstrated by laser scanning confocal fluorescence microscopy using different chimeric cGFP fusion proteins. Phylogenetic analysis shows that no homologues of cNAPL and its related nuclear counterparts are present in prokaryotic genomes. These data indicate that the chloroplast protein described here is a novel member of the NAP family and most probably has not been acquired from a prokaryotic endosymbiont

Microbiome-derived carnitine mimics as previously unknown mediators of gut-brain axis communication

Alterations to the gut microbiome are associated with various neurological diseases, yet evidence of causality and identity of microbiome-derived compounds that mediate gut-brain axis interaction remain elusive. Here, we identify two previously unknown bacterial metabolites 3-methyl-4-(trimethylammonio)butanoate and 4-(trimethylammonio)pentanoate, structural analogs of carnitine that are present in both gut and brain of specific pathogen-free mice but absent in germ-free mice. We demonstrate that these compounds are produced by anaerobic commensal bacteria from the family Lachnospiraceae (Clostridiales) family, colocalize with carnitine in brain white matter, and inhibit carnitine-mediated fatty acid oxidation in a murine cell culture model of central nervous system white matter. This is the first description of direct molecular inter-kingdom exchange between gut prokaryotes and mammalian brain cells, leading to inhibition of brain cell function.Additional co-authors: Emily K. Osterweil, Andrew S. MacDonald, Chris J. Schofield, Saverio Tardito, Josephine Bunch, Gillian Douce, Julia M. Edgar, RuAngelie Edrada-Ebel, Richard J. A. Goodwin, Richard Burchmore, Daniel M. Wal

Translocator protein is a marker of activated microglia in rodent models but not human neurodegenerative diseases

Microglial activation plays central roles in neuroinflammatory and neurodegenerative diseases. Positron emission tomography (PET) targeting 18 kDa Translocator Protein (TSPO) is widely used for localising inflammation in vivo, but its quantitative interpretation remains uncertain. We show that TSPO expression increases in activated microglia in mouse brain disease models but does not change in a non-human primate disease model or in common neurodegenerative and neuroinflammatory human diseases. We describe genetic divergence in the TSPO gene promoter, consistent with the hypothesis that the increase in TSPO expression in activated myeloid cells depends on the transcription factor AP1 and is unique to a subset of rodent species within the Muroidea superfamily. Finally, we identify LCP2 and TFEC as potential markers of microglial activation in humans. These data emphasise that TSPO expression in human myeloid cells is related to different phenomena than in mice, and that TSPO-PET signals in humans reflect the density of inflammatory cells rather than activation state.Published versionThe authors thank the UK MS Society for financial support (grant number: C008-16.1). DRO was funded by an MRC Clinician Scientist Award (MR/N008219/1). P.M.M. acknowledges generous support from Edmond J Safra Foundation and Lily Safra, the NIHR Senior Investigator programme and the UK Dementia Research Institute which receives its funding from DRI Ltd., funded by the UK Medical Research Council, Alzheimer’s Society, and Alzheimer’s Research UK. P.M.M. and D.R.O. thank the Imperial College Healthcare Trust-NIHR Biomedical Research Centre for infrastructure support and the Medical Research Council for support of TSPO studies (MR/N016343/1). E.A. was supported by the ALS Stichting (grant “The Dutch ALS Tissue Bank”). P.M. and B.B.T. are funded by the Swiss National Science Foundation (projects 320030_184713 and 310030_212322, respectively). S.T. was supported by an “Early Postdoc.Mobility” scholarship (P2GEP3_191446) from the Swiss National Science Foundation, a “Clinical Medicine Plus” scholarship from the Prof Dr. Max Cloëtta Foundation (Zurich, Switzerland), from the Jean et Madeleine Vachoux Foundation (Geneva, Switzerland) and from the University Hospitals of Geneva. This work was funded by NIH grants U01AG061356 (De Jager/Bennett), RF1AG057473 (De Jager/Bennett), and U01AG046152 (De Jager/Bennett) as part of the AMP-AD consortium, as well as NIH grants R01AG066831 (Menon) and U01AG072572 (De Jager/St George-Hyslop)