Comparative transcriptomics of extreme phenotypes of human HIV-1 infection and SIV infection in sooty mangabey and rhesus macaque

High levels of HIV-1 replication during the chronic phase of infection usually correlate with rapid progression to severe immunodeficiency. However, a minority of highly viremic individuals remains asymptomatic and maintains high CD4⁺ T cell counts. This tolerant profile is poorly understood and reminiscent of the widely studied nonprogressive disease model of SIV infection in natural hosts. Here, we identify transcriptome differences between rapid progressors (RPs) and viremic nonprogressors (VNPs) and highlight several genes relevant for the understanding of HIV-1-induced immunosuppression. RPs were characterized by a specific transcriptome profile of CD4⁺ and CD8⁺ T cells similar to that observed in pathogenic SIV-infected rhesus macaques. In contrast, VNPs exhibited lower expression of interferon-stimulated genes and shared a common gene regulation profile with nonpathogenic SIV-infected sooty mangabeys. A short list of genes associated with VNP, including CASP1, CD38, LAG3, TNFSF13B, SOCS1, and EEF1D, showed significant correlation with time to disease progression when evaluated in an independent set of CD4⁺ T cell expression data. This work characterizes 2 minimally studied clinical patterns of progression to AIDS, whose analysis may inform our understanding of HIV pathogenesis.

Trends of mean and extreme temperature indices since 1874 at low-elevation sites in the Southern Alps

We describe the recovery of three daily meteorological records for the southern Alps (Domodossola, Riva del Garda, and Rovereto), all starting in the second half of the nineteenth century. We use these new data, along with additional records, to study regional changes in the mean temperature and extreme indices of heat waves and cold spells frequency and duration over the period 1874–2015. The records are homogenized using subdaily cloud cover observations as a constraint for the statistical model, an approach that has never been applied before in the literature. A case study based on a record of parallel observations between a traditional meteorological window and a modern screen shows that the use of cloud cover can reduce the root-mean-square error of the homogenization by up to 30% in comparison to an unaided statistical correction. We find that mean temperature in the southern Alps has increased by 1.4°C per century over the analyzed period, with larger increases in daily minimum temperatures than maximum temperatures. The number of hot days in summer has more than tripled, and a similar increase is observed in duration of heat waves. Cold days in winter have dropped at a similar rate. These trends are mainly caused by climate change over the last few decades.

Constraints on the thermal evolution of the Adriatic margin during Jurassic continental break-up: U–Pb dating of rutile from the Ivrea–Verbano Zone, Italy

The Ivrea–Verbano Zone (IVZ), northern Italy, exposes an attenuated section through the Permian lower crust that records high-temperature metamorphism under lower crustal conditions and a protracted history of extension and exhumation associated partly with the Jurassic opening of the Alpine Tethys ocean. This study presents SHRIMP U–Pb geochronology of rutile from seven granulite facies metapelites from the base of the IVZ, collected from locations spanning ~35 km along the strike of Paleozoic fabrics. Rutile crystallised during Permian high-temperature metamorphism and anatexis, yet all samples give Jurassic rutile U–Pb ages that record cooling through 650–550 °C. Rutile age distributions are dominated by a peak at ~160 Ma, with a subordinate peak at ~175 Ma. Both ~160 and ~175 Ma age populations show excellent agreement between samples, indicating that the two distinctive cooling stages they record were synchronous on a regional scale. The ~175 Ma population is interpreted to record cooling in the footwall of rift-related faults and shear zones, for which widespread activity in the Lower Jurassic has been documented along the western margin of the Adriatic plate. The ~160 Ma age population postdates the activity of all known rift-related structures within the Adriatic margin, but coincides with extensive gabbroic magmatism and exhumation of sub-continental mantle to the floor of the Alpine Tethys, west of the Ivrea Zone. We propose that this ~160 Ma early post-rift age population records regional cooling following episodic heating of the distal Adriatic margin, likely related to extreme lithospheric thinning and associated advection of the asthenosphere to shallow levels. The partial preservation of the ~175 Ma age cluster suggests that the post-rift (~160 Ma) heating pulse was of short duration. The regional consistency of the data presented here, which is in contrast to many other thermochronometers in the IVZ, demonstrates the value of the rutile U–Pb technique for probing the thermal evolution of high-grade metamorphic terrains. In the IVZ, a significant decoupling between Zr-in-rutile temperatures and U–Pb ages of rutile is observed, with the two systems recording events ~120 Ma apart.

The stigma of mental illness in Southern Ghana: attitudes of the urban population and patients' views

PURPOSE: Stigma is a frequent accompaniment of mental illness leading to a number of detrimental consequences. Most research into the stigma connected to mental illness was conducted in the developed world. So far, few data exist on countries in sub-Saharan Africa and no data have been published on population attitudes towards mental illness in Ghana. Even less is known about the stigma actually perceived by the mentally ill persons themselves. METHOD: A convenience sample of 403 participants (210 men, mean age 32.4 ± 12.3 years) from urban regions in Accra, Cape Coast and Pantang filled in the Community Attitudes towards the Mentally Ill (CAMI) questionnaire. In addition, 105 patients (75 men, mean age 35.9 ± 11.0 years) of Ghana's three psychiatric hospitals (Accra Psychiatry Hospital, Ankaful Hospital, Pantang Hospital) answered the Perceived Stigma and Discrimination Scale. RESULTS: High levels of stigma prevailed in the population as shown by high proportions of assent to items expressing authoritarian and socially restrictive views, coexisting with agreement with more benevolent attitudes. A higher level of education was associated with more positive attitudes on all subscales (Authoritarianism, Social Restrictiveness, Benevolence and Acceptance of Community Based Mental Health Services). The patients reported a high degree of experienced stigma with secrecy concerning the illness as a widespread coping strategy. Perceived stigma was not associated with sex or age. DISCUSSION: The extent of stigmatising attitudes within the urban population of Southern Ghana is in line with the scant research in other countries in sub-Saharan Africa and mirrored by the experienced stigma reported by the patients. These results have to be seen in the context of the extreme scarcity of resources within the Ghanaian psychiatric system. Anti-stigma efforts should include interventions for mentally ill persons themselves and not exclusively focus on public attitudes.

Seasonal variation and sources of low molecular weight organic acids in precipitation in the rural area of Anshun

Low mol. wt. (LMW) org. acids are important and ubiquitous chem. constituents in the atm. A comprehensive study of the chem. compn. of pptn. was carried out from June 2007 to June 2008 at a rural site in Anshun, in the west of Guizhou Province, China. During this period, 118 rainwater samples were collected and the main LMW carboxylic acids were detd. using ion chromatog. The av. pH of rainwater was 4.89 which is a typical acidic value. The most abundant carboxylic acids were formic acid (vol. wt. mean concn.: 8.77 μmol L-1) and acetic acid (6.90 μmol L-1), followed by oxalic acid (2.05 μmol L-1). The seasonal variation of concns. and wet deposition fluxes of org. acids indicated that direct vegetation emissions were the main sources of the org. acids. Highest concns. were obsd. in winter and were ascribed to the low winter rainfall and the contribution of other air pollution sources northeast of the study area. The ratio of formic and acetic acids in the pptn. ([F/A]T) was proposed as an indicator of pollution source. This suggested that the pollution resulted from direct emissions from natural or anthropogenic sources. Comparison with acid pptn. in other urban and rural areas in Guizhou showed that there was a decreasing contribution of LMW org. acids to free acidity and all anions in rainwater from urban to remote rural areas. Consequently, it is necessary to control emissions of org. acids to reduce the frequency of acid rain, esp. in rural and remote areas. [on SciFinder(R)]

[Feline hemoplasmas in Switzerland: identification of a novel species, diagnosis, prevalence, and clinical importance]

Two feline hemotropic mycoplasma spp. (aka hemoplasma) have previously been recognized. We recently discovered a third novel species in a cat with hemolytic anemia, designated 'Candidatus Mycoplasma turicensis', which is closely related to rodent haemoplasmas. This novel species induced anemia after experimental transmission to two SPF cats. Three quantitative real-time PCR assays were newly designed and applied to an epidemiological study surveying the Swiss pet cat population. Blood samples from 713 healthy and ill cats were analyzed. Up to 104 parameters per cat (detailed questionnaire, case history, laboratory parameters and retroviral infections) were evaluated. 'Candidatus Mycoplasma haemominutum' infection was more prevalent (8.5%) than Mycoplasma haemofelis (0.5%) and 'Candidatus Mycoplasma turicensis' (1%). Hemoplasma infections were associated with male gender, outdoor access, and old age, but not with disease or anemia. Infections were more frequently found in the South and West of Switzerland. Several hemoplasma infected cats, some acutely infected, others co-infected with FIV or FeLV, showed hemolytic anemia indicating that additional factors might play a role in the pathogenesis of the disease.

Assessment of the prevalence of Trichinella spp. in red foxes and Eurasian lynxes from Switzerland

Trichinella spp. larvae have not been detected in Swiss pigs, horses, or wild boar for many decades, whereas the parasite was repeatedly isolated from red foxes and Eurasian lynxes. Whenever the isolated larvae could be subjected to genotyping, T. britovi was found as infective agent. The present study was initiated to re-assess the epidemiological situation of Trichinella infection in Swiss carnivorous wildlife, namely in red foxes and lynxes. Tissue samples from 1,298 foxes were collected between 2006 and 2007, and those of 55 lynxes between 1999 and 2007. All samples were tested by a standard artificial digestion method and a multiplex-PCR to determine the species and/or genotypes of recovered larvae. Trichinella larvae were found in 21 foxes (1.6%) and 15 lynxes (27.3%), and T. britovi was identified as infecting species in all cases. The geographic distribution of positive foxes showed two main clusters: one in Central Switzerland and one in the West of the country, where also many lynxes were found to be positive. While the prevalence for Trichinella infection in foxes was not statistically correlated with sex or age class, the prevalence in lynx was significantly higher in males compared to females, and in adults compared to juveniles.

Relative Energy Balance, CKD, and Risk of Cardiovascular and All-Cause Mortality.

BACKGROUND Mortality risk for people with chronic kidney disease is substantially greater than that for the general population, increasing to a 7-fold greater risk for those on dialysis therapy. Higher body mass index, generally due to higher energy intake, appears protective for people on dialysis therapy, but the relationship between energy intake and survival in those with reduced kidney function is unknown. STUDY DESIGN Prospective cohort study with a median follow-up of 14.5 (IQR, 11.2-15.2) years. SETTING & PARTICIPANTS Blue Mountains Area, west of Sydney, Australia. Participants in the general community enrolled in the Blue Mountains Eye Study (n=2,664) who underwent a detailed interview, food frequency questionnaire, and physical examination including body weight, height, blood pressure, and laboratory tests. PREDICTORS Relative energy intake, food components (carbohydrates, total sugars, fat, protein, and water), and estimated glomerular filtration rate (eGFR). Relative energy intake was dichotomized at 100%, and eGFR, at 60mL/min/1.73m(2). OUTCOMES All-cause and cardiovascular mortality. MEASUREMENTS All-cause and cardiovascular mortality using unadjusted and adjusted Cox proportional regression models. RESULTS 949 people died during follow-up, 318 of cardiovascular events. In people with eGFR<60mL/min/1.73m(2) (n=852), there was an increased risk of all-cause mortality (HR, 1.48; P=0.03), but no increased risk of cardiovascular mortality (HR, 1.59; P=0.1) among those with higher relative energy intake compared with those with lower relative energy intake. Increasing intake of carbohydrates (HR per 100g/d, 1.50; P=0.04) and total sugars (HR per 100g/d, 1.62; P=0.03) was associated significantly with increased risk of cardiovascular mortality. LIMITATIONS Under-reporting of energy intake, baseline laboratory and food intake values only, white population. CONCLUSIONS Increasing relative energy intake was associated with increased all-cause mortality in patients with eGFR<60mL/min/1.73m(2). This effect may be mediated by increasing total sugars intake on subsequent cardiovascular events.

A test of genetic association among male nuptial coloration, female mating preference, and male aggression bias within a polymorphic population of cichlid fish

Both inter- and intrasexual selection have been implicated in the origin and maintenance of species-rich taxa with diverse sexual traits. Simultaneous disruptive selection by female mate choice and male-male competition can, in theory, lead to speciation without geographical isolation if both act on the same male trait. Female mate choice can generate discontinuities in gene flow, while male-male competition can generate negative frequency-dependent selection stabilizing the male trait polymorphism. Speciation may be facilitated when mating preference and/or aggression bias are physically linked to the trait they operate on. We tested for genetic associations among female mating preference, male aggression bias and male coloration in the Lake Victoria cichlid Pundamilia. We crossed females from a phenotypically variable population with males from both extreme ends of the phenotype distribution in the same population (blue or red). Male offspring of a red sire were significantly redder than males of a blue sire, indicating that intra-population variation in male coloration is heritable. We tested mating preferences of female offspring and aggression biases of male offspring using binary choice tests. There was no evidence for associations at the family level between female mating preferences and coloration of sires, but dam identity had a significant effect on female mate preference. Sons of the red sire directed significantly more aggression to red than blue males, whereas sons of the blue sire did not show any bias. There was a positive correlation among individuals between male aggression bias and body coloration, possibly due to pleiotropy or physical linkage, which could facilitate the maintenance of color polymorphism.

Morphology and evolution of the ejecta of Hale crater in Argyre basin, Mars: Results from high resolution mapping

We use various data sets, including images from the High Resolution Imaging Science Experiment camera (HiRISE), to examine the ejecta of the generally fresh-looking Hale crater that occurs in the rugged mountain terrain of Nereidum Montes in the northern rim materials of the Argyre impact structure on Mars. Our investigation reveals that the distal parts of the Hale crater ejecta and other basin deposits behave like viscous flows, which we attribute to the secondary flow of ejecta mixed with water–ice-rich basin materials. Consistent with water-enrichment of the basin materials, our mapping further reveals occasionally deformed surfaces, including highly conspicuous features such as mounds and fractured plateaus that we interpret to be a result of periglacial modification, subsequent (including possibly present-day) to the transient localized melting and fluvial erosion caused by Hale-impact-generated heating. In particular, our morphometric analysis of a well-defined valley system west of Hale crater suggests that it may have been formed through hydrologic/glacial activity prior to the Hale impact, with additional modification resulting from the impact and subsequent geologic and hydrologic phenomena including glacial and periglacial activity.

Influence of Geographical Origin and Ethnicity on Mortality in Patients on Antiretroviral Therapy in Canada, Europe, and the United States

Our objective was to assess differences in all-cause mortality, as well as AIDS and non-AIDS death rates, among patients started on antiretroviral therapy (ART) according to their geographical origin and ethnicity/race in Europe, Canada, and the United States. METHODS: This was a collaboration of 19 cohort studies of human immunodeficiency virus-positive subjects who have initiated ART (ART Cohort Collaboration) between 1998 and 2009. Adjusted mortality hazard ratios (AHRs) were estimated using Cox regression. A competing risk framework was used to estimate adjusted subdistribution hazard ratios for AIDS and non-AIDS mortality. RESULTS: Of 46 648 European patients, 16.3% were from sub-Saharan Africa (SSA), 5.1% Caribbean and Latin America, 1.6% North Africa and Middle East, and 1.7% Asia/West; of 1371 patients from Canada, 14.9% were First Nations and 22.4% migrants, and of 7742 patients from North America, 55.5% were African American and 6.6% Hispanic. Migrants from SSA (AHR, 0.79; 95% confidence interval [CI], .68-.92) and Asia/West (AHR, 0.62; 95% CI, .41-.92) had lower mortality than Europeans; these differences appeared mainly attributable to lower non-AIDS mortality. Compared with white Canadians, mortality in Canadian First Nations people (AHR, 1.48; 95% CI, .96-2.29) was higher, both for AIDS and non-AIDS mortality rates. Among US patients, when compared with whites, African Americans had higher AIDS and non-AIDS mortality, and hazard ratios for all-cause mortality increased with time on ART. CONCLUSIONS: The lower mortality observed in migrants suggests "healthy migrant" effects, whereas the higher mortality in First Nations people and African Americans in North America suggests social inequality gaps. KEYWORDS: HIV infection, antiretroviral therapy, ethnic minorities, migrants Comment in Addressing disparities in HIV mortality: antiretroviral therapy is necessary but not sufficient. [Clin Infect Dis. 2013]

Diffusive equilibration of N2, O2 and CO2 mixing ratios in a 1.5-million-years-old ice core

In the framework of the International Partnerships in Ice Core Sciences, one of the most important targets is to retrieve an Antarctic ice core that extends over the last 1.5 million years (i.e. an ice core that enters the climate era when glacial–interglacial cycles followed the obliquity cycles of the earth). In such an ice core the annual layers of the oldest ice would be thinned by a factor of about 100 and the climatic information of a 10 000 yr interval would be contained in less than 1 m of ice. The gas record in such an Antarctic ice core can potentially reveal the role of greenhouse gas forcing on these 40 000 yr cycles. However, besides the extreme thinning of the annual layers, also the long residence time of the trapped air in the ice and the relatively high ice temperatures near the bedrock favour diffusive exchanges. To investigate the changes in the O2 / N2 ratio, as well as the trapped CO2 concentrations, we modelled the diffusive exchange of the trapped gases O2, N2 and CO2 along the vertical axis. However, the boundary conditions of a potential drilling site are not yet well constrained and the uncertainties in the permeation coefficients of the air constituents in the ice are large. In our simulations, we have set the drill site ice thickness at 2700 m and the bedrock ice temperature at 5–10 K below the ice pressure melting point. Using these conditions and including all further uncertainties associated with the drill site and the permeation coefficients, the results suggest that in the oldest ice the precessional variations in the O2 / N2 ratio will be damped by 50–100%, whereas CO2 concentration changes associated with glacial–interglacial variations will likely be conserved (simulated damping 5%). If the precessional O2 / N2 signal will have disappeared completely in this future ice core, orbital tuning of the ice-core age scale will be limited.

Reconstruction of a flash flood with large wood transport and its influence on hazard patterns in an ungauged mountain basin

The reconstruction of past flash floods in ungauged basins leads to a high level of uncertainty, which increases if other processes are involved such as the transport of large wood material. An important flash flood occurred in 1997 in Venero Claro (Central Spain), causing significant economic losses. The wood material clogged bridge sections, raising the water level upstream. The aim of this study was to reconstruct this event, analysing the influence of woody debris transport on the flood hazard pattern. Because the reach in question was affected by backwater effects due to bridge clogging, using only high water mark or palaeostage indicators may overestimate discharges, and so other methods are required to estimate peak flows. Therefore, the peak discharge was estimated (123 ± 18 m3 s–1) using indirect methods, but one-dimensional hydraulic simulation was also used to validate these indirect estimates through an iterative process (127 ± 33 m3 s–1) and reconstruct the bridge obstruction to obtain the blockage ratio during the 1997 event (~48%) and the bridge clogging curves. Rainfall–Runoff modelling with stochastic simulation of different rainfall field configurations also helped to confirm that a peak discharge greater than 150 m3 s–1 is very unlikely to occur and that the estimated discharge range is consistent with the estimated rainfall amount (233 ± 27 mm). It was observed that the backwater effect due to the obstruction (water level ~7 m) made the 1997 flood (~35-year return period) equivalent to the 50-year flood. This allowed the equivalent return period to be defined as the recurrence interval of an event of specified magnitude, which, where large woody debris is present, is equivalent in water depth and extent of flooded area to a more extreme event of greater magnitude. These results highlight the need to include obstruction phenomena in flood hazard analysis.

A Global Trend towards Democratic Convergence? A Lijphartian Analysis of Advanced Democracies.

The article offers a systematic analysis of the comparative trajectory of international democratic change. In particular, it focuses on the resulting convergence or divergence of political systems, borrowing from the literatures on institutional change and policy convergence. To this end, political-institutional data in line with Arend Lijphart’s (1999, 2012) empirical theory of democracy for 24 developed democracies between 1945 and 2010 are analyzed. Heteroscedastic multilevel models allow for directly modeling the development of the variance of types of democracy over time, revealing information about convergence, and adding substantial explanations. The findings indicate that there has been a trend away from extreme types of democracy in single cases, but no unconditional trend of convergence can be observed. However, there are conditional processes of convergence. In particular, economic globalization and the domestic veto structure interactively influence democratic convergence.