AQPX-cluster aquaporins and aquaglyceroporins are asymmetrically distributed in trypanosomes

Major Intrinsic Proteins (MIPs) are membrane channels that permeate water and other small solutes. Some trypanosomatid MIPs mediate the uptake of antiparasitic compounds, placing them as potential drug targets. However, a thorough study of the diversity of these channels is still missing. Here we place trypanosomatid channels in the sequence-function space of the large MIP superfamily through a sequence similarity network. This analysis exposes that trypanosomatid aquaporins integrate a distant cluster from the currently defined MIP families, here named aquaporin X (AQPX). Our phylogenetic analyses reveal that trypanosomatid MIPs distribute exclusively between aquaglyceroporin (GLP) and AQPX, being the AQPX family expanded in the Metakinetoplastina common ancestor before the origin of the parasitic order Trypanosomatida. Synteny analysis shows how African trypanosomes specifically lost AQPXs, whereas American trypanosomes specifically lost GLPs. AQPXs diverge from already described MIPs on crucial residues. Together, our results expose the diversity of trypanosomatid MIPs and will aid further functional, structural, and physiological research needed to face the potentiality of the AQPXs as gateways for trypanocidal drugs.Fil: Tesan, Fiorella Carla. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Lorenzo Lopez, Juan Ramiro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Alleva, Karina Edith. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Fox, Ana Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentin

Women's Preferences Regarding Infant or Maternal Antiretroviral Prophylaxis for Prevention of Mother-To-Child Transmission of HIV during Breastfeeding and Their Views on Option B+ in Dar es Salaam, Tanzania.

The WHO 2010 guidelines for prevention of mother-to-child transmission (PMTCT) of HIV recommended prophylactic antiretroviral treatment (ART) either for infants (Option A) or mothers (Option B) during breastfeeding for pregnant women with a CD4 count of >350 cell/µL in low-income countries. In 2012, WHO proposed that all HIV-infected pregnant women should receive triple ART for life (B+) irrespective of CD4 count. Tanzania has recently switched from Option A to B+, with a few centers practicing B. However, more information on the real-life feasibility of these options is needed. This qualitative study explored women's preferences for Option A vs B and their views on Option B+ in Dar es Salaam, Tanzania. We conducted four focus group discussions with a total of 27 pregnant women with unknown HIV status, attending reproductive and child health clinics, and 31 in-depth interviews among HIV-infected pregnant and post-delivery women, 17 of whom were also asked about B+. Most participants were in favor of Option B compared to A. The main reasons for choosing Option B were: HIV-associated stigma, fear of drug side-effects on infants and difficult logistics for postnatal drug adherence. Some of the women asked about B+ favored it as they agreed that they would eventually need ART for their own survival. Some were against B+ anticipating loss of motivation after protecting the child, fearing drug side-effects and not feeling ready to embark on lifelong medication. Some were undecided. Option B was preferred. Since Tanzania has recently adopted Option B+, women with CD4 counts of >350 cell/µL should be counseled about the possibility to "opt-out" from ART after cessation of breastfeeding. Drug safety and benefits, economic concerns and available resources for laboratory monitoring and evaluation should be addressed during B+ implementation to enhance long-term feasibility and effectiveness

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

The Transcriptome of the Intraerythrocytic Developmental Cycle of Plasmodium falciparum

Plasmodium falciparum is the causative agent of the most burdensome form of human malaria, affecting 200–300 million individuals per year worldwide. The recently sequenced genome of P. falciparum revealed over 5,400 genes, of which 60% encode proteins of unknown function. Insights into the biochemical function and regulation of these genes will provide the foundation for future drug and vaccine development efforts toward eradication of this disease. By analyzing the complete asexual intraerythrocytic developmental cycle (IDC) transcriptome of the HB3 strain of P. falciparum, we demonstrate that at least 60% of the genome is transcriptionally active during this stage. Our data demonstrate that this parasite has evolved an extremely specialized mode of transcriptional regulation that produces a continuous cascade of gene expression, beginning with genes corresponding to general cellular processes, such as protein synthesis, and ending with Plasmodium-specific functionalities, such as genes involved in erythrocyte invasion. The data reveal that genes contiguous along the chromosomes are rarely coregulated, while transcription from the plastid genome is highly coregulated and likely polycistronic. Comparative genomic hybridization between HB3 and the reference genome strain (3D7) was used to distinguish between genes not expressed during the IDC and genes not detected because of possible sequence variations. Genomic differences between these strains were found almost exclusively in the highly antigenic subtelomeric regions of chromosomes. The simple cascade of gene regulation that directs the asexual development of P. falciparum is unprecedented in eukaryotic biology. The transcriptome of the IDC resembles a “just-in-time” manufacturing process whereby induction of any given gene occurs once per cycle and only at a time when it is required. These data provide to our knowledge the first comprehensive view of the timing of transcription throughout the intraerythrocytic development of P. falciparum and provide a resource for the identification of new chemotherapeutic and vaccine candidates

Ethical issues relating to the banking of umbilical cord blood in Mexico

<p>Abstract</p> <p>Background</p> <p>Umbilical cord banks are a central component, as umbilical cord tissue providers, in both medical treatment and scientific research with stem cells. But, whereas the creation of umbilical cord banks is seen as successful practice, it is perceived as a risky style of play by others. This article examines and discusses the ethical, medical and legal considerations that arise from the operation of umbilical cord banks in Mexico.</p> <p>Discussion</p> <p>A number of experts have stated that the use of umbilical cord goes beyond the mere utilization of human tissues for the purpose of treatment. This tissue is also used in research studies: genetic studies, studies to evaluate the effectiveness of new antibiotics, studies to identify new proteins, etc. Meanwhile, others claim that the law and other norms for the functioning of cord banks are not consistent and are poorly defined. Some of these critics point out that the confidentiality of donor information is handled differently in different places. The fact that private cord banks offer their services as "biological insurance" in order to obtain informed consent by promising the parents that the tissue that will be stored insures the health of their child in the future raises the issue of whether the consent is freely given or given under coercion. Another consideration that must be made in relation to privately owned cord banks has to do with the ownership of the stored umbilical cord.</p> <p>Summary</p> <p>Conflicts between moral principles and economic interests (non-moral principles) cause dilemmas in the clinical practice of umbilical cord blood storage and use especially in privately owned banks. This article presents a reflection and some of the guidelines that must be followed by umbilical cord banks in order to deal with these conflicts. This reflection is based on the fundamental notions of ethics and public health and seeks to be a contribution towards the improvement of umbilical cord banks' performance.</p

Gender-specific association of body composition with inflammatory and adipose-related markers in healthy elderly Europeans from the NU-AGE study

Objectives: The aim of this work was to examine the cross-sectional relationship between body composition (BC) markers for adipose and lean tissue and bone mass, and a wide range of specific inflammatory and adipose-related markers in healthy elderly Europeans. Methods: A whole-body dual-energy X-ray absorptiometry (DXA) scan was made in 1121 healthy (65–79 years) women and men from five European countries of the “New dietary strategies addressing the specific needs of elderly population for a healthy aging in Europe” project (NCT01754012) cohort to measure markers of adipose and lean tissue and bone mass. Pro-inflammatory (IL-6, IL-6Rα, TNF-α, TNF-R1, TNF-R2, pentraxin 3, CRP, alpha-1-acid glycoprotein, albumin) and anti-inflammatory (IL-10, TGF-β1) molecules as well as adipose-related markers such as leptin, adiponectin, ghrelin, and resistin were measured by magnetic bead-based multiplex-specific immunoassays and biochemical assays. Results: BC characteristics were different in elderly women and men, and more favorable BC markers were associated with a better adipose-related inflammatory profile, with the exception of skeletal muscle mass index. No correlation was found with the body composition markers and circulating levels of some standard pro- and anti-inflammatory markers like IL-6, pentraxin 3, IL-10, TGF-β1, TNF-α, IL-6Rα, glycoprotein 130, TNF-α-R1, and TNF-α-R2. Conclusions: The association between BC and inflammatory and adipose-related biomarkers is crucial in decoding aging and pathophysiological processes, such as sarcopenia. DXA can help in understanding how the measurement of fat and muscle is important, making the way from research to clinical practice. Key Points: • Body composition markers concordantly associated positively or negatively with adipose-related and inflammatory markers, with the exception of skeletal muscle mass index. • No correlation was found with the body composition markers and circulating levels of some standard pro- and anti-inflammatory markers like IL-6, pentraxin 3, IL-10, TGF-β1, TNF-α, IL-6Rα, gp130, TNF-α-R1, and TNF-α-R2. • Skeletal muscle mass index (SMI) shows a good correlation with inflammatory profile in age-related sarcopenia

“In the Suitcase was a Boy”: Representing Transnational Child Trafficking in Contemporary Crime Fiction.

This chapter investigates representations of transnational child trafficking in contemporary crime fiction, focusing specifically on the depiction of child trafficking and its victims. Beyer examines the role of crime fiction in raising reader awareness of human trafficking and of the child victims’ predicament and plight, considering didactic dimensions of the genre and how it tends to erase victims in the aftermath of crime. Through detailed examinations of representations of child trafficking and its social and cultural contexts in selected post-2000 British and Scandinavian crime fiction texts, the chapter argues that crime fiction can be seen to engage explicitly in public and private debates around human trafficking, and, through its popular outreach, has the potential to affect popular perceptions of human trafficking and its victims

Global trends of hand and wrist trauma : a systematic analysis of fracture and digit amputation using the Global Burden of Disease 2017 Study

Background As global rates of mortality decrease, rates of non-fatal injury have increased, particularly in low Socio-demographic Index (SDI) nations. We hypothesised this global pattern of non-fatal injury would be demonstrated in regard to bony hand and wrist trauma over the 27-year study period. Methods The Global Burden of Diseases, Injuries, and Risk Factors Study 2017 was used to estimate prevalence, age-standardised incidence and years lived with disability for hand trauma in 195 countries from 1990 to 2017. Individual injuries included hand and wrist fractures, thumb amputations and non-thumb digit amputations. Results The global incidence of hand trauma has only modestly decreased since 1990. In 2017, the age-standardised incidence of hand and wrist fractures was 179 per 100 000 (95% uncertainty interval (UI) 146 to 217), whereas the less common injuries of thumb and non-thumb digit amputation were 24 (95% UI 17 to 34) and 56 (95% UI 43 to 74) per 100 000, respectively. Rates of injury vary greatly by region, and improvements have not been equally distributed. The highest burden of hand trauma is currently reported in high SDI countries. However, low-middle and middle SDI countries have increasing rates of hand trauma by as much at 25%. Conclusions Certain regions are noted to have high rates of hand trauma over the study period. Low-middle and middle SDI countries, however, have demonstrated increasing rates of fracture and amputation over the last 27 years. This trend is concerning as access to quality and subspecialised surgical hand care is often limiting in these resource-limited regions.Peer reviewe

Global trends of hand and wrist trauma: a systematic analysis of fracture and digit amputation using the Global Burden of Disease 2017 Study

Background: As global rates of mortality decrease, rates of non-fatal injury have increased, particularly in low Socio-demographic Index (SDI) nations. We hypothesised this global pattern of non-fatal injury would be demonstrated in regard to bony hand and wrist trauma over the 27-year study period. Methods: The Global Burden of Diseases, Injuries, and Risk Factors Study 2017 was used to estimate prevalence, age-standardised incidence and years lived with disability for hand trauma in 195 countries from 1990 to 2017. Individual injuries included hand and wrist fractures, thumb amputations and non-thumb digit amputations. Results: The global incidence of hand trauma has only modestly decreased since 1990. In 2017, the age- standardised incidence of hand and wrist fractures was 179 per 100 000 (95% uncertainty interval (UI) 146 to 217), whereas the less common injuries of thumb and non-thumb digit amputation were 24 (95% UI 17 to 34) and 56 (95% UI 43 to 74) per 100 000, respectively. Rates of injury vary greatly by region, and improvements have not been equally distributed. The highest burden of hand trauma is currently reported in high SDI countries. However, low-middle and middle SDI countries have increasing rates of hand trauma by as much at 25%. Conclusions: Certain regions are noted to have high rates of hand trauma over the study period. Low-middle and middle SDI countries, however, have demonstrated increasing rates of fracture and amputation over the last 27 years. This trend is concerning as access to quality and subspecialised surgical hand care is often limiting in these resource-limited regions.publishedVersio

Frontally mediated inhibitory processing and white matter microstructure: age and alcoholism effects

RationaleThe NOGO P3 event-related potential is a sensitive marker of alcoholism, relates to EEG oscillation in the δ and θ frequency ranges, and reflects activation of an inhibitory processing network. Degradation of white matter tracts related to age or alcoholism should negatively affect the oscillatory activity within the network.ObjectiveThis study aims to evaluate the effect of alcoholism and age on δ and θ oscillations and the relationship between these oscillations and measures of white matter microstructural integrity.MethodsData from ten long-term alcoholics to 25 nonalcoholic controls were used to derive P3 from Fz, Cz, and Pz using a visual GO/NOGO protocol. Total power and across trial phase synchrony measures were calculated for δ and θ frequencies. DTI, 1.5 T, data formed the basis of quantitative fiber tracking in the left and right cingulate bundles and the genu and splenium of the corpus callosum. Fractional anisotropy and diffusivity (λL and λT) measures were calculated from each tract.ResultsNOGO P3 amplitude and δ power at Cz were smaller in alcoholics than controls. Lower δ total power was related to higher λT in the left and right cingulate bundles. GO P3 amplitude was lower and GO P3 latency was longer with advancing age, but none of the time-frequency analysis measures displayed significant age or diagnosis effects.ConclusionsThe relation of δ total power at CZ with λT in the cingulate bundles provides correlational evidence for a functional role of fronto-parietal white matter tracts in inhibitory processing