Host erythrocyte polymorphisms and exposure to Plasmodium falciparum in Papua New Guinea

Contains fulltext : 69991.pdf (publisher's version ) (Open Access)BACKGROUND: The protection afforded by human erythrocyte polymorphisms against the malaria parasite, Plasmodium falciparum, has been proposed to be due to reduced ability of the parasite to invade or develop in erythrocytes. If this were the case, variable levels of parasitaemia and rates of seroconversion to infected-erythrocyte variant surface antigens (VSA) should be seen in different host genotypes. METHODS: To test this hypothesis, P. falciparum parasitaemia and anti-VSA antibody levels were measured in a cohort of 555 asymptomatic children from an area of intense malaria transmission in Papua New Guinea. Linear mixed models were used to investigate the effect of alpha+-thalassaemia, complement receptor-1 and south-east Asian ovalocytosis, as well as glucose-6-phosphate dehydrogenase deficiency and ABO blood group on parasitaemia and age-specific seroconversion to VSA. RESULTS: No host polymorphism showed a significant association with both parasite prevalence/density and age-specific seroconversion to VSA. CONCLUSION: Host erythrocyte polymorphisms commonly found in Papua New Guinea do not effect exposure to blood stage P. falciparum infection. This contrasts with data for sickle cell trait and highlights that the above-mentioned polymorphisms may confer protection against malaria via distinct mechanisms

Attenuation by all-trans-retinoic acid of sodium chloride-enhanced gastric carcinogenesis induced by N-methyl-N′-nitro-N-nitrosoguanidine in Wistar rats

The effect of prolonged administration of all-trans-retinoic acid (RA) on sodium chloride-enhanced gastric carcinogenesis induced by N-methyl-N′-nitro-N-nitrosoguanidine, and the labelling and apoptotic indices and immunoreactivity of transforming growth factor (TGF) α in the gastric cancers was investigated in Wistar rats. After 25 weeks of carcinogen treatment, the rats were given chow pellets containing 10% sodium chloride and subcutaneous injections of RA at doses of 0.75 or 1.5 mg kg−1 body weight every other day. In week 52, oral supplementation with sodium chloride significantly increased the incidence of gastric cancers compared with the untreated controls. Long-term administration of RA at both doses significantly reduced the incidence of gastric cancers, which was enhanced by oral administration of sodium chloride. RA at both doses significantly decreased the labelling index and TGF-α immunoreactivity of gastric cancers, which were enhanced by administration of sodium chloride, and significantly increased the apoptotic index of cancers, which was lowered by administration of sodium chloride. These findings suggest that RA attenuates gastric carcinogenesis, enhanced by sodium chloride, by increasing apoptosis, decreasing DNA synthesis, and reducing TGF-α expression in gastric cancers. © 1999 Cancer Research Campaig

Huntingtin facilitates polycomb repressive complex 2

Huntington's disease (HD) is caused by expansion of the polymorphic polyglutamine segment in the huntingtin protein. Full-length huntingtin is thought to be a predominant HEAT repeat α-solenoid, implying a role as a facilitator of macromolecular complexes. Here we have investigated huntingtin's domain structure and potential intersection with epigenetic silencer polycomb repressive complex 2 (PRC2), suggested by shared embryonic deficiency phenotypes. Analysis of a set of full-length recombinant huntingtins, with different polyglutamine regions, demonstrated dramatic conformational flexibility, with an accessible hinge separating two large α-helical domains. Moreover, embryos lacking huntingtin exhibited impaired PRC2 regulation of Hox gene expression, trophoblast giant cell differentiation, paternal X chromosome inactivation and histone H3K27 tri-methylation, while full-length endogenous nuclear huntingtin in wild-type embryoid bodies (EBs) was associated with PRC2 subunits and was detected with trimethylated histone H3K27 at Hoxb9. Supporting a direct stimulatory role, full-length recombinant huntingtin significantly increased the histone H3K27 tri-methylase activity of reconstituted PRC2 in vitro, and structure–function analysis demonstrated that the polyglutamine region augmented full-length huntingtin PRC2 stimulation, both in HdhQ111 EBs and in vitro, with reconstituted PRC2. Knowledge of full-length huntingtin's α-helical organization and role as a facilitator of the multi-subunit PRC2 complex provides a novel starting point for studying PRC2 regulation, implicates this chromatin repressive complex in a neurodegenerative disorder and sets the stage for further study of huntingtin's molecular function and the impact of its modulatory polyglutamine region

Online Social Networking and Addiction—A Review of the Psychological Literature

Social Networking Sites (SNSs) are virtual communities where users can create individual public profiles, interact with real-life friends, and meet other people based on shared interests. They are seen as a ‘global consumer phenomenon’ with an exponential rise in usage within the last few years. Anecdotal case study evidence suggests that ‘addiction’ to social networks on the Internet may be a potential mental health problem for some users. However, the contemporary scientific literature addressing the addictive qualities of social networks on the Internet is scarce. Therefore, this literature review is intended to provide empirical and conceptual insight into the emerging phenomenon of addiction to SNSs by: (1) outlining SNS usage patterns, (2) examining motivations for SNS usage, (3) examining personalities of SNS users, (4) examining negative consequences of SNS usage, (5) exploring potential SNS addiction, and (6) exploring SNS addiction specificity and comorbidity. The findings indicate that SNSs are predominantly used for social purposes, mostly related to the maintenance of established offline networks. Moreover, extraverts appear to use social networking sites for social enhancement, whereas introverts use it for social compensation, each of which appears to be related to greater usage, as does low conscientiousness and high narcissism. Negative correlates of SNS usage include the decrease in real life social community participation and academic achievement, as well as relationship problems, each of which may be indicative of potential addiction

"From the moment i wake up i will use it?every day, very hour": A qualitative study on the patterns of adolescents' mobile touch screen device use from adolescent and parent perspectives

Background: The use of mobile touch screen devices, e.g. smartphones and tablet computers, has become increasingly prevalent among adolescents. However, little is known about how adolescents use these devices and potential influences on their use. Hence, this qualitative study explored adolescents' perceptions on their patterns of use and factors influencing use, and perceptions and concerns from parents. Methods: Semi-structured interviews were conducted with adolescents (n = 36; 11 to 18 years) and their parents/caregivers (n = 28) in Singapore recruited to represent males and females across a range of ages from different socioeconomic groups. Prompts covered weekday and weekend use patterns, types of activities, perspectives on amount of use, parental control measures and concerns. Interviews were recorded and transcribed. Transcripts were coded and thematic analysis was carried out. Results: Smartphone was the most common mobile device owned and used by many of the adolescents, while only some used a tablet. Many adolescents and their parents felt that adolescents' MTSD use was high, frequent and ubiquitous, with frequent checking of device and multitasking during use. Reported influences of use included functional, personal and external influences. Some of the influences were irresistibility of mobile devices, lack of self-control, entertainment or relaxation value, and high use by peers, family and for schoolwork that contributed to high use, or school/parental control measures and lack of internet availability that limited use. Most adolescents were generally unconcerned about their use and perceived their usage as appropriate, while most parents expressed several concerns about their adolescents' use and perceived their usage as excessive. Conclusions: This study has provided rich insights into the patterns and influences of contemporary mobile device use by adolescents. Mobile device use has become an integral part of adolescents' daily routines, and was affected by several functional, personal and external influences which either facilitated or limited their use. There also seemed to be a strong inclination for adolescents to frequently check and use their mobile devices. There is an urgent need to understand the implications of these common adolescent behaviours to inform advice for wise mobile device use by adolescents

Axonal Varicosity Density as an Index of Local Neuronal Interactions

Diffuse transmission is an important non-synaptic communication mode in the cerebral neocortex, in which neurotransmitters released from en passant varicosities interact with surrounding cells. In a previous study we have shown that the cholinergic axonal segments which were in the microproximity with dopaminergic fibers possessed a greater density of en passant varicosities compared to more distant segments, suggesting an activity-dependent level of en passant varicosities in the axonal zone of interaction. To further evaluate this plastic relationship, the density of cholinergic varicosities was quantified on fiber segments within the microproximity of activated or non-activated pyramidal cells of the prefrontal cortex (mPFC). Repetitive 14 days patterned visual stimulation paired with an electrical stimulation of the cholinergic fibers projecting to the mPFC from the HDB was performed to induce persistent axonal plastic changes. The c-Fos early gene immunoreactivity was used as a neuronal activity marker of layer V pyramidal cells, labelled with anti-glutamate transporter EAAC1. Cholinergic fibers were labeled with anti-ChAT (choline acetyltransferase) immunostaining. The density of ChAT+ varicosities on and the length of fiber segments within the 3 µm microproximity of c-Fos positive/negative pyramidal cells were evaluated on confocal images. More than 50% of the pyramidal cells in the mPFC were c-Fos immunoreactive. Density of ChAT+ varicosities was significantly increased within 3 µm vicinity of activated pyramidal cells (0.50±0.01 per µm of ChAT+ fiber length) compared to non-activated cells in this group (0.34±0.001; p≤0.05) or control rats (0.32±0.02; p≤0.05). Different types of stimulation (visual, HDB or visual/HDB) induced similar increase of the density of ChAT+ varicosities within microproximity of activated pyramidal cells. This study demonstrated at the subcellular level an activity-dependent enrichment of ChAT+ varicosities in the axonal zone of interaction with other neuronal elements

Effect of an Education Programme for South Asians with Asthma and Their Clinicians: A Cluster Randomised Controlled Trial (OEDIPUS).

BACKGROUND: People with asthma from ethnic minority groups experience significant morbidity. Culturally-specific interventions to reduce asthma morbidity are rare. We tested the hypothesis that a culturally-specific education programme, adapted from promising theory-based interventions developed in the USA, would reduce unscheduled care for South Asians with asthma in the UK. METHODS: A cluster randomised controlled trial, set in two east London boroughs. 105 of 107 eligible general practices were randomised to usual care or the education programme. Participants were south Asians with asthma aged 3 years and older with recent unscheduled care. The programme had two components: the Physician Asthma Care Education (PACE) programme and the Chronic Disease Self Management Programme (CDSMP), targeted at clinicians and patients with asthma respectively. Both were culturally adapted for south Asians with asthma. Specialist nurses, and primary care teams from intervention practices were trained using the PACE programme. South Asian participants attended an outpatient appointment; those registered with intervention practices received self-management training from PACE-trained specialist nurses, a follow-up appointment with PACE-trained primary care practices, and an invitation to attend the CDSMP. Patients from control practices received usual care. Primary outcome was unscheduled care. FINDINGS: 375 south Asians with asthma from 84 general practices took part, 183 registered with intervention practices and 192 with control practices. Primary outcome data were available for 358/375 (95.5%) of participants. The intervention had no effect on time to first unscheduled attendance for asthma (Adjusted Hazard Ratio AHR = 1.19 95% CI 0.92 to 1.53). Time to first review in primary care was reduced (AHR = 2.22, (1.67 to 2.95). Asthma-related quality of life and self-efficacy were improved at 3 months (adjusted mean difference -2.56, (-3.89 to -1.24); 0.44, (0.05 to 0.82) respectively. CONCLUSIONS: A multi-component education programme adapted for south Asians with asthma did not reduce unscheduled care but did improve follow-up in primary care, self-efficacy and quality of life. More effective interventions are needed for south Asians with asthma

Genomic Binding Profiling of the Fission Yeast Stress-Activated MAPK Sty1 and the bZIP Transcriptional Activator Atf1 in Response to H2O2

10.1371/journal.pone.0011620PLoS ONE57

Sensitization and Interoception as Key Neurological Concepts in Osteopathy and Other Manual Medicines

Historically, approaches used in manual medicine to explain patient reported symptoms have been focused on the so-called exteroceptive paradigm. Arguably, this mindset lacks an appropriate "reading system" able to interpret musculoskeletal disorders from a different perspective, where the properties of the nervous system are embraced into a more holistic and functional-related context. Interestingly, if the underpinning mechanisms of a given treatment scenario/effect are taking into account, the majority of research outcomes focuses on a proprioceptive/exteroceptive explanation, leaving ting aside the additional or even central role of interoception. Currently, to date, the application of theoretical knowledge acquired on the relatively recent neuroscientific concepts and evidence concerning of interoception, sensitization, touch, autonomic functions, inflammation, and pain into a clinical/research manual medicine scenario is lacking, even if theoretically, the impact on the possible etiological mechanisms and treatment effects seems to be important. Here, we propose the conceptual foundations for a new way of interpreting and reading patients' clinical reported outcomes scenario based on interoception and sensitization. We argue that this will provide a foundation to create the ground for future research focusing on the hypotheses that manual therapies, specifically osteopathy, can intercede with sensitization states, at all levels, using interoceptive pathways

Changes in protein expression in mussels Mytilus galloprovincialis dietarily exposed to PVP/PEI coated silver nanoparticles at different seasons

Potential toxic effects of Ag NPs ingested through the food web and depending on the season have not been addressed in marine bivalves. This work aimed to assess differences in protein expression in the digestive gland of female mussels after dietary exposure to Ag NPs in autumn and spring. Mussels were fed daily with microalgae previously exposed for 24 hours to 10 µg/L of PVP/PEI coated 5 nm Ag NPs. After 21 days, mussels significantly accumulated Ag in both seasons and Ag NPs were found within digestive gland cells and gills. Two-dimensional electrophoresis distinguished 104 differentially expressed protein spots in autumn and 142 in spring. Among them, chitinase like protein-3, partial and glyceraldehyde-3-phosphate dehydrogenase, that are involved in amino sugar and nucleotide sugar metabolism, carbon metabolism, glycolysis/gluconeogenesis and the biosynthesis of amino acids KEGG pathways, were overexpressed in autumn but underexpressed in spring. In autumn, pyruvate metabolism, citrate cycle, cysteine and methionine metabolism and glyoxylate and dicarboxylate metabolism were altered, while in spring, proteins related to the formation of phagosomes and hydrogen peroxide metabolism were differentially expressed. Overall, protein expression signatures depended on season and Ag NPs exposure, suggesting that season significantly influences responses of mussels to NP exposure.This work has been funded by the Spanish Ministry of Economy and Competitiveness (NanoSilverOmics project MAT2012-39372), Basque Government (SAIOTEK project S-PE13UN142 and Consolidated Research Group GIC IT810-13) and the University of the Basque Country UPV/EHU (UFI 11/37 and PhD fellowship to N.D.). This study had also the support of Fundação para a Ciência e Tecnologia (FCT) from Portugal through the Strategic Project UID/MAH00350/2013 granted to CIMA. The contribution of K. Mehennaoui was possible within the project NanoGAM (AFR-PhD-9229040) and M. Mikolaczyk was supported by a PhD fellowship from the French Ministry of Higher Education and Research.info:eu-repo/semantics/acceptedVersio