Potential health impacts of heavy metals on HIV-infected population in USA.

Noninfectious comorbidities such as cardiovascular diseases have become increasingly prevalent and occur earlier in life in persons with HIV infection. Despite the emerging body of literature linking environmental exposures to chronic disease outcomes in the general population, the impacts of environmental exposures have received little attention in HIV-infected population. The aim of this study is to investigate whether individuals living with HIV have elevated prevalence of heavy metals compared to non-HIV infected individuals in United States. We used the National Health and Nutrition Examination Survey (NHANES) 2003-2010 to compare exposures to heavy metals including cadmium, lead, and total mercury in HIV infected and non-HIV infected subjects. In this cross-sectional study, we found that HIV-infected individuals had higher concentrations of all heavy metals than the non-HIV infected group. In a multivariate linear regression model, HIV status was significantly associated with increased blood cadmium (p=0.03) after adjusting for age, sex, race, education, poverty income ratio, and smoking. However, HIV status was not statistically associated with lead or mercury levels after adjusting for the same covariates. Our findings suggest that HIV-infected patients might be significantly more exposed to cadmium compared to non-HIV infected individuals which could contribute to higher prevalence of chronic diseases among HIV-infected subjects. Further research is warranted to identify sources of exposure and to understand more about specific health outcomes

DODAB and DODAC bilayer-like aggregates in the micromolar surfactant concentration domain

In the millimolar concentration domain (typically 1 mM), dioctadecyldimethylammonium bromide and chloride (DODAX, X representing Br- or Cl- counterions) molecules assemble in water as large unilamellar vesicles. Differential scanning calorimetry (DSC) is a suitable technique to obtain the melting temperature (Tm) characteristic of surfactant bilayers, while fluorescence spectroscopy detects formation of surfactant aggregates, like bilayers. These two techniques were combined to investigate the assemble of DODAX molecules at micromolar concentrations, from 10 to 100 micromolar. At 1 mM surfactant, Tm ~ 45 ºC and 49 oC, respectively for DODAB and DODAC. DSC and fluorescence of Nile Red were used to show the formation of DODAX aggregates, at the surfactant concentration as low as 10 micromolar, whose Tm decreases monotonically with increasing DODAX concentration to attain the value for the ordinary vesicles. The data indicate that these aggregates are organized as bilayer-like structures.Fundação para a Ciência e a Tecnologia (FCT

A membrane-inserted structural model of the yeast mitofusin Fzo1

Mitofusins are large transmembrane GTPases of the dynamin-related protein family, and are required for the tethering and fusion of mitochondrial outer membranes. Their full-length structures remain unknown, which is a limiting factor in the study of outer membrane fusion. We investigated the structure and dynamics of the yeast mitofusin Fzo1 through a hybrid computational and experimental approach, combining molecular modelling and all-atom molecular dynamics simulations in a lipid bilayer with site-directed mutagenesis and in vivo functional assays. The predicted architecture of Fzo1 improves upon the current domain annotation, with a precise description of the helical spans linked by flexible hinges, which are likely of functional significance. In vivo site-directed mutagenesis validates salient aspects of this model, notably, the long-distance contacts and residues participating in hinges. GDP is predicted to interact with Fzo1 through the G1 and G4 motifs of the GTPase domain. The model reveals structural determinants critical for protein function, including regions that may be involved in GTPase domain-dependent rearrangements

Clostridium difficile infection.

Infection of the colon with the Gram-positive bacterium Clostridium difficile is potentially life threatening, especially in elderly people and in patients who have dysbiosis of the gut microbiota following antimicrobial drug exposure. C. difficile is the leading cause of health-care-associated infective diarrhoea. The life cycle of C. difficile is influenced by antimicrobial agents, the host immune system, and the host microbiota and its associated metabolites. The primary mediators of inflammation in C. difficile infection (CDI) are large clostridial toxins, toxin A (TcdA) and toxin B (TcdB), and, in some bacterial strains, the binary toxin CDT. The toxins trigger a complex cascade of host cellular responses to cause diarrhoea, inflammation and tissue necrosis - the major symptoms of CDI. The factors responsible for the epidemic of some C. difficile strains are poorly understood. Recurrent infections are common and can be debilitating. Toxin detection for diagnosis is important for accurate epidemiological study, and for optimal management and prevention strategies. Infections are commonly treated with specific antimicrobial agents, but faecal microbiota transplants have shown promise for recurrent infections. Future biotherapies for C. difficile infections are likely to involve defined combinations of key gut microbiota

A New Chanidae (Ostariophysii: Gonorynchiformes) from the Cretaceous of Brazil with Affinities to Laurasian Gonorynchiforms from Spain

Based on specimens originally referred to as “Dastilbe minor”, a nomem-nudum, we describe a new genus of Chanidae †Nanaichthys longipinnus nov. gen. and sp. which exhibits several diagnostic characters such as the absence of orbitosphenoid and basisphenoid, anteriorly displaced quadrate-mandibular articulation, laterally expanded supraneurals, an acute angle between the preopercular limbs, expansion at the angle between the preopercular limbs, and a curved maxillary articular process. Its occurrence and supposed relationship within the Chanidae reinforce the influence of the Mediterranean Tethys over the Gondwanan main rift system prior to the Aptian/Albian highstands

microRNA-324 mediates bone homeostasis and the regulation of osteoblast and osteoclast differentiation and activity

\ua9 2024 The Author(s). MicroRNAs (miRNAs) modulate the expression of other RNA molecules. One miRNA can target many transcripts, allowing each miRNA to play key roles in many biological pathways. Defects in bone homeostasis result in common age-related diseases including osteoporosis. Serum levels of miR-324-3p positively correlate with several features of bone maintenance. In contrast here, using in vivo micro-computed tomography and histology, global miR-324-null mice demonstrated increased bone mineral density and both trabecular and cortical thickness, with effect magnitudes increasing with age. The bone marrow of miR-324-null mice had reduced lipid content while TRAP staining revealed a decrease in osteoclasts, with histomorphometry demonstrating an increased rate of bone formation. Ex vivo assays showed that the high bone mass phenotype of miR-324-null mice resulted from both increased osteoblast activity and decreased osteoclastogenesis. RNA-seq analysis of osteoblasts, osteoclasts and bone marrow macrophages and target validation assays identified that the osteoclast fusion regulator Pin1 and the master osteogenic regulator Runx2 were targets of miR-324-5p in osteoclast lineage cells and osteoblasts, respectively. Indeed, in vitro Runx2 overexpression recapitulated the increased osteogenesis and decreased adipogenesis phenotype observed in vivo by the loss of miR-324. Overall, these data demonstrate the importance of miR-324 in bone homeostasis by regulating aspects of both bone formation and remodelling. Elucidation of pathways regulated by miR-324 offer promise for the treatment of bone diseases such as osteoporosis

Search for Dark Matter and Supersymmetry with a Compressed Mass Spectrum in the Vector Boson Fusion Topology in Proton-Proton Collisions at root s=8 TeV

Peer reviewe

Assessment of cognitive status in patients with type 2 diabetes through the mini-mental status examination: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Diabetes is considered an independent risk factor for cognitive impairment and some studies observed through neuropsychological tests that cognitive disfunction affects both elderly and younger patients with diabetes. The aims of this study were to evaluate the cognitive status of outpatients with type 2 diabetes and to evaluate factors associated with impaired function.</p> <p>Methods</p> <p>A cross-sectional study was conducted in a group of type 2 diabetic outpatients. They were asked to undergo the Mini-Mental State Examination (MMSE) during routine ambulatory visits between April 2006 and January 2007, with the highest pontuation of the test being 30 points. Patients were classified as having possible dementia according to years of study. Exclusion criteria were blindness, illiterately, stroke, Alzheimer disease and psychiatric disorder. Results are presented as median (interquartile range) or mean ± SD.</p> <p>Results</p> <p>The study group was composed of 346 type 2 diabetic outpatients (216 females), aged 58,6 ± 12,1 years and with duration of diabetes of 12,3 ± 9,1 years. Hypertension was present in 77,2%. The total MMSE score achieved was 26 points (16 - 30) and was correlated with years of study (R²= 0,39, p < 0,001) and 'per capita' income (R²= 0,22, p < 0,0001) and duration of diabetes (R2 = - 0,13, p = 0,01). Patients who needed help to take their medications obtained worst performance in the MMSE (23,16 ± 3,55 <it>vs </it>25,7 ± 2,84, p < 0,01) and were more likely to present possible dementia (p < 0,01). Forty two subjects (12.1%) had diagnosis of possible dementia and this was also associated with years of study (p = 0,045). No association was observed between possible dementia and total MMSE scores with A1C levels.</p> <p>Conclusions</p> <p>We conclude that patients with type 2 diabetes should be regularly evaluated for their cognitive function, because duration of disease could be associated with decline in cognition. The early implementation of mini mental which is a simple method of execution can be done to detect early stages of dementia. This test could be an important tool to access the ability of patient to understand their disease and treatment.</p

Bio+mine project: empowering the community to develop a site-specific system for the rehabilitation of a legacy mine

The rehabilitation of legacy mines continues to be a big challenge because of the difficulties in returning them to safe and stable conditions and ensuring that the mined-out areas become productive to support the economic activity of the host community. Previous efforts are often focused on purely technical and environmental aspects, leading to resistance from the local community due to their exclusion from the rehabilitation process. To address the issues associated with legacy mines and lack of participation of the community, we have developed a project, Biodiversity Positive Mining For The Net Zero Challenge (Bio + Mine), focusing on the abandoned Sto. Niño copper mine (Benguet, Philippines). The mine was closed in 1982 without a plan involving local stakeholders and leaving a significant ongoing negative legacy. Using the social-ecological-technological system framework, we will explore the intersections of the structure and functions of socio-economicdemographic, ecological, and technological data useful in devising a more inclusive mitigation strategy for the reconstruction of the supporting ecosystem. We aim to develop a site-specific system, underpinned by the local community's knowledge and practices, that can be a model for wider implementation in other legacy and active mines worldwide