Steady-state mycophenolate mofetil pharmacokinetic parameters enable prediction of systemic lupus erythematosus clinical flares: an observational cohort study

Introduction  

The aim of this study was to determine whether mycophenolate mofetil (MMF) pharmacokinetics (PK) under combined MMF and prednisone remission-maintenance therapy can predict systemic lupus erythematosus (SLE) clinical flares.     

Molecular cloning and characterization of a novel RING zinc-finger protein gene up-regulated under in vitro salt stress in cassava

Cassava (Manihot esculenta Crantz) is one of the world’s most important food crops. It is cultivated mainly in developing countries of tropics, since its root is a major source of calories for low-income people due to its high productivity and resistance to many abiotic and biotic factors. A previous study has identified a partial cDNA sequence coding for a putative RING zinc finger in cassava storage root. The RING zinc finger protein is a specialized type of zinc finger protein found in many organisms. Here, we isolated the full-length cDNA sequence coding for M. esculenta RZF (MeRZF) protein by a combination of 5′ and 3′ RACE assays. BLAST analysis showed that its deduced amino acid sequence has a high level of similarity to plant proteins of RZF family. MeRZF protein contains a signature sequence motif for a RING zinc finger at its C-terminal region. In addition, this protein showed a histidine residue at the fifth coordination site, likely belonging to the RING-H2 subgroup, as confirmed by our phylogenetic analysis. There is also a transmembrane domain in its N-terminal region. Finally, semi-quantitative RT-PCR assays showed that MeRZF expression is increased in detached leaves treated with sodium chloride. Here, we report the first evidence of a RING zinc finger gene of cassava showing potential role in response to salt stress.     

Muscular Weakness in Individuals with HIV Associated with a Disorganization of the Cortico-Spinal Tract: A Multi-Modal MRI Investigation

Motor impairment is highly prevalent in HIV-infected patients. Here, we assess associations between peripheral muscular deficits as evaluated by the 5 sit-to-stand test (5STS) and structural integrity of the motor system at a central level. Eighty-six HIV-infected patients receiving combination antiretroviral therapy and with no major cerebral events, underwent an MRI scan and the 5STS. Out of 86 participants, forty presented a score greater than two standard deviations above mean normative scores calculated for the 5STS and were therefore considered as motor-impaired. MRI-structural cerebral parameters were compared to the unimpaired participants. Fractional Anisotropy (FA), Axial Diffusivity (AD) and Radial Diffusivity (RD), reflecting microstructural integrity, were extracted from Diffusion-Tensor MRI. Global and regional cerebral volumes or thicknesses were extracted from 3D-T1 morphological MRI. Whereas the two groups did not differ for any HIV variables, voxel-wise analysis revealed that motor-impaired participants present low FA values in various cortico-motor tracts and low AD in left cortico-spinal tract. However, they did not present reduced volumes or thicknesses of the precentral cortices compared to unimpaired participants. The absence of alterations in cortical regions holding motor-neurons might argue against neurodegenerative process as an explanation of White Matter (WM) disorganization.     

Construction of a Plasmodium falciparum Rab-interactome identifies CK1 and PKA as Rab-effector kinases in malaria parasites

Background information

The pathology causing stages of the human malaria parasite Plasmodium falciparum reside within red blood cells that are devoid of any regulated transport system. The parasite, therefore, is entirely responsible for mediating vesicular transport within itself and in the infected erythrocyte cytoplasm, and it does so in part via its family of 11 Rab GTPases. Putative functions have been ascribed to Plasmodium Rabs due to their homology with Rabs of yeast, particularly with Saccharomyces that has an equivalent number of rab/ypt genes and where analyses of Ypt function is well characterized.

Results

Rabs are important regulators of vesicular traffic due to their capacity to recruit specific effectors. In order to identify P. falciparum Rab (PfRab) effectors, we first built a Ypt‐interactome by exploiting genetic and physical binding data available at the Saccharomyces genome database (SGD). We then constructed a PfRab‐interactome using putative parasite Rab‐effectors identified by homology to Ypt‐effectors. We demonstrate its potential by wet‐bench testing three predictions; that casein kinase‐1 (PfCK1) is a specific Rab5B interacting protein and that the catalytic subunit of cAMP‐dependent protein kinase A (PfPKA‐C) is a PfRab5A and PfRab7 effector.

Conclusions

The establishment of a shared set of physical Ypt/PfRab‐effector proteins sheds light on a core set Plasmodium Rab‐interactants shared with yeast. The PfRab‐interactome should benefit vesicular trafficking studies in malaria parasites. The recruitment of PfCK1 to PfRab5B+ and PfPKA‐C to PfRab5A+ and PfRab7+ vesicles, respectively, suggests that PfRab‐recruited kinases potentially play a role in early and late endosome function in malaria parasites.     

Dissociating the Neural Correlates of Intra-Item and Inter-Item Working-Memory Binding

Background

Integration of information streams into a unitary representation is an important task of our cognitive system. Within working memory, the medial temporal lobe (MTL) has been conceptually linked to the maintenance of bound representations. In a previous fMRI study, we have shown that the MTL is indeed more active during working-memory maintenance of spatial associations as compared to non-spatial associations or single items. There are two explanations for this result, the mere presence of the spatial component activates the MTL, or the MTL is recruited to bind associations between neurally non-overlapping representations.

Methodology/Principal Findings

The current fMRI study investigates this issue further by directly comparing intrinsic intra-item binding (object/colour), extrinsic intra-item binding (object/location), and inter-item binding (object/object). The three binding conditions resulted in differential activation of brain regions. Specifically, we show that the MTL is important for establishing extrinsic intra-item associations and inter-item associations, in line with the notion that binding of information processed in different brain regions depends on the MTL.

Conclusions/Significance

Our findings indicate that different forms of working-memory binding rely on specific neural structures. In addition, these results extend previous reports indicating that the MTL is implicated in working-memory maintenance, challenging the classic distinction between short-term and long-term memory systems.     

AIDS-Related Stigma and Mental Disorders among People Living with HIV: A Cross-Sectional Study in Cambodia

Background

AIDS-related stigma and mental disorders are the most common conditions in people living with HIV (PLHIV). We therefore conducted this study to examine the association of AIDS-related stigma and discrimination with mental disorders among PLHIV in Cambodia.

Methods

A two-stage cluster sampling method was used to select 1,003 adult PLHIV from six provinces. The People Living with HIV Stigma Index was used to measure stigma and discrimination, and a short version of general health questionnaire (GHQ-12) was used to measure mental disorders. Multivariate logistic regression analysis was conducted.

Results

The reported experiences of discrimination in communities in the past 12 months ranged from 0.8% for reports of being denied health services to 42.3% for being aware of being gossiped about. Internal stigma was also common ranging from 2.8% for avoiding going to a local clinic and/or hospital to 59.6% for deciding not to have (more) children. The proportions of PLHIV who reported fear of stigma and discrimination ranged from 13.9% for fear of being physically assaulted to 34.5% for fear of being gossiped about. The mean score of GHQ-12 was 3.2 (SD = 2.4). After controlling for several potential confounders, higher levels of mental disorders (GHQ-12≥ 4) remained significantly associated with higher levels of experiences of stigma and discrimination in family and communities (AOR = 1.9, 95% CI = 1.4–2.6), higher levels of internal stigma (AOR = 1.7, 95% CI = 1.2–2.3), and higher levels of fear of stigma and discrimination in family and communities (AOR = 1.5, 95% CI = 1.1–2.2).

Conclusions

AIDS-related stigma and discrimination among PLHIV in Cambodia are common and may have potential impacts on their mental health conditions. These findings indicate a need for community-based interventions to reduce stigma and discrimination in the general public and to help PLHIV to cope with this situation.