Characterizing Patients with Recurrent Urinary Tract Infections in Vesicoureteral Reflux: A Pilot Study of the Urinary Proteome

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Highlights

• •Urinary proteomes of patients with recurrent UTI, renal scarring, and VUR.
• •80 proteins differentially expressed, compared to healthy controls.
• •62 proteins may be indicative of susceptibility for UTI.
• •Altered acute phase response, extracellular matrix and carbohydrate metabolism.

     

Extent and ecological consequences of hunting in Central African rainforests in the twenty-first century

Humans have hunted wildlife in Central Africa for millennia. Today, however, many species are being rapidly extirpated and sanctuaries for wildlife are dwindling. Almost all Central Africa''s forests are now accessible to hunters. Drastic declines of large mammals have been caused in the past 20 years by the commercial trade for meat or ivory. We review a growing body of empirical data which shows that trophic webs are significantly disrupted in the region, with knock-on effects for other ecological functions, including seed dispersal and forest regeneration. Plausible scenarios for land-use change indicate that increasing extraction pressure on Central African forests is likely to usher in new worker populations and to intensify the hunting impacts and trophic cascade disruption already in progress, unless serious efforts are made for hunting regulation. The profound ecological changes initiated by hunting will not mitigate and may even exacerbate the predicted effects of climate change for the region. We hypothesize that, in the near future, the trophic changes brought about by hunting will have a larger and more rapid impact on Central African rainforest structure and function than the direct impacts of climate change on the vegetation. Immediate hunting regulation is vital for the survival of the Central African rainforest ecosystem.     

Structural determinants of multimerization and dissociation in 2-Cys peroxiredoxin chaperone function

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Hemoglobin redox reactions and oxidative stress

Abstract

The role of hemoglobin in transporting oxygen is dependent on the reversible binding of oxygen to Fe(II) hemoglobin with molecular oxygen released at reduced oxygen pressures. The partially oxygenated hemoglobin formed with the release of oxygen from hemoglobin is susceptible to redox reactions where the functional Fe(II) heme is oxidized to Fe(III) and the substrate is reduced. In this article, we review two important redox reactions of hemoglobin and discuss the ramifications of these reactions. The reduction of oxygen to superoxide starts a cascade of oxidative reactions, which are a source for red cell-induced oxidative stress. The reduction of nitrite to nitric oxide produces a labile form of nitric oxide that can be a source for oxidative stress, but can also have important physiological functions.     

Effects of bone marrow mesenchymal stromal cells on gross motor function measure scores of children with cerebral palsy: a preliminary clinical study

Background aimsPre-clinical evidence indicates that autologous bone marrow-derived mesenchymal stromal cell (BM-MSC) transplantation improves motor function in patients with central nervous system disorders.MethodsAfter providing informed consent, 52 patients with cerebral palsy (CP) who met the study criteria received BM-MSC transplantation. Gross motor function was assessed using the Gross Motor Function Measure (GMFM)-88 and GMFM-66 scales at baseline (before transplantation) and at 1 month, 6 months and 18 months post-transplantation. The participants completed the trial without visible side effects. The GMFM-66 percentile (motor growth curves) was used as the control index of motor function to exclude the interference of improvement with age.ResultsThe score domains A, B, C and D and the total GMFM-88 and GMFM-66 scores in participants increased at 1 month, 6 months and 18 months post-transplantation compared with the baseline value (P < 0.01). The scores of domain E also increased at 6 months and 18 months post-transplantation, although they were not significantly increased at 1 month post-transplantation. There were significant increases in the GMFM-66 score and the GMFM-66 percentile corresponding to patient age and Gross Motor Function Classification System level after cell transplantation.ConclusionsAutologous BM-MSC transplantation appears to be a feasible, safe and effective therapy for patients with CP. The treatment improved the development of children with CP with regard to motor function.     

The subtype-specific molecular function of SPDEF in breast cancer and insights into prognostic significance

Breast cancer (BC) is a molecular diverse disease which becomes the most common malignancy among women worldwide. There are four BC subtypes (Luminal A, Luminal B, HER2-enriched and Basal-like) robustly established following gene expression pattern-based characterization, behave significant differences in terms of their incidence, risk factors, prognosis and therapeutic sensitivity. Thus, there is an urgent need to provide mechanism research, treatment strategies and/or prognosis evaluation based on the patient stratification of BC subtypes. The prostate-derived ETS factor SPDEF was first identified as an activator of prostate specific antigen, and then, the involvements in many aspects of BC have been proposed. However, the subtype-specific molecular function of SPDEF in BC and insights into prognostic significance have not been clearly elucidated. This study demonstrated for the first time that SPDEF may play a diversity role in the expression levels, clinicopathologic importance, biological function and prognostic evaluation in BC via bioinformatics and experimental evidence, which mainly depends on different BC subtyping. In summary, our findings would help to better understand the possible mechanisms of various BC subtypes and to find possible candidate genes for prognostic and therapeutic usage.     

Reprogramming Substrate and Catalytic Promiscuity of Tryptophan Prenyltransferases

Prenylation is a process widely prevalent in primary and secondary metabolism, contributing to functionality and chemical diversity in natural systems. Due to their high regio- and chemoselectivities, prenyltransferases are also valuable tools for creation of new compounds by chemoenzymatic synthesis and synthetic biology. Over the last ten years, biochemical and structural investigations shed light on the mechanism and key residues that control the catalytic process, but to date crucial information on how certain prenyltransferases control regioselectivity and chemoselectivity is still lacking. Here, we advance a general understanding of the enzyme family by contributing the first structure of a tryptophan C5-prenyltransferase 5-DMATS. Additinally, the structure of a bacterial tryptophan C6-prenyltransferase 6-DMATS was solved. Analysis and comparison of both substrate-bound complexes led to the identification of key residues for catalysis. Next, site-directed mutagenesis was successfully implemented to not only modify the prenyl donor specificity but also to redirect the prenylation, thereby switching the regioselectivity of 6-DMATS to that of 5-DMATS. The general strategy of structure-guided protein engineering should be applicable to other related prenyltransferases, thus enabling the production of novel prenylated compounds.     

The robustness of a network of ecological networks to habitat loss

There have been considerable advances in our understanding of the tolerance of species interaction networks to sequential extinctions of plants and animals. However, communities of species exist in a mosaic of habitats, and the vulnerability of habitats to anthropogenic change varies. Here, we model the cascading effects of habitat loss, driven by plant extinctions, on the robustness of multiple animal groups. Our network is constructed from empirical observations of 11 animal groups in 12 habitats on farmland. We simulated sequential habitat removal scenarios: randomly; according to prior information; and with a genetic algorithm to identify best‐ and worst‐case permutations of habitat loss. We identified two semi‐natural habitats (waste ground and hedgerows together comprising < 5% of the total area of the farm) as disproportionately important to the integrity of the overall network. Our approach provides a new tool for network ecologists and for directing the management and restoration of multiple‐habitat sites.     

The role of 14-3-3 proteins in cell signalling pathways and virus infection

14-3-3 proteins are highly conserved in species ranging from yeast to mammals and regulate numerous signalling pathways via direct interactions with proteins carrying phosphorylated 14-3-3–binding motifs. Recent studies have shown that 14-3-3 proteins can also play a role in viral infections. This review summarizes the biological functions of 14-3-3 proteins in protein trafficking, cell-cycle control, apoptosis, autophagy and other cell signal transduction pathways, as well as the associated mechanisms. Recent findings regarding the role of 14-3-3 proteins in viral infection and innate immunity are also reviewed.     

Relationship between somatosensory function and the spinothalamocortical pathway in chronic stroke patients

Abstract

Diffusion tensor tractography (DTT) allows for identification and evaluation of the spinothalamic tract and its thalamocortical pathway (STP). We attempted to investigate the relationship between tactile sensation and the STP in chronic stroke patients. We measured fractional anisotropy, mean diffusivity, and tract volume of the STP. The tactile sensation score of the affected side in patients with preserved STP integrity was higher compared with that of patients with an interrupted STP. The remaining volume and integrity of the STP in the affected hemisphere were important factors for tactile sensation of the affected side in chronic patients with intracerebral hemorrhage (ICH).