Although as many as half of all proteins are thought to require a metal cofactor, the metalloproteomes of microorganisms remain relatively unexplored. Microorganisms from different environments are ...likely to vary greatly in the metals that they assimilate, not just among the metals with well-characterized roles but also those lacking any known function. Herein we investigated the metal utilization of two microorganisms that were isolated from very similar environments and are of interest because of potential roles in the immobilization of heavy metals, such as uranium and chromium. The metals assimilated and their concentrations in the cytoplasm of Desulfovibrio vulgaris strain Hildenborough (DvH) and Enterobacter cloacae strain Hanford (EcH) varied dramatically, with a larger number of metals present in Enterobacter. For example, a total of 9 and 19 metals were assimilated into their cytoplasmic fractions, respectively, and DvH did not assimilate significant amounts of zinc or copper whereas EcH assimilated both. However, bioinformatic analysis of their genome sequences revealed a comparable number of predicted metalloproteins, 813 in DvH and 953 in EcH. These allowed some rationalization of the types of metal assimilated in some cases (Fe, Cu, Mo, W, V) but not in others (Zn, Nd, Ce, Pr, Dy, Hf and Th). It was also shown that U binds an unknown soluble protein in EcH but this incorporation was the result of extracellular U binding to cytoplasmic components after cell lysis.
Objective: To evaluate the effects of neurodynamic mobilization on the fluid dynamics of the tibial nerve in cadavers.
Background: Evidence showing patients benefit from neural mobilization is ...limited. Mechanisms responsible for changes in patient symptoms are unclear.
Methods: Bilateral lower limbs of six unembalmed cadavers (n = 12) were randomized into matched pairs and dissected to expose the tibial nerve proximal to the ankle. Dye composed of Toulidine blue and plasma was injected into the nerve. The longitudinal dye spread was measured pre- and post-mobilization. The experimental group received the intervention consisting of 30 repetitions of passive ankle range of motion over the course of 1 minute. The matched control limb received no mobilization. Data were analysed using a 2×2 repeated measures ANOVA with subsequent t-tests for pairwise comparisons.
Results: Mean dye spread was 23·8±10·2 mm, a change of 5·4±4·7% in the experimental limb as compared to 20·7±6·0 mm, a change of −1·5±3·9% in the control limb. The ANOVA was significant (P⩽0·02) for interaction between group (experimental/control) and time (pre-mobilization/post-mobilization). t-test results were significant between pre- and post-mobilization of the experimental leg (P = 0·01), and between control and experimental limbs post-mobilization (P⩽0·02).
Conclusion: Passive neural mobilization induces dispersion of intraneural fluid. This may be clinically significant in the presence of intraneural edema found in pathological nerves such as those found in compression syndromes.
Kuru reached epidemic proportions by the mid-twentieth century among the Fore people of New Guinea and disappeared after the abolition of cannibalistic rituals. To determine susceptibility to kuru ...and its role in the spread and elimination of the epidemic, we analyzed the PRNP gene coding sequences in 5 kuru patients; no germline mutations were found. Analysis of the PRNP 129 methionine (M)/valine (V) polymorphism in 80 patients and 95 unaffected controls demonstrated that the kuru epidemic preferentially affected individuals with the M/M genotype. A higher representation of M/M carriers was observed among the affected young Fore males entering the age of risk, whereas a lower frequency of M/M homozygotes was found among the survivors. M/V and V/V genotypes predisposed to a lower risk of disease development and longer incubation times. These findings are relevant to the current outbreak of variant Creutzfeldt-Jakob disease (vCJD) in the United Kingdom, because all vCJD patients tested thus far have been M/M carriers.
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•High resolution mapping of HVR1 and glycosylation sites’ impact on CD81 binding, antibody binding and virus neutralization.•Viral mutants lacking HVR1 and selected glycosylation ...sites are functional.•These mutants expose the viral CD81 binding site and conserved cross-neutralization epitopes.•E2 proteins with these mutations induce cross-binding and non-interfering antibodies in mice.
Induction of cross-reactive antibodies targeting conserved epitopes of the envelope proteins E1E2 is a key requirement for an hepatitis C virus vaccine. Conserved epitopes like the viral CD81-binding site are targeted by rare broadly neutralizing antibodies. However, these viral segments are occluded by variable regions and glycans. We aimed to identify antigens exposing conserved epitopes and to characterize their immunogenicity.
We created hepatitis C virus variants with mutated glycosylation sites and/or hypervariable region 1 (HVR1). Exposure of the CD81 binding site and conserved epitopes was quantified by soluble CD81 and antibody interaction and neutralization assays. E2 or E1-E2 heterodimers with mutations causing epitope exposure were used to immunize mice. Vaccine-induced antibodies were examined and compared with patient-derived antibodies.
Mutant viruses bound soluble CD81 and antibodies targeting the CD81 binding site with enhanced efficacy. Mice immunized with E2 or E1E2 heterodimers incorporating these modifications mounted strong, cross-binding, and non-interfering antibodies. E2-induced antibodies neutralized the autologous virus but they were not cross-neutralizing.
Viruses lacking the HVR1 and selected glycosylation sites expose the CD81 binding site and cross-neutralization antibody epitopes. Recombinant E2 proteins carrying these modifications induce strong cross-binding but not cross-neutralizing antibodies.
Conserved viral epitopes can be made considerably more accessible for binding of potently neutralizing antibodies by deletion of hypervariable region 1 and selected glycosylation sites. Recombinant E2 proteins carrying these mutations are unable to elicit cross-neutralizing antibodies suggesting that exposure of conserved epitopes is not sufficient to focus antibody responses on production of cross-neutralizing antibodies.
Microglia are a primary cellular component of the CNS innate immune system. Their response to conserved pathogen motifs is inherent and leads to the release of cytoactive factors that impact ...surrounding neurons and glia. The microglial response is modified by the local tissue environment and by “global” factors such as gender. Exposure to estrogen and testosterone, in general, down regulate microglia and peripheral macrophage function, promoting an anti-inflammatory phenotype. Other global factors, however, can “override” the gender-based effects demonstrated by estrogen or testosterone. Apolipoprotein E (APOE) genotype and the expression of specific isoforms of apolipoprotein E differentially regulate microglial and peripheral macrophage function. Our studies have shown that the presence of the APOE4 gene, a known risk factor for AD and other neurodegenerative diseases, promotes a pro-inflammatory macrophage phenotype in neonatal microglia. However, in adult mice, the APOE genotype-specific effect depends on gender. Peritoneal macrophages from female adult APOE3 and APOE4 targeted replacement mice do not demonstrate an APOE genotype-specific response, whereas adult male APOE4 targeted replacement mice show enhanced macrophage responsiveness compared to adult male APOE3 mice. At least part of the altered macrophage response in APOE4 male mice may be due to differences in androgen receptor sensitivity to testosterone. These data re-enforce the concept that classical activation in macrophages has multiple levels of regulation, dictated by competing or synergistic factors and genotype.
Between ca. 6000 BC and ca. 500 BC, barley cultivation spread across the continent of Europe from the extreme south to the extreme north. Carbon-dating would suggest that this spread, and indeed the ...spread of crop cultivation generally, varied in its pace, with ‘delays’ at certain points along its route. Such delays in the spread of agriculture have been explained as resulting from the slow assimilation of agricultural practices by existing indigenous human populations or as the time taken for the crops to adapt to novel climatic conditions, such as altered temperature regimes and day-lengths. A mutant form of the photoperiod response gene, Ppd-H1, causes barley to be non-responsive to long days, while the wild-type responsive form allows plants to flower in response to long days. We sequenced this gene in 65 ‘historic’ barley accessions, from the late 19th and early 20th centuries, in order to explore the potential role of environmental adaptation in the spread of agriculture. We chose to use ‘historic’ material, to complement the richer patterns in extant genetic lines, by spreading the data range in both time and space. Our ‘historic’ barley data shows a latitudinal divide in the Ppd-H1 gene similar to that found in extant lines, but with clearer geographical resolution, and extending northwards into the Arctic Circle. We discuss the implications of our results in relation to the dynamics of agricultural spread across Europe.
The mechanism linking the
APOE4 gene with increased susceptibility for Alzheimer’s disease (AD) and poorer outcomes following closed head injury and stroke is unknown. One potential link is ...activation of the innate immune system in the CNS. Our previously published data demonstrated that apolipoprotein E regulates production of nitric oxide, a critical cytoactive factor released by immune active macrophages. To determine if immune regulation is different in the presence of apolipoprotein E4 compared to apolipoprotein E3, we have measured NO production by peritoneal and CNS macrophages (microglia) cultured from transgenic mice that only express the human apoE4 or apoE3 protein isoform. Significantly more NO was produced in
APOE4 mice compared to
APOE3 transgenic mice that only express human apoE3 protein. Similarly, monocyte derived macrophages from humans carrying
APOE4 gene alleles also produce significantly greater NO than those individuals with
APOE3. The mechanism for this isoform-specific difference in NO production is not known and multiple sites in the NO production pathway may be affected. Expression of inducible nitric oxide synthase (iNOS) mRNA and protein are not significantly different between the
APOE3 and
APOE4 mice, suggesting that induction of iNOS is not a primary cause of the increased NO production in
APOE4 animals. One alternative regulatory mechanism that demonstrates isoform specificity is arginine transport, which is greater in microglia from
APOE4 transgenic mice compared to microglia from
APOE3 mice. Increased transport is consistent with an increased production of NO and may reflect a direct or indirect effect of the
APOE genotype on microglial arginine uptake and microglial activation in general. Overall, greater NO production in
APOE4 carriers where characteristically high levels of oxidative/nitrosative stress are found in diseases such as AD provides a mechanism that potentially explains the genetic association between
APOE4 and human diseases.
To inform future psychosocial interventions for HIV-infected women, five focus groups were conducted with 29 HIV-infected women (72% African American). Sessions were audio-recorded, transcribed, and ...coded by two raters. HIV-specific stressors included difficulties with serostatus disclosure, HIV medication adherence, and HIV-related discrimination. Stressors not directly linked to HIV were described as more concerning and included mental health or substance use problems, relationship challenges, caretaking for children or grandchildren, and financial difficulties. Participants suggested that interventions provide social support from other HIV-infected women, consistent case management and social work services, and forums to acquire additional information about HIV and treatment options.
Oxygen Reservoir Bags Simulating Chest Pathology: A Case Series Brown, Sharon E., MBBS, BSC, MRCS, FRCR; Macanovic, Mladen, MBBS, BSC, MRCS, FRCR; Williams, Michael P., MBBCH, MA, FRCR, MBA
The Journal of emergency medicine,
12/2012, Letnik:
43, Številka:
6
Journal Article
Recenzirano
Abstract Background We present a series of plain chest radiographs taken in acute settings, with artifactual projections from oxygen reservoir bags. These artifacts are shown to simulate chest ...pathology in each case. Objectives The identification of artifacts on imaging prevents misdiagnosis and potential mistreatment of patients in acute settings. We highlight patterns of findings caused by the projection of oxygen reservoir bags in radiographs taken in the emergency setting. Case Reports We present plain chest films in 4 patients taken in the acute setting, either in the emergency department or acute admissions unit. In this case series, oxygen reservoir bags simulate pneumothoraces, lung edges, and bullous disease. Conclusion Artifacts on chest radiographs are potential causes of misdiagnosis and subsequent inappropriate treatment. By highlighting the patterns created by the projection of oxygen reservoir bags, emergency physicians, radiologists, and reporting radiographers will be aware of the potential problems.
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