This paper presents a rural exemplar house built in San Francisco de Raymina (a high Andean village 3700 masl) in southern Peru that integrates passive and sustainable solar heating techniques. A ...climatic analysis of this village was carried out using measurements of meteorological parameters recorded throughout a whole year. The annually averaged temperature, relative humidity and horizontal daily solar energy were 8.3 °C, 73.1% and 5.2 kWh/m2, respectively. The temperatures outside and inside the most rural dwellings are almost the same, so they do not offer any protection specially, during nights when the temperature can reach values below zero. The thermal behavior of the house was modeled with the m2m tool, and an experimental validation was carried out. With the use of m2m, it was possible to create an energy balance during the month of June 2014 (the winter cold and dry season) to determine the energy loss/gain contributions by each wall and to assess how air exchanges (the flow rates of which were deduced using an inversion approach, as they could not be directly measured) between the exterior and interior influence the thermal behavior of the whole house. Infiltration contributed approximately 48.6% of the daily energy losses, while the main solar gains were from the skylights (21.8%) and the adobe walls, which absorbed heat during the day and released heat at night.
Introduction:
Ischemic tolerance (IT) refers to a state where cells are resistant to the damaging effects caused by periods of ischemia. In a clinical scenario, the IT phenomenon would be activated ...by a recent transient ischemic attack (TIA) before an ischemic stroke (IS). The characterization of inflammatory protein expression patterns will contribute to improved understanding of IT.
Methods:
A total of 477 IS patients from nine hospitals, recruited between January 2011 and January 2016, were included in the current study and divided in three groups: 438 (91.9%) patients without previous TIA (group 1), 22 (4.6%) patients who suffered TIA 24 h before IS (group 2), and 17 (3.5%) patients who suffered TIA between 24 h and 7 days prior to IS (group 3). An inflammatory biomarker panel (IL-6, NT-proBNP, hsCRP, hs-Troponin, NSE, and S-100b) on plasma and a cytokine antibody array was performed to achieve the preconditioning signature potentially induced by TIA phenomena. Primary outcome was modified rankin scale (mRs) score at 90 days.
Results:
Recent previous TIA was associated with better clinical outcome at 90 days (median mRS of group 1: 2.0 1.0–4.0; group 2: 2.0 0.0–3.0; group 3: 1.0 0–2.5;
p
= 0.086) and smaller brain lesion (group 1: 3.7 0.7–18.3; group 2: 0.8 0.3–8.9; group 3: 0.6 0.1–5.5 mL;
p
= 0.006). All inflammation biomarkers were down regulated in the groups of recent TIA prior to IS compared to those who did not suffer a TIA events. Moreover, a cytokine antibody array revealed 30 differentially expressed proteins between the three groups. Among them, HRG1-alpha (Fold change 74.4 between group 1 and 2; 74.2 between group 1 and 3) and MAC-1 (Fold change 0.05 between group 1 and 2; 0.06 between group 1 and 3) expression levels would better stratify patients with TIA 7 days before IS. These two proteins showed an earlier inflammation profile that was not detectable by the biomarker panel.
Conclusion:
Inflammatory pathways were activated by transient ischemic attack, however the period of time between this event and a further ischemic stroke could be determined by a protein signature that would contribute to define the role of ischemic tolerance induced by TIA.
Streck tubes are commonly used to collect blood samples to preserve cell-free circulating DNA. They contain imidazolidinyl urea as a formaldehyde-releasing agent to stabilize cells. We investigated ...whether the released formaldehyde leads to crosslinking of intracellular proteins. Therefore, we employed a shotgun proteomics experiment on human peripheral blood mononuclear cells (PBMCs) that were isolated from blood collected in Streck tubes, EDTA tubes, EDTA tubes containing formaldehyde, or EDTA tubes containing allantoin. The identified crosslinks were validated in parallel reaction monitoring LC/MS experiments. In total, we identified and validated 45 formaldehyde crosslinks in PBMCs from Streck tubes, which were also found in PBMCs from formaldehyde-treated blood, but not in EDTA- or allantoin-treated samples. Most were derived from cytoskeletal proteins and histones, indicating the ability of Streck tubes to fix cells. In addition, we confirm a previous observation that formaldehyde crosslinking of proteins induces a +24 Da mass shift more frequently than a +12 Da shift. The crosslinking capacity of Streck tubes needs to be considered when selecting blood-collection tubes for mass-spectrometry-based proteomics or metabolomic experiments.
Small vessel strokes (SVS) and intracerebral haemorrhages (ICH) are acute outcomes of cerebral small vessel disease (SVD). Genetic studies combining both phenotypes have identified three loci ...associated with both traits. However, the genetic cis-regulation at the protein level associated with SVD has not been studied before. We performed a proteome-wide association study (PWAS) using FUSION to integrate a genome-wide association study (GWAS) and brain proteomic data to discover the common mechanisms regulating both SVS and ICH. Dorsolateral prefrontal cortex (dPFC) brain proteomes from the ROS/MAP study (N = 376 subjects and 1443 proteins) and the summary statistics for the SVS GWAS from the MEGASTROKE study (N = 237,511) and multi-trait analysis of GWAS (MTAG)-ICH−SVS from Chung et al. (N = 240,269) were selected. We performed PWAS and then a co-localization analysis with COLOC. The significant and nominal results were validated using a replication dPFC proteome (N = 152). The replicated results (q-value < 0.05) were further investigated for the causality relationship using summary data-based Mendelian randomization (SMR). One protein (ICA1L) was significantly associated with SVS (z-score = −4.42 and p-value = 9.6 × 10−6) and non-lobar ICH (z-score = −4.8 and p-value = 1.58 × 10−6) in the discovery PWAS, with a high co-localization posterior probability of 4. In the validation PWAS, ICA1L remained significantly associated with both traits. The SMR results for ICA1L indicated a causal association of protein expression levels in the brain with SVS (p-value = 3.66 × 10−5) and non-lobar ICH (p-value = 1.81 × 10−5). Our results show that the association of ICA1L with SVS and non-lobar ICH is conditioned by the cis-regulation of its protein levels in the brain.
Medication errors, one of the most common medical errors, cost the United States more than $40 billion annually.1 With well over 19,000 marketable prescription drugs, it stands to reason that ...prescribers, in addition to pharmacies, are making mistakes.2 Although hospitals remain the primary focus of national and international patient safety,3 community pharmacy personnel have a unique opportunity to catch these mistakes and prevent those near-misses in inpatient and outpatient settings, and it only takes a few seconds. A recent systematic review stated that "Between 1.7% and 24% of prescriptions are erroneously delivered, and 1.5% to 4% of these errors result in patient injury. ...one of the most common medical errors is errors caused by paper transcription. Osmani F, Arab-Zozani M, Shahali Z, Lotfi F. Evaluation of the effectiveness of electronic prescription in reducing medical and medical errors (systematic review study).
A large fraction of genome variation between individuals is comprised of submicroscopic copy number variation of genomic DNA segments. We assessed the relative contribution of structural changes and ...gene dosage alterations on phenotypic outcomes with mouse models of Smith-Magenis and Potocki-Lupski syndromes. We phenotyped mice with 1n (Deletion/+), 2n (+/+), 3n (Duplication/+), and balanced 2n compound heterozygous (Deletion/Duplication) copies of the same region. Parallel to the observations made in humans, such variation in gene copy number was sufficient to generate phenotypic consequences: in a number of cases diametrically opposing phenotypes were associated with gain versus loss of gene content. Surprisingly, some neurobehavioral traits were not rescued by restoration of the normal gene copy number. Transcriptome profiling showed that a highly significant propensity of transcriptional changes map to the engineered interval in the five assessed tissues. A statistically significant overrepresentation of the genes mapping to the entire length of the engineered chromosome was also found in the top-ranked differentially expressed genes in the mice containing rearranged chromosomes, regardless of the nature of the rearrangement, an observation robust across different cell lineages of the central nervous system. Our data indicate that a structural change at a given position of the human genome may affect not only locus and adjacent gene expression but also "genome regulation." Furthermore, structural change can cause the same perturbation in particular pathways regardless of gene dosage. Thus, the presence of a genomic structural change, as well as gene dosage imbalance, contributes to the ultimate phenotype.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Mutations in the TRPC6 calcium channel (Transient receptor potential channel 6) gene have been associated with familiar forms of Focal and Segmental Glomerulosclerosis (FSGS) affecting children and ...adults. In addition, acquired glomerular diseases are associated with increased expression levels of TRPC6. However, the exact role of TRPC6 in the pathogenesis of FSGS remains to be elucidated. In this work we describe the generation and phenotypic characterization of three different transgenic mouse lines with podocyte-specific overexpression of the wild type or any of two mutant forms of Trpc6 (P111Q and E896K) previously related to FSGS. Consistent with the human phenotype a non-nephrotic range of albuminuria was detectable in almost all transgenic lines. The histological analysis demonstrated that the transgenic mice developed a kidney disease similar to human FSGS. Differences of 2-3 folds in the presence of glomerular lesions were found between the non transgenic and transgenic mice expressing Trpc6 in its wild type or mutant forms specifically in podocytes. Electron microscopy of glomerulus from transgenic mice showed extensive podocyte foot process effacement. We conclude that overexpression of Trpc6 (wild type or mutated) in podocytes is sufficient to cause a kidney disease consistent with FSGS. Our results contribute to reinforce the central role of podocytes in the etiology of FSGS. These mice constitute an important new model in which to study future therapies and outcomes of this complex disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
is the most widely distributed malaria parasite affecting humans worldwide, causing ~5 million cases yearly. Despite the disease's extensive burden, there are gaps in the knowledge of the ...pathophysiological mechanisms by which
invades reticulocytes. In contrast, this crucial step is better understood for
the less widely distributed but more often fatal malaria parasite. This discrepancy is due to the difficulty of studying
's exclusive invasion of reticulocytes, which represent 1-2% of circulating cells. Its accurate targeting mechanism has not yet been clarified, hindering the establishment of long-term continuous in vitro culture systems. So far, only three reticulocyte invasion pathways have been characterised based on parasite interactions with DARC, TfR1 and CD98 host proteins. However, exposing the parasite's alternative invasion mechanisms is currently being considered, opening up a large field for exploring the entry receptors used by
for invading host cells. New methods must be developed to ensure better understanding of the parasite to control malarial transmission and to eradicate the disease. Here, we review the current state of knowledge on cellular and molecular mechanisms of
s merozoite invasion to contribute to a better understanding of the parasite's biology, pathogenesis and epidemiology.
Introduction: Obesity promotes hypothalamic inflammation and local morphological changes in astrocytes, including the increased expression of the astrocytic biomarker glial fibrillary acidic protein ...(GFAP), which is seen as a sign of neuroinflammation.
Objective: This study aimed to observe the astrocytic expression of GFAP in different brain areas from female rats that received a hypercaloric (HD) or a normocaloric (ND) diet during puberty (F0 generation) as well as in their male pups (F1 generation).
Methods: Female rats received highly palatable HD (Ensure®) or ND from postnatal day (PND) 23-65. On PND90-95, some were euthanized for the immunohistochemical study and some were mated to obtain the F1 generation. Male pups were immunochallenged on PND50 with lipopolysaccharide (LPS, 100 μg/kg) or 0.9% saline solution (1 mL/kg) intraperitoneal injection. Body weight (BW) and retroperitoneal fat weight (RFW) were recorded on PND95 for F0 generation and on PND50 for F1 generation. GFAP expression for both generations was assessed by morphometry in the parietal/frontal cortex, corpus callosum, nucleus accumbens, arcuate/periventricular nuclei of hypothalamus, pons, molecular/granular layers of cerebellum.
Results: Female rats fed with HD presented a significant increase in the GFAP expression in all evaluated areas as well as in the RFW. Male rats born from mothers that received HD showed decreased GFAP expression, BW and RFW when treated with LPS in relation to those from mothers fed with ND.
Discussion: HD induced astrogliosis in several brain areas in females from F0 generation and an adaptive phenotypic change of decreased GFAP expression in males from F1 generation after LPS challenge.
Celotno besedilo
Dostopno za:
DOBA, FSPLJ, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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