Early Clinical and Subclinical Visual Evoked Potential and Humphrey's Visual Field Defects in Cryptococcal Meningitis.

Cryptococcal induced visual loss is a devastating complication in survivors of cryptococcal meningitis (CM). Early detection is paramount in prevention and treatment. Subclinical optic nerve dysfunction in CM has not hitherto been investigated by electrophysiological means. We undertook a prospective study on 90 HIV sero-positive patients with culture confirmed CM. Seventy-four patients underwent visual evoked potential (VEP) testing and 47 patients underwent Humphrey's visual field (HVF) testing. Decreased best corrected visual acuity (BCVA) was detected in 46.5% of patients. VEP was abnormal in 51/74 (68.9%) right eyes and 50/74 (67.6%) left eyes. VEP P100 latency was the main abnormality with mean latency values of 118.9 (±16.5) ms and 119.8 (±15.7) ms for the right and left eyes respectively, mildly prolonged when compared to our laboratory references of 104 (±10) ms (p<0.001). Subclinical VEP abnormality was detected in 56.5% of normal eyes and constituted mostly latency abnormality. VEP amplitude was also significantly reduced in this cohort but minimally so in the visually unimpaired. HVF was abnormal in 36/47 (76.6%) right eyes and 32/45 (71.1%) left eyes. The predominant field defect was peripheral constriction with an enlarged blind spot suggesting the greater impact by raised intracranial pressure over that of optic neuritis. Whether this was due to papilloedema or a compartment syndrome is open to further investigation. Subclinical HVF abnormalities were minimal and therefore a poor screening test for early optic nerve dysfunction. However, early optic nerve dysfunction can be detected by testing of VEP P100 latency, which may precede the onset of visual loss in CM

Influence of Ni Catalyst Layer and TiN Diffusion Barrier on Carbon Nanotube Growth Rate

Dense, vertically aligned multiwall carbon nanotubes were synthesized on TiN electrode layers for infrared sensing applications. Microwave plasma-enhanced chemical vapor deposition and Ni catalyst were used for the nanotubes synthesis. The resultant nanotubes were characterized by SEM, AFM, and TEM. Since the length of the nanotubes influences sensor characteristics, we study in details the effects of changing Ni and TiN thickness on the physical properties of the nanotubes. In this paper, we report the observation of a threshold Ni thickness of about 4 nm, when the average CNT growth rate switches from an increasing to a decreasing function of increasing Ni thickness, for a process temperature of 700°C. This behavior is likely related to a transition in the growth mode from a predominantly “base growth” to that of a “tip growth.” For Ni layer greater than 9 nm the growth rate, as well as the CNT diameter, variations become insignificant. We have also observed that a TiN barrier layer appears to favor the growth of thinner CNTs compared to a SiO2 layer

Cervical disc herniation and cervical spondylosis surgically treated by Cloward procedure: a 10-year-minimum follow-up study

BACKGROUND: Cervical degenerative pathology produces pain and disability, and if conservative treatment fails, surgery is indicated. The aim of this study was to determined whether anterior decompression and interbody fusion according to Cloward is effective for treating segmental cervical degenerative pathology and whether the results are durable after a 10-year-minimum follow-up. MATERIALS AND METHODS: Fifty-one patients affected by single-level cervical degenerative pathology between C4 and C7 were surgically treated by the Cloward procedure. Clinical evaluation was rated using the Neck Disability Index (NDI) and the visual analog scale (VAS). At last follow-up, the outcomes were rated according to Odom's criteria. On radiographs, the sagittal segmental alignment (SSA) of the affected level and the sagittal alignment of the cervical spine (SACS) were measured. RESULTS: Average NDI was 34 preoperatively and 11 at last follow-up. Average VAS was 7 preoperatively and 1 at last follow-up. According to Odom's criteria, the outcome was considered excellent in 18 cases, good in 22, and fair in 11. Average SSA was 0.5 +/- 2.1 preoperatively, 1.8 +/- 3.8 at 6 months, and 1.8 +/- 5.7 at last follow-up. Average SACS was 16.5 +/- 4.0 preoperatively, 20.9 +/- 5.8 at 6 months, and 19.9 +/- 6.4 at last follow-up. Degenerative changes at the adjacent levels were observed in 18 patients (35.3%). CONCLUSIONS: The Cloward procedure proved to be a suitable and effective technique for treating segmental cervical degenerative pathology, allowing good clinical and radiographic outcomes even at a long-term follow-up

Tuning the electronic properties of boron nitride nanotube by mechanical uni-axial deformation: a DFT study

The effect of uni-axial strain on the electronic properties of (8,0) zigzag and (5,5) armchair boron nitride nanotubes (BNNT) is addressed by density functional theory calculation. The stress-strain profiles indicate that these two BNNTS of differing types display very similar mechanical properties, but there are variations in HOMO-LUMO gaps at different strains, indicating that the electronic properties of BNNTs not only depend on uni-axial strain, but on BNNT type. The variations in nanotube geometries, partial density of states of B and N atoms, B and N charges are also discussed for (8,0) and (5,5) BNNTs at different strains

The opposing transcriptional functions of Sin3a and c-Myc are required to maintain tissue homeostasis.

How the proto-oncogene c-Myc balances the processes of stem-cell self-renewal, proliferation and differentiation in adult tissues is largely unknown. We explored c-Myc's transcriptional roles at the epidermal differentiation complex, a locus essential for skin maturation. Binding of c-Myc can simultaneously recruit (Klf4, Ovol-1) and displace (Cebpa, Mxi1 and Sin3a) specific sets of differentiation-specific transcriptional regulators to epidermal differentiation complex genes. We found that Sin3a causes deacetylation of c-Myc protein to directly repress c-Myc activity. In the absence of Sin3a, genomic recruitment of c-Myc to the epidermal differentiation complex is enhanced, and re-activation of c-Myc-target genes drives aberrant epidermal proliferation and differentiation. Simultaneous deletion of c-Myc and Sin3a reverts the skin phenotype to normal. Our results identify how the balance of two transcriptional key regulators can maintain tissue homeostasis through a negative feedback loop

Adaptive Evolution and the Birth of CTCF Binding Sites in the Drosophila Genome

Changes in the physical interaction between cis-regulatory DNA sequences and proteins drive the evolution of gene expression. However, it has proven difficult to accurately quantify evolutionary rates of such binding change or to estimate the relative effects of selection and drift in shaping the binding evolution. Here we examine the genome-wide binding of CTCF in four species of Drosophila separated by between ~2.5 and 25 million years. CTCF is a highly conserved protein known to be associated with insulator sequences in the genomes of human and Drosophila. Although the binding preference for CTCF is highly conserved, we find that CTCF binding itself is highly evolutionarily dynamic and has adaptively evolved. Between species, binding divergence increased linearly with evolutionary distance, and CTCF binding profiles are diverging rapidly at the rate of 2.22% per million years (Myr). At least 89 new CTCF binding sites have originated in the Drosophila melanogaster genome since the most recent common ancestor with Drosophila simulans. Comparing these data to genome sequence data from 37 different strains of Drosophila melanogaster, we detected signatures of selection in both newly gained and evolutionarily conserved binding sites. Newly evolved CTCF binding sites show a significantly stronger signature for positive selection than older sites. Comparative gene expression profiling revealed that expression divergence of genes adjacent to CTCF binding site is significantly associated with the gain and loss of CTCF binding. Further, the birth of new genes is associated with the birth of new CTCF binding sites. Our data indicate that binding of Drosophila CTCF protein has evolved under natural selection, and CTCF binding evolution has shaped both the evolution of gene expression and genome evolution during the birth of new genes

Identification of pediatric septic shock subclasses based on genome-wide expression profiling

<p>Abstract</p> <p>Background</p> <p>Septic shock is a heterogeneous syndrome within which probably exist several biological subclasses. Discovery and identification of septic shock subclasses could provide the foundation for the design of more specifically targeted therapies. Herein we tested the hypothesis that pediatric septic shock subclasses can be discovered through genome-wide expression profiling.</p> <p>Methods</p> <p>Genome-wide expression profiling was conducted using whole blood-derived RNA from 98 children with septic shock, followed by a series of bioinformatic approaches targeted at subclass discovery and characterization.</p> <p>Results</p> <p>Three putative subclasses (subclasses A, B, and C) were initially identified based on an empiric, discovery-oriented expression filter and unsupervised hierarchical clustering. Statistical comparison of the three putative subclasses (analysis of variance, Bonferonni correction, <it>P </it>< 0.05) identified 6,934 differentially regulated genes. K-means clustering of these 6,934 genes generated 10 coordinately regulated gene clusters corresponding to multiple signaling and metabolic pathways, all of which were differentially regulated across the three subclasses. Leave one out cross-validation procedures indentified 100 genes having the strongest predictive values for subclass identification. Forty-four of these 100 genes corresponded to signaling pathways relevant to the adaptive immune system and glucocorticoid receptor signaling, the majority of which were repressed in subclass A patients. Subclass A patients were also characterized by repression of genes corresponding to zinc-related biology. Phenotypic analyses revealed that subclass A patients were younger, had a higher illness severity, and a higher mortality rate than patients in subclasses B and C.</p> <p>Conclusion</p> <p>Genome-wide expression profiling can identify pediatric septic shock subclasses having clinically relevant phenotypes.</p

Metabolic profile and psychological variables after bariatric surgery: association with weight outcomes

Purpose This study aims to examine associations between metabolic profile and psychological variables in post-bariatric patients and to investigate if metabolic and psychological variables, namely high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), glycated hemoglobin (HbA 1c), impulsivity, psychological distress, depressive and eating disorder symptoms are independently associated with percentage of excess weight loss (%EWL) after bariatric surgery.Methods One hundred and fifty bariatric patients (BMI = 33.04 +/- 5.8 kg/m(2)) who underwent to bariatric surgery for more than 28.63 +/- 4.9 months were assessed through a clinical interview, a set of self-report measures and venous blood samples. Pearson's correlations were used to assess correlations between %EWL, metabolic and psychological variables. Multiple linear regression was conducted to investigate which metabolic and psychological variables were independently associated with %EWL, while controlling for type of surgery.Results Higher TG blood levels were associated with higher disordered eating, psychological distress and depression scores. HDL-C was associated with higher depression scores. Both metabolic and psychological variables were associated with %EWL. Regression analyses showed that, controlling for type of surgery, higher % EWL is significantly and independently associated with less disordered eating symptoms and lower TG and HbA_1c blood concentrations (R-2 aj = 0.383, F (4, 82) = 14.34, p < 0.000).Conclusion An association between metabolic and psychological variables, particularly concerning TG blood levels, disordered eating and psychological distress/depression was found. Only higher levels of disordered eating, TG and HbA_1c showed and independent correlation with less weight loss. Targeting maladaptive eating behaviors may be a reasonable strategy to avoid weight regain and optimize health status post-operatively.This research was partially supported by Fundacao para a Ciencia e a Tecnologia/Foundation for Science and Technology through European Union COMPETE program Grant to Eva Conceicao (IF/01219/2014) and (PTDC/MHC-PCL/4974/2012), doctoral scholarship (SFRH/BD/104159/2014) to Ana Pinto-Bastos and doctoral scholarship (SFRH/BD/104182/2014) to Sofia Ramalho

Integrated Genome-Scale Prediction of Detrimental Mutations in Transcription Networks

A central challenge in genetics is to understand when and why mutations alter the phenotype of an organism. The consequences of gene inhibition have been systematically studied and can be predicted reasonably well across a genome. However, many sequence variants important for disease and evolution may alter gene regulation rather than gene function. The consequences of altering a regulatory interaction (or “edge”) rather than a gene (or “node”) in a network have not been as extensively studied. Here we use an integrative analysis and evolutionary conservation to identify features that predict when the loss of a regulatory interaction is detrimental in the extensively mapped transcription network of budding yeast. Properties such as the strength of an interaction, location and context in a promoter, regulator and target gene importance, and the potential for compensation (redundancy) associate to some extent with interaction importance. Combined, however, these features predict quite well whether the loss of a regulatory interaction is detrimental across many promoters and for many different transcription factors. Thus, despite the potential for regulatory diversity, common principles can be used to understand and predict when changes in regulation are most harmful to an organism

Combining ChIP-chip and Expression Profiling to Model the MoCRZ1 Mediated Circuit for Ca2+/Calcineurin Signaling in the Rice Blast Fungus

Significant progress has been made in defining the central signaling networks in many organisms, but collectively we know little about the downstream targets of these networks and the genes they regulate. To reconstruct the regulatory circuit of calcineurin signal transduction via MoCRZ1, a Magnaporthe oryzae C2H2 transcription factor activated by calcineurin dephosphorylation, we used a combined approach of chromatin immunoprecipitation - chip (ChIP-chip), coupled with microarray expression studies. One hundred forty genes were identified as being both a direct target of MoCRZ1 and having expression concurrently differentially regulated in a calcium/calcineurin/MoCRZ1 dependent manner. Highly represented were genes involved in calcium signaling, small molecule transport, ion homeostasis, cell wall synthesis/maintenance, and fungal virulence. Of particular note, genes involved in vesicle mediated secretion necessary for establishing host associations, were also found. MoCRZ1 itself was a target, suggesting a previously unreported autoregulation control point. The data also implicated a previously unreported feedback regulation mechanism of calcineurin activity. We propose that calcium/calcineurin regulated signal transduction circuits controlling development and pathogenicity manifest through multiple layers of regulation. We present results from the ChIP-chip and expression analysis along with a refined model of calcium/calcineurin signaling in this important plant pathogen