Zigzag-shaped nickel nanowires via organometallic template-free route

In this manuscript, the formation of nickel nanowires (average size: several tens to hundreds of μm long and 1.0-1.5 μm wide) at low temperature is found to be driven by dewetting of liquid organometallic precursors during spin coating process and by self-assembly of Ni clusters. Elaboration of metallic thin films by low temperature deposition technique makes the preparation process compatible with most of the substrates. The use of iron and cobalt precursor shows that the process could be extended to other metallic systems. In this work, AFM and SEM are used to follow the assembly of Ni clusters into straight or zigzag lines. The formation of zigzag structure is specific to the Ni precursor at appropriate preparation parameters. This template free process allows a control of anisotropic structures with homogeneous sizes and angles on standard Si/SiO2 surface

Quiet in class: classification, noise and the dendritic cell algorithm

Theoretical analyses of the Dendritic Cell Algorithm (DCA) have yielded several criticisms about its underlying structure and operation. As a result, several alterations and fixes have been suggested in the literature to correct for these findings. A contribution of this work is to investigate the effects of replacing the classification stage of the DCA (which is known to be flawed) with a traditional machine learning technique. This work goes on to question the merits of those unique properties of the DCA that are yet to be thoroughly analysed. If none of these properties can be found to have a benefit over traditional approaches, then “fixing” the DCA is arguably less efficient than simply creating a new algorithm. This work examines the dynamic filtering property of the DCA and questions the utility of this unique feature for the anomaly detection problem. It is found that this feature, while advantageous for noisy, time-ordered classification, is not as useful as a traditional static filter for processing a synthetic dataset. It is concluded that there are still unique features of the DCA left to investigate. Areas that may be of benefit to the Artificial Immune Systems community are suggested

Suppression of Cdc27B expression induces plant defence responses

Non-host resistance is the most general form of disease resistance in plants because it is effective against most phytopathogens. The importance of hypersensitive responses (HRs) in non-host resistance of Nicotiana species to the oomycete Phytophthora is clear. INF1 elicitin, an elicitor obtained from the late-blight pathogen Phytophthora infestans, is sufficient to induce a typical HR in Nicotiana species. The molecular mechanisms that underlie the non-host resistance component of plant defence responses have been investigated using differential-display polymerase chain reaction (PCR) in a model HR system between INF1 elicitin and tobacco BY-2 cells. Differential-display PCR has revealed that Cdc27B is down-regulated in tobacco BY- 2 cells after treatment with INF1 elicitin. Cdc27B is one of 13 essential components of the anaphase- promoting complex or cyclosome ( APC/ C)-type E3 ubiquitin ligase complex in yeast. This APC/C-type E3 ubiquitin ligase complex regulates G2-to-M phase transition of the cell cycle by proteolytic degradation. In this study, we investigated the roles of this gene, NbCdc27B, in plant defence responses using virus-induced gene silencing. Suppression of NbCdc27B in Nicotiana benthamiana plants induced defence responses and a gain of resistance to Colletotrichum lagenarium fungus. Elicitin-induced hypersensitive cell death (HCD) was inhibited mildly in plants silenced with tobacco rattle virus:: Cdc27B. Cdc27B could manage the signalling pathways of plant defence responses as a negative regulator without HCD.</p

Mutation of the Diamond-Blackfan Anemia Gene Rps7 in Mouse Results in Morphological and Neuroanatomical Phenotypes

The ribosome is an evolutionarily conserved organelle essential for cellular function. Ribosome construction requires assembly of approximately 80 different ribosomal proteins (RPs) and four different species of rRNA. As RPs co-assemble into one multi-subunit complex, mutation of the genes that encode RPs might be expected to give rise to phenocopies, in which the same phenotype is associated with loss-of-function of each individual gene. However, a more complex picture is emerging in which, in addition to a group of shared phenotypes, diverse RP gene-specific phenotypes are observed. Here we report the first two mouse mutations (Rps7(Mtu) and Rps7(Zma)) of ribosomal protein S7 (Rps7), a gene that has been implicated in Diamond-Blackfan anemia. Rps7 disruption results in decreased body size, abnormal skeletal morphology, mid-ventral white spotting, and eye malformations. These phenotypes are reported in other murine RP mutants and, as demonstrated for some other RP mutations, are ameliorated by Trp53 deficiency. Interestingly, Rps7 mutants have additional overt malformations of the developing central nervous system and deficits in working memory, phenotypes that are not reported in murine or human RP gene mutants. Conversely, Rps7 mouse mutants show no anemia or hyperpigmentation, phenotypes associated with mutation of human RPS7 and other murine RPs, respectively. We provide two novel RP mouse models and expand the repertoire of potential phenotypes that should be examined in RP mutants to further explore the concept of RP gene-specific phenotypes.This research was supported in part by the Intramural Research Program of NHGRI, NIH, and the Wellcome Trust and by NHMRC Australia grant 366746. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Mutations in TUBG1, DYNC1H1, KIF5C and KIF2A cause malformations of cortical development and microcephaly

The genetic causes of malformations of cortical development (MCD) remain largely unknown. Here we report the discovery of multiple pathogenic missense mutations in TUBG1, DYNC1H1 and KIF2A, as well as a single germline mosaic mutation in KIF5C, in subjects with MCD. We found a frequent recurrence of mutations in DYNC1H1, implying that this gene is a major locus for unexplained MCD. We further show that the mutations in KIF5C, KIF2A and DYNC1H1 affect ATP hydrolysis, productive protein folding and microtubule binding, respectively. In addition, we show that suppression of mouse Tubg1 expression in vivo interferes with proper neuronal migration, whereas expression of altered gamma-tubulin proteins in Saccharomyces cerevisiae disrupts normal microtubule behavior. Our data reinforce the importance of centrosomal and microtubule-related proteins in cortical development and strongly suggest that microtubule-dependent mitotic and postmitotic processes are major contributors to the pathogenesis of MCD

Marginalisation, discrimination and the health of Latino immigrant day labourers in a central North Carolina community

The morbidity and mortality of Latino immigrants in the United States (US) stem from a complex mix of policy, culture, discrimination, and economics. Immigrants working as day labourers may be particularly vulnerable to the negative influences of these social factors due to limited access to social, financial, and legal resources. We aimed to understand how the health of male Latino day labourers in North Carolina, US is influenced by their experiences interacting with their community and perceptions of their social environment. To respond to our research questions, we conducted three focus groups (n=9, n =10, n=10) and a photovoice project (n=5) with Latino male immigrants between October 2013 and March 2014. We conducted a thematic analysis of transcripts from the discussions in the focus groups and the group of Photovoice participants. We found that men's health and well-being were primarily shaped by their experiences and feelings of discrimination and marginalization. We identified three main links between discrimination/marginalization and poor health: (1) dangerous work resulted in workplace injuries or illnesses, (2) unsteady employment caused stress, anxiety and insufficient funds for health care, and (3) exclusionary policies and treatment resulted in limited healthcare accessibility. Health promotion with Latino immigrant men in new settlement areas could benefit from community-building activities, addressing discrimination, augmenting the reach of formal health care, and building upon the informal mechanisms that immigrants rely on to meet their health needs. Reforms to immigration and labour policies are also essential to addressing these structural barriers to health for these men

Transcriptional profiling of fibroblasts from patients with mutations in MCT8 and comparative analysis with the human brain transcriptome

Thyroid hormone (TH) is crucial for normal brain development. TH transporters control TH homeostasis in brain as evidenced by the complex endocrine and neurological phenotype of patients with mutations in monocarboxylate transporter 8 (MCT8). We investigated the mechanisms of disease by analyzing gene expression profiles in fibroblasts from patients with MCT8 mutations. Studying MCT8 and its transcriptional context in different comprehensive spatial and temporal human brain transcriptome data sets revealed distinct region-specific MCT8 expression. Furthermore, MCT8 demonstrated a clear age-dependent decrease, suggesting its importance in early brain development. Performing comparative transcriptome analysis, we linked the genes differentially expressed (DE) in patient fibroblasts to the human brain transcriptome. DE genes in patient fibroblasts were strongly over-represented among genes highly correlated with MCT8 expression in brain. Furthermore, using the same approach we identified which genes in the classical TH signaling pathway are affected in patients. Finally, we provide evidence that the TRα2 receptor variant is closely connected to MCT8. The present study provides amolecular basis for understanding which pathways are likely affected in the brains of patients with mutations in MCT8. Our data regarding a functional relationship between MCT8 and TRα2 suggest an unanticipated role for TRα2 in the (patho)physiology of TH signaling in the brain. This study demonstrates how genome-wide expression data from patient-derived non-neuronal tissue related to the human brain transcriptome may be successfully employed to improve our understanding of neurological disease

X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes

X-linked intellectual disability (XLID) is a clinically and genetically heterogeneous disorder. During the past two decades in excess of 100 X-chromosome ID genes have been identified. Yet, a large number of families mapping to the X-chromosome remained unresolved suggesting that more XLID genes or loci are yet to be identified. Here, we have investigated 405 unresolved families with XLID. We employed massively parallel sequencing of all X-chromosome exons in the index males. The majority of these males were previously tested negative for copy number variations and for mutations in a subset of known XLID genes by Sanger sequencing. In total, 745 X-chromosomal genes were screened. After stringent filtering, a total of 1297 non-recurrent exonic variants remained for prioritization. Co-segregation analysis of potential clinically relevant changes revealed that 80 families (20%) carried pathogenic variants in established XLID genes. In 19 families, we detected likely causative protein truncating and missense variants in 7 novel and validated XLID genes (CLCN4, CNKSR2, FRMPD4, KLHL15, LAS1L, RLIM and USP27X) and potentially deleterious variants in 2 novel candidate XLID genes (CDK16 and TAF1). We show that the CLCN4 and CNKSR2 variants impair protein functions as indicated by electrophysiological studies and altered differentiation of cultured primary neurons from Clcn4−/− mice or after mRNA knock-down. The newly identified and candidate XLID proteins belong to pathways and networks with established roles in cognitive function and intellectual disability in particular. We suggest that systematic sequencing of all X-chromosomal genes in a cohort of patients with genetic evidence for X-chromosome locus involvement may resolve up to 58% of Fragile X-negative cases

Cardiopulmonary Changes with Moderate Decompression in Rats

Sprague-Dawley rats were compressed to 616 kPa for 120 min then decompressed at 38 kPa/min to assess the cardiovascular and pulmonary responses to moderate decompression stress. In one series of experiments the rats were chronically instrumented with Doppler ultrasonic probes for simultaneous measurement of blood pressure, cardiac output, heart rate, left and right ventricular wall thickening fraction, and venous bubble detection. Data were collected at base-line, throughout the compression/decompression protocol, and for 120 min post decompression. In a second series of experiments the pulmonary responses to the decompression protocol were evaluated in non-instrumented rats. Analyses included blood gases, pleural and bronchoalveolar lavage (BAL) protein and hemoglobin concentration, pulmonary edema, BAL and lung tissue phospholipids, lung compliance, and cell counts. Venous bubbles were directly observed in 90% of the rats where immediate post-decompression autopsy was performed and in 37% using implanted Doppler monitors. Cardiac output, stroke volume, and right ventricular wall thickening fractions were significantly decreased post decompression, whereas systemic vascular resistance was increased suggesting a decrease in venous return. BAL Hb and total protein levels were increased 0 and 60 min post decompression, pleural and plasma levels were unchanged. BAL white blood cells and neutrophil percentages were increased 0 and 60 min post decompression and pulmonary edema was detected. Venous bubbles produced with moderate decompression profiles give detectable cardiovascular and pulmonary responses in the rat