Hsp21potentiates antifungal drug tolerance in Candida albicans

Peer reviewedPublisher PD

Device Optimization of Tris-Aluminum (Alq3) Based Bilayer Organic Light Emitting Diode Structures

In this work we present detailed analysis of the emitted radiation spectrum from tris(8-hydroxyquinoline) aluminum (Alq3) based bilayer OLEDs as a function of: the choice of cathode, the thickness of organic layers, and the position of the hole transport layer/Alq3 interface. The calculations fully take into account dispersion in the glass substrate, the indium tin oxide anode, and in the organic layers, as well as the dispersion in the metal cathode. Influence of the incoherent transparent substrate (1 mm glass substrate) is also fully accounted for. Four cathode structures have been considered: Mg/Ag, Ca/Ag, LiF/Al, and Ag. For the hole transport layer, N,N'-diphenyl-N,N'-(3-methylphenyl)-1,1'-biphenyl-4,4'-diamine (TPD) and N,N'-di(naphthalene-1-yl)-N,N'-diphenylbenzidine (NPB) were considered. As expected, emitted radiation is strongly dependent on the position of the emissive layer inside the cavity and its distance from the metal cathode. Although our optical model for an OLED does not explicitly include exciton quenching in vicinity of the metal cathode, designs placing the emissive layer near the cathode are excluded to avoid unrealistic results. Guidelines for designing devices with optimum emission efficiency are presented. Finally, several different devices were fabricated and characterized and experimental and calculated emission spectra were compared

Outcomes of Cardiac Screening in Adolescent Soccer Players.

BACKGROUND: Reports on the incidence and causes of sudden cardiac death among young athletes have relied largely on estimated rates of participation and varied methods of reporting. We sought to investigate the incidence and causes of sudden cardiac death among adolescent soccer players in the United Kingdom. METHODS: From 1996 through 2016, we screened 11,168 adolescent athletes with a mean (±SD) age of 16.4±1.2 years (95% of whom were male) in the English Football Association (FA) cardiac screening program, which consisted of a health questionnaire, physical examination, electrocardiography, and echocardiography. The FA registry was interrogated to identify sudden cardiac deaths, which were confirmed with autopsy reports. RESULTS: During screening, 42 athletes (0.38%) were found to have cardiac disorders that are associated with sudden cardiac death. A further 225 athletes (2%) with congenital or valvular abnormalities were identified. After screening, there were 23 deaths from any cause, of which 8 (35%) were sudden deaths attributed to cardiac disease. Cardiomyopathy accounted for 7 of 8 sudden cardiac deaths (88%). Six athletes (75%) with sudden cardiac death had had normal cardiac screening results. The mean time between screening and sudden cardiac death was 6.8 years. On the basis of a total of 118,351 person-years, the incidence of sudden cardiac death among previously screened adolescent soccer players was 1 per 14,794 person-years (6.8 per 100,000 athletes). CONCLUSIONS: Diseases that are associated with sudden cardiac death were identified in 0.38% of adolescent soccer players in a cohort that underwent cardiovascular screening. The incidence of sudden cardiac death was 1 per 14,794 person-years, or 6.8 per 100,000 athletes; most of these deaths were due to cardiomyopathies that had not been detected on screening. (Funded by the English Football Association and others.)

West Nile virus vector Culex modestus established in southern England

Background: The risk posed to the United Kingdom by West Nile virus (WNV) has previously been considered low, due to the absence or scarcity of the main Culex sp. bridge vectors. The mosquito Culex modestus is widespread in southern Europe, where it acts as the principle bridge vector of WNV. This species was not previously thought to be present in the United Kingdom. Findings: Mosquito larval surveys carried out in 2010 identified substantial populations of Cx. modestus at two sites in marshland in southeast England. Host-seeking-adult traps placed at a third site indicate that the relative seasonal abundance of Cx. modestus peaks in early August. DNA barcoding of these specimens from the United Kingdom and material from southern France confirmed the morphological identification. Conclusions: Cx. modestus appears to be established in the North Kent Marshes, possibly as the result of a recent introduction. The addition of this species to the United Kingdom’s mosquito fauna may increase the risk posed to the United Kingdom by WNV

Small but crucial : the novel small heat shock protein Hsp21 mediates stress adaptation and virulence in Candida albicans

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Hsp90 orchestrates transcriptional regulation by Hsf1 and cell wall remodelling by MAPK signalling during thermal adaptation in a pathogenic yeast

Acknowledgments We thank Rebecca Shapiro for creating CaLC1819, CaLC1855 and CaLC1875, Gillian Milne for help with EM, Aaron Mitchell for generously providing the transposon insertion mutant library, Jesus Pla for generously providing the hog1 hst7 mutant, and Cathy Collins for technical assistance.Peer reviewedPublisher PD

Expression of survivin, a novel inhibitor of apoptosis and cell cycle regulatory protein, in pancreatic adenocarcinoma

Survivin is unique for its expression in human malignancies but not in normal adult cells. It has been implicated in sensitisation to chemotherapy and as a prognostic marker in several common cancers. Immunohistochemistry for Survivin, P53 and BCL-2 expression as well as cell proliferative index (Ki-67) and apoptosis index (TUNEL) was conducted on 52 pancreatic and 12 ampullary adenocarcinomas. Survivin was detected in the cytoplasm of carcinoma cells in 46 (88%) of pancreatic tumours. P53 and BCL-2 were detected in 54% and 12% of pancreatic tumours, respectively. Proliferative index was 26.2±10.5% and apoptosis index was 1.38±0.69%. Prevalence of Survivin expression was significantly higher in P53-positive than in P53-negative cases (P=0.05) but was not associated with BCL-2 expression. Incrementally higher weighted scores of Survivin expression were associated with increased proliferative index (P=0.001). Furthermore, there was linear correlation between increased proliferative index and higher apoptosis index (P<0.001). Surprisingly, higher scores of Survivin expression were associated with increased apoptosis index (P=0.007). Survival characteristics were not influenced by Survivin, P53 or BCL-2 expression, apoptosis index or proliferative index. Ampullary carcinoma showed Survivin expression in 83% of cases. However, unlike pancreatic carcinoma, there was no correlation between Survivin and P53 expression or proliferative index. In conclusion, Survivin is expressed in the majority of pancreatic adenocarcinomas and correlates with both cellular proliferation and apoptosis. Molecular manipulation of Survivin expression may enhance chemotherapy and radiation therapy for pancreatic cancer

Susceptibility of Anopheles stephensi to Plasmodium gallinaceum: A Trait of the Mosquito, the Parasite, and the Environment

Vector susceptibility to Plasmodium infection is treated primarily as a vector trait, although it is a composite trait expressing the joint occurrence of the parasite and the vector with genetic contributions of both. A comprehensive approach to assess the specific contribution of genetic and environmental variation on "vector susceptibility" is lacking. Here we developed and implemented a simple scheme to assess the specific contributions of the vector, the parasite, and the environment to "vector susceptibility." To the best of our knowledge this is the first study that employs such an approach.We conducted selection experiments on the vector (while holding the parasite "constant") and on the parasite (while holding the vector "constant") to estimate the genetic contributions of the mosquito and the parasite to the susceptibility of Anopheles stephensi to Plasmodium gallinaceum. We separately estimated the realized heritability of (i) susceptibility to parasite infection by the mosquito vector and (ii) parasite compatibility (transmissibility) with the vector while controlling the other. The heritabilities of vector and the parasite were higher for the prevalence, i.e., fraction of infected mosquitoes, than the corresponding heritabilities of parasite load, i.e., the number of oocysts per mosquito.The vector's genetics (heritability) comprised 67% of "vector susceptibility" measured by the prevalence of mosquitoes infected with P. gallinaceum oocysts, whereas the specific contribution of parasite genetics (heritability) to this trait was only 5%. Our parasite source might possess minimal genetic diversity, which could explain its low heritability (and the high value of the vector). Notably, the environment contributed 28%. These estimates are relevant only to the particular system under study, but this experimental design could be useful for other parasite-host systems. The prospects and limitations of the genetic manipulation of vector populations to render the vector resistant to the parasite are better considered on the basis of this framework

A Phenotypic Profile of the Candida albicans Regulatory Network

Candida albicans is a normal resident of the gastrointestinal tract and also the most prevalent fungal pathogen of humans. It last shared a common ancestor with the model yeast Saccharomyces cerevisiae over 300 million years ago. We describe a collection of 143 genetically matched strains of C. albicans, each of which has been deleted for a specific transcriptional regulator. This collection represents a large fraction of the non-essential transcription circuitry. A phenotypic profile for each mutant was developed using a screen of 55 growth conditions. The results identify the biological roles of many individual transcriptional regulators; for many, this work represents the first description of their functions. For example, a quarter of the strains showed altered colony formation, a phenotype reflecting transitions among yeast, pseudohyphal, and hyphal cell forms. These transitions, which have been closely linked to pathogenesis, have been extensively studied, yet our work nearly doubles the number of transcriptional regulators known to influence them. As a second example, nearly a quarter of the knockout strains affected sensitivity to commonly used antifungal drugs; although a few transcriptional regulators have previously been implicated in susceptibility to these drugs, our work indicates many additional mechanisms of sensitivity and resistance. Finally, our results inform how transcriptional networks evolve. Comparison with the existing S. cerevisiae data (supplemented by additional S. cerevisiae experiments reported here) allows the first systematic analysis of phenotypic conservation by orthologous transcriptional regulators over a large evolutionary distance. We find that, despite the many specific wiring changes documented between these species, the general phenotypes of orthologous transcriptional regulator knockouts are largely conserved. These observations support the idea that many wiring changes affect the detailed architecture of the circuit, but not its overall output