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

Peer reviewedPublisher PD

Three-gene predictor of clinical outcome for gastric cancer patients treated with chemotherapy

To identify transcriptional profiles predictive of the clinical benefit of cisplatin and fluorouracil (CF) chemotherapy to gastric cancer patients, endoscopic biopsy samples from 96 CF-treated metastatic gastric cancer patients were prospectively collected before therapy and analyzed using high-throughput transcriptional profiling and array comparative genomic hybridization. Transcriptional profiling identified 917 genes that are correlated with poor patient survival after CF at P<0.05 (poor prognosis signature), in which protein synthesis and DNA replication/recombination/repair functional categories are enriched. A survival risk predictor was then constructed using genes, which are included in the poor prognosis signature and are contained within identified genomic amplicons. The combined expression of three genes—MYC, EGFR and FGFR2—was an independent predictor for overall survival of 27 CF-treated patients in the validation set (adjusted P=0.017), and also for survival of 40 chemotherapy-treated gastric cancer patients in a published data set (adjusted P=0.026). Thus, combined expression of MYC, EGFR and FGFR2 is predictive of poor survival in CF-treated metastatic gastric cancer patients

Status and Prospects of ZnO-Based Resistive Switching Memory Devices

In the advancement of the semiconductor device technology, ZnO could be a prospective alternative than the other metal oxides for its versatility and huge applications in different aspects. In this review, a thorough overview on ZnO for the application of resistive switching memory (RRAM) devices has been conducted. Various efforts that have been made to investigate and modulate the switching characteristics of ZnO-based switching memory devices are discussed. The use of ZnO layer in different structure, the different types of filament formation, and the different types of switching including complementary switching are reported. By considering the huge interest of transparent devices, this review gives the concrete overview of the present status and prospects of transparent RRAM devices based on ZnO. ZnO-based RRAM can be used for flexible memory devices, which is also covered here. Another challenge in ZnO-based RRAM is that the realization of ultra-thin and low power devices. Nevertheless, ZnO not only offers decent memory properties but also has a unique potential to be used as multifunctional nonvolatile memory devices. The impact of electrode materials, metal doping, stack structures, transparency, and flexibility on resistive switching properties and switching parameters of ZnO-based resistive switching memory devices are briefly compared. This review also covers the different nanostructured-based emerging resistive switching memory devices for low power scalable devices. It may give a valuable insight on developing ZnO-based RRAM and also should encourage researchers to overcome the challenges

Full-length human placental sFlt-1-e15a isoform induces distinct maternal phenotypes of preeclampsia in mice

<div><p>Objective</p><p>Most anti-angiogenic preeclampsia models in rodents utilized the overexpression of a truncated soluble fms-like tyrosine kinase-1 (sFlt-1) not expressed in any species. Other limitations of mouse preeclampsia models included stressful blood pressure measurements and the lack of postpartum monitoring. We aimed to 1) develop a mouse model of preeclampsia by administering the most abundant human placental sFlt-1 isoform (hsFlt-1-e15a) in preeclampsia; 2) determine blood pressures in non-stressed conditions; and 3) develop a survival surgery that enables the collection of fetuses and placentas and postpartum (PP) monitoring.</p><p>Methods</p><p>Pregnancy status of CD-1 mice was evaluated with high-frequency ultrasound on gestational days (GD) 6 and 7. Telemetry catheters were implanted in the carotid artery on GD7, and their positions were verified by ultrasound on GD13. Mice were injected through tail-vein with adenoviruses expressing hsFlt-1-e15a (n = 11) or green fluorescent protein (GFP; n = 9) on GD8/GD11. Placentas and pups were delivered by cesarean section on GD18 allowing PP monitoring. Urine samples were collected with cystocentesis on GD6/GD7, GD13, GD18, and PPD8, and albumin/creatinine ratios were determined. GFP and hsFlt-1-e15a expression profiles were determined by qRT-PCR. Aortic ring assays were performed to assess the effect of hsFlt-1-e15a on endothelia.</p><p>Results</p><p>Ultrasound predicted pregnancy on GD7 in 97% of cases. Cesarean section survival rate was 100%. Mean arterial blood pressure was higher in hsFlt-1-e15a-treated than in GFP-treated mice (∆MAP = 13.2 mmHg, p = 0.00107; GD18). Focal glomerular changes were found in hsFlt-1-e15a -treated mice, which had higher urine albumin/creatinine ratios than controls (109.3±51.7μg/mg vs. 19.3±5.6μg/mg, p = 4.4x10^-2; GD18). Aortic ring assays showed a 46% lesser microvessel outgrowth in hsFlt-1-e15a-treated than in GFP-treated mice (p = 1.2x10^-2). Placental and fetal weights did not differ between the groups. One mouse with liver disease developed early-onset preeclampsia-like symptoms with intrauterine growth restriction (IUGR).</p><p>Conclusions</p><p>A mouse model of late-onset preeclampsia was developed with the overexpression of hsFlt-1-e15a, verifying the <i>in vivo</i> pathologic effects of this primate-specific, predominant placental sFlt-1 isoform. HsFlt-1-e15a induced early-onset preeclampsia-like symptoms associated with IUGR in a mouse with a liver disease. Our findings support that hsFlt-1-e15a is central to the terminal pathway of preeclampsia, and it can induce the full spectrum of symptoms in this obstetrical syndrome.</p></div

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Localization and broadband follow-up of the gravitational-wave transient GW150914

A gravitational-wave (GW) transient was identified in data recorded by the Advanced Laser Interferometer Gravitational-wave Observatory (LIGO) detectors on 2015 September 14. The event, initially designated G184098 and later given the name GW150914, is described in detail elsewhere. By prior arrangement, preliminary estimates of the time, significance, and sky location of the event were shared with 63 teams of observers covering radio, optical, near-infrared, X-ray, and gamma-ray wavelengths with ground- and space-based facilities. In this Letter we describe the low-latency analysis of the GW data and present the sky localization of the first observed compact binary merger. We summarize the follow-up observations reported by 25 teams via private Gamma-ray Coordinates Network circulars, giving an overview of the participating facilities, the GW sky localization coverage, the timeline, and depth of the observations. As this event turned out to be a binary black hole merger, there is little expectation of a detectable electromagnetic (EM) signature. Nevertheless, this first broadband campaign to search for a counterpart of an Advanced LIGO source represents a milestone and highlights the broad capabilities of the transient astronomy community and the observing strategies that have been developed to pursue neutron star binary merger events. Detailed investigations of the EM data and results of the EM follow-up campaign are being disseminated in papers by the individual teams

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Biotechnological Perspective of Reactive Oxygen Species (ROS)-Mediated Stress Tolerance in Plants

All environmental cues lead to develop secondary stress conditions like osmotic and oxidative stress conditions that reduces average crop yields by more than 50% every year. The univalent reduction of molecular oxygen (O2) in metabolic reactions consequently produces superoxide anions (O2•−) and other reactive oxygen species (ROS) ubiquitously in all compartments of the cell that disturbs redox potential and causes threat to cellular organelles. The production of ROS further increases under stress conditions and especially in combination with high light intensity. Plants have evolved different strategies to minimize the accumulation of excess ROS like avoidance mechanisms such as physiological adaptation, efficient photosystems such as C4 or CAM metabolism and scavenging mechanisms through production of antioxidants and antioxidative enzymes. Ascorbate-glutathione pathway plays an important role in detoxifying excess ROS in plant cells, which includes superoxide dismutase (SOD) and ascorbate peroxidase (APX) in detoxifying O2•−radical and hydrogen peroxide (H2O2) respectively, monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR) and glutathione reductase (GR) involved in recycling of reduced substrates such as ascorbate and glutathione. Efficient ROS management is one of the strategies used by tolerant plants to survive and perform cellular activities under stress conditions. The present chapter describes different sites of ROS generation and and their consequences under abiotic stress conditions and also described the approaches to overcome oxidative stress through genomics and genetic engineering