Background

Kidney injury associated with cold storage is a determinant of delayed graft function and the long-term outcome of transplanted kidneys, but the underlying mechanism remains elusive. We previously reported a role of protein kinase C- (PKC) in renal tubular injury during cisplatin nephrotoxicity and albumin-associated kidney injury, but whether PKC is involved in ischemic or transplantation-associated kidney injury is unknown.

Methods

To investigate PKC’s potential role in injury during cold storage–associated transplantation, we incubated rat kidney proximal tubule cells in University of Wisconsin (UW) solution at 4°C for cold storage, returning them to normal culture medium at 37°C for rewarming. We also stored kidneys from donor mice in cold UW solution for various durations, followed by transplantation into syngeneic recipient mice.

Results

We observed PKC activation in both in vitro and in vivo models of cold-storage rewarming or transplantation. In the mouse model, PKC was activated and accumulated in mitochondria, where it mediated phosphorylation of a mitochondrial fission protein, dynamin-related protein 1 (Drp1), at serine 616. Drp1 activation resulted in mitochondrial fission or fragmentation, accompanied by mitochondrial damage and tubular cell death. Deficiency of PKC in donor kidney ameliorated Drp1 phosphorylation, mitochondrial damage, tubular cell death, and kidney injury during cold storage–associated transplantation. PKC deficiency also improved the repair and function of the renal graft as a life-supporting kidney. An inhibitor of PKC, V1-1, protected kidneys against cold storage–associated transplantation injury.

Conclusions

These results indicate that PKC is a key mediator of mitochondrial damage and renal tubular injury in cold storage–associated transplantation and may be an effective therapeutic target for improving renal transplant outcomes.

VOLUME 287 (2012) PAGES 44508–44517In Fig. 1A, the wrong image for the control group was presented. The authors inadvertently cropped the control images in Fig. 1, A and E, from the same raw image. Fig. 1A has now been corrected and does not affect the results or conclusions of the work. The authors sincerely apologize for their mistake during figure preparation and for any inconvenience this may have caused readers.jbc;295/19/6781/F1F1F1Figure 1A.

Histone H2B monoubiquitylation (H2Bub1) has central functions in multiple DNA-templated processes, including gene transcription, DNA repair, and replication. H2Bub1 also is required for the trans-histone regulation of H3K4 and H3K79 methylation. Although previous studies have elucidated the basic mechanisms that establish and remove H2Bub1, we have only an incomplete understanding of how H2Bub1 is regulated. We report here that the histone H4 basic patch regulates H2Bub1. Yeast cells with arginine-to-alanine mutations in the H4 basic patch (H42RA) exhibited a significant loss of global H2Bub1. H42RA mutant yeast strains also displayed chemotoxin sensitivities similar to, but less severe than, strains containing a complete loss of H2Bub1. We found that the H4 basic patch regulates H2Bub1 levels independently of interactions with chromatin remodelers and separately from its regulation of H3K79 methylation. To measure H2B ubiquitylation and deubiquitination kinetics in vivo, we used a rapid and reversible optogenetic tool, the light-inducible nuclear exporter, to control the subcellular location of the H2Bub1 E3 ligase, Bre1. The ability of Bre1 to ubiquitylate H2B was unaffected in the H42RA mutant. In contrast, H2Bub1 deubiquitination by SAGA-associated Ubp8, but not by Ubp10, increased in the H42RA mutant. Consistent with a function for the H4 basic patch in regulating SAGA deubiquitinase activity, we also detected increased SAGA-mediated histone acetylation in H4 basic patch mutants. Our findings uncover that the H4 basic patch has a regulatory function in SAGA-mediated histone modifications.

Approximately half of all pediatric tracheostomies are performed in infants younger than 1 year. Most tracheostomies in patients in the NICU are performed in cases of chronic respiratory failure requiring prolonged mechanical ventilation or upper airway obstruction. With improvements in ventilation and management of long-term intubation, indications for tracheostomy and perioperative management in this population continue to evolve. Evidence-based protocols to guide routine postoperative care, prevent and manage tracheostomy emergencies including accidental decannulation and tube obstruction, and attempt elective decannulation are sparse. Clinician awareness of safe tracheostomy practices and larger, prospective studies in infants are needed to improve clinical care of this vulnerable population.

Laterites preserved on both sides of the Western Ghats Escarpment of Peninsular India have formed by long-term lateritic weathering essentially after India–Seychelles continental break-up following Deccan Traps emplacement (c. 63 myr ago). Supergene manganese ores of the Western Ghats were formed on Late Archean manganese protores. Among Mn oxides composing the ores, cryptomelane (K-rich Mn oxide) was characterized and dated by ⁴⁰Ar/³⁹Ar geochronology. Measured ages complement those previously obtained in other South Indian manganese ores from the hinterland plateau and further document three major weathering periods, c. 53–44, c. 39–22 and c. 14–10 Ma, the last being documented for the first time in India. These periods coincide with global palaeoclimatic proxies and date the lateritic weathering of three successive palaeolandscapes of the Western Ghats that evolved under slow denudation (c. 8 m Ma^–1) over the last 44 myr and were mostly incised during the Neogene (<22 Ma). This indicates that the Western Ghats are a relict of a South Indian plateau preserved at the headwaters of very long east-flowing river systems and above the Western Ghats Escarpment. Topography and denudation history of this landscape do not require Neogene tilt of the Peninsula as recently proposed.

Supplementary material: Full details of field and sample description, methods and analytical data including electron probe microanalyses of cryptomelane, and isotopic analyses and degassing spectra of irradiated cryptomelane grains are available at https://doi.org/10.6084/m9.figshare.c.4726661

The Northern Paraguai Belt, at the SE border of the Amazonian Craton, central Brazil, has been interpreted as a Brasiliano–Pan-African (c. 650–600 Ma) belt with a foreland basin, recording collisional polyphase tectonism and greenschist-facies metamorphism extending from the late Precambrian to the Cambrian–Ordovician. New structural investigations indicate that the older metasedimentary rocks of the Cuiabá Group represent a Tonian–Cryogenian basement assemblage deformed in two contemporaneous fault-bounded structural sub-domains of wrench-dominated (rake <10°) and contraction-dominated (rake ~30–40°) sinistral transpression, with tectonic vergence towards the SE. The younger late Cryogenian to early Cambrian sedimentary rocks lying to the NW of the Cuiabá Group are non-metamorphic and display only pervasive brittle transtension characterized by normal-oblique faults, fractures and forced drag folds with no consistent vergence pattern. Our analyses suggest that an unconformity separates the metasedimentary Cuiabá Group basement of the Northern Paraguai Belt from the unmetamorphosed sedimentary cover. It is proposed that the latter units were deposited during a post-glacial marine transgression (after c. 635 Ma) in a post-collisional basin. The Paraguai Belt basement and its post-collisional sedimentary cover share a number of significant geological similarities with sequences in the Bassarides Belt and Taoudéni Basin in the SW portion of the West African Craton.

Infections due to methicillin-resistant Staphylococcus aureus (MRSA) are present worldwide and represent a major public health concern. The capability of PCR followed by high-resolution melt (HRM) curve analysis for the detection of community-associated and livestock-associated MRSA strains and the identification of staphylococcal protein A (spa) locus was evaluated in 74 MRSA samples which were isolated from the environment, humans, and pigs on a single piggery. PCR-HRM curve analysis identified four spa types among MRSA samples and differentiated MRSA strains accordingly. A nonsubjective differentiation model was developed according to genetic confidence percentage values produced by tested samples, which did not require visual interpretation of HRM curve results. The test was carried out at different settings, and result data were reanalyzed and confirmed with DNA sequencing. PCR-HRM curve analysis proved to be a robust and reliable test for spa typing and can be used as a tool in epidemiological studies.

High-constitutive activity of the DNA damage response protein checkpoint kinase 1 (CHK1) has been shown in glioblastoma (GBM) cell lines and in tissue sections. However, whether constitutive activation and overexpression of CHK1 in GBM plays a functional role in tumorigenesis or has prognostic significance is not known. We interrogated multiple glioma patient cohorts for expression levels of CHK1 and the oncogene cancerous inhibitor of protein phosphatase 2A (CIP2A), a known target of high-CHK1 activity, and examined the relationship between these two proteins in GBM. Expression levels of CHK1 and CIP2A were independent predictors for reduced overall survival across multiple glioma patient cohorts. Using siRNA and pharmacologic inhibitors we evaluated the impact of their depletion using both in vitro and in vivo models and sought a mechanistic explanation for high CIP2A in the presence of high-CHK1 levels in GBM and show that; (i) CHK1 and pSTAT3 positively regulate CIP2A gene expression; (ii) pSTAT3 and CIP2A form a recursively wired transcriptional circuit; and (iii) perturbing CIP2A expression induces GBM cell senescence and retards tumor growth in vitro and in vivo. Taken together, we have identified an oncogenic transcriptional circuit in GBM that can be destabilized by targeting CIP2A.

Implications:

High expression of CIP2A in gliomas is maintained by a CHK1-dependent pSTAT3–CIP2A recursive loop; interrupting CIP2A induces cell senescence and slows GBM growth adding impetus to the development of CIP2A as an anticancer drug target.

The histone demethylase JMJD1A plays a key functional role in spermatogenesis, sex determination, stem cell renewal, and cancer via removing mono- and di-methyl groups from H3K9 to epigenetically control gene expression. However, its role in prostate cancer progression remains unclear. Here, we found JMJD1A was significantly elevated in prostate cancer tissue compared with matched normal tissue. Ectopic JMJD1A expression in prostate cancer cells promoted proliferation, migration, and invasion in vitro, and tumorigenesis in vivo; JMJD1A knockdown exhibited the opposite effects. Mechanically, we revealed that JMJD1A directly interacted with the Snail gene promoter and regulated its transcriptional activity, promoting prostate cancer progression both in vitro and in vivo. Furthermore, we found that JMJD1A transcriptionally activated Snail expression via H3K9me1 and H3K9me2 demethylation at its special promoter region. In summary, our studies reveal JMJD1A plays an important role in regulating proliferation and progression of prostate cancer cells though Snail, and thus highlight JMJD1A as potential therapeutic target for advanced prostate cancer.

Implications:

Our studies identify that JMJD1A promotes the proliferation and progression of prostate cancer cells through enabling Snail transcriptional activation, and thus highlight JMJD1A as potential therapeutic target for advanced prostate cancer.

Sickle cell disease (SCD) is associated with overactive bladder (OAB). Detrusor overactivity, a component of OAB, is present in an SCD mouse, but the molecular mechanisms for this condition are not well-defined. We hypothesize that nitric oxide (NO)/ ras homolog gene family (Rho) A/Rho-associated kinase (ROCK) dysregulation is a mechanism for detrusor overactivity and that NO-releasing nanoparticles (NO-nps), a novel NO delivery system, may serve to treat this condition. Male adult SCD transgenic, combined endothelial NO synthases (eNOSs) and neuronal NOS (nNOS) gene-deficient (dNOS^–/–), and wild-type (WT) mice were used. Empty nanoparticle or NO-np was injected into the bladder, followed by cystometric studies. The expression levels of phosphorylated eNOS (Ser-1177), protein kinase B (Akt) (Ser-473), nNOS (Ser-1412), and myosin phosphatase target subunit 1 (MYPT1) (Thr-696) were assessed in the bladder. SCD and dNOS^–/– mice had a greater (P < 0.05) number of voiding and nonvoiding contractions compared with WT mice, and they were normalized by NO-np treatment. eNOS (Ser-1177) and AKT (Ser-473) phosphorylation were decreased (P < 0.05) in the bladder of SCD compared with WT mice and reversed by NO-np. Phosphorylated MYPT1, a marker of the RhoA/ROCK pathway, was increased (P < 0.05) in the bladder of SCD mice compared with WT and reversed by NO-np. nNOS phosphorylation on positive (Ser-1412) regulatory site was decreased (P < 0.05) in the bladder of SCD mice compared with WT and was not affected by NO-np. NO-nps did not affect any of the measured parameters in WT mice. In conclusion, dysregulation of NO and RhoA/ROCK pathways is associated with detrusor overactivity in SCD mice; NO-np reverses these molecular derangements in the bladder and decreases detrusor overactivity.

SIGNIFICANCE STATEMENT

Voiding abnormalities commonly affect patients with sickle cell disease (SCD) but are problematic to treat. Clarification of the science for this condition in an animal model of SCD may lead to improved interventions for it. Our findings suggest that novel topical delivery of a vasorelaxant agent nitric oxide into the bladder of these mice corrects overactive bladder by improving deranged bladder physiology regulatory signaling.

¹⁸F-rhPSMA-7 (radiohybrid prostate-specific membrane antigen [PSMA]) is a novel ligand for PET imaging. Here, we present data from a retrospective analysis using PET/CT and PET/MRI examinations to investigate the efficacy of ¹⁸F-rhPSMA-7 PET for primary N-staging of patients with prostate cancer (PC) compared with morphologic imaging (CT or MRI) and validated by histopathology. Methods: Data from 58 patients with high-risk PC (according to the D’Amico criteria) who were staged with ¹⁸F-rhPSMA-7 PET/CT or PET/MRI at our institution between July 2017 and June 2018 were reviewed. The patients had a median prescan prostate-specific antigen value of 12.2 ng/mL (range, 1.2–81.6 ng/mL). The median injected activity of ¹⁸F-rhPSMA-7 was 327 MBq (range, 132–410 MBq), with a median uptake time of 79.5 min (range, 60–153 min). All patients underwent subsequent radical prostatectomy and extended pelvic lymph node dissection. The presence of lymph node metastases was determined by an experienced reader independently for both the PET and the morphologic datasets using a template-based analysis on a 5-point scale. Patient-level and template-based results were both compared with histopathologic findings. Results: Lymph node metastases were present in 18 patients (31.0%) and were located in 52 of 375 templates (13.9%). Receiver-operating-characteristic analyses showed ¹⁸F-rhPSMA-7 PET to perform significantly better than morphologic imaging on both patient-based and template-based analyses (areas under curve, 0.858 vs. 0.649 [P = 0.012] and 0.765 vs. 0.589 [P < 0.001], respectively). On patient-based analyses, the sensitivity, specificity, and accuracy of ¹⁸F-rhPSMA-7 PET were 72.2%, 92.5%, and 86.2%, respectively, and those of morphologic imaging were 50.0%, 72.5%, and 65.5%, respectively. On template-based analyses, the sensitivity, specificity, and accuracy of ¹⁸F-rhPSMA-7 PET were 53.8%, 96.9%, and 90.9%, respectively, and those of morphologic imaging were 9.6%, 95.0%, and 83.2%, respectively. Conclusion: ¹⁸F-rhPSMA-7 PET is superior to morphologic imaging for N-staging of high-risk primary PC. The efficacy of ¹⁸F-rhPSMA-7 is similar to published data for ⁶⁸Ga-PSMA-11.

The Henry Buckley Collection of Planktonic Foraminifera at the Natural History Museum in London (NHMUK) consists of 1665 single-taxon slides housing 23 897 individuals from 203 sites in all the major ocean basins, as well as a vast research library of Scanning Electron Microscope (SEM) photomicrographs. Buckley picked the material from the NHMUK Ocean-Bottom Deposit Collection and also from fresh tow samples. However, his collection remains largely unused as he was discouraged by his managers in the Mineralogy Department from working on or publicizing the collection. Nevertheless, Buckley published pioneering papers on isotopic interpretation of oceanographic and climatic change and was one of the first workers to investigate foraminiferal wall structure using the SEM technique. Details of the collection and images of each slide are available via the NHMUK Data Portal (http://dx.doi.org/10.5519/0035055). The Buckley Collection and its associated Ocean-Bottom Deposit Collection have great potential for taxon-specific studies as well as geochemical work, and both collections are available on request.

An exceptionally well-preserved specimen of the articulated rhodophyte Permocalculus, compared with P. tenellus sensu Elliott, 1955, is described from fine-grained Upper Permian limestones of the Khuff Formation of Saudi Arabia. Longitudinal medullary and sheaf-like cortical filaments extend through the uniserial series of elongate-globular, concave- and convex-terminating, interlocking segments for which they are interpreted to have functioned in articulation. The filaments tend to splay and branch laterally into the cortex where they terminate at the pores. At the terminal aperture, the filaments extend as bifurcating and possibly trifurcating branches and may serve as the origin of a new segment. Numerous elongate-globular chambers, up to five in each row and intimately involved with the filaments, are developed in the outer medulla and are considered to represent reproductive sporangia. The specimen is considered to have occupied predominantly low-energy, normal to slightly elevated salinity, shallow conditions within the subtidal regime of a lagoon.

Testosterone is an important determinant of endothelial function and vascular health in men. As both factors play a role in mortality after allogeneic stem cell transplantation (alloSCT), we retrospectively evaluated the impact of pre-transplant testosterone levels on outcome in male patients undergoing alloSCT. In the discovery cohort (n=346), an impact on outcome was observed only in the subgroup of patients allografted for acute myeloid leukemia (AML) (n=176, hereafter termed ‘training cohort’). In the training cohort, lower pre-transplant testosterone levels were significantly associated with shorter overall survival (OS) [hazard ratio (HR) for a decrease of 100 ng/dL: 1.11, P=0.045]. This was based on a higher hazard of non-relapse mortality (NRM) (cause-specific HR: 1.25, P=0.013), but not relapse (cause-specific HR: 1.06, P=0.277) in the multivariable models. These findings were replicated in a confirmation cohort of 168 male patients allografted for AML in a different center (OS, HR: 1.15, P=0.012 and NRM, cause-specific HR: 1.23; P=0.008). Next, an optimized cut-off point for pre-transplant testosterone was derived from the training set and evaluated in the confirmation cohort. In multivariable models, low pre-transplant testosterone status (<250 ng/dL) was associated with worse OS (hazard ratio 1.95, P=0.021) and increased NRM (cause-specific HR 2.68, P=0.011) but not with relapse (cause-specific HR: 1.28, P=0.551). Our findings may provide a rationale for prospective studies on testosterone/androgen assessment and supplementation in male patients undergoing alloSCT for AML.

Tranexamic acid (TXA) is an anti-fibrinolytic agent that acts by inhibiting plasminogen activation and fibrinolysis. Although its first clinical use dates back more than 50 years, this hemostatic agent is still the object of intense clinical and developmental research. In particular, renewed interest in TXA has arisen following evidence that it has a beneficial effect in reducing blood loss in a variety of medical and surgical conditions at increased risk of bleeding. Given this characteristic, TXA is currently considered a mainstay of Patient Blood Management programs aimed at reducing patients’ exposure to allogeneic blood transfusion. Importantly, recent large randomized controlled trials have consistently documented that the use of TXA confers a survival advantage in a number of globally critical clinical conditions associated with acute bleeding, including traumatic injury and post-partum hemorrhage, without increasing the thromboembolic risk.

Biological nitrogen fixation can be an important source of nitrogen in tropical forests that serve as a major CO₂ sink. Extensive deforestation of the Amazon is known to influence microbial communities and the biogeochemical cycles they mediate. However, it is unknown how diazotrophs (nitrogen-fixing microorganisms) respond to deforestation and subsequent ecosystem conversion to agriculture, as well as whether they can recover in secondary forests that are established after agriculture is abandoned. To address these knowledge gaps, we combined a spatially explicit sampling approach with high-throughput sequencing of nifH genes. The main objectives were to assess the functional distance decay relationship of the diazotrophic bacterial community in a tropical forest ecosystem and to quantify the roles of various factors that drive the observed changes in the diazotrophic community structure. We observed an increase in local diazotrophic diversity (α-diversity) with a decrease in community turnover (β-diversity), associated with a shift in diazotrophic community structure as a result of the forest-to-pasture conversion. Both diazotrophic community turnover and structure showed signs of recovery in secondary forests. Changes in the diazotrophic community were primarily driven by the change in land use rather than differences in geochemical characteristics or geographic distances. The diazotroph communities in secondary forests resembled those in primary forests, suggesting that at least partial recovery of diazotrophs is possible following agricultural abandonment.

IMPORTANCE The Amazon region is a major tropical forest region that is being deforested at an alarming rate to create space for cattle ranching and agriculture. Diazotrophs (nitrogen-fixing microorganisms) play an important role in supplying soil N for plant growth in tropical forests. It is unknown how diazotrophs respond to deforestation and whether they can recover in secondary forests that establish after agriculture is abandoned. Using high-throughput sequencing of nifH genes, we characterized the response of diazotrophs’ β-diversity and identified major drivers of changes in diazotrophs from forest-to-pasture and pasture-to-secondary-forest conversions. Studying the impact of land use change on diazotrophs is important for a better understanding of the impact of deforestation on tropical forest ecosystem functioning, and our results on the potential recovery of diazotrophs in secondary forests imply the possible restoration of ecosystem functions in secondary forests.

The measurement of neuron-specific enolase (NSE) in serum is frequently requested for diagnosis, risk stratification, and treatment monitoring of neuroblastoma (NB) in the pediatric population. However, authoritative clinical practice guidelines advise about the poor diagnostic performance of NSE.We critically appraised the available literature evaluating the diagnostic and prognostic value of NSE in the management of NB, paying special attention to the definition of appropriate threshold levels. In addition, we discuss the interfering conditions causing artifactual increases of NSE concentrations in serum and potentially influencing the clinical evaluation of patients with suspected NB.No definitive evidence supports the use of serum NSE for diagnosis and monitoring of NB. The risk of obtaining false-positive NSE results associated with confounders (e.g., sample hemolysis) and other pathophysiologic conditions (e.g., inflammation) is remarkable and hampers the diagnostic value of this test. NSE may be helpful to define the risk of death of patients with NB, mainly in the advanced stages of disease. However, further studies validating currently marketed immunoassays and defining threshold values useful for this scope are warranted.

The RESTORE-IMI 1 phase 3 trial demonstrated the efficacy and safety of imipenem-cilastatin (IMI) combined with relebactam (REL) for treating imipenem-nonsusceptible infections. The objective of this analysis was to compare the outcomes among patients meeting eligibility requirements based on central laboratory susceptibility versus local laboratory susceptibility. Patients with serious infections caused by imipenem-nonsusceptible, colistin-susceptible, and imipenem-REL-susceptible pathogens were randomized 2:1 to IMI-REL plus placebo or colistin plus IMI for 5 to 21 days. The primary endpoint was a favorable overall response. Key endpoints included the clinical response and all-cause mortality. We compared outcomes between the primary microbiological modified intent-to-treat (mMITT) population, where eligibility was based on central laboratory susceptibility testing, and the supplemental mMITT (SmMITT) population, where eligibility was based on local, site-level testing. The SmMITT (n = 41) and MITT (n = 31) populations had similar baseline characteristics, including sex, age, illness severity, and renal function. In both analysis populations, favorable overall response rates in the IMI-REL treatment group were >70%. Favorable clinical response rates at day 28 were 71.4% for IMI-REL and 40.0% for colistin plus IMI in the mMITT population, whereas they were 75.0% for IMI-REL and 53.8% for colistin plus IMI in the SmMITT population. Day 28 all-cause mortality rates were 9.5% for IMI-REL and 30.0% for colistin plus IMI in the mMITT population, whereas they were 10.7% for IMI-REL and 23.1% for colistin plus IMI in the SmMITT population. The outcomes in the SmMITT population were generally consistent with those in the mMITT population, suggesting that outcomes may be applicable to the real-world use of IMI-REL for treating infections caused by imipenem-nonsusceptible Gram-negative pathogens. (This study has been registered at ClinicalTrials.gov under identifier NCT02452047.)

Clinical benefit of immune checkpoint blockade in glioblastoma (GBM) is rare, and we hypothesize that tumor clonal evolution and the immune microenvironment are key determinants of response. Here, we present a detailed molecular characterization of the intratumoral and immune heterogeneity in an IDH wild-type, MGMT-negative GBM patient who plausibly benefited from anti-PD-1 therapy with an unusually long 25-mo overall survival time. We leveraged multiplex immunohistochemistry, RNA-seq, and whole-exome data from the primary tumor and three resected regions of recurrent disease to survey regional tumor-immune interactions, genomic instability, mutation burden, and expression profiles. We found significant regional heterogeneity in the neoantigenic and immune landscape, with a differential T-cell signature among recurrent sectors, a uniform loss of focal amplifications in EGFR, and a novel subclonal EGFR mutation. Comparisons with recently reported correlates of checkpoint blockade in GBM and with TCGA-GBM revealed appreciable intratumoral heterogeneity that may have contributed to a differential PD-1 blockade response.

Store-operated calcium (Ca²⁺) entry (SOCE) occurs through a widely distributed family of ion channels activated by the loss of Ca²⁺ from the endoplasmic reticulum (ER). The best understood of these is the Ca²⁺ release-activated Ca²⁺ (CRAC) channel, which is notable for its unique activation mechanism as well as its many essential physiological functions and the diverse pathologies that result from dysregulation. In response to ER Ca²⁺ depletion, CRAC channels are formed through a diffusion trap mechanism at ER–plasma membrane (PM) junctions, where the ER Ca²⁺-sensing stromal interaction molecule (STIM) proteins bind and activate hexamers of Orai pore-forming proteins to trigger Ca²⁺ entry. Cell biological studies are clarifying the architecture of ER–PM junctions, their roles in Ca²⁺ and lipid transport, and functional interactions with cytoskeletal proteins. Molecular structures of STIM and Orai have inspired a multitude of mutagenesis and electrophysiological studies that reveal potential mechanisms for how STIM is toggled between inactive and active states, how it binds and activates Orai, and the importance of STIM-binding stoichiometry for opening the channel and establishing its signature characteristics of extremely high Ca²⁺ selectivity and low Ca²⁺ conductance.

BACKGROUND AND PURPOSE:

Diffuse intrinsic pontine glioma is a lethal childhood brain cancer with dismal prognosis and MR imaging is the primary methodology used for diagnosis and monitoring. Our aim was to determine whether advanced diffusion, perfusion, and permeability MR imaging metrics predict survival and pseudoprogression in children with newly diagnosed diffuse intrinsic pontine glioma.

MATERIALS AND METHODS:

A clinical trial using the poly (adenosine diphosphate ribose) polymerase (PARP) inhibitor veliparib concurrently with radiation therapy, followed by maintenance therapy with veliparib + temozolomide, in children with diffuse intrinsic pontine glioma was conducted by the Pediatric Brain Tumor Consortium. Standard MR imaging, DWI, dynamic contrast-enhanced perfusion, and DSC perfusion were performed at baseline and approximately every 2 months throughout treatment. ADC histogram metrics of T2-weighted FLAIR and enhancing tumor volume, dynamic contrast-enhanced permeability metrics for enhancing tumors, and tumor relative CBV from DSC perfusion MR imaging were calculated. Baseline values, post-radiation therapy changes, and longitudinal trends for all metrics were evaluated for associations with survival and pseudoprogression.

RESULTS:

Fifty children were evaluable for survival analyses. Higher baseline relative CBV was associated with shorter progression-free survival (P = .02, Q = 0.089) and overall survival (P = .006, Q = 0.055). Associations of higher baseline mean transfer constant from the blood plasma into the extravascular extracellular space with shorter progression-free survival (P = .03, Q = 0.105) and overall survival (P = .03, Q = 0.102) trended toward significance. An increase in relative CBV with time was associated with shorter progression-free survival (P < .001, Q < 0.001) and overall survival (P = .004, Q = 0.043). Associations of longitudinal mean extravascular extracellular volume fraction with progression-free survival (P = .03, Q = 0.104) and overall survival (P = .03, Q = 0.105) and maximum transfer constant from the blood plasma into the extravascular extracellular space with progression-free survival (P = .03, Q = 0.102) trended toward significance. Greater increases with time were associated with worse outcomes. True radiologic progression showed greater post-radiation therapy decreases in mode_ADC_FLAIR compared with pseudoprogression (means, –268.15 versus –26.11, P = .01.)

CONCLUSIONS:

ADC histogram, perfusion, and permeability MR imaging metrics in diffuse intrinsic pontine glioma are useful in predicting survival and pseudoprogression.

BACKGROUND AND PURPOSE:

Detailed insight into the composition of thrombi retrieved from patients with ischemic stroke by mechanical thrombectomy might improve pathophysiologic understanding and therapy. Thus, this study searched for links between histologic thrombus composition and stroke subtypes and mechanical thrombectomy results.

MATERIALS AND METHODS:

Thrombi from 85 patients who had undergone mechanical thrombectomy for acute ischemic stroke between December 2016 and March 2018 were studied retrospectively. Thrombi were examined histologically. Preinterventional imaging features, stroke subtypes, and interventional parameters were re-analyzed. Statistical analysis was performed with the Kruskal-Wallis test, Mann-Whitney U test, or Spearman correlation as appropriate.

RESULTS:

Cardioembolic thrombi had a higher percentage of macrophages and a tendency toward more platelets than thrombi of large-artery atherosclerotic stenosis (P = .021 and .003) or the embolic stroke of undetermined source (P = .037 and .099) subtype. Thrombi prone to fragmentation required the combined use of contact aspiration and stent retrieval (P = .021) and were associated with an increased number of retrieving maneuvers (P = .001), longer procedural times (P = .001), and a higher lymphocyte content (P = .035).

CONCLUSIONS:

We interpreted the higher macrophage and platelet content in cardioembolic thrombi compared with large-artery atherosclerotic stenosis or embolic stroke of undetermined source thrombi as an indication that the latter type might be derived from an atherosclerotic plaque rather than from an undetermined cardiac source. The extent of thrombus fragmentation was associated with a more challenging mechanical thrombectomy and a higher lymphocyte content of the thrombi. Thus, thrombus fragmentation not only might be caused by the recanalization procedure but also might be a feature of a lymphocyte-rich, difficult-to-retrieve subgroup of thrombi.

BACKGROUND AND PURPOSE:

Accurate differentiation between glioblastoma and solitary brain metastasis is of vital importance clinically. This study aimed to investigate the potential value of the inflow-based vascular-space-occupancy MR imaging technique, which has no need for an exogenous contrast agent, in differentiating glioblastoma and solitary brain metastasis and to compare it with DSC MR imaging.

MATERIALS AND METHODS:

Twenty patients with glioblastoma and 22 patients with solitary brain metastasis underwent inflow-based vascular-space-occupancy and DSC MR imaging with a 3T clinical scanner. Two neuroradiologists independently measured the maximum inflow-based vascular-space-occupancy–derived arteriolar CBV and DSC-derived CBV values in intratumoral regions and peritumoral T2-hyperintense regions, which were normalized to the contralateral white matter (relative arteriolar CBV and relative CBV, inflow-based vascular-space-occupancy relative arteriolar CBV, and DSC-relative CBV). The intraclass correlation coefficient, Student t test, or Mann-Whitney U test and receiver operating characteristic analysis were performed.

RESULTS:

All parameters of both regions had good or excellent interobserver reliability (0.74~0.89). In peritumoral T2-hyperintese regions, DSC-relative CBV (P < .001), inflow-based vascular-space-occupancy arteriolar CBV (P = .001), and relative arteriolar CBV (P = .005) were significantly higher in glioblastoma than in solitary brain metastasis, with areas under the curve of 0.94, 0.83, and 0.72 for discrimination, respectively. In the intratumoral region, both inflow-based vascular-space-occupancy arteriolar CBV and relative arteriolar CBV were significantly higher in glioblastoma than in solitary brain metastasis (both P < .001), with areas under the curve of 0.91 and 0.90, respectively. Intratumoral DSC-relative CBV showed no significant difference (P = .616) between the 2 groups.

CONCLUSIONS:

Inflow-based vascular-space-occupancy has the potential to discriminate glioblastoma from solitary brain metastasis, especially in the intratumoral region.

The trade war between the United States and China has turned real estate investors' interest to Southeast Asian countries, in which the Vietnamese industrial market emerges as a bright spot in the region.

According to Batdongsan.com.vn’s real estate market report for the third quarter (Q3) of 2019, besides the attraction of traditional markets, resort real estate segment is witnessing the rise of emerging markets. Notably, Hanoi investors overwhelmed in term of the number of searches for resort real estate on the website.

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- The building is located at 22 Nguyen Thien Thuat, Tan Lap, Nha Trang city. - Nice and strong house, modern design, spacious and airy living space with 2 frontages of road - Land area: 96m2 - Construction area: 576 m2. Wide frontage: 5 m wide, 19.6 m long, 1 ground floor for bus...

- Sublease investor commits to profit within 6 years , plan price 25$/m2 - Area: 191.2m2 - Price: $1,060,000 -The Developer is the company of Fraser Singapore which is very famous in other countries because this is the first project in Vietnam so the Developer sells with not much...

The upsurge of land price leads to a real estate bubble, pushing up production costs, creating a virtual tendency and gradually increasing bad debt.

One of the most notable changes introduced by Vietnam’s new 2014 property law and its regulations is the revision of the right for overseas Vietnamese, foreign individuals and organizations to own residential houses.

Regardless of age, all first-time real estate investors are prone to making the same mistakes. Here are some dos and don’ts for new investors.

Many people see buy-to-rent as an attractive income investment in a time of low rates and stock market volatility. But if you are considering investing in property - or improving your returns on a buy-to-rent you already own - it's important to do things right.

Tens of thousands of new apartments enter the Ho Chi Minh City market every year, putting pressure on investors who want to reap returns from rental apartments.

Assassin’s Creed Valhalla creative director Ashraf Ismail previously stated the game will feature a "large map" in terms of England. There will be four major English kingdoms: Wessex, Northumbria, East Anglia, and Mercia. There will also be three major cities: London, Winchester and Jórvík (now called York).

Since the game takes place in southern England Ismail was asked via Twitter if the game will feature Stonehenge and he replied "oh, can you ever!" with a GIF of a man nodding yes. 

Here is an overview of the game:

In Assassin’s Creed Valhalla, you are Eivor, a fierce Viking warrior raised on tales of battle and glory. Explore a dynamic and beautiful open world set against the brutal backdrop of England’s Dark Ages. Raid your enemies, grow your settlement, and build your political power in your quest to earn your place among the gods in Valhalla.

Key Features:

• Write Your Viking Saga – Advanced RPG mechanics allow you to shape the growth of your character and influence the world around you. With every choice you make, from political alliances and combat strategy to dialogue and gear progression, you will carve your own path to glory.
• Visceral Combat System – Dual-wield powerful weapons such as axes, swords, and even shields to relive the ruthless fighting style of the Viking warriors. Brutally decapitate your foes, vanquish them from afar, or stealthily assassinate targets with your hidden blade. Challenge yourself with the most varied collection of deadly enemies ever found in an Assassin’s Creed game.
• A Dark Age Open World – Sail from the harsh and mysterious shores of Norway to the beautiful but forbidding kingdoms of England and beyond. Immerse yourself in the Viking way of life through fishing, hunting, drinking games, and more.
• Lead Epic Raids – Launch massive assaults against Saxon troops and fortresses throughout England. Lead your clan in surprise attacks from your longship and pillage enemy territories to bring riches and resources back to your people.
• Grow Your Settlement – Construct and upgrade buildings that allow for deep customization, including a barracks, blacksmith, tattoo parlor, and more. Recruit new members to your clan and personalize your Viking experience.
• Mercenary Vikings – Create and customize a unique Viking raider within your clan and share it online with friends to use during their own raids.

Assassin’s Creed Valhalla will launch for Xbox Series X, PlayStation 5, PlayStation 4, Xbox One, Windows PC, and Google Stadia in Holiday 2020. The game will support Smart Delivery on the Xbox. This means if you purchase the game on the Xbox One or Xbox Series X, you will automatically gain access to the other version of the game. 

A life-long and avid gamer, William D'Angelo was first introduced to VGChartz in 2007. After years of supporting the site, he was brought on in 2010 as a junior analyst, working his way up to lead analyst in 2012. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel dedicated to gaming Let's Plays and tutorials. You can contact the author at wdangelo@vgchartz.com or on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/443400/assassins-creed-valhalla-to-feature-stonehenge/

Publisher Warner Bros. Interactive Entertainment and developer NetherRealms Studios have announced a new expansion for Mortal Kombat 11 called Aftermath. It will release on May 26.

The Mortal Kombat 11: Aftermath expansion adds a new cinematic story, three characters and three new skins for $39.99. The three new characters are Fujin, Sheeva, and RoboCop).

A $59.99 Mortal Kombat: Aftermath Kollection has also been announced. It includes the base game, Kombat Pack DLC and the Aftermath expansion. 

View the announcement trailer for the expansion and RoboCop reveal trailer below:

Here is an overview of the expansion:

Mortal Kombat 11: Aftermath is a new expansion for the hit videogame, Mortal Kombat 11, the best-selling title in franchise history that was named Fighting Game of the Year at the 2019 D.I.C.E. Awards. Developed by award-winning NetherRealm Studios, Mortal Kombat 11: Aftermath expands the critically acclaimed story campaign with an all-new, cinematic narrative centered around trust and deceit, while also adding new playable characters in returning Mortal Kombat fighters, Fujin and Sheeva, and guest character, RoboCop, who is making his series debut.

Key Features:

• Franchise-First Story Expansion – The critically acclaimed story campaign continues with an all-new cinematic narrative that picks up directly where Mortal Kombat 11 left off. Fire God Liu Kang, the new keeper of time and protector of Earthrealm, must now enlist the help of unlikely allies and familiar foes to forge a new history as the fate of two worlds hang in the balance.
• Exciting New Characters Join the Roster – New playable characters join the fight with the triumphant return of Fujin, the God of Wind who serves as Earthrealm’s protector alongside his brother Raiden, and Sheeva, the fourarmed, half-human and half-dragon queen of the ancient Shokan race. RoboCop, the iconic, highly advanced cybernetic police officer, makes his first appearance in the franchise, continuing the pedigree of popular Mortal Kombat guest fighters. RoboCop in Mortal Kombat 11: Aftermath features the voice and likeness of actor Peter Weller, who portrayed the popular character in both the original RoboCop (1987) film and RoboCop 2 (1990) sequel. Mortal Kombat 11: Aftermath will also include three new character skin packs to be released over time.
• Fan-Favorite Stages, Stage Fatalities & Friendships Return – In conjunction with the Mortal Kombat 11: Aftermath release, all Mortal Kombat 11 owners will have access to a free content update featuring new Stages, including the return of the Klassic Dead Pool and Soul Chamber arenas; Stage Fatalities, the fan-favorite finishing moves that use the environment to destroy opponents; and the popular Friendships feature, allowing players to take down their adversaries with a hint of kindness.
• New Players Can Join the Fight with Mortal Kombat 11: Aftermath Kollection – Offers the perfect opportunity for new players to join the fight, featuring all characters, story content, game modes and pre-order bonuses in one ultimate package. This compilation includes Mortal Kombat 11 along with all content from Mortal Kombat 11: Aftermath and the previously released Mortal Kombat 11 Kombat Pack, containing six playable characters—Shang Tsung, Nightwolf, Sindel, Terminator T-800, The Joker and Spawn – plus 25 additional character skins. The Mortal Kombat 11: Aftermath Kollection can be pre-ordered for $59.99 (SRP) with digital pre-orders offering immediate access to Mortal Kombat 11 and the Kombat Pack upon purchase. The physical version will be available this June in the Americas only.
• Upgrade Options for Current Mortal Kombat 11 Owners – Those who have already purchased Mortal Kombat 11 can pre-order the Mortal Kombat 11 Aftermath expansion for $39.99 (SRP) or the Mortal Kombat 11: Aftermath + Kombat Pack Bundle for $49.99 (SRP).
• Pre-order for Exclusive Content – All preorders* receive the Eternal Klash Skin Pack at launch, featuring three new character skin variants – “Unbound Rage” Scorpion inspired by Mortal Kombat (2011), “Son of Arctika” Sub-Zero inspired by Mortal Kombat: Deception and “Kori Power” Frost, a Klassic version of the Lin Kuie warrior.
• Best-In-Class, Brutal Kombat – Mortal Kombat 11 is the latest installment in the critically acclaimed franchise, providing a deeper and more personalized experience than ever before. The best-selling title is packed to the brim with multiple features and modes for all players, including the Story mode, Custom Character Variation System, Towers of Time, Kombat League, The Krypt and the signature roster returning and franchise-first fighters, all equipped with powerful Krushing Blows and unique Fatalities that display devastatingly brutal cinematic visuals.

A life-long and avid gamer, William D'Angelo was first introduced to VGChartz in 2007. After years of supporting the site, he was brought on in 2010 as a junior analyst, working his way up to lead analyst in 2012. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel dedicated to gaming Let's Plays and tutorials. You can contact the author at wdangelo@vgchartz.com or on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/443404/mortal-kombat-11-aftermath-expansion-announced-adds-3-new-characters-and-new-story/

Publisher Sony Interactive Entertainment and developer Naughty Dog have released the story trailer for The Last of Us Part II ahead of the game's release next month.

View the trailer below:

Here is an overview of the game:

Five years after their dangerous journey across the post-pandemic United States, Ellie and Joel have settled down in Jackson, Wyoming. Living amongst a thriving community of survivors has allowed them peace and stability, despite the constant threat of the infected and other, more desperate survivors. When a violent event disrupts that peace, Ellie embarks on a relentless journey to carry out justice and find closure. As she hunts those responsible one by one, she is confronted with the devastating physical and emotional repercussions of her actions.

Key Features:

• A Complex and Emotional Story – Experience the escalating moral conflicts created by Ellie’s relentless pursuit of vengeance. The cycle of violence left in her wake will challenge your notions of right versus wrong, good versus evil, and hero versus villain.

  A Beautiful Yet Dangerous World – Set out on Ellie’s journey, taking her from the peaceful mountains and forests of Jackson to the lush, overgrown ruins of greater Seattle. Encounter new survivor groups, unfamiliar and treacherous environments, and terrifying evolutions of the infected. Brought to life by the latest iteration of the Naughty Dog engine, the deadly characters and world are more realistic and meticulously detailed than ever before.

• Tense and Desperate Action-Survival Gameplay – New and evolved gameplay systems deliver upon the life-or-death stakes of Ellie’s journey through the hostile world. Feel her desperate struggle for survival through improved features such as high-intensity melee combat, fluid movement, and dynamic stealth. A broad variety of weapons, crafting items, skills, and upgrades allows you to personalize Ellie’s capabilities to your play style.

A life-long and avid gamer, William D'Angelo was first introduced to VGChartz in 2007. After years of supporting the site, he was brought on in 2010 as a junior analyst, working his way up to lead analyst in 2012. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel dedicated to gaming Let's Plays and tutorials. You can contact the author at wdangelo@vgchartz.com or on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/443406/the-last-of-us-part-ii-story-trailer-released/

Sony has released the US PlayStation Store downloads charts for March 2020. Final Fantasy VII Remake topped the PS4 charts, Beat Saber topped the PlayStation VR charts, and Call of Duty: Warzone topped the Free-to-Play Games chart. Fortnite – The Iris Pack topped the DLC and Expansions chart.

Here is the complete list of charts:

	PS4 Games
1	Final Fantasy VII Remake
2	Call of Duty: Modern Warfare
3	NBA 2K20
4	Grand Theft Auto V
5	Call of Duty: Modern Warfare 2 Campaign Remastered
6	Resident Evil 3
7	Minecraft
8	EA Sports FIFA 20
9	Monopoly Plus
10	Marvel’s Spider-Man
11	Madden NFL 20
12	Tom Clancy’s Rainbow Six Siege
13	Uno
14	Predator: Hunting Grounds
15	MLB The Show 20
16	Red Dead Redemption 2
17	Need for Speed Heat
18	Rocket League
19	God of War
20	Kingdom Hearts III

	PS VR Games
1	Beat Saber
2	Creed Rise to Glory
3	Job Simulator
4	Rick and Morty: Virtual Rick-ality
5	Arizona Sunshine
6	Superhot VR
7	Vacation Simulator
8	Drunkn Bar Fight
9	Astro Bot Rescue Mission
10	The Room VR: A Dark Matter

	Free-to-Play Games
1	Call of Duty: Warzone
2	Fortnite
3	Apex Legends
4	Destiny 2
5	Brawlhalla
6	Dauntless
7	3on3 FreeStyle
8	Warframe
9	Paladins
10	Warface

	DLC and Expansions
1	Fortnite – The Iris Pack
2	GTA Online: Criminal Enterprise Starter Pack
3	Fortnite – Bassassin Challenge Pack
4	Marvel’s Spider-Man: The City That Never Sleeps
5	Mortal Kombat 11 Kombat Pack
6	Call of Duty: Modern Warfare – Atlanta FaZe Pack
7	Need for Speed Heat – McLaren F1 Black Market Delivery
8	Call of Duty Black Ops III: Zombies Chronicles
9	Dragon Ball Z: Kakarot Season Pass
10	Mortal Kombat 11 – Shao Kahn

A life-long and avid gamer, William D'Angelo was first introduced to VGChartz in 2007. After years of supporting the site, he was brought on in 2010 as a junior analyst, working his way up to lead analyst in 2012. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel dedicated to gaming Let's Plays and tutorials. You can contact the author at wdangelo@vgchartz.com or on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/443430/final-fantasy-vii-remake-tops-the-us-playstation-store-downloads-in-april-2020/

Sony has released the Europe PlayStation Store downloads charts for April 2020. Grand Theft Auto V topped the PS4 charts, Blood and Truth topped the PlayStation VR charts, and Call of Duty: Warzone topped the Free-to-Play Games chart. Fortnite – The Iris Pack topped the DLC and Expansions chart.

Final Fantasy VII Remake debuted in fourth on the PS4 charts. Resident Evil 3 debuted in 10th place.

Here is the complete list of charts:

PlayStation 4

1. Grand Theft Auto V (3)
2. EA SPORTS FIFA 20 (2)
3. Call of Duty: Modern Warfare (1)
4. FINAL FANTASY VII REMAKE (New)
5. NBA 2K20 (RE)
6. Call of Duty: Modern Warfare 2 Campaign Remastered (20)
7. EA SPORTS UFC 3 (RE)
8. Minecraft (5)
9. Marvel’s Spider-Man (RE)
10. RESIDENT EVIL 3 (New)
11. MONOPOLY PLUS (RE)
12. Rocket League (11)
13. Assassin’s Creed Odyssey (10)
14. Days Gone (RE)
15. TOM CLANCY’S RAINBOW SIX | SIEGE (RE)
16. Red Dead Redemption 2 (19)
17. The Crew 2 (13)
18. Tom Clancy’s The Division 2 (RE)
19. eFootball PES 2020 (RE)
20. Need for Speed Heat (RE)

PlayStation VR

1. Blood and Truth (5)
2. Beat Saber (1)
3. Creed: Rise to Glory (9)
4. Job Simulator (2)
5. RICK AND MORTY: VIRTUAL RICK-ALITY (RE)
6. ASTRO BOT Rescue Mission (RE)
7. Until Dawn: Rush of Blood (RE)
8. BOXVR (RE)
9. Farpoint (RE)
10. SUPERHOT VR (4)

DLC

1. Fortnite – The Iris Pack (1)
2. Fortnite – Bassassin Challenge Pack (3)
3. GTA Online: Criminal Enterprise Starter Pack (5)
4. Marvel’s Spider-Man: The City That Never Sleeps – Season Pass (RE)
5. Assassin’s Creed Odyssey – Season pass (RE)
6. Fortnite: Save the World – Standard Founder’s Pack (10)
7. The Division 2 – Warlords of New York – Expansion (2)
8. Need for Speed Heat – McLaren F1 Black Market Delivery (6)
9. Modern Warfare – Atlanta FaZe Pack (New)
10. Assassin’s Creed Origins – The Hidden Ones (RE)

Free-to-Play

1. Call of Duty: Warzone (1)
2. Fortnite (2)
3. Apex Legends (3)
4. Brawlhalla (5)
5. DON’T EVEN THINK (New)
6. eFootball PES 2020 LITE (4)
7. Destiny 2 (New)
8. WORLD OF WARSHIPS: LEGENDS (7)
9. DRAGON BALL XENOVERSE 2 Lite Version (6)
10. Paladins (9)

A life-long and avid gamer, William D'Angelo was first introduced to VGChartz in 2007. After years of supporting the site, he was brought on in 2010 as a junior analyst, working his way up to lead analyst in 2012. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel dedicated to gaming Let's Plays and tutorials. You can contact the author at wdangelo@vgchartz.com or on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/443431/gtav-tops-the-eu-playstation-store-downloads-in-april-2020-final-fantasy-vii-remake-debuts-in-4th/

Two Windsor men face multiple drug, property and weapon charges after police pulled over a vehicle for a traffic violation Thursday night. At around 8 p.m., officers from the Windsor police property crimes unit in the area of Tecumseh Road East and Mercer Road saw a black Chrysler 300 commit a traffic violation, police said […]

As anticipated due to the COVID-19 pandemic, Windsor’s unemployment rate closed in on historic levels in April as it reached 12.9 per cent of the labour force, according to the latest numbers released Friday by Statistics Canada. There were 21,800 people in the Windsor area recorded as being unemployed in the latest StatsCan survey. But […]

Ancestors is the latest attempt to gamify millions of years of evolution but doesn't have the excitement gene, says Jacob Aron

Inside a mountain in the Arctic, Microsoft is building a backup of open-source software that it says will keep the code safe for 1000 years

Back in early March Apple announced that it would closing the majority of its physical stores worldwide. Roughly seven weeks later Australian Apple stores will be re-opening their doors around the country later this week. More »

Big Oil Companies Face Tough Comparisons as Earnings Near American and European oil giants spend a lot of time talking about their differentiated strategies and approaches to hot-button issues such as climate change. But their bottom lines are still primarily driven by the same common factor: commodity prices. That shared reality doesn’t bode well for […]

Premier League clubs are fearful that a significant number of first-team stars may refuse to return to action if the league's Project Restart plan gets the green light.

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A group of astronomers has called for legal action to stop the launch of thousands of satellites designed by companies like SpaceX and OneWeb to beam high-speed internet around the world