Secunia Security Advisory - A vulnerability has been reported in Juniper Junos, which can be exploited by malicious people to bypass certain security restrictions.

Cisco C690 Email Security Appliance version 11.0.2-044 IronPort remote host header injection exploit.

Cisco AnyConnect Secure Mobility Client for Windows version 4.8.01090 suffer from a privilege escalation vulnerability due to insecure handling of path names.

Debian Linux Security Advisory 4590-1 - It was discovered that the lmtpd component of the Cyrus IMAP server created mailboxes with administrator privileges if the "fileinto" was used, bypassing ACL checks.

Windows Defender Antivirus version 4.18.1908.7-0 suffers from a file extension spoofing vulnerability.

A heap memory buffer overflow vulnerability exists within the WebKit's JavaScriptCore JSArray::sort(...) method. The exploit for this vulnerability is javascript code which shows how to use it for memory corruption of internal JS objects (Unit32Array and etc.) and subsequent arbitrary code execution (custom ARM/x64 payloads can be pasted into the JS code). This exploit affects Apple Safari version 6.0.1 for iOS 6.0 and OS X 10.7/8. Earlier versions may also be affected. It was obtained through the Packet Storm Bug Bounty program.

A heap memory buffer overflow vulnerability exists within the WebKit's JavaScriptCore JSArray::sort(...) method. This method accepts the user-defined JavaScript function and calls it from the native code to compare array items. If this compare function reduces array length, then the trailing array items will be written outside the "m_storage->m_vector[]" buffer, which leads to the heap memory corruption. This finding was purchased through the Packet Storm Bug Bounty program.

Red Hat Security Advisory 2020-0903-01 - The zsh shell is a command interpreter usable as an interactive login shell and as a shell script command processor. Zsh resembles the ksh shell, but includes many enhancements. Zsh supports command-line editing, built-in spelling correction, programmable command completion, shell functions, a history mechanism, and more. An issue with insecure dropping of privileges when unsetting PRIVILEGED option was addressed.

This Metasploit module exploits an arbitrary command execution vulnerability in Webmin versions 1.900 and below. Any user authorized to the "Java file manager" and "Upload and Download" fields, to execute arbitrary commands with root privileges. In addition, "Running Processes" field must be authorized to discover the directory to be uploaded. A vulnerable file can be printed on the original files of the Webmin application. The vulnerable file we are uploading should be integrated with the application. Therefore, a ".cgi" file with the vulnerability belong to webmin application should be used. The module has been tested successfully with Webmin version 1.900 over Debian 4.9.18.

Global apparel retailer Gap Inc. announced that it has signed a 90-MW virtual power purchase agreement (VPPA) for the Aurora Wind Project with Enel Green Power North America, marking one of the largest offsite renewable energy contracts by an apparel retailer.

Kansai Electric Power Co. Inc. announces that the 290-MW Nam Ngiep 1 hydropower plant has begun commercial operations.

Review update: The 2020 Mercedes-Benz AMG GLC 43 SUV "nose" the right spice level These are halcyon days for fleet-footed crossover SUVs. Saucy ‘utes like the 2020 Mercedes-Benz GLC 43 AMG hardly look like they’re just as quick as their smaller siblings but stopwatches don’t lie. 5 things to know about Uconnect 5 Uconnect 5, the...

Developer SN Aboitiz Power-Ifugao has said it remains committed to developing the 390-MW Alimit hydropower project in the Philippines, pending consent from indigenous groups impacted by its construction.

The World Bank has approved US$390 million in additional financing to be used by Pakistan's Water and Power Development Authority for extensions of its Tarbela hydroelectric plant.

India’s Cabinet Committee on Economic Affairs announced today it has approved investment for the generation component of the 900-MW Arun 3 hydropower project on Arun River in Sankhuwasabha district of eastern Nepal, for an estimated Rs. 5723.72 crore (US$854.4 million).
 

The International Council of Nurses (ICN) have said that at least 90,000 healthcare workers worldwide are believed to have been infected with Covid-19, and possibly twice that, amid reports of continuing shortages of protective equipment, the Guardian reports. The disease has killed more than 260 nurses. The ICN urges authorities to keep more accurate records to help prevent the virus from spreading among staff and patients.

The World Bank has approved US$390 million in additional financing to be used by Pakistan's Water and Power Development Authority for extensions of its Tarbela hydroelectric plant.

Sur la base d'une mod�lisation, l'Oms estime que 190.000 personnes pourraient perdre la vie � cause du coronavirus qui infectera entre 29 � 44 millions d'Africains. ......

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The photo, Reese Witherspoon shared, is from the premiere of the film "Nowhere" in 1997

Like other sci-fi before it, it imagined the present year as a post-apocalyptic wasteland.

Rawalpindi : The Public Facilitation Centre of Rawalpindi Cantonment Board , during the last seven days, received 163 complaints regarding electricity, water supply and sanitation problems in the cantonment areas and resolved 90 of them.According to RCB spokesman, Qaiser Mehmood, the RCB’s...

Microchip Solves Interoperability Challenges of Delivering up to 90 Watts of Power Over Ethernet Wiring

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Nearly 90 cases of the novel coronavirus have been recorded among employees of Polyus Krasnoyarsk, a unit of Russia's largest gold producer Polyus , the regional branch of Russia's consumer health watchdog said on Saturday.

Before the COVID-19 pandemic upended people's lives, Americans were already feeling more stressed than they did a generation ago. Now, new research finds that no group is feeling the impact of additional stress more than middle-aged people.

Title: Middle Age More Stressful Now Than in 1990s: Study
Category: Health News
Created: 5/7/2020 12:00:00 AM
Last Editorial Review: 5/8/2020 12:00:00 AM

ABSTRACT

Protein homeostasis is critical for proliferation and viability of all organisms. For Candida albicans, protein homeostasis also modulates the transition between yeast and filamentous forms, which is critical for virulence. A key regulator of morphogenesis is the molecular chaperone Hsp90, which mediates proteostasis under physiological and stress conditions. Hsp90 regulates morphogenesis by repressing cyclic AMP-protein kinase A (cAMP-PKA) signaling, such that inhibition of Hsp90 causes filamentation in the absence of an inducing cue. We explored the effect of perturbation of another facet of protein homeostasis and discovered that morphogenesis is also regulated by the proteasome, a large 33-subunit protein complex consisting of a 20S catalytic core and two 19S regulatory particles, which controls degradation of intracellular proteins. We identified a conserved role of the proteasome in morphogenesis as pharmacological inhibition of the proteasome induced filamentation of C. albicans and the related species Candida dubliniensis, Candida tropicalis, Candida krusei, and Candida parapsilosis. For C. albicans, genetic depletion of any of 29 subunits of the 19S or 20S particle induced filamentation. Filaments induced by inhibition of either the proteasome or Hsp90 have shared structural characteristics, such as aberrant nuclear content, and shared genetic dependencies, such as intact cAMP-PKA signaling. Consistent with a functional connection between these facets of protein homeostasis that modulate morphogenesis, we observed that proteasome inhibition results in an accumulation of ubiquitinated proteins that overwhelm Hsp90 function, relieving Hsp90-mediated repression of morphogenesis. Together, our findings provide a mechanism whereby interconnected facets of proteostasis regulate C. albicans morphogenesis.

IMPORTANCE Fungi cause life-threatening infections and pose a serious threat to human health as there are very few effective antifungal drugs. Candida albicans is a major human fungal pathogen and cause of morbidity and mortality in immunocompromised individuals. A key trait that enables C. albicans virulence is its ability to transition between yeast and filamentous forms. Understanding the mechanisms regulating this virulence trait can facilitate the development of much-needed, novel therapeutic strategies. A key regulator of morphogenesis is the molecular chaperone Hsp90, which is crucial for proteostasis. Here, we expanded our understanding of how proteostasis regulates fungal morphogenesis and identified the proteasome as a repressor of filamentation in C. albicans and related species. Our work suggests that proteasome inhibition overwhelms Hsp90 function, thereby inducing morphogenesis. This work provides a foundation for understanding the role of the proteasome in fungal virulence and offers potential for targeting the proteasome to disarm fungal pathogens.

As yet, very few vaccine candidates with activity in animals against Mycobacterium tuberculosis infection have been tested as therapeutic postexposure vaccines. We recently described two pools of mycobacterial proteins with this activity, and here we describe further studies in which four of these proteins (Rv1738, Rv2032, Rv3130, and Rv3841) were generated as a fusion polypeptide and then delivered in a novel yeast-based platform (Tarmogen) which itself has immunostimulatory properties, including activation of Toll-like receptors. This platform can deliver antigens into both the class I and class II antigen presentation pathways and stimulate strong Th1 and Th17 responses. In mice this fusion vaccine, designated GI-19007, was immunogenic and elicited strong gamma interferon (IFN-) and interleukin-17 (IL-17) responses; despite this, they displayed minimal prophylactic activity in mice that were subsequently infected with a virulent clinical strain. In contrast, in a therapeutic model in the guinea pig, GI-19007 significantly reduced the lung bacterial load and reduced lung pathology, particularly in terms of secondary lesion development, while significantly improving survival in one-third of these animals. In further studies in which guinea pigs were vaccinated with BCG before challenge, therapeutic vaccination with GI-19007 initially improved survival versus that of animals given BCG alone, although this protective effect was gradually lost at around 400 days after challenge. Given its apparent ability to substantially limit bacterial dissemination within and from the lungs, GI-19007 potentially can be used to limit lung damage as well as facilitating chemotherapeutic regimens in infected individuals.

In vitro approaches for predicting drug-drug interactions (DDIs) caused by alterations in transporter protein regulation are not well established. However, reports of transporter regulation via nuclear receptor (NR) modulation by drugs are increasing. This study examined alterations in transporter protein levels in sandwich-cultured human hepatocytes (SCHH; n = 3 donors) measured by liquid chromatography–tandem mass spectrometry–based proteomic analysis after treatment with N-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-N-(2,2,2-trifluoroethyl)benzenesulfonamide (T0901317), the first described synthetic liver X receptor agonist. T0901317 treatment (10 μM, 48 hours) decreased the levels of organic cation transporter (OCT) 1 (0.22-, 0.43-, and 0.71-fold of control) and organic anion transporter (OAT) 2 (0.38-, 0.38-, and 0.53-fold of control) and increased multidrug resistance protein (MDR) 1 (1.37-, 1.48-, and 1.59-fold of control). The induction of NR downstream gene expression supports the hypothesis that T0901317 off-target effects on farnesoid X receptor and pregnane X receptor activation are responsible for the unexpected changes in OCT1, OAT2, and MDR1. Uptake of the OCT1 substrate metformin in SCHH was decreased by T0901317 treatment. Effects of decreased OCT1 levels on metformin were simulated using a physiologically-based pharmacokinetic (PBPK) model. Simulations showed a clear decrease in metformin hepatic exposure resulting in a decreased pharmacodynamic effect. This DDI would not be predicted by the modest changes in simulated metformin plasma concentrations. Altogether, the current study demonstrated that an approach combining SCHH, proteomic analysis, and PBPK modeling is useful for revealing tissue concentration–based DDIs caused by unexpected regulation of hepatic transporters by NR modulators.

OBJECTIVE

No study has reported global disability burden estimates for individual diabetes-related lower-extremity complications (DRLECs). The Global Burden of Disease (GBD) study presents a robust opportunity to address this gap.

Mutation and translocation of fibroblast growth factor receptors often lead to aberrant signaling and cancer. This work focuses on the t(8;22)(p11;q11) chromosomal translocation which creates the breakpoint cluster region (BCR) fibroblast growth factor receptor1 (FGFR1) (BCR-FGFR1) fusion protein. This fusion occurs in stem cell leukemia/lymphoma, which can progress to atypical chronic myeloid leukemia, acute myeloid leukemia, or B-cell lymphoma. This work focuses on the biochemical characterization of BCR-FGFR1 and identification of novel therapeutic targets. The tyrosine kinase activity of FGFR1 is required for biological activity as shown using transformation assays, interleukin-3 independent cell proliferation, and liquid chromatography/mass spectroscopy analyses. Furthermore, BCR contributes a coiled-coil oligomerization domain, also essential for oncogenic transformation by BCR-FGFR1. The importance of salt bridge formation within the coiled-coil domain is demonstrated, as disruption of three salt bridges abrogates cellular transforming ability. Lastly, BCR-FGFR1 acts as a client of the chaperonin heat shock protein 90 (Hsp90), suggesting that BCR-FGFR1 relies on Hsp90 complex to evade proteasomal degradation. Transformed cells expressing BCR-FGFR1 are sensitive to the Hsp90 inhibitor Ganetespib, and also respond to combined treatment with Ganetespib plus the FGFR inhibitor BGJ398. Collectively, these data suggest novel therapeutic approaches for future stem cell leukemia/lymphoma treatment: inhibition of BCR oligomerization by disruption of required salt bridges; and inhibition of the chaperonin Hsp90 complex.