The Juniper SRX suffers from a dual-homed swapfile overflow error that can cause denial of service conditions.

Installed solar capacity in the United States exceeded 10 GW for the third year in a row in 2018, and the pace of growth is expected to continue. The first quarter of 2019 was the strongest in the history of the U.S. solar market, according to a recent report from Solar Energy Industries Association (SEIA) and Wood Mackenzie Power & Renewables. Yet inefficient and costly project financing inhibits many solar developers from tapping into the market’s true potential.

Installed solar capacity in the United States exceeded 10 GW for the third year in a row in 2018, and the pace of growth is expected to continue. The first quarter of 2019 was the strongest in the history of the U.S. solar market, according to a recent report from Solar Energy Industries Association (SEIA) and Wood Mackenzie Power & Renewables. Yet inefficient and costly project financing inhibits many solar developers from tapping into the market’s true potential.

The COVID 19 pandemic has brought mental health and wellbeing to the fore in many organisations. These issues have become more prominent across workplaces in recent years but we are now facing unprecedented challenges of supporting distributed workf...

By East-West Center HONOLULU (October 4, 2019)—President Donald Trump first laid out a vision for a “free and open Indo-Pacific” at the November 2017 Asia-Pacific Economic Cooperation (APEC) Summit in Vietnam. From the start, statements describing the emerging US Indo-Pacific strategy have recognized the central role of Southeast Asia. The US approach to the Indo-Pacific focuses on three vital areas: enhancing shared prosperity, championing good governance and civil society, and ensuring a peaceful and secure regional order. Two recent visitors to the East-West Center described the potential role of the 10-member Association of Southeast Asian Nations (ASEAN) in the US Indo-Pacific strategy and spelled out several steps that the United States needs to take to strengthen US-ASEAN...

This is a summary only. Click the title for the full article, or visit www.EastWestCenter.org/Research-Wire for more.

Sexual and reproductive health and pandemics might seem to be unrelated topics, but large and dense populations are drivers of the high velocity transmission of COVID-19, and there are lessons to be learned for the future. Gains made in women’s sexual reproductive health and rights just took several steps backward in the midst of the […]

The post Why Reproductive Rights Must Be a Critical Part of Our Arsenal to Fight Pandemics appeared first on Inter Press Service.

SEIBERSDORF, Austria: Shortages of materials needed in tests for the novel coronavirus remain "critical", according to the head of a UN lab, which is supplying countries with COVID-19 detection kits.In particular the chemical reagents for the tests are still in short supply, said Giovanni Cattoli,...

SEIBERSDORF: Shortages of materials needed in tests for the novel coronavirus remain “critical”, according to the head of a UN lab, which is supplying countries with COVID-19 detection kits. In particular the chemical reagents for the tests are still in short supply, said Giovanni...

ABSTRACT

Synthesis and cleavage of the cell wall polymer peptidoglycan (PG) are carefully orchestrated processes and are essential for the growth and survival of bacteria. Yet, the function and importance of many enzymes that act on PG in Mycobacterium tuberculosis remain to be elucidated. We demonstrate that the activity of the N-acetylmuramyl-l-alanine amidase Ami1 is dispensable for cell division in M. tuberculosis in vitro yet contributes to the bacterium’s ability to persist during chronic infection in mice. Furthermore, the d,l-endopeptidase RipA, a predicted essential enzyme, is dispensable for the viability of M. tuberculosis but required for efficient cell division in vitro and in vivo. Depletion of RipA sensitizes M. tuberculosis to rifampin and to cell envelope-targeting antibiotics. Ami1 helps sustain residual cell division in cells lacking RipA, but the partial redundancy provided by Ami1 is not sufficient during infection, as depletion of RipA prevents M. tuberculosis from replicating in macrophages and leads to dramatic killing of the bacteria in mice. Notably, RipA is essential for persistence of M. tuberculosis in mice, suggesting that cell division is required during chronic mouse infection. Despite the multiplicity of enzymes acting on PG with redundant functions, we have identified two PG hydrolases that are important for M. tuberculosis to replicate and persist in the host.

IMPORTANCE Tuberculosis (TB) is a major global heath burden, with 1.6 million people succumbing to the disease every year. The search for new drugs to improve the current chemotherapeutic regimen is crucial to reducing this global health burden. The cell wall polymer peptidoglycan (PG) has emerged as a very successful drug target in bacterial pathogens, as many currently used antibiotics target the synthesis of this macromolecule. However, the multitude of genes encoding PG-synthesizing and PG-modifying enzymes with apparent redundant functions has hindered the identification of novel drug targets in PG synthesis in Mycobacterium tuberculosis. Here, we demonstrate that two PG-cleaving enzymes are important for virulence of M. tuberculosis. In particular, the d,l-endopeptidase RipA represents a potentially attractive drug target, as its depletion results in the clearance of M. tuberculosis from the host and renders the bacteria hypersusceptible to rifampin, a frontline TB drug, and to several cell wall-targeting antibiotics.

Key Points

Gamma interferon (IFN-)-induced innate immune responses play important roles in the inhibition of Toxoplasma gondii infection. It has been reported that IFN- stimulates non-acidification-dependent growth restriction of T. gondii in HeLa cells, but the mechanism remains unclear. Here, we found that -aminobutyric acid (GABA) receptor-associated protein-like 2 (GABARAPL2) plays a critical role in parasite restriction in IFN--treated HeLa cells. GABARAPL2 is recruited to membrane structures surrounding parasitophorous vacuoles (PV). Autophagy adaptors are required for the proper localization and function of GABARAPL2 in the IFN- -induced immune response. These findings provide further understanding of a noncanonical autophagy pathway responsible for IFN--dependent inhibition of T. gondii growth in human HeLa cells and demonstrate the critical role of GABARAPL2 in this response.

In mammalian cells, alphavirus replication complexes are anchored to the plasma membrane. This interaction with lipid bilayers is mediated through the viral methyl/guanylyltransferase nsP1 and reinforced by palmitoylation of cysteine residue(s) in the C-terminal region of this protein. Lipid content of membranes supporting nsP1 anchoring remains poorly studied. Here, we explore the membrane binding capacity of nsP1 with regard to cholesterol. Using the medically important chikungunya virus (CHIKV) as a model, we report that nsP1 cosegregates with cholesterol-rich detergent-resistant membrane microdomains (DRMs), also called lipid rafts. In search for the critical factor for cholesterol partitioning, we identify nsP1 palmitoylated cysteines as major players in this process. In cells infected with CHIKV or transfected with CHIKV trans-replicase plasmids, nsP1, together with the other nonstructural proteins, are detected in DRMs. While the functional importance of CHIKV nsP1 preference for cholesterol-rich membrane domains remains to be determined, we observed that U18666A- and imipramine-induced sequestration of cholesterol in late endosomes redirected nsP1 to these compartments and simultaneously dramatically decreased CHIKV genome replication. A parallel study of Sindbis virus (SINV) revealed that nsP1 from this divergent alphavirus displays a low affinity for cholesterol and only moderately segregates with DRMs. Behaviors of CHIKV and SINV with regard to cholesterol, therefore, match with the previously reported differences in the requirement for nsP1 palmitoylation, which is dispensable for SINV but strictly required for CHIKV replication. Altogether, this study highlights the functional importance of nsP1 segregation with DRMs and provides new insight into the functional role of nsP1 palmitoylated cysteines during alphavirus replication.

IMPORTANCE Functional alphavirus replication complexes are anchored to the host cell membranes through the interaction of nsP1 with the lipid bilayers. In this work, we investigate the importance of cholesterol for such an association. We show that nsP1 has affinity for cholesterol-rich membrane microdomains formed at the plasma membrane and identify conserved palmitoylated cysteine(s) in nsP1 as the key determinant for cholesterol affinity. We demonstrate that drug-induced cholesterol sequestration in late endosomes not only redirects nsP1 to this compartment but also dramatically decreases genome replication, suggesting the functional importance of nsP1 targeting to cholesterol-rich plasma membrane microdomains. Finally, we show evidence that nsP1 from chikungunya and Sindbis viruses displays different sensitivity to cholesterol sequestering agents that parallel with their difference in the requirement for nsP1 palmitoylation for replication. This research, therefore, gives new insight into the functional role of palmitoylated cysteines in nsP1 for the assembly of functional alphavirus replication complexes in their mammalian host.

BACKGROUND:Electrical impedance tomography (EIT) is a noninvasive, portable lung imaging technique that provides functional distribution of ventilation. We aimed to describe the relationship between the distribution of ventilation by mode of ventilation and level of oxygenation impairment in children who are critically ill. We also aimed to describe the safety of EIT application.METHODS:A prospective observational study of EIT images obtained from subjects in the pediatric ICU. Images were categorized by whether the subjects were on intermittent mandatory ventilation (IMV), continuous spontaneous ventilation, or no positive-pressure ventilation. Images were categorized by the level of oxygenation impairment when using SpO2/FIO2. Distribution of ventilation is described by the center of ventilation.RESULTS:Sixty-four images were obtained from 25 subjects. Forty-two images obtained during IMV with a mean ± SD center of ventilation of 55 ± 6%, 14 images during continuous spontaneous ventilation with a mean ± SD center of ventilation of 48.1 ± 11%, and 8 images during no positive-pressure ventilation with a mean ± SD center of ventilation of 47.5 ± 10%. Seventeen images obtained from subjects with moderate oxygenation impairment with a mean ± SD center of ventilation of 59.3 ± 1.9%, 12 with mild oxygenation impairment with a mean ± SD center of ventilation of 52.6 ± 2.3%, and 4 without oxygenation impairment with a mean ± SD center of ventilation of 48.3 ± 4%. There was more ventral distribution of ventilation with IMV versus continuous spontaneous ventilation (P = .009), with IMV versus no positive-pressure ventilation (P = .01) cohorts, and with moderate oxygenation impairment versus cohorts without oxygenation impairment (P = .009). There were no adverse events related to the placement and use of EIT in our study.CONCLUSIONS:Children who had worse oxygen impairment or who received controlled modes of ventilation had more ventral distribution of ventilation than those without oxygen impairment or the subjects who were spontaneously breathing. The ability of EIT to detect changes in the distribution of ventilation in real time may allow for distribution-targeted mechanical ventilation strategies to be deployed proactively; however, future studies are needed to determine the effectiveness of such a strategy.

PURPOSE

Operational failures are system-level errors in the supply of information, equipment, and materials to health care personnel. We aimed to review and synthesize the research literature to determine how operational failures in primary care affect the work of primary care physicians.

Clinicians from two hospitals in Boston report that the majority of even the sickest patients with COVID-19 -- those who require ventilators in intensive care units -- get better when they receive existing guideline-supported treatment for respiratory failure.

Chandigarh, May 9: Hockey legend Balbir Singh Sr, a triple Olympic gold medallist, has been admitted to a city hospital in critical condition. The 96-year-old was taken to a private hospital from his residence in Sector 36 in Chandigarh, where

Forest fires are raging in the contaminated area near the Chernobyl nuclear power plant, but officials insist there is no radiation threat.

Follow our live Covid-19 updates HERE Coronavirus: The symptoms

NHS doctors and nurses on the frontline are now being asked to treat coronavirus patients without full-length gowns if necessary, ahead of expected shortages.

Around two-thirds of coronavirus patients who required advanced respiratory support in intensive care have died, according to a study of critical care outcomes.