National Assembly Speaker Thandi Modise has expressed her disinterest in participating in any virtual meeting over the platform Zoom as the national legislature came under criticism on social media for opening itself to hacking.

Hyundai Motor is currently in the works to develop a pickup truck model for the U.S. market. Michael O'Brien, vice president in charge of product planning for Hyundai Motor America, said on August 22 in a press conference, "The top management approved a project to develop a pickup truck model." Pickup trucks are highly popular in the United States. There is only one pickup truck model available in Korea, which is Ssangyong Motor's Korando Sports.Hyundai Motor unveiled a pickup truck concept mode...

Le Conseil sup�rieur de la Magistrature a �mis, tard dans la soir�e de samedi, une note fixant les modalit�s de la reprise progressive du travail dans les tribunaux au cours de la prochaine p�riode. ......

The African football legends provided inspiration for many during their playing days ......

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The European Commission (the "EC") presented two proposals on 5 December 2012, as part of its State Aid Modernisation initiative. The proposals will include amendments to two key State aid instruments, the Enabling Regulation and...

On 29 September 2016, the French Competition Authority (l’Autorité de la concurrence - the “Autorité”) imposed a fine of EUR 2.4 million on 37 model agencies and their main trade association, the SYNAM, in relation to...

While fines recently imposed by the French and UK data protection supervisory authorities have been high, the supervisory authorities in Germany have so far imposed rather moderate penalties. This could now be changed by a new model for calculating ...

Earlier this week, the Internet revisited clips of America’s Next Top Model, which premiered in 2003 on UPN and has aged pretty badly ever since, in which host ... More » ......

One of the issues which accommodation teams in the Education Sector will be grappling with will be students trying to terminate their accommodation contracts early because of the Coronavirus outbreak. The impact this will have on the institution&rsq...

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Educational institutions are having to navigate through unchartered territory with regards to their student accommodation, implementing the recent government guidance in relation to Covid-19 to ensure the safety of both staff and students. Although ...

Within weeks, the Covid-19 epidemic was classified by the World Health Organization (WHO) as an epidemic of international significance, triggering a pre-agreed WHO response. By the end of the first week of April, more than 1.3 million people had been confirmed as infected, with over 65,000 deaths across the world. Many governments of developing, especially […]

The post Kerala Covid-19 Response Model for Emulation appeared first on Inter Press Service.

The country's lockdown model is being lauded by the WHO, but it's a unique case whose death rate is much worse than its neighbors.

From exotic animals to spectacles and chandeliers, Michael Laver’s “The Dutch East India Company in Early Modern Japan” shows how well-placed gifts were essential in ...

Ninjala is sure to deliver Splatoon fans a new mess of fun and the rest of the world gets a peek at the buzz behind ...

Twenty-first century evangelists and missionaries are confronted with a vastly different world to that of the early church. In the realms of communication and technology, the changes are immense. And in the eyes of many church growth proponents, a lot of modern advancements have left the Bible looking older than ever.

NANKANA SAHIB: Punjab Governor Chudhary Muhammad Sarwar has said that the world has seen the RSS agenda of Modi government and its atrocities on innocent Kashmiris in the Indian Occupied Kashmir.He said this during his visit to the Gurdwara Janamasthan where he distributed ration bags among the...

China’s military may have been spared any coronavirus infections, but the global health crisis has slowed the progress of Chinese President Xi Jinping’s plan to transform the People’s Liberation Army into a modern fighting force capable of long-range power-projecting operations, experts say.According to China’s defence ministry, the world’s largest armed force – with about 2.3 million personnel – has had zero confirmed cases of Covid-19. In contrast, the US and Russian militaries, ranked second…

Prague Daily Monitor

The Prague Transport Authority (DPP) is funding a project to extend the tram track from Sídliště Modřany to Nové Dvory. The extension will be 1.8 kilometers long and cost about CZK 350 million. The target completion date would be 2027.

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The government needs to encourage innovative technology that resonates with our requirements.

NEW DELHI: Since the election results were announced last week — handing out a clear mandate to the Narendra Modi-led BJP — real estate brokers across the country have been prodding buyers to book their dream homes fast, since with a stable government on the cards, builders could increase prices any time soon. Business for thousands of brokers has been thin over the last year or so as negative sentiment engulfed the market and home sales tanked. Investors fled and genuine home buyers waited anxiously to see if a new stable government can infuse life into the economy. “It might just be a case of brokers trying to perk up […]

dsPIC33CK64MC105 General Purpose Plug-In Module (PIM) Information Sheet

dsPIC33CK64MC105 Motor Control Plug-In Module (PIM) Information Sheet for External Op Amp Configuration

dsPIC33CK64MC105 Motor Control Plug-In Module (PIM) Information Sheet for Internal Op Amp Configuration

NEW DELHI: India’s top medical research body has turned down a proposal by the Modi government to test water from the Ganges river as a cure for coronavirus, ThePrint news portal said on Thursday.

It said the Indian Council of Medical Research (ICMR) turned down the government’s “request” to conduct research on a theory that Gangajal, or water from Ganges river, could possibly cure Covid-19.

Speaking to ThePrint, a source in the ICMR said the agency has refused to get involved as it is focussing on the Covid-19 battle and doesn’t want to waste time on other research amid the pandemic.

The move came after the country’s apex medical research body received a “request” from the Ministry of Jal Shakti to conduct “further research” on a proposal by an NGO, Atulya Ganga, said an ICMR official, who didn’t wish to be named.

In its letter last month, Mr Atulya had cited the presence of a “ninja virus”, called bacteriophage, in Ganges water that could cure Covid-19, the disease caused by the new coronavirus. Bacteriophage is a special type of virus that eats harmful bacteria, the letter said.

According ThePrint, the NGO asked the government on April 3 to conduct a study on the possibility of this virus acting as a cure. It sent a copy each to the ministry and the Prime Minister’s Office (PMO). The ministry’s National Mission for Clean Ganga, the department administering the Modi government’s ambitious Namami Gange programme, then wrote to ICMR on April 30 requesting a clinical trial.

The ICMR then held a meeting to discuss the idea, but refused to proceed, offering only its “help” to the NGO, ThePrint said. “We had indeed received a letter from the Ministry of Jal Shakti for such research. The experts at ICMR also held a meeting on this matter. Then we asked those proposing this research that you should tell us about hospitals and doctors that are ready and willing to conduct some research on it. We will certainly help them in this regard,” said the ICMR official.

“As of now we are still treating plasma therapy as a trial for treatment for corona (Covid-19), then how can we so quickly accept a virus called bacteriophage, found in the water of Ganges, as a cure? Right now, there is no logic in the argument that the virus found in Ganga’s water can indeed fight the coronavirus disease,” added the official.

However, he added that if the ministry takes an initiative into the matter then ICMR will extend its assistance to it.

Speaking to ThePrint, Dr Rajnikant Srivastava, ICMR’s head of the Department of Research Management, Policy Planning and Communication, in Delhi and Director of Regional Medical Research Centre, Gorakhpur, said: “A presentation was made after the Jal Shakti ministry’s proposal. The matter is at a very preliminary stage. Nothing has been decided on the future course of action. We will support the Jal Shakti ministry in all the work it does on this front.”

A senior official of the Ministry of Jal Shakti, meanwhile, said there are several special properties in the river and many people were demanding research on them.

Published in Dawn, May 8th, 2020

TNS Property market in the tricity and its periphery is coming back to life with fresh transactions and possessions being handed over in the existing projects Though the chill in the air has shown no signs of slackening so far in 2014, there are signs of a thaw in the realty scene in the tricity and its periphery areas in the new year. While 2013 had been tagged as one of the most dismal years for the property market in the Chandigarh, Panchkula and Mohali area by market watchers, no miracles were foreseen for 2014 in view of the soaring inflation figures, low GDP growth and impending general elections. But […]

ADB and the Government of Mongolia today signed $40 million in loans and a $2 million Japan Fund for Poverty Reduction grant to support the modernization of government-owned irrigation networks and vegetable production in Mongolia.

Kolkata and ADB are working systematically to update the city’s ancient urban systems after years of piecemeal approaches

With the Narendra Modi government taking charge on Tuesday, real estate players hope the sector will get due priority, which will help bring the economy back to 8-9 percent growth. “The new government will pave way for realty reforms and take concrete steps to implement its promise given in the BJP manifesto to ensure housing for all in eight years,” Confederation of Real Estate Developers’ Associations of India (Credai) Lalit Kumar Jain said. The merger of Housing and Urban Development Department will ensure coordination and proper control, he said. “The new government will bring in a positive change to developers and buyers in the otherwise dark era that has been […]

On Monday, the government rolled out the promised “package of reforms” to boost the country’s exports. The commerce ministry notified the Amended Rules, 2013, for special economic zones (SEZs) launched with much fanfare over seven years ago. However, real estate developers are not very enthused by the amended policy. The reason, they say, is not just policy, but several other factors that have stifled the growth of a sector, which posted growth of over 121 per cent in exports in 2009-10. As per the amended policy, the minimum land requirement norms have been eased, graded scale for minimum land criteria has been introduced, an exit policy for SEZ units has […]

NORTHRIDGE, Calif.—HARMAN Professional Solutions, the global leader in audio, video, lighting and control systems, today announced the AKG Lyra ultra-HD, multi-mode USB microphone will be making its 2020 tradeshow season debut at the 2020 NAMM show in...

Genetically modified diamondback moths designed to replace pesticides by wiping out female moths have been released in New York state

Modifying bacteria found in the guts of bees could help protect the insects against lethal infections affecting hives worldwide

The data centres servicing our beloved digital devices gobble huge amounts of electricity. A new way to think about heat and energy could help us meet growing demand without burning through the world's resources

Britain's Tate Modern gallery in London reveals additional building called the 'Switch House' which will open to the public on June 17.

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Physical and chemical DNA-damaging agents are used widely in the treatment of cancer. Double-strand break (DSB) lesions in DNA are the most deleterious form of damage and, if left unrepaired, can effectively kill cancer cells. DNA-dependent protein kinase (DNA-PK) is a critical component of nonhomologous end joining (NHEJ), one of the two major pathways for DSB repair. Although DNA-PK has been considered an attractive target for cancer therapy, the development of pharmacologic DNA-PK inhibitors for clinical use has been lagging. Here, we report the discovery and characterization of a potent, selective, and orally bioavailable DNA-PK inhibitor, M3814 (peposertib), and provide in vivo proof of principle for DNA-PK inhibition as a novel approach to combination radiotherapy. M3814 potently inhibits DNA-PK catalytic activity and sensitizes multiple cancer cell lines to ionizing radiation (IR) and DSB-inducing agents. Inhibition of DNA-PK autophosphorylation in cancer cells or xenograft tumors led to an increased number of persistent DSBs. Oral administration of M3814 to two xenograft models of human cancer, using a clinically established 6-week fractionated radiation schedule, strongly potentiated the antitumor activity of IR and led to complete tumor regression at nontoxic doses. Our results strongly support DNA-PK inhibition as a novel approach for the combination radiotherapy of cancer. M3814 is currently under investigation in combination with radiotherapy in clinical trials.

This article describes the development of medical competencies for oral medicine specialty training in the UK and Ireland by a collaborative working group using a modified Delphi technique. The current specialty training curriculum for oral medicine (OM) in the UK was developed by a working group including members of the British Society for Oral Medicine (BSOM) and members of the Specialty Advisory Committee for Additional Dental Specialties (SACADS) and adopted by the UK General Dental Council (GDC) in 2010. When the curriculum was developed, the entry requirements for specialty training in OM included undergraduate degrees in both dentistry and medicine. At the time of adoption, the requirement for a medical degree was removed. Medical competencies were assumed to have been delivered in medical undergraduate and postgraduate training. Accordingly, there was a need to define the medical competencies for OM specialty training to benefit trainees, trainers, and assessors. In 2018, a group comprising specialty trainers, recent former specialty trainees, and current specialty trainees in OM held face-to-face meetings in addition to email discussions and developed an updated curriculum document to better reflect the medical competencies required in specialty training. A collaborative modified Delphi approach was used to evaluate medical foundation competencies and to include only those that were considered relevant to OM specialty training. A list of relevant and achievable medical competencies was determined that has been approved by SACADS and will be incorporated into a revised OM curriculum from the UK GDC. The newly agreed-upon document for medical competencies in OM specialty training will serve as a reference for trainees, trainers, and assessors and reflects a successful use of a modified Delphi approach.

The formation and properties of liquid-ordered (Lo) lipid domains (rafts) in the plasma membrane are still poorly understood. This limits our ability to manipulate ordered lipid domain-dependent biological functions. Giant plasma membrane vesicles (GPMVs) undergo large-scale phase separations into coexisting Lo and liquid-disordered lipid domains. However, large-scale phase separation in GPMVs detected by light microscopy is observed only at low temperatures. Comparing Förster resonance energy transfer-detected versus light microscopy-detected domain formation, we found that nanodomains, domains of nanometer size, persist at temperatures up to 20°C higher than large-scale phases, up to physiologic temperature. The persistence of nanodomains at higher temperatures is consistent with previously reported theoretical calculations. To investigate the sensitivity of nanodomains to lipid composition, GPMVs were prepared from mammalian cells in which sterol, phospholipid, or sphingolipid composition in the plasma membrane outer leaflet had been altered by cyclodextrin-catalyzed lipid exchange. Lipid substitutions that stabilize or destabilize ordered domain formation in artificial lipid vesicles had a similar effect on the thermal stability of nanodomains and large-scale phase separation in GPMVs, with nanodomains persisting at higher temperatures than large-scale phases for a wide range of lipid compositions. This indicates that it is likely that plasma membrane nanodomains can form under physiologic conditions more readily than large-scale phase separation. We also conclude that membrane lipid substitutions carried out in intact cells are able to modulate the propensity of plasma membranes to form ordered domains. This implies lipid substitutions can be used to alter biological processes dependent upon ordered domains.

ABSTRACT

Arthritogenic alphaviruses such as Ross River and Chikungunya viruses cause debilitating muscle and joint pain and pose significant challenges in the light of recent outbreaks. How host immune responses are orchestrated after alphaviral infections and lead to musculoskeletal inflammation remains poorly understood. Here, we show that myositis induced by Ross River virus (RRV) infection is driven by CD11b^hi Ly6C^hi inflammatory monocytes and followed by the establishment of a CD11b^hi Ly6C^lo CX₃CR1⁺ macrophage population in the muscle upon recovery. Selective modulation of CD11b^hi Ly6C^hi monocyte migration to infected muscle using immune-modifying microparticles (IMP) reduced disease score, tissue damage, and inflammation and promoted the accumulation of CX₃CR1⁺ macrophages, enhancing recovery and resolution. Here, we detail the role of immune pathology, describing a poorly characterized muscle macrophage subset as part of the dynamics of alphavirus-induced myositis and tissue recovery and identify IMP as an effective immunomodulatory approach. Given the lack of specific treatments available for alphavirus-induced pathologies, this study highlights a therapeutic potential for simple immune modulation by IMP in infected individuals in the event of large alphavirus outbreaks.

IMPORTANCE Arthritogenic alphaviruses cause debilitating inflammatory disease, and current therapies are restricted to palliative approaches. Here, we show that following monocyte-driven muscle inflammation, tissue recovery is associated with the accumulation of CX₃CR1⁺ macrophages in the muscle. Modulating inflammatory monocyte infiltration using immune-modifying microparticles (IMP) reduced tissue damage and inflammation and enhanced the formation of tissue repair-associated CX₃CR1⁺ macrophages in the muscle. This shows that modulating key effectors of viral inflammation using microparticles can alter the outcome of disease by facilitating the accumulation of macrophage subsets associated with tissue repair.

ABSTRACT

Host-associated microbial communities are shaped by extrinsic and intrinsic factors to the holobiont organism. Environmental factors and microbe-microbe interactions act simultaneously on the microbial community structure, making the microbiome dynamics challenging to predict. The coral microbiome is essential to the health of coral reefs and sensitive to environmental changes. Here, we develop a dynamic model to determine the microbial community structure associated with the surface mucus layer (SML) of corals using temperature as an extrinsic factor and microbial network as an intrinsic factor. The model was validated by comparing the predicted relative abundances of microbial taxa to the relative abundances of microbial taxa from the sample data. The SML microbiome from Pseudodiploria strigosa was collected across reef zones in Bermuda, where inner and outer reefs are exposed to distinct thermal profiles. A shotgun metagenomics approach was used to describe the taxonomic composition and the microbial network of the coral SML microbiome. By simulating the annual temperature fluctuations at each reef zone, the model output is statistically identical to the observed data. The model was further applied to six scenarios that combined different profiles of temperature and microbial network to investigate the influence of each of these two factors on the model accuracy. The SML microbiome was best predicted by model scenarios with the temperature profile that was closest to the local thermal environment, regardless of the microbial network profile. Our model shows that the SML microbiome of P. strigosa in Bermuda is primarily structured by seasonal fluctuations in temperature at a reef scale, while the microbial network is a secondary driver.

IMPORTANCE Coral microbiome dysbiosis (i.e., shifts in the microbial community structure or complete loss of microbial symbionts) caused by environmental changes is a key player in the decline of coral health worldwide. Multiple factors in the water column and the surrounding biological community influence the dynamics of the coral microbiome. However, by including only temperature as an external factor, our model proved to be successful in describing the microbial community associated with the surface mucus layer (SML) of the coral P. strigosa. The dynamic model developed and validated in this study is a potential tool to predict the coral microbiome under different temperature conditions.

ABSTRACT

Human genetics influence a range of pathological and clinical phenotypes in respiratory infections; however, the contributions of disease modifiers remain underappreciated. We exploited the Collaborative Cross (CC) mouse genetic-reference population to map genetic modifiers that affect the severity of Pseudomonas aeruginosa lung infection. Screening for P. aeruginosa respiratory infection in a cohort of 39 CC lines exhibits distinct disease phenotypes ranging from complete resistance to lethal disease. Based on major changes in the survival times, a quantitative-trait locus (QTL) was mapped on murine chromosome 3 to the genomic interval of Mb 110.4 to 120.5. Within this locus, composed of 31 protein-coding genes, two candidate genes, namely, dihydropyrimidine dehydrogenase (Dpyd) and sphingosine-1-phosphate receptor 1 (S1pr1), were identified according to the level of genome-wide significance and disease gene prioritization. Functional validation of the S1pr1 gene by pharmacological targeting in C57BL/6NCrl mice confirmed its relevance in P. aeruginosa pathophysiology. However, in a cohort of Canadian patients with cystic fibrosis (CF) disease, regional genetic-association analysis of the syntenic human locus on chromosome 1 (Mb 97.0 to 105.0) identified two single-nucleotide polymorphisms (rs10875080 and rs11582736) annotated to the Dpyd gene that were significantly associated with age at first P. aeruginosa infection. Thus, there is evidence that both genes might be implicated in this disease. Our results demonstrate that the discovery of murine modifier loci may generate information that is relevant to human disease progression.

IMPORTANCE Respiratory infection caused by P. aeruginosa is one of the most critical health burdens worldwide. People affected by P. aeruginosa infection include patients with a weakened immune system, such as those with cystic fibrosis (CF) genetic disease or non-CF bronchiectasis. Disease outcomes range from fatal pneumonia to chronic life-threatening infection and inflammation leading to the progressive deterioration of pulmonary function. The development of these respiratory infections is mediated by multiple causes. However, the genetic factors underlying infection susceptibility are poorly known and difficult to predict. Our study employed novel approaches and improved mouse disease models to identify genetic modifiers that affect the severity of P. aeruginosa lung infection. We identified candidate genes to enhance our understanding of P. aeruginosa infection in humans and provide a proof of concept that could be exploited for other human pathologies mediated by bacterial infection.

ABSTRACT

The cell cycle is a critical component of cellular proliferation, differentiation, and response to stress, yet its role in the regulation of intracellular symbioses is not well understood. To explore host-symbiont cell cycle coordination in a marine symbiosis, we employed a model for coral-dinoflagellate associations: the tropical sea anemone Aiptasia (Exaiptasia pallida) and its native microalgal photosymbionts (Breviolum minutum and Breviolum psygmophilum). Using fluorescent labeling and spatial point-pattern image analyses to characterize cell population distributions in both partners, we developed protocols that are tailored to the three-dimensional cellular landscape of a symbiotic sea anemone tentacle. Introducing cultured symbiont cells to symbiont-free adult hosts increased overall host cell proliferation rates. The acceleration occurred predominantly in the symbiont-containing gastrodermis near clusters of symbionts but was also observed in symbiont-free epidermal tissue layers, indicating that the presence of symbionts contributes to elevated proliferation rates in the entire host during colonization. Symbiont cell cycle progression differed between cultured algae and those residing within hosts; the endosymbiotic state resulted in increased S-phase but decreased G₂/M-phase symbiont populations. These phenotypes and the deceleration of cell cycle progression varied with symbiont identity and host nutritional status. These results demonstrate that host and symbiont cells have substantial and species-specific effects on the proliferation rates of their mutualistic partners. This is the first empirical evidence to support species-specific regulation of the symbiont cell cycle within a single cnidarian-dinoflagellate association; similar regulatory mechanisms likely govern interpartner coordination in other coral-algal symbioses and shape their ecophysiological responses to a changing climate.

IMPORTANCE Biomass regulation is critical to the overall health of cnidarian-dinoflagellate symbioses. Despite the central role of the cell cycle in the growth and proliferation of cnidarian host cells and dinoflagellate symbionts, there are few studies that have examined the potential for host-symbiont coregulation. This study provides evidence for the acceleration of host cell proliferation when in local proximity to clusters of symbionts within cnidarian tentacles. The findings suggest that symbionts augment the cell cycle of not only their enveloping host cells but also neighboring cells in the epidermis and gastrodermis. This provides a possible mechanism for rapid colonization of cnidarian tissues. In addition, the cell cycles of symbionts differed depending on nutritional regime, symbiotic state, and species identity. The responses of cell cycle profiles to these different factors implicate a role for species-specific regulation of symbiont cell cycles within host cnidarian tissues.

ABSTRACT

Pyocin S5 (PyoS5) is a potent protein bacteriocin that eradicates the human pathogen Pseudomonas aeruginosa in animal infection models, but its import mechanism is poorly understood. Here, using crystallography, biophysical and biochemical analyses, and live-cell imaging, we define the entry process of PyoS5 and reveal links to the transport mechanisms of other bacteriocins. In addition to its C-terminal pore-forming domain, elongated PyoS5 comprises two novel tandemly repeated kinked 3-helix bundle domains that structure-based alignments identify as key import domains in other pyocins. The central domain binds the lipid-bound common polysaccharide antigen, allowing the pyocin to accumulate on the cell surface. The N-terminal domain binds the ferric pyochelin transporter FptA while its associated disordered region binds the inner membrane protein TonB1, which together drive import of the bacteriocin across the outer membrane. Finally, we identify the minimal requirements for sensitizing Escherichia coli toward PyoS5, as well as other pyocins, and suggest that a generic pathway likely underpins the import of all TonB-dependent bacteriocins across the outer membrane of Gram-negative bacteria.

IMPORTANCE Bacteriocins are toxic polypeptides made by bacteria to kill their competitors, making them interesting as potential antibiotics. Here, we reveal unsuspected commonalities in bacteriocin uptake pathways, through molecular and cellular dissection of the import pathway for the pore-forming bacteriocin pyocin S5 (PyoS5), which targets Pseudomonas aeruginosa. In addition to its C-terminal pore-forming domain, PyoS5 is composed of two tandemly repeated helical domains that we also identify in other pyocins. Functional analyses demonstrate that they have distinct roles in the import process. One recognizes conserved sugars projected from the surface, while the other recognizes a specific outer membrane siderophore transporter, FptA, in the case of PyoS5. Through engineering of Escherichia coli cells, we show that pyocins can be readily repurposed to kill other species. This suggests basic ground rules for the outer membrane translocation step that likely apply to many bacteriocins targeting Gram-negative bacteria.