Check here each week to keep up with the latest from John MacArthur's pulpit at Grace Community Church.

Check here each week to keep up with the latest from John MacArthur's pulpit at Grace Community Church.

Check here each week to keep up with the latest from John MacArthur's pulpit at Grace Community Church.

Check here each week to keep up with the latest from John MacArthur's pulpit at Grace Community Church.

Procuring authorities and private sector contractors have for some years struggled with the application of the Freedom of Information Act to PFI/PPP procurement processes, and to the legal documentation that results from them. Procuring authorities...

Following a recent change in the law relating to the supply of electricity and gas, landlords of multi-occupancy premises must now allow their tenants to connect to energy suppliers of the tenants' choice.  The landlord can only refuse if it is...

A serious manhunt is presently ongoing to arrest the hoodlums, the police said

The post Suspected hoodlums kill police officer in Edo appeared first on Premium Times Nigeria.

Dayo Johnson – Akure All the unclaimed and unburied corpses in Ondo government morgues across the State would be given mass burial in the next one month. Health commissioner Dr. Wahab Adegbenro said this in a statement issued by his Press Office Abooluwa Famakinwa in Akure. Adegbenro has therefore called on relations of the deceased
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The post Unclaimed corpses in Ondo government morgues to be given mass burial — Akeredolu appeared first on Vanguard News.

[Dalsan Radio] The United States Embassy in Mogadishu calls on the Somali Government and people to allow and encourage transparent reporting on the impact of the COVID-19 pandemic to facilitate the critical efforts to protect and preserve the health and safety of the people of Somalia.

Farhana Haque Rahman is Senior Vice President of IPS Inter Press Service; a journalist and communications expert, she is a former senior official of the United Nations Food and Agriculture Organization and the International Fund for Agricultural Development.

The post Press Freedom Needs Protection from Pandemic too appeared first on Inter Press Service.

The post Freedom of the Press as a Guarantee for Human Dignity and Well-Being appeared first on Inter Press Service.

ONLINE HIGH-LEVEL DIALOGUE Moderated by Jorge Ramos (journalist & author, Univision)

 
4 May 2020, 17:00-18:15 CET (GMT+2) / 11:00am-12:15pm EDT

 
JOIN LIVE: http://en.unesco.org/commemorations/worldpressfreedomday
 

The post Press Freedom and Tackling Disinformation in the COVID-19 context appeared first on Inter Press Service.

A powerful American faith rights watchdog has called for India, which claims to be a multi-religious democracy, to be globally blacklisted over concerning major breaches of religious freedoms,...

[[ This is a content summary only. Visit my website for full links, other content, and more! ]]

A powerful American faith rights watchdog has called for India, which claims to be a multi-religious democracy, to be globally blacklisted over concerning major breaches of religious freedoms,...

[[ This is a content summary only. Visit my website for full links, other content, and more! ]]

A powerful American faith rights watchdog has called for India, which claims to be a multi-religious democracy, to be globally blacklisted over concerning major breaches of religious freedoms,...

[[ This is a content summary only. Visit my website for full links, other content, and more! ]]

“His ultimate passion was for good governance and his advocacy was to help save the environment. He was a highly principled man who sought refuge in his faith.”

The post Dumaguete mourns death of broadcaster 2 days after World Press Freedom Day appeared first on Bulatlat.

“We are alarmed that soon, other media outlets would follow. Without the freedom of the press, there is the danger of other freedoms to be lost. God forbid, these are the first 'test signs' of curtailing other rights.”

The post ABS-CBN shutdown may lead to curtailing of more rights, says press freedom fighter Edita Burgos appeared first on Bulatlat.

“Di ko akalain na ang kalayaan na na-achieve natin noong 1986 ay manganganib uli ngayon.” (I did not expect that the freedom we had achieved in 1986 would be threatened once again.)

The post Veteran journalists urge the public to defend press freedom, democratic rights appeared first on Bulatlat.

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

Every sound makes a difference. This is of particular importance while playing today’s technology-powered and immersive video games. Since its inception, JBL has introduced countless innovative audio solutions that unlock unforgettable experiences....

Boredom can be unpleasant, but we can learn from some of the world's dullest people how to keep ourselves amused, says boredom researcher James Danckert

Title: Austedo (deutetrabenazine)
Category: Medications
Created: 4/17/2020 12:00:00 AM
Last Editorial Review: 4/17/2020 12:00:00 AM

Title: Entyvio (vedolizumab)
Category: Medications
Created: 4/17/2020 12:00:00 AM
Last Editorial Review: 4/17/2020 12:00:00 AM

Title: What Is a Choledochojejunostomy?
Category: Procedures and Tests
Created: 5/6/2020 12:00:00 AM
Last Editorial Review: 5/6/2020 12:00:00 AM

Dental students in North American dental schools are exposed to faculty members with various professional backgrounds. These faculty members may include dentists, dental hygienists, and scientists without clinical dental credentials. The practice of dental hygienists’ educating predoctoral dental students has not been well documented. The aims of this two-part study were to investigate the parameters of didactic, preclinical, and clinical instruction of dental students by dental hygienist faculty members in North American dental schools and to explore dental students’ perceptions of this form of teaching. In part one, a survey was sent electronically to the clinical or academic affairs deans of all 76 American Dental Education Association (ADEA) member dental schools in 2017. Twenty-nine responded, for a 38.2% response rate. In 76% of the responding schools, dental hygienists were teaching dental students. Most respondents reported that, in their schools, the minimum degree required to teach didactically was a master’s, while a bachelor’s degree was required for preclinical and clinical courses. There was no significant association between dental hygienists’ instructing dental students and having a dental hygiene educational program at the institution. In part two of the study, a questionnaire was completed by 102 graduating dental students (85% response rate) at one U.S. university to evaluate the impact of dental hygienist educators. Among the respondents, 87% reported feeling that dental hygienists were very effective educators. There were no significant differences in responses between traditional and advanced standing international dental students. This study found that dental hygienists were educating dental students in many North American dental schools and were doing so in curricular content beyond periodontics and that their educational contributions at a sample school were valued by the dental students there.

ABSTRACT

The synergy between Mycobacterium tuberculosis and human immunodeficiency virus-1 (HIV-1) interferes with therapy and facilitates the pathogenesis of both human pathogens. Fundamental mechanisms by which M. tuberculosis exacerbates HIV-1 infection are not clear. Here, we show that exosomes secreted by macrophages infected with M. tuberculosis, including drug-resistant clinical strains, reactivated HIV-1 by inducing oxidative stress. Mechanistically, M. tuberculosis-specific exosomes realigned mitochondrial and nonmitochondrial oxygen consumption rates (OCR) and modulated the expression of host genes mediating oxidative stress response, inflammation, and HIV-1 transactivation. Proteomics analyses revealed the enrichment of several host factors (e.g., HIF-1α, galectins, and Hsp90) known to promote HIV-1 reactivation in M. tuberculosis-specific exosomes. Treatment with a known antioxidant—N-acetyl cysteine (NAC)—or with inhibitors of host factors—galectins and Hsp90—attenuated HIV-1 reactivation by M. tuberculosis-specific exosomes. Our findings uncover new paradigms for understanding the redox and bioenergetics bases of HIV-M. tuberculosis coinfection, which will enable the design of effective therapeutic strategies.

IMPORTANCE Globally, individuals coinfected with the AIDS virus (HIV-1) and with M. tuberculosis (causative agent of tuberculosis [TB]) pose major obstacles in the clinical management of both diseases. At the heart of this issue is the apparent synergy between the two human pathogens. On the one hand, mechanisms induced by HIV-1 for reactivation of TB in AIDS patients are well characterized. On the other hand, while clinical findings clearly identified TB as a risk factor for HIV-1 reactivation and associated mortality, basic mechanisms by which M. tuberculosis exacerbates HIV-1 replication and infection remain poorly characterized. The significance of our research is in identifying the role of fundamental mechanisms such as redox and energy metabolism in catalyzing HIV-M. tuberculosis synergy. The quantification of redox and respiratory parameters affected by M. tuberculosis in stimulating HIV-1 will greatly enhance our understanding of HIV-M. tuberculosis coinfection, leading to a wider impact on the biomedical research community and creating new translational opportunities.

Reactive oxygen and nitrogen species have been implicated in many biological processes and diseases, including immune responses, cardiovascular dysfunction, neurodegeneration, and cancer. These chemical species are short-lived in biological settings, and detecting them in these conditions and diseases requires the use of molecular probes that form stable, easily detectable, products. The chemical mechanisms and limitations of many of the currently used probes are not well-understood, hampering their effective applications. Boronates have emerged as a class of probes for the detection of nucleophilic two-electron oxidants. Here, we report the results of an oxygen-18–labeling MS study to identify the origin of oxygen atoms in the oxidation products of phenylboronate targeted to mitochondria. We demonstrate that boronate oxidation by hydrogen peroxide, peroxymonocarbonate, hypochlorite, or peroxynitrite involves the incorporation of oxygen atoms from these oxidants. We therefore conclude that boronates can be used as probes to track isotopically labeled oxidants. This suggests that the detection of specific products formed from these redox probes could enable precise identification of oxidants formed in biological systems. We discuss the implications of these results for understanding the mechanism of conversion of the boronate-based redox probes to oxidant-specific products.

3-Mercaptopyruvate sulfur transferase (MPST) catalyzes the desulfuration of 3-mercaptopyruvate (3-MP) and transfers sulfane sulfur from an enzyme-bound persulfide intermediate to thiophilic acceptors such as thioredoxin and cysteine. Hydrogen sulfide (H2S), a signaling molecule implicated in many physiological processes, can be released from the persulfide product of the MPST reaction. Two splice variants of MPST, differing by 20 amino acids at the N terminus, give rise to the cytosolic MPST1 and mitochondrial MPST2 isoforms. Here, we characterized the poorly-studied MPST1 variant and demonstrated that substitutions in its Ser–His–Asp triad, proposed to serve a general acid–base role, minimally affect catalytic activity. We estimated the 3-MP concentration in murine liver, kidney, and brain tissues, finding that it ranges from 0.4 μmol·kg−1 in brain to 1.4 μmol·kg−1 in kidney. We also show that N-acetylcysteine, a widely-used antioxidant, is a poor substrate for MPST and is unlikely to function as a thiophilic acceptor. Thioredoxin exhibits substrate inhibition, increasing the KM for 3-MP ∼15-fold compared with other sulfur acceptors. Kinetic simulations at physiologically-relevant substrate concentrations predicted that the proportion of sulfur transfer to thioredoxin increases ∼3.5-fold as its concentration decreases from 10 to 1 μm, whereas the total MPST reaction rate increases ∼7-fold. The simulations also predicted that cysteine is a quantitatively-significant sulfane sulfur acceptor, revealing MPST's potential to generate low-molecular-weight persulfides. We conclude that the MPST1 and MPST2 isoforms are kinetically indistinguishable and that thioredoxin modulates the MPST-catalyzed reaction in a physiologically-relevant concentration range.

The Clay-with-flints Formation outcrops on the high chalk plateaux and interfluves of the chalk downs in southern England. Both current and historical definitions of the Clay-with-flints are detailed and important distinctions are identified with other deposits that appear identical but are formed in different ways. Historically pedological or geomorphological studies have been carried out on the deposit. Engineering studies are only carried out where the deposit is crossed by infrastructure. The physical and chemical processes acting on the deposit and the resulting effects on the physical properties are discussed.

Xiaofei Cao, Sergio Lilla, Zhenbo Cao, Marie Anne Pringle, Ojore B. V. Oka, Philip J. Robinson, Tomasz Szmaja, Marcel van Lith, Sara Zanivan, and Neil J. Bulleid

Folding of proteins entering the mammalian secretory pathway requires the insertion of the correct disulfides. Disulfide formation involves both an oxidative pathway for their insertion and a reductive pathway to remove incorrectly formed disulfides. Reduction of these disulfides is crucial for correct folding and degradation of misfolded proteins. Previously, we showed that the reductive pathway is driven by NADPH generated in the cytosol. Here, by reconstituting the pathway using purified proteins and ER microsomal membranes, we demonstrate that the thioredoxin reductase system provides the minimal cytosolic components required for reducing proteins within the ER lumen. In particular, saturation of the pathway and its protease sensitivity demonstrates the requirement for a membrane protein to shuttle electrons from the cytosol to the ER. These results provide compelling evidence for the crucial role of the cytosol in regulating ER redox homeostasis, ensuring correct protein folding and facilitating the degradation of misfolded ER proteins.

Purpose:

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer, which can be effectively controlled by immunotherapy with PD-1/PD-L1 checkpoint inhibitors. However, a significant proportion of patients are characterized by primary therapy resistance. Predictive biomarkers for response to immunotherapy are lacking.

The incredible benefits of strength training are only just becoming apparent. That's good timing, when working out indoors is beneficial to everyone's health

A new biography of Harry and Meghan will "go beyond the headlines" and "reveal unknown details" of the couple's life together.

Lethbridge police are being investigated by an outside force after handcuffing a woman in a stormtrooper costume outside a Star Wars-themed business earlier this week. But still the force faces accusations that not enough is being done to investigate what happened.

Nadezhda Azhgikhina

The post Freedom of Speech Is Under the Gun as the Virus Spreads in Russia appeared first on The Nation.

"Now there is a stage three and stage four of digitisation, we will take a call on this only after taking all things into account."

Karen Cumming is finding a way to deal with delayed hip surgery

A cornucopia of huge pop names came together for an unprecedented cultural and technological event

(Matador)
The indie maverick is a purveyor of all styles on his studiously eclectic 12th album

There’s a strange psychological cross-pollination going on behind the mask that Will Toledo, the artist mostly known as Car Seat Headrest, sports on the cover of his 12th album. Indulging an alter ego called Trait, Making a Door Less Open seeks out deliberately eclectic hybrids of his wry, lo-fi indie rock style (heir to the likes of Beck, Lou Barlow and Eels) and the satirical EDM he and his drummer Andrew Katz make as 1 Trait Danger. The result is much better than anyone who’s heard the latter, who often veer perilously close to a Bloodhound Gang remix project, might expect: Can’t Cool Me Down has a sultry 80s electropop feel, while the roil of self-deprecation and naked emotion on There Must Be More Than Blood underlines Toledo’s debt to LCD Soundsystem.

The new styles don’t all gel. The sleazy, fuzzy synth-rocker Hollywood is pleasingly punchy, but brought down by facile lyrics (apparently Tinsel Town isn’t the dreamland it’s cracked up to be – who knew?). Two sister songs – the lumpen alt-rock Deadlines (Hostile) and the Hot Chip-with-extra-dour Deadlines (Thoughtful) – fail to charm, while What’s With You Lately is a wan, mopey strum that seems to have wandered in from an entirely different, very bad record. But on the likes of the pulsing, uplifting Famous and Life Worth Missing, Toledo finds new energy.

The This Morning presenter made the most of the sunny weather with a spot of gardening

Welcome to the Evening Standard's live blog covering the latest transfer news and rumours from the Premier League and beyond.

Real Madrid could be set to finish the season at the Alfredo Di Stefano Stadium at their training ground in Valdebebas as works continue to renovate their Santiago Bernabeu home.

Welcome to the Evening Standard's live blog covering the latest transfer news and rumours from the Premier League and beyond.

Tottenham should consider selling Tanguy Ndombele if it means getting Nelson Semedo and Samuel Umtiti, says former Spurs striker Darren Bent.

Tanguy Ndombele's time at Tottenham could be over after just one year as Barcelona are reportedly ready to offer Samuel Umtiti and Nelson Semedo in exchange for the midfielder.

Police in Malaysia confirm they are investigating a journalist over her reporting on mass raids targeting migrants and refugees amid the COVID-19 pandemic.