While Singer said there is “nothing new about Evangelical fundamentalist Christians seeking to convert Jews to Christianity,” he noted that the method that GOD TV is using is “completely novel.”

In early February, he was kidnapped for 24 hours, before he was freed by the police. A self-proclaimed prophet named Joe Williams is suspected of ordering the kidnapping.

Foreign-currency exposures on an economy’s external balance sheet may jeopardize financial stability when the exchange rate depreciates.

Foreign-currency exposures on an economy’s external balance sheet may jeopardize financial stability when the exchange rate depreciates.

Indigenous elders from Alaska to Australia have come together to deliver some tough love in a new film for Earth Day. Francis Maguire reports.

ABSTRACT

Channelrhodopsins guide algal phototaxis and are widely used as optogenetic probes for control of membrane potential with light. "Bacteriorhodopsin-like" cation channelrhodopsins (BCCRs) from cryptophytes differ in primary structure from other CCRs, lacking usual residues important for their cation conductance. Instead, the sequences of BCCR match more closely those of rhodopsin proton pumps, containing residues responsible for critical proton transfer reactions. We report 19 new BCCRs which, together with the earlier 6 known members of this family, form three branches (subfamilies) of a phylogenetic tree. Here, we show that the conductance mechanisms in two subfamilies differ with respect to involvement of the homolog of the proton donor in rhodopsin pumps. Two BCCRs from the genus Rhodomonas generate photocurrents that rapidly desensitize under continuous illumination. Using a combination of patch clamp electrophysiology, absorption, Raman spectroscopy, and flash photolysis, we found that the desensitization is due to rapid accumulation of a long-lived nonconducting intermediate of the photocycle with unusually blue-shifted absorption with a maximum at 330 nm. These observations reveal diversity within the BCCR family and contribute to deeper understanding of their independently evolved cation channel function.

IMPORTANCE Cation channelrhodopsins, light-gated channels from flagellate green algae, are extensively used as optogenetic photoactivators of neurons in research and recently have progressed to clinical trials for vision restoration. However, the molecular mechanisms of their photoactivation remain poorly understood. We recently identified cryptophyte cation channelrhodopsins, structurally different from those of green algae, which have separately evolved to converge on light-gated cation conductance. This study reveals diversity within this new protein family and describes a subclade with unusually rapid desensitization that results in short transient photocurrents in continuous light. Such transient currents have not been observed in the green algae channelrhodopsins and are potentially useful in optogenetic protocols. Kinetic UV-visible (UV-vis) spectroscopy and photoelectrophysiology reveal that the desensitization is caused by rapid accumulation of a nonconductive photointermediate in the photochemical reaction cycle. The absorption maximum of the intermediate is 330 nm, the shortest wavelength reported in any rhodopsin, indicating a novel chromophore structure.

Background

Water and solute transport across epithelia can occur via the transcellular or paracellular pathways. Tight junctions play a key role in mediating paracellular ion reabsorption in the kidney. In the renal collecting duct, which is a typical absorptive tight epithelium, coordination between transcellular sodium reabsorption and paracellular permeability may prevent the backflow of reabsorbed sodium to the tubular lumen along a steep electrochemical gradient.

Methods

To investigate whether transcellular sodium transport controls tight-junction composition and paracellular permeability via modulating expression of the transmembrane protein claudin-8, we used cultured mouse cortical collecting duct cells to see how overexpression or silencing of epithelial sodium channel (ENaC) subunits and claudin-8 affect paracellular permeability. We also used conditional kidney tubule–specific knockout mice lacking ENaC subunits to assess the ENaC’s effect on claudin-8 expression.

Results

Overexpression or silencing of the ENaC -subunit was associated with parallel and specific changes in claudin-8 abundance. Increased claudin-8 abundance was associated with a reduction in paracellular permeability to sodium, whereas decreased claudin-8 abundance was associated with the opposite effect. Claudin-8 overexpression and silencing reproduced these functional effects on paracellular ion permeability. Conditional kidney tubule–specific ENaC -subunit knockout mice displayed decreased claudin-8 expression, confirming the cell culture experiments' findings. Importantly, ENaC β-subunit or α-subunit silencing or kidney tubule–specific β-ENaC or α-ENaC knockout mice did not alter claudin-8 abundance.

Conclusions

Our data reveal the specific coupling between ENaC -subunit and claudin-8 expression. This coupling may play an important role in preventing the backflow of reabsorbed solutes and water to the tubular lumen, as well as in coupling paracellular and transcellular sodium permeability.

The Larne and Portpatrick basins, located in the North Channel between SW Scotland and Northern Ireland, have been the target of a small programme of petroleum exploration activities since 1971. A total of five hydrocarbon exploration wells have been drilled within the two basins, although as of yet no commercial discoveries have been made. The presence of hydrocarbon shows alongside the discovery of two good-quality reservoir–seal couplets within Triassic and underlying Permian strata has encouraged exploration within the region. The focus of this study is to evaluate the geology and hydrocarbon prospectivity of the Portpatrick Basin and the offshore section of the Larne Basin. This is achieved through the use of seismic reflection data, and gravity and aeromagnetic data, alongside sedimentological, petrophysical and additional available datasets from both onshore and offshore wells, boreholes and previously published studies. The primary reservoir interval, the Lower–Middle Triassic Sherwood Sandstone Group (c. 600–900 m gross thickness), is distributed across both basins and shows good to excellent porosity (10–25%) and permeability (10–1000 mD) within the Larne Basin. The Middle–Late Triassic Mercia Mudstone Group should provide an excellent top seal where present due to the presence of thick regionally extensive halite deposits, although differential erosion has removed this seal from the margins of the Larne and Portpatrick basins. The Carboniferous, which has been postulated to contain organic-rich source-rock horizons, as inferred from their presence in adjacent basins, has not yet been penetrated within the depocentre of either basin. There is, therefore, some degree of uncertainty regarding the quality and distribution of a potential source rock. The interpretation of seismic reflection profiles presented here, alongside the occurrence of hydrocarbon shows, indicates the presence of organic-rich pre-Permian sedimentary rocks within both basins. 1D petroleum system modelling of the Larne-2 borehole shows that the timing of hydrocarbon generation and migration within the basins is a significant risk, with many traps post-dating the primary hydrocarbon charge. Well-failure analysis has revealed that trap breach associated with kilometre-scale uplift events, and the drilling of wells off-structure due to a lack of good-quality subsurface data, have contributed to the lack of discoveries. While the Larne and Portpatrick basins have many elements required for a working petroleum system, along with supporting hydrocarbon shows, the high risks coupled with the small scale of potential discoveries makes the Portpatrick Basin and offshore section of the Larne Basin poorly prospective for oil and gas discovery.

Thematic collection: This article is part of the Under-explored plays and frontier basins of the UK continental shelf collection available at: http://www.lyellcollection.org/cc/under-explored-plays-and-frontier-basins-of-the-uk-continental-shelf

Liling Niu, Fuyun Wu, Kaili Li, Jing Li, Shenyuan L. Zhang, Junjie Hu, and Qian Wang

Store-operated Ca²⁺ entry (SOCE) is critical for numerous Ca²⁺-related processes. The activation of SOCE requires engagement between stromal interaction molecule 1 (STIM1) molecules on the endoplasmic reticulum and Ca²⁺ release-activated channel (CRAC) Orai on the plasma membrane. However, the molecular details of their interactions remain elusive. Here, we analyzed STIM1-Orai interactions using synthetic peptides derived from the N- and C-termini of Orai channels (Orai-NT and Orai-CT, respectively) and purified fragments of STIM1. The binding of STIM1 to Orai-NT is hydrophilic based, whereas binding to the Orai-CT is mostly hydrophobic. STIM1 decreases its affinity for Orai-CT when Orai-NT is present, supporting a stepwise interaction. Orai3-CT exhibits stronger binding to STIM1 than Orai1-CT, largely due to the shortness of one helical turn. The role of newly identified residues was confirmed by co-immunoprecipitation and Ca²⁺ imaging using full-length molecules. Our results provide important insight into CRAC gating by STIM1.

PF-05089771 is an aryl sulfonamide Nav1.7 channel blocker that binds to the inactivated state of Nav1.7 channels with high affinity but binds only weakly to channels in the resting state. Such aryl sulfonamide Nav1.7 channel blockers bind to the extracellular surface of the S1-S4 voltage-sensor segment of homologous Domain 4, whose movement is associated with inactivation. This binding site is different from that of classic sodium channel inhibitors like lidocaine, which also bind with higher affinity to the inactivated state than the resting state but bind at a site within the pore of the channel. The common dependence on gating state with distinct binding sites raises the possibility that inhibition by aryl sulfonamides and by classic local anesthetics might show an interaction mediated by their mutual state dependence. We tested this possibility by examining the state-dependent inhibition by PF-05089771 and lidocaine of human Nav1.7 channels expressed in human embryonic kidney 293 cells. At –80 mV, where a small fraction of channels are in an inactivated state under drug-free conditions, inhibition by PF-05089771 was both enhanced and speeded in the presence of lidocaine. The results suggest that lidocaine binding to the channel enhances PF-05089771 inhibition by altering the equilibrium between resting states (with D4S4 in the inner position) and inactivated states (with D4S4 in the outer position). The gating state–mediated interaction between the compounds illustrates a principle applicable to many state-dependent agents.

SIGNIFICANCE STATEMENT

The results show that lidocaine enhances the degree and rate of inhibition of Nav1.7 channels by the aryl sulfonamide compound PF-05089771, consistent with state-dependent binding by lidocaine increasing the fraction of channels presenting a high-affinity binding site for PF-05089771 and suggesting that combinations of agents targeted to the pore-region binding site of lidocaine and the external binding site of aryl sulfonamides may have synergistic actions.

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.

All the profits from the track will go to the Brigada Cascos Rojos, an independent aid squad set up to help those affected by the riots. Chilean producer MAGA channels the fury of the civil protests taking place throughout Chile in the moody visual from Juegos Artificiales for their new track, ‘Calma’. “On October 18 […]

The post MAGA channels the fury of the Chilean protests on ‘Calma’ appeared first on FACT Magazine.

UFC returns to action this weekend with an action-packed card of action from Florida.The mixed martial arts organisation comes back after a coronavirus-enforced hiatus on Saturday night in Jacksonville with a 11-fight bill headlined by Tony Ferguson’s clash against Justin Gaethje for the interim lightweight title.

UFC returns to action this weekend with an action-packed card of action from Florida.The mixed martial arts organisation comes back after a coronavirus-enforced hiatus on Saturday night in Jacksonville with a 11-fight bill headlined by Tony Ferguson’s clash against Justin Gaethje for the interim lightweight title.

Some 140 people were found making their way to Britain by the Border Force and brought ashore at Dover, according to Sky News.

'Watching everyone's reaction to Joe Exotic was far better than the series itself,' one viewer wrote

'Reasons to be Cheerful with Matt Lucas' will start on 26 April

The beloved presenting duo will film the series, called Keep Reading and Carry On, in their own homes

Channel 4 show saw Bake Off judge ask if the Japanese eat bread, and give a Michelin-starred chef a Pot Noodle

TV host joked she may still be wearing slippers when show returns to Channel 4 studio in the coming months

Programme was announced at the Edinburgh Television Festival

MTV, Nickelodeon, Paramount Network and TV Land are among the channels launching on YouTube TV in the coming months.

She and Prince William dialled in from their Norfolk home

Football fans will have the chance to embark upon a nostalgic journey over the next few weeks as ITV screen the 1996 European Championships in their entirety.

MELBOURNE jogger Erica O’Donnell has gone viral after delivering the ultimate gaffe during a vox pop interview with Channel Seven.

The channel will also feature Sheila E.

Islanders have been finding ways to mark the anniversary and help the spirit of the Liberation shine during difficult circumstances.

A leaked expert report shows the Queensland Government was advised to stop further gas fracking in the state's sensitive Channel Country, but a separate department already extended gas exploration until 2030.

It’s a unique and troubling time. We are all of course concerned about the coronavirus and its disruption to our personal and professional lives.

I presume that life will return to normal later this year. But what happens then? Will there be long-term changes to how the drug channel operates? Will we see permanent changes in behavior, policy, and industry structure?

To answer these questions, I want to tap the collective insights of Drug Channels’ 30,000+ audience.


This survey should take 10 minutes or less. I will provide a full review of the results next week on Drug Channels. The survey will close on March 20.

You can respond anonymously. Any information you provide will be kept confidential. Per Drug Channels' long-standing policy, I never publish, release, or disclose any personal data without your permission.

Thanks in advance for sharing your insights.

Regards,
Adam

First, let me say thank you to all of the healthcare workers who are putting themselves at risk during this crisis.

As I noted last week, many of the crucial issues for our healthcare system will remain after we all get through this challenging period. In that regard, here’s a look at some noteworthy news from the past month:

• Sanofi discloses new data about insulin prices

• Excellent new academic research on list vs. net drug prices

• Three notable researchers overturn their earlier research on drug costs

• Amazon switches PBM vendors for some of its employees

Plus, we unveil the teaser trailer for Drug Channels Video!

P.S. Join the more than 9,000 followers of my daily links to neat stuff at @DrugChannels on Twitter. My recent tweets have highlighted such topics as:

• How GoodRx shares patients’ prescription data
• 2019 drug trend at Prime Therapeutics
• Controversy about the independent pharmacy market
• A new $5 generic mail order program, Medicare Part D reform
• Retail pharmacy’s future
• Job openings at Amazon 
• Frozen cookie dough
• And much more!

I have also been tweeting many under-the-radar stories about how the coronavirus affects drug channels.
Read more »

In 2006, I launched the Drug Channels website to explore the economics of the U.S. reimbursement and distribution system for prescription pharmaceuticals. More than 30,000 professionals in the pharmaceutical and related industries rely on Drug Channels for timely analysis and provocative, fact-based insights.

Today, I am pleased to announce the launch of our new delivery platform: Drug Channels Video!

You can look forward to:

• Information and analysis via our new YouTube channel (Never fear. I’ll still be publishing articles on the website every week.)

• Livestream video webinars (Stay tuned next week for an announcement about our first two events.)

• Private, live virtual keynotes and remote presentations (Email me to schedule a safe social distancing event for your team.)

• Online video courses (Coming later in 2020)

Please watch my brief video introduction below. (Click here if you can’t see the video.)


I hope you and your families stay safe and healthy in these challenging times. I look forward to reconnecting with you in person soon.

Will home infusion growth be a long-overdue correction for the buy -and-bill channel or a temporary blip that will soon vanish?

For some time, I have been tracking the evolution of the buy-and-bill system for provider-administered drugs. The data have shown that hospital outpatient departments have been displacing physician offices. Amid this shift, home infusion providers have accounted for a minority of commercial medical benefit spending and a tiny share of Medicare Part B spending.

However, the coronavirus pandemic is triggering new growth in home infusion for buy-and-bill products. Below, I highlight the early signs of a marketplace change. I believe that some of these short-term shifts in the buy-and-bill market will persist even after we have recovered from COVID-19. They may even slow the runaway growth of the 340B Drug Pricing Program.

If not, then I suppose we'll just keep living in a world with limited home infusion over and over.

In early May, Drug Channels Institute will host two live video webinars: Industry Update and COVID-19 Impact: Retail & Specialty Pharmacies (May 1) and Industry Update and COVID-19 Impact: PBMs & Payers (May 8). CLICK HERE TO LEARN MORE AND SIGN UP. DCI will donate 20% of all profits from these events to The Center for Disaster Philanthropy’s COVID-19 Response Fund. Watch my video invitation below.

Read more »

Rumor has it that Spring has finally reached our worldwide headquarters here in beautiful downtown Philadelphia. (See photo at right.) While we wait to go outside, please enjoy this month’s selection of noteworthy news:

• The outlook for drug prices

• A outstanding (and free!) resource for tracking COVID-19 daily data

• What’s up with community oncology practices?

Plus, I share my favorite chart of 2020 (so far).

P.S. Join the more than 9,200 followers of my curated links to neat stuff at @DrugChannels on Twitter. My recent tweets have highlighted: Prime Therapeutics new gene therapy offering, AmerisourceBergen’s laudable deal with the Justice Department, the Costco/Instacart deal, Rite Aid’s new CEO, clinical trial trends, vaccine pricing, and much more! I have also been tweeting under-the-radar stories about how the coronavirus is affecting drug channels.

Tomorrow (May 1), Drug Channels Institute will host the first of two live video webinars: Industry Update and COVID-19 Impact: Retail & Specialty Pharmacies. We'll host the second video webinar—Industry Update and COVID-19 Impact: PBMs & Payers—on May 8. CLICK HERE TO LEARN MORE AND SIGN UP. Contact Paula Fein (paula@drugchannelsinstitute.com) for our special promo codes for multiple viewing sites. DCI will donate 20% of all profits from these events to The Center for Disaster Philanthropy’s COVID-19 Response Fund.

Read more »

This week, I’m rerunning some popular posts while I prepare for this Friday’s video webinar: Industry Update and COVID-19 Impact: PBMs & Payers.

Life was very different when I originally published today’s article. 2020 is not turning out to be quite what any of us expected. However, the pandemic has exposed some intriguing pros and cons of vertical consolidation. Click here to see the original post and comments from December 2019.

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The largest insurers, PBMs, and specialty pharmacies have now combined into vertically-integrated organizations. As I explain below, these companies have also been rapidly integrating with healthcare providers.

I also provide an updated look at these companies and highlight strategies that they are using—or could use—to control the channel. I believe that these insurer / PBM / specialty pharmacy / provider organizations are poised to restructure U.S. drug channels by exerting greater control over patient access, sites of care/dispensing, and pricing.

If they can effectively coordinate their sprawling business operations, they will pose a substantial threat of disruption to the existing commercial strategies of pharma companies.

Will they succeed by better managing care and costs, or merely by extracting higher profits from our convoluted system?
Read more »

Selling directly to health care practitioners, supplement companies can foster open dialogue about their products; but, every regulation applies to products in this channel, too.

We all miss those vacations where we did nothing but leave the windows open to the beach and gazed longingly into the lapping surf, or slept under the stars while camping and listening to the crickets, or sang Christmas carols in front of a crackling

The past year has seen mounting consciousness of issues of violence, harassment and targeted abuse of women due to the #MeToo movement, which has led to accountability for several powerful men accused of abusing women, and greater awareness of women’s day-to-day experiences. And yet, as alleged sexual abuser Brett Kavanaugh’s confirmation to the Supreme Court […]

The Hong Kong airport is using several latest disinfection technologies including a full-body disinfection channel and cleaning robots to reduce the risk of the COVID-19 spread.

The disinfection channel is an enclosed facility similar to a telephone booth in size where users can complete disinfection and sanitizing procedures in 40 seconds, the city's Airport Authority (AA) said in a statement on Sunday.

The interior surface of the facility is equipped with antimicrobial coating which can remotely kill virus and bacteria on human bodies and clothing by using the technologies of photocatalyst and "nano needles" Xinhua news agency quoted the AA as saying, noting that the Hong Kong International Airport is the world's first to use the facility.

Currently, the disinfection channel is used by public health staff who bear quarantine duties at the airport.

Autonomous cleaning robots have also been used to ensure thorough disinfection of public areas and passenger facilities at the airport.

The cylindrical robots, equipped with ultra violet light sterilizer and air sterilizer, operate round-the-clock in public toilets and key operating areas in the terminal building, the AA said.

The robots can move around autonomously and sterilize up to 99.99 per cent of bacteria in its vicinity, including both the air and object surfaces, in just 10 minutes.

Besides, the AA is also conducting a pilot test of applying antimicrobial coating at all passenger facilities, including check-in counters, baggage trolleys and elevator buttons, among others.

After completion of the trial in May, the AA will consider implementing it as a long term disinfection measure. Hong Kong has reported 1,037 coronavirus cases with four deaths.

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It has been said many times that there is very little irrigation development in Africa, that there is little water storage per head of population, that this adds up to high vulnerability to droughts.

It has been said many times that there is very little irrigation development in Africa, that there is little water storage per head of population, that this adds up to high vulnerability to droughts.

Company: Confidential
Qualification: Bachelor Of Technology (B.Tech/B.E)
Experience: 2 to 6
Salary: 4.00 to 7.50
location: Bengaluru / Bangalore
Ref: 24792580
Summary: Channel Sales • Electronics, Computer Science or IT Engineering preferred • Min 1 years of experience in Security (CCTV, Biometrics,....

A Telugu local channel named Every^ is caught illegally playing Yash and Srinidhi Shetty's KGF: Chapter 1. The makers are now preparing to take legal action against the channel.

This report develops a framework that classifies investments according to different types of financing instruments and investment funds, and highlights the risk mitigants and transaction enablers that intermediaries can use to mobilise institutionally held capital.

YouTube TV is expanding its lineup of channels thanks to a new, multi-year distribution agreement with ViacomCBS, announced this morning. The Google-owned streaming TV service is gaining 14 new ViacomCBS channels as a result of the deal, including news, sports, and entertainment offerings. It will also continue to carry CBS broadcast stations, CBS Sports Network, […]