For years, the Orleans Parish District Attorney's Office in Louisiana issued fake subpoenas to witnesses and crime victims. Unlike subpoenas used in ongoing prosecutions, these were used during the investigation process to compel targets to talk to law enforcement. They weren't signed by judges or issued by court clerks but they did state in bold letters across the top that "A FINE AND IMPRISONMENT MAY BE OPPOSED FOR FAILURE TO OBEY THIS NOTICE."

Recipients of these bogus subpoenas sued the DA's office. In early 2019, a federal court refused to grant absolute immunity to the DA's office for its use of fake subpoenas to compel cooperation from witnesses. The court pointed out that issuing its own subpoenas containing threats of imprisonment bypassed an entire branch of the government to give the DA's office power it was never supposed to have.

Allegations that the Individual Defendants purported to subpoena witnesses without court approval, therefore, describe more than a mere procedural error or expansion of authority. Rather, they describe the usurpation of the power of another branch of government.

The court stated that extending immunity would be a judicial blessing of this practice, rather than a deterrent against continued abuse by the DA's office.

The DA's office appealed. The Fifth Circuit Appeals Court took the case, but it seemed very unimpressed by the office's assertions. Here's how it responded during oral arguments earlier this year:

“Threat of incarceration with no valid premise?” Judge Jennifer Elrod said at one point during arguments. She later drew laughter from some in the audience when she said, “This argument is fascinating.”

“These are pretty serious assertions of authority they did not have,” said Judge Leslie Southwick, who heard arguments with Elrod and Judge Catharina Haynes.

The Appeals Court has released its ruling [PDF] and it will allow the lawsuit to proceed. The DA's office has now been denied immunity twice. Absolute immunity shields almost every action taken by prosecutors during court proceedings. But these fake subpoenas were sent to witnesses whom prosecutors seemingly had no interest in ever having testify in court. This key difference means prosecutors will have to face the state law claims brought by the plaintiffs.

Based upon the pleadings before us at this time, it could be concluded that Defendants’ creation and use of the fake subpoenas was not “intimately associated with the judicial phase of the criminal process,” but rather fell into the category of “those investigatory functions that do not relate to an advocate’s preparation for the initiation of a prosecution or for judicial proceedings.” See Hoog-Watson v. Guadalupe Cty., 591 F.3d 431, 438 (5th Cir. 2009)

[...]

Defendants were not attempting to control witness testimony during a break in judicial proceedings. Instead, they allegedly used fake subpoenas in an attempt to pressure crime victims and witnesses to meet with them privately at the Office and share information outside of court. Defendants never used the fake subpoenas to compel victims or witnesses to testify at trial. Such allegations are of investigative behavior that was not “intimately associated with the judicial phase of the criminal process.”

Falling further outside the judicial process was the DA's office itself, which apparently felt the judicial system didn't need to be included in its subpoena efforts.

In using the fake subpoenas, Individual Defendants also allegedly intentionally avoided the judicial process that Louisiana law requires for obtaining subpoenas.

The case returns to the lower court where the DA's office will continue to face the state law claims it hoped it would be immune from. The Appeals Court doesn't say the office won't ultimately find some way to re-erect its absolute immunity shield, but at this point, it sees nothing on the record that says prosecutors should be excused from being held responsible for bypassing the judicial system to threaten crime victims and witnesses with jail time.

-Album Details- Title: NJBP Concert Archives I ~ANCIENT FESTIVAL~ Publisher: SuperSweep Catalog Number: SRVD-5001 Release Date: July 6th, 2019 Ripped by: Razakin -Info- Recording of the New Japan BGM Philharmonic Orchestra’s Ancient Festival concert, which was full of Yuzo Koshiro goodness from the Scheme to Streets of Rage and Etrian Odyssey, and as a main […]

BACKGROUND The live attenuated BPZE1 vaccine candidate induces protection against B. pertussis and prevents nasal colonization in animal models. Here we report on the responses in humans receiving a single intranasal administration of BPZE1.METHODS We performed multiple assays to dissect the immune responses induced in humans (n = 12) receiving BPZE1, with particular emphasis on the magnitude and characteristics of the antibody responses. Such responses were benchmarked to adolescents (n = 12) receiving the complete vaccination program of the currently used acellular pertussis vaccine (aPV). Using immunoproteomics analysis, potentially novel immunogenic B. pertussis antigens were identified.RESULTS All BPZE1 vaccinees showed robust B. pertussis–specific antibody responses with regard to significant increase in 1 or more of the following parameters: IgG, IgA, and memory B cells to B. pertussis antigens. BPZE1–specific T cells showed a Th1 phenotype, and the IgG exclusively consisted of IgG1 and IgG3. In contrast, all aPV vaccines showed a Th2-biased response. Immunoproteomics profiling revealed that BPZE1 elicited broader and different antibody specificities to B. pertussis antigens as compared with the aPV that primarily induced antibodies to the vaccine antigens. Moreover, BPZE1 was superior at inducing opsonizing antibodies that stimulated ROS production in neutrophils and enhanced bactericidal function, which was in line with the finding that antibodies against adenylate cyclase toxin were only elicited by BPZE1.CONCLUSION The breadth of the antibodies, the Th1-type cellular response, and killing mechanisms elicited by BPZE1 may hold prospects of improving vaccine efficacy and protection against B. pertussis transmission.TRIAL REGISTRATION ClinicalTrials.gov NCT02453048, NCT00870350.FUNDING ILiAD Biotechnologies, Swedish Research Council (Vetenskapsrådet), Swedish Heart-Lung Foundation.

La compañía energética BP anunció el lanzamiento de su aplicación móvil BPme, desarrollada con capacidades de inteligencia artificial (IA) de IBM Watson, buscando mejorar constantemente la experiencia de los usuarios de las estaciones de servicio de BP en México.

Ten years ago, April 20, 11 men on the Deepwater Horizon were incinerated when the BP/Transocean oil rig blew out and exploded. Just 17 months before the Deepwater Horizon destroyed 600 miles of Gulf Coast, BP covered up a

The post Deepwater Horizon: BP’s SECOND Blowout<div id='sec-title'>The Secret History - 10 Year Anniversary</div> appeared first on Greg Palast.

LOS ÁNGELES – Hoy, la Agencia de Protección Ambiental (EPA, por sus siglas en inglés) y la Oficina de Comercio Internacional de Aduanas y Protección Fronteriza (CBP) de los EE. UU.

LOS ANGELES – Today, the U.S. Environmental Protection Agency (EPA) and U.S. Customs and Border Protection (CBP) announced they have prevented a significant number of shipments of illegal health products from entering the Los Angeles International Airport (LAX).

SAN FRANCISCO – Today, the U.S. Environmental Protection Agency (EPA) and U.S. Customs and Border Protection (CBP) announced they have prevented a significant number of shipments of illegal health products from entering the San Francisco International Airport (SFO).

Tá go leor oibrithe a bhí ar an íosphá náisiúnta níos fearr as anois más amhlaidh go bhfuil siad ag fáil an liúntais dífhostaíochta €350 sa tseachtain a tugadh isteach i mí an Mhárta, de réir staidéir nua.

Attorneys for UCLA and University of California want to block a subpoena request made Jorge Salcedo, an ex-soccer coach implicated in the admissions scandal.

My colleague Tanya Beckett has conducted a rare and fascinating interview with Viktor Vekselberg, one of the billionaire oligarchs who co-own TNK-BP with BP - and who have fallen out with BP over BP's desire to form a business relationship with Rosneft, Russia's largest energy group, which would involve BP and Rosneft taking stakes in each other.

Because of the tensions that have arisen with AAR, the group that represents the oligarchs, BP in collaboration with Rosneft would dearly love to buy AAR's half share in TNK-BP. But their offer of $27bn for 50% of TNK-BP, which values the whole of TNK-BP at $54bn, was rejected earlier this month.

All may not be lost for BP, however. Mr Vekselberg suggests that a sale is possible. He tells Tanya Beckett:

"Of course it can be happen, for sure. If it will be [an] interesting proposal for us according to our understanding of (the) valuation of this company, of course we can accept. So far we have not received this."

So what would be an "interesting" valuation of TNK-BP? Well those close to the oligarchs say that they value TNK-BP at more than $70bn.

It's not clear BP and Rosneft are prepared to pay as much that. The difficulty for BP is that if it fails to reach an accommodation with Mr Vekselberg and his colleagues on price, then it will be stuck in a difficult place - because BP will have been publicly humiliated by the failure to consummate the Rosneft deal and will somehow have to rebuild relations with AAR in order to continue to extract billions of dollars in dividends from TNK-BP.

BP's partnership with AAR is in tatters, as Mr Vekselberg makes clear, in emotive terms, because of AAR's conviction, upheld in arbitration proceedings, that BP's proposed deal with Rosneft breached its contract with AAR:

"The picture is really simple. TNK-BP was created eight years ago, 2003. It was created like [a] joint venture between Russian shareholders and BP, huge global player... The company grew very active; it's now one of the best companies - not just Russian but internationally, because we have investment outside Russia...
 
And really I personally was surprised, I was surprised why BP decided to do something which [was] not according to our shareholders agreement. I am not surprised why BP would like to do this but I am surprised why they did it without any consulting or even just like, just inform us about that (sic). I was very upset, I am still upset even now".

Mr Vekselberg says he is "not so interested in money". The billionaire
adds: "I have enough money, for my life, for my family, for all that".
But "we are businessmen, we are not ideological or something", so of course a sale to BP and Rosneft "can happen".

So what would occur if BP and Rosneft were to make him several billion dollars richer? "I am already very upset" he says "but I will [be] double upset if I have to decide to sell. It's because I dedicated for this company almost like 15 years".

These remarks by Mr Vekselberg are a sign that the impasse over the purchase by BP and Rosneft of AAR's stake in TNK-BP can be overcome.
It offers hope to BP, perhaps for the first time, that it may be able to buy AAR out of the joint venture by the time of the May 16 extended deadline set by Rosneft.

But here's the question? Is the price that Mr Vekselberg and his fellow billionaires will accept one that BP's owners will see as acceptable?

Some of them are already dubious about the terms of the new partnership it wants to form with Rosneft. At a time when BP remains financially stretched by the costs of the disaster in the Gulf of Mexico, BP's shareholders won't want it to further enrich Mr Vekselberg more than is strictly necessary.

For more on the Vekselberg interview, see Russia Business Report.

İngiliz petrol devi BP, yılın 2. çeyreğinde kârının, geçen yılın aynı dönemine kıyasla yüzde 53 azaldığını duyurdu. BP, bu duruma gerekçe olarak, petrol fiyatlarının düşük olmasını gösterdi.

The Sheriff Civilian Oversight Commission voted Thursday to subpoena L.A. County Sheriff Alex Villanueva for testimony regarding the coronavirus outbreak in the jails.

velocityconf: Call for speakers and registration is open for @webperfdays in Silicon Valley http://t.co/cJKBmynkjI June 22, Google HQ (cc @sfwebperf)

Mutations in retinaldehyde-binding protein 1 (RLBP1), encoding the visual cycle protein cellular retinaldehyde-binding protein (CRALBP), cause an autosomal recessive form of retinal degeneration. By binding to 11-cis-retinoid, CRALBP augments the isomerase activity of retinoid isomerohydrolase RPE65 (RPE65) and facilitates 11-cis-retinol oxidation to 11-cis-retinal. CRALBP also maintains the 11-cis configuration and protects against unwanted retinaldehyde activity. Studying a sibling pair that is compound heterozygous for mutations in RLBP1/CRALBP, here we expand the phenotype of affected individuals, elucidate a previously unreported phenotype in RLBP1/CRALBP carriers, and demonstrate consistencies between the affected individuals and Rlbp1/Cralbp−/− mice. In the RLBP1/CRALBP-affected individuals, nonrecordable rod-specific electroretinogram traces were recovered after prolonged dark adaptation. In ultrawide-field fundus images, we observed radially arranged puncta typical of RLBP1/CRALBP-associated disease. Spectral domain-optical coherence tomography (SD-OCT) revealed hyperreflective aberrations within photoreceptor-associated bands. In short-wavelength fundus autofluorescence (SW-AF) images, speckled hyperautofluorescence and mottling indicated macular involvement. In both the affected individuals and their asymptomatic carrier parents, reduced SW-AF intensities, measured as quantitative fundus autofluorescence (qAF), indicated chronic impairment in 11-cis-retinal availability and provided information on mutation severity. Hypertransmission of the SD-OCT signal into the choroid together with decreased near-infrared autofluorescence (NIR-AF) provided evidence for retinal pigment epithelial cell (RPE) involvement. In Rlbp1/Cralbp−/− mice, reduced 11-cis-retinal levels, qAF and NIR-AF intensities, and photoreceptor loss were consistent with the clinical presentation of the affected siblings. These findings indicate that RLBP1 mutations are associated with progressive disease involving RPE atrophy and photoreceptor cell degeneration. In asymptomatic carriers, qAF disclosed previously undetected visual cycle deficiency.

Human leukocyte antigen (HLA) B*51:01 and endoplasmic reticulum aminopeptidase 1 (ERAP1) are strongly genetically associated with Behcet's disease (BD). Previous studies have defined two subgroups of HLA-B*51 peptidome containing proline (Pro) or alanine (Ala) at position 2 (P2). Little is known about the unconventional non-Pro/Ala2 HLA-B*51-bound peptides. We aimed to study the features of this novel subpeptidome, and investigate its regulation by ERAP1. CRISPR-Cas9 was used to generate an HLA-ABC-triple knockout HeLa cell line (HeLa.ABC-KO), which was subsequently transduced to express HLA-B*51:01 (HeLa.ABC-KO.B51). ERAP1 was silenced using lentiviral shRNA. Peptides bound to HLA-B*51:01 were eluted and analyzed by mass spectrometry. The characteristics of non-Pro/Ala2, Pro2, and Ala2 peptides and their alteration by ERAP1 silencing were investigated. Effects of ERAP1 silencing on cell surface expression of HLA-B*51:01 were studied using flow cytometry. More than 20% of peptides eluted from HLA-B*51:01 lacked Pro or Ala at P2. This unconventional group of HLA-B*51:01-bound peptides was relatively enriched for 8-mers (with relatively fewer 9-mers) compared with the Pro2 and Ala2 subpeptidomes and had similar N-terminal and C-terminal residue usages to Ala2 peptides (with the exception of the less abundant leucine at position ). Knockdown of ERAP1 increased the percentage of non-Pro/Ala2 from 20% to ~40%, increased the percentage of longer (10-mer and 11-mer) peptides eluted from HLA-B*51:01 complexes, and abrogated the predominance of leucine at P1. Interestingly knockdown of ERAP1 altered the length and N-terminal residue usage of non-Ala2&Pro2 and Ala2 but not the Pro2 peptides. Finally, ERAP1 silencing regulated the expression levels of cell surface HLA-B*51 in a cell-type-dependent manner. In conclusion, we have used a novel methodology to identify an unconventional but surprisingly abundant non-Pro/Ala2 HLA-B*51:01 subpeptidome. It is increased by knockdown of ERAP1, a gene affecting the risk of developing BD. This has implications for theories of disease pathogenesis.

Liye Chen
May 1, 2020; 19:871-883
Research

Human leukocyte antigen (HLA) B*51:01 and endoplasmic reticulum aminopeptidase 1 (ERAP1) are strongly genetically associated with Behcet's disease (BD). Previous studies have defined two subgroups of HLA-B*51 peptidome containing proline (Pro) or alanine (Ala) at position 2 (P2). Little is known about the unconventional non-Pro/Ala2 HLA-B*51-bound peptides. We aimed to study the features of this novel subpeptidome, and investigate its regulation by ERAP1. CRISPR-Cas9 was used to generate an HLA-ABC-triple knockout HeLa cell line (HeLa.ABC-KO), which was subsequently transduced to express HLA-B*51:01 (HeLa.ABC-KO.B51). ERAP1 was silenced using lentiviral shRNA. Peptides bound to HLA-B*51:01 were eluted and analyzed by mass spectrometry. The characteristics of non-Pro/Ala2, Pro2, and Ala2 peptides and their alteration by ERAP1 silencing were investigated. Effects of ERAP1 silencing on cell surface expression of HLA-B*51:01 were studied using flow cytometry. More than 20% of peptides eluted from HLA-B*51:01 lacked Pro or Ala at P2. This unconventional group of HLA-B*51:01-bound peptides was relatively enriched for 8-mers (with relatively fewer 9-mers) compared with the Pro2 and Ala2 subpeptidomes and had similar N-terminal and C-terminal residue usages to Ala2 peptides (with the exception of the less abundant leucine at position ). Knockdown of ERAP1 increased the percentage of non-Pro/Ala2 from 20% to ~40%, increased the percentage of longer (10-mer and 11-mer) peptides eluted from HLA-B*51:01 complexes, and abrogated the predominance of leucine at P1. Interestingly knockdown of ERAP1 altered the length and N-terminal residue usage of non-Ala2&Pro2 and Ala2 but not the Pro2 peptides. Finally, ERAP1 silencing regulated the expression levels of cell surface HLA-B*51 in a cell-type-dependent manner. In conclusion, we have used a novel methodology to identify an unconventional but surprisingly abundant non-Pro/Ala2 HLA-B*51:01 subpeptidome. It is increased by knockdown of ERAP1, a gene affecting the risk of developing BD. This has implications for theories of disease pathogenesis.

Shwetha K. Shetty
Apr 1, 2020; 61:546-559
Methods

Minjuan Ma
Mar 30, 2020; 0:jlr.RA120000664v1-jlr.RA120000664
Research Articles

Xia Meng
May 1, 2020; 61:591-591
Images in Lipid Research

Matt Egan is back in the hosting chair to chat with producer Chris about the Samsung Galaxy Note 7 and how we feel about phablets. Techworld.com editor Charlotte Jee comes in to explain what is going on at the GDS (government digital service) and why we should care (13:00). Then online editor at Techworld.com Scott Carey chats Instagram stories, why it is a blatant rip off of Snapchat stories and how the social media giant can get away with being so brazen (22:00).  

See acast.com/privacy for privacy and opt-out information.

David Price leads the line this week to see how Samsung's Galaxy S8 came out fighting in London and New York this week. It's blown up! But not like that. Had to get that joke (poorly) out of the way. Chris Martin tells all. Then (18 mins) Cam Mitchell takes aim at Home Secretary Amber Rudd's ill advised comments on encryption and wanting government backdoor access to WhatsApp. Does her basic misunderstanding of privacy rights and how tech works extend to the wider population? And then Dom Preston (31 mins) tells us why Hollywood gone and done another flop, and why Ghost in the Shell is a red (or Scarlett!!!!!) mark against remakes.  

See acast.com/privacy for privacy and opt-out information.

Excessive lipid deposition is a hallmark of nonalcoholic fatty liver disease (NAFLD). Although much has been learned about the enzymes and metabolites involved in NAFLD, few studies have focused on the role of long non-coding RNAs (lncRNAs) in hepatic lipid accumulation. Here, using in vitro and in vivo models of NAFLD, we found that the lncRNA Gm15622 is highly expressed in the liver of obese mice fed a high-fat diet (HFD) and in murine liver (AML-12) cells treated with free fatty acids. Investigating the molecular mechanism in the liver-enriched expression of Gm15622 and its effects on lipid accumulation in hepatocytes and on NAFLD pathogenesis, we found that Gm15622 acts as a sponge for the microRNA miR-742-3p. This sponging activity increased the expression of the transcriptional regulator sterol regulatory element–binding transcription factor 1c (SREBP-1c) and promoted lipid accumulation in the liver of the HFD mice and AML-12 cells. Moreover, further results indicated that metformin suppresses Gm15622 and alleviates NAFLD-associated lipid deposition in mice. In conclusion, we have identified an lncRNA Gm15622–miR-742-3p–SREBP-1c regulatory circuit associated with NAFLD in mice, a finding that significantly advances our insight into how lipid metabolism and accumulation are altered in this metabolic disorder. Our results also suggest that Gm15622 may be a potential therapeutic target for managing NAFLD.

The composition-function relationship of HDL particles and its effects on the mechanisms driving coronary heart disease (CHD) is poorly understood. We tested the hypothesis that the functionality of HDL particles is significantly influenced by their lipid composition. Using a novel 3D-separation method, we isolated five different-sized HDL subpopulations from CHD patients who had low preβ-1 functionality (low-F) (ABCA1-dependent cholesterol-efflux normalized for preβ-1 concentration) and controls who had either low-F or high preβ-1 functionality (high-F). Molecular numbers of apoA-I, apoA-II, and eight major lipid classes were determined in each subpopulation by LC-MS. The average number of lipid molecules decreased from 422 in the large spherical α-1 particles to 57 in the small discoid preβ-1 particles. With decreasing particle size, the relative concentration of free cholesterol (FC) decreased in α-mobility but not in preβ-1 particles. Preβ-1 particles contained more lipids than predicted; 30% of which were neutral lipids (cholesteryl ester and triglyceride), indicating that these particles were mainly remodeled from larger particles not newly synthesized. There were significant correlations between HDL-particle functionality and the concentrations of several lipids. Unexpectedly, the phospholipid:FC ratio was significantly correlated with large-HDL-particle functionality but not with preβ-1 functionality. There was significant positive correlation between particle functionality and total lipids in high-F controls, indicating that the lipid-binding capacity of apoA-I plays a major role in the cholesterol efflux capacity of HDL particles. Functionality and lipid composition of HDL particles are significantly correlated and probably both are influenced by the lipid-binding capacity of apoA-I.

The hydrolysis of triglycerides in triglyceride-rich lipoproteins by LPL is critical for the delivery of triglyceride-derived fatty acids to tissues, including heart, skeletal muscle, and adipose tissues. Physiologically active LPL is normally bound to the endothelial cell protein glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1), which transports LPL across endothelial cells, anchors LPL to the vascular wall, and stabilizes LPL activity. Disruption of LPL-GPIHBP1 binding significantly alters triglyceride metabolism and lipid partitioning. In this study, we modified the NanoLuc® Binary Technology split-luciferase system to develop a novel assay that monitors the binding of LPL to GPIHBP1 on endothelial cells in real time. We validated the specificity and sensitivity of the assay using endothelial lipase and a mutant version of LPL and found that this assay reliably and specifically detected the interaction between LPL and GPIHBP1. We then interrogated various endogenous and exogenous inhibitors of LPL-mediated lipolysis for their ability to disrupt the binding of LPL to GPIHBP1. We found that angiopoietin-like (ANGPTL)4 and ANGPTL3-ANGPTL8 complexes disrupted the interactions of LPL and GPIHBP1, whereas the exogenous LPL blockers we tested (tyloxapol, poloxamer-407, and tetrahydrolipstatin) did not. We also found that chylomicrons could dissociate LPL from GPIHBP1 and found evidence that this dissociation was mediated in part by the fatty acids produced by lipolysis. These results demonstrate the ability of this assay to monitor LPL-GPIHBP1 binding and to probe how various agents influence this important complex.

Mutations in retinaldehyde-binding protein 1 (RLBP1), encoding the visual cycle protein cellular retinaldehyde-binding protein (CRALBP), cause an autosomal recessive form of retinal degeneration. By binding to 11-cis-retinoid, CRALBP augments the isomerase activity of retinoid isomerohydrolase RPE65 (RPE65) and facilitates 11-cis-retinol oxidation to 11-cis-retinal. CRALBP also maintains the 11-cis configuration and protects against unwanted retinaldehyde activity. Studying a sibling pair that is compound heterozygous for mutations in RLBP1/CRALBP, here we expand the phenotype of affected individuals, elucidate a previously unreported phenotype in RLBP1/CRALBP carriers, and demonstrate consistencies between the affected individuals and Rlbp1/Cralbp−/− mice. In the RLBP1/CRALBP-affected individuals, nonrecordable rod-specific electroretinogram traces were recovered after prolonged dark adaptation. In ultrawide-field fundus images, we observed radially arranged puncta typical of RLBP1/CRALBP-associated disease. Spectral domain-optical coherence tomography (SD-OCT) revealed hyperreflective aberrations within photoreceptor-associated bands. In short-wavelength fundus autofluorescence (SW-AF) images, speckled hyperautofluorescence and mottling indicated macular involvement. In both the affected individuals and their asymptomatic carrier parents, reduced SW-AF intensities, measured as quantitative fundus autofluorescence (qAF), indicated chronic impairment in 11-cis-retinal availability and provided information on mutation severity. Hypertransmission of the SD-OCT signal into the choroid together with decreased near-infrared autofluorescence (NIR-AF) provided evidence for retinal pigment epithelial cell (RPE) involvement. In Rlbp1/Cralbp−/− mice, reduced 11-cis-retinal levels, qAF and NIR-AF intensities, and photoreceptor loss were consistent with the clinical presentation of the affected siblings. These findings indicate that RLBP1 mutations are associated with progressive disease involving RPE atrophy and photoreceptor cell degeneration. In asymptomatic carriers, qAF disclosed previously undetected visual cycle deficiency.

Orioles right-hander Hunter Harvey had hopped off a backfield mound at the club's Spring Training complex and exhaled. He was one of 14 pitchers scheduled to face hitters as part of the club's first full-squad workout on Monday, and now that he had, Harvey was asked to recall when was the last time he threw competitive pitches.

Excessive fructose consumption is closely linked to the pathogenesis of metabolic disease. Carbohydrate response element-binding protein (ChREBP) is a transcription factor essential for fructose tolerance in mice. However, the functional significance of liver ChREBP in fructose metabolism remains unclear. Here, we show that liver ChREBP protects mice against fructose-induced hepatotoxicity by regulating liver glycogen metabolism and ATP homeostasis. Liver-specific ablation of ChREBP did not compromise fructose tolerance, but rather caused severe transaminitis and hepatomegaly with massive glycogen overload in mice fed a high-fructose diet, while no obvious inflammation, cell death, or fibrosis was detected in the liver. In addition, liver ATP contents were significantly decreased by ChREBP deficiency in the fed state, which was rendered more pronounced by fructose feeding. Mechanistically, liver contents of glucose-6-phosphate (G6P), an allosteric activator of glycogen synthase, were markedly increased in the absence of liver ChREBP, while fasting-induced glycogen breakdown was not compromised. Furthermore, hepatic overexpression of LPK, a ChREBP target gene in glycolysis, could effectively rescue glycogen overload and ATP reduction, as well as mitigate fructose-induced hepatotoxicity in ChREBP-deficient mice. Taken together, our findings establish a critical role of liver ChREBP in coping with hepatic fructose stress and protecting from hepatotoxicity by regulating LPK.

BP on Friday announced plans to increase disclosure on its efforts to fight climate change after requests from two groups of investors.

Subprime mortgages have been linked to a meltdown in housing and questionable Wall Street practices, and they may have been the original domino that set off America's current economic crisis.

So, you wanted to follow this nice website for new content, but it doesn’t have an RSS feed yet? Don’t…

Spanish translation of the BIS press release about the BIS Quarterly Review, March 2018

Spanish translation of the BIS Quarterly Review, March 2018

Spanish translation of the BIS Quarterly Review, June 2018

Spanish translation of the Press Release on the pre-release of two special chapters of the Annual Economic Report of the BIS, 17 June 2018. Trust is the missing link in today's cryptocurrencies - Cryptocurrencies' model of generating trust limits their potential to replace conventional money, the Bank for International Settlements (BIS) writes in its Annual Economic Report (AER), a new title launched this year.

Spanish translation of the BIS press release about the BIS Quarterly Review, September 2018

Spanish translation of the BIS Quarterly Review, September 2018

Spanish translation of the BIS press release about the BIS Quarterly Review, December 2018

Spanish translation of the BIS Quarterly Review, December 2018

Spanish translation of the BIS press release about the BIS Quarterly Review, March 2019

Spanish translation of the BIS Quarterly Review, March 2019

Spanish translation of the BIS press release on the presentation of the Annual Economic Report 2019, 30 June 2019.

KBP-7072 is a semi-synthetic aminomethylcycline with broad-spectrum activity against Gram-positive and Gram-negative pathogens including multidrug resistant bacterial strains. The pharmacokinetics (PK) of KBP-7072 after oral and intravenous (IV) administration of single and multiple doses were investigated in animal models including during fed and fasted states and also evaluated the protein binding and excretion characteristics. In Sprague-Dawley (SD) rats, Beagle dogs, and CD-1 mice, KBP-7072 demonstrated a linear PK profile after administration of single oral and IV and multiple oral doses. Oral bioavailability ranged from 12% to 32%. Mean T_max ranged from 0.5 to 4 hours, and mean half-life ranged from approximately 6 to 11 hours. Administration of oral doses in the fed state resulted in a marked reduction in C_max and AUC compared with dosing in fasted animals. The mean bound fractions of KBP-7072 were 77.5%, 69.8%, 64.5%, 69.3%, and 69.2% in mouse, rat, dog, monkey, and human plasma, respectively. Following a single 22.5 mg/kg oral dose of KBP-7072 in SD rats, cumulative excretion in feces was 64% and in urine was 2.5% of the administered dose. The PK results in animal models are consistent with single and multiple ascending dose studies in healthy volunteers and confirm the suitability of KBP-7072 for once daily oral and IV administration in clinical studies.

As resistance to artemisinins (current frontline drugs in malaria treatment) emerges in south East Asia, there is an urgent need to identify the genetic determinants and understand the molecular mechanisms underpinning such resistance. Such insights could lead to prospective interventions to contain resistance and prevent the eventual spread to other malaria endemic regions. Artemisinin reduced susceptibility in South East Asia (SEA) has been primarily linked to mutations in P. falciparum Kelch-13, which is currently widely recognised as a molecular marker of artemisinin resistance. However, 2 mutations in a ubiquitin hydrolase, UBP-1, have been previously associated with artemisinin reduced susceptibility in a rodent model of malaria and some cases of UBP-1 mutation variants associating with artemisinin treatment failure have been reported in Africa and SEA. In this study, we have employed CRISPR-Cas9 genome editing and pre-emptive drug pressures to test these artemisinin susceptibility associated mutations in UBP-1 in P. berghei sensitive lines in vivo. Using these approaches, we have shown that the V2721F UBP-1 mutation results in reduced artemisinin susceptibility, while the V2752F mutation results in resistance to chloroquine and moderately impacts tolerance to artemisinins. Genetic reversal of the V2752F mutation restored chloroquine sensitivity in these mutant lines while simultaneous introduction of both mutations could not be achieved and appears to be lethal. Interestingly, these mutations carry a detrimental growth defect, which would possibly explain their lack of expansion in natural infection settings. Our work has provided independent experimental evidence on the role of UBP-1 in modulating parasite responses to artemisinin and chloroquine under in vivo conditions.