Producer Chris dives in this week to discuss the HTC 10 release, and why it's difficult to get excited about good mobile phones. Then Techworld.com editor Charlotte Jee chats Facebook chatbots and other F8 news (12:30). Finally, editor at Digitalartsonline.co.uk Neil Bennett jumps in to discuss the new Amazon e-reader (31:00) Kindle Oasis and why everyone is kicking off about the price.  

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Episode 73 sees David Price lead Scott Carey, Miriam Harris and Henry Burrell into a critique of Mark Zuckerberg's decision to go into a VR tour of Puerto Rico. Disaster tourism at its finest/worst.

Henry then discusses the new Kindle Oasis, which for the firs time is waterproof - but very expensive and quietly released.

Finally we all chip in to ask why Blade Runner 2049 is quite so overtly sexist in its portrayal of women. There be spoilers.

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Oxidized low-density lipoprotein (oxLDL) is a known risk factor for atherogenesis. This study aimed to reveal structural features of oxLDL present in human circulation related to atherosclerosis. When LDL was fractionated on an anion-exchange column, in vivo-oxLDL, detected by the anti-oxidized phosphatidylcholine (oxPC) monoclonal antibody, was recovered in flow-through and electronegative LDL (LDL(-)) fractions. The amount of the electronegative in vivo-oxLDL, namely oxLDL in LDL(-) fraction, present in patients with acute myocardial infarction (AMI) was three-fold higher than that observed in healthy subjects. Surprisingly, LDL(-) fraction contained apoA1 in addition to apoB, and HDL-sized particles were observed with transmission electron microscopy. In LDL(-) fractions, acrolein adducts were identified at all lysine residues in apoA1, with only a small number of acrolein-modified residues were identified in apoB. The amount of oxPC adducts of apoB was higher in LDL(-) than in L1 fraction as determined using western blotting. The electronegative in vivo-oxLDL was immunologically purified from the LDL(-) fraction with an anti-oxPC monoclonal antibody. Majority of PC species was not oxidized, whereas oxPC and lysoPC did not accumulate. Here, we propose that there are two types of in vivo-oxLDL in human circulating plasma and the electronegative in vivo-oxLDL accompanies oxidized HDL.

Atherogenic LDL particles are physicochemically and metabolically heterogeneous. Can bioactive lipid cargo differentiate LDL subclasses, and thus potential atherogenicity?  What is the effect of statin treatment? Obese, hypertriglyceridemic, hypercholesterolemic males (n=12; Lp(a) <10 mg/dL) received pitavastatin calcium (4mg/day) for 180 days in a single-phase, unblinded study. The lipidomic profiles (23 lipid classes) of five LDL subclasses fractionated from baseline and post-statin plasmas were determined by LC-MS. At baseline and on statin treatment, very small dense LDL (LDL5) was preferentially enriched (up to 3-fold) in specific lysophospholipids (lysophosphatidylcholine (LPC); lysophosphatidylinositol (LPI); lyso-platelet activating factor (LPC(O)); 9,0.2 and 0.14 mol/mol apoB respectively; all p<0.001 versus LDL1-4), suggesting  elevated inflammatory potential per particle. In contrast, lysophosphatidylethanolamine was uniformly distributed among LDL subclasses. Statin treatment markedly reduced absolute plasma concentrations of all LDL subclasses (up to 33.5%), including LPC, LPI and LPC(O) contents (up to -52%), consistent with reduction in cardiovascular risk. Despite such reductions, lipotoxic ceramide load per particle in LDL1-5 (1.5 - 3 mol/mol apoB; 3 - 7 mmol/mol phosphatidylcholine) was either conserved or elevated. Bioactive lipids may constitute biomarkers for the cardiometabolic risk associated with specific LDL subclasses in atherogenic dyslipidemia at baseline, and with residual risk on statin therapy.

6 April 2020

23 April 2020

The development of the HUPO-PSI's (Proteomics Standards Initiative) standard data formats and MIAPE (Minimum Information About a Proteomics Experiment) guidelines should improve proteomics data sharing within the scientific community. Proteomics journals have encouraged the use of these standards and guidelines to improve the quality of experimental reporting and ease the evaluation and publication of manuscripts. However, there is an evident lack of bioinformatics tools specifically designed to create and edit standard file formats and reports, or embed them within proteomics workflows. In this article, we describe a new web-based software suite (The ProteoRed MIAPE web toolkit) that performs several complementary roles related to proteomic data standards. Firstly, it can verify the reports fulfill the minimum information requirements of the corresponding MIAPE modules, highlighting inconsistencies or missing information. Secondly, the toolkit can convert several XML-based data standards directly into human readable MIAPE reports stored within the ProteoRed MIAPE repository. Finally, it can also perform the reverse operation, allowing users to export from MIAPE reports into XML files for computational processing, data sharing or public database submission. The toolkit is thus the first application capable of automatically linking the PSI's MIAPE modules with the corresponding XML data exchange standards, enabling bidirectional conversions. This toolkit is freely available at http://www.proteored.org/MIAPE/.

1 January 2007 , Number 2

For all the cynicism it has evoked, the United States’ Iraq Study Group report might still lead to a regional diplomatic process, which could ease Iran and the US into negotiations. A grand bargain is very unlikely, but with Washington at the table, there might be enough advantage for both sides in a gradual process to halt the current slide towards a deeper confrontation.

Pyruvate kinase M2 (PKM2) links metabolic and inflammatory dysfunction in atherosclerotic coronary artery disease; however, its role in oxidized LDL (Ox-LDL)-induced macrophage foam cell formation and inflammation is unknown and therefore was studied. In recombinant mouse granulocyte-macrophage colony-stimulating factor-differentiated murine bone marrow-derived macrophages, early (1–6 h) Ox-LDL treatment induced PKM2 tyrosine 105 phosphorylation and promotes its nuclear localization. PKM2 regulates aerobic glycolysis and inflammation because PKM2 shRNA or Shikonin abrogated Ox-LDL-induced hypoxia-inducible factor-1α target genes lactate dehydrogenase, glucose transporter member 1, interleukin 1β (IL-1β) mRNA expression, lactate, and secretory IL-1β production. PKM2 inhibition significantly increased Ox-LDL-induced ABCA1 and ABCG1 protein expression and NBD-cholesterol efflux to apoA1 and HDL. PKM2 shRNA significantly inhibited Ox-LDL-induced CD36, FASN protein expression, DiI-Ox-LDL binding and uptake, and cellular total cholesterol, free cholesterol, and cholesteryl ester content. Therefore, PKM2 regulates lipid uptake and efflux. DASA-58, a PKM2 activator, downregulated LXR-α, ABCA1, and ABCG1, and augmented FASN and CD36 protein expression. Peritoneal macrophages showed similar results. Ox-LDL induced PKM2- SREBP-1 interaction and FASN expression in a PKM2-dependent manner. Therefore, this study suggests a role for PKM2 in Ox-LDL-induced aerobic glycolysis, inflammation, and macrophage foam cell formation.

Liver-derived serum amyloid A (SAA) is present in plasma where it is mainly associated with HDL and from which it is cleared more rapidly than are the other major HDL-associated apolipoproteins. Although evidence suggests that lipid-free and HDL-associated forms of SAA have different activities, the pathways by which SAA associates and disassociates with HDL are poorly understood. In this study, we investigated SAA lipidation by hepatocytes and how this lipidation relates to the formation of nascent HDL particles. We also examined hepatocyte-mediated clearance of lipid-free and HDL-associated SAA. We prepared hepatocytes from mice injected with lipopolysaccharide or an SAA-expressing adenoviral vector. Alternatively, we incubated primary hepatocytes from SAA-deficient mice with purified SAA. We analyzed conditioned media to determine the lipidation status of endogenously produced and exogenously added SAA. Examining the migration of lipidated species, we found that SAA is lipidated and forms nascent particles that are distinct from apoA-I-containing particles and that apoA-I lipidation is unaltered when SAA is overexpressed or added to the cells, indicating that SAA is not incorporated into apoA-I-containing HDL during HDL biogenesis. Like apoA-I formation, generation of SAA-containing particles was dependent on ABCA1, but not on scavenger receptor class B type I. Hepatocytes degraded significantly more SAA than apoA-I. Taken together, our results indicate that SAA’s lipidation and metabolism by the liver is independent of apoA-I and that SAA is not incorporated into HDL during HDL biogenesis.

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.

Loss of pancreatic β-cell mass and function as a result of sustained ER stress is a core step in the pathogenesis of diabetes mellitus type 2. The complex control of β-cells and insulin production involves hedgehog (Hh) signaling pathways as well as cholesterol-mediated effects. In fact, data from studies in humans and animal models suggest that HDL protects against the development of diabetes through inhibition of ER stress and β-cell apoptosis. We investigated the mechanism by which HDL inhibits ER stress and apoptosis induced by thapsigargin, a sarco/ER Ca²⁺-ATPase inhibitor, in β-cells of a rat insulinoma cell line, INS1e. We further explored effects on the Hh signaling receptor Smoothened (SMO) with pharmacologic agonists and inhibitors. Interference with sterol synthesis or efflux enhanced β-cell apoptosis and abrogated the anti-apoptotic activity of HDL. During ER stress, HDL facilitated the efflux of specific oxysterols, including 24-hydroxycholesterol (OHC). Supplementation of reconstituted HDL with 24-OHC enhanced and, in cells lacking ABCG1 or the 24-OHC synthesizing enzyme CYP46A1, restored the protective activity of HDL. Inhibition of SMO countered the beneficial effects of HDL and also LDL, and SMO agonists decreased β-cell apoptosis in the absence of ABCG1 or CYP46A1. The translocation of the SMO-activated transcription factor glioma-associated oncogene GLI-1 was inhibited by ER stress but restored by both HDL and 24-OHC. In conclusion, the protective effect of HDL to counter ER stress and β-cell death involves the transport, generation, and mobilization of oxysterols for activation of the Hh signaling receptor SMO

The pregnane X receptor (PXR) is a nuclear receptor that can be activated by numerous drugs and xenobiotic chemicals. PXR thereby functions as a xenobiotic sensor to coordinately regulate host responses to xenobiotics by transcriptionally regulating many genes involved in xenobiotic metabolism. We have previously reported that PXR has pro-atherogenic effects in animal models, but how PXR contributes to atherosclerosis development in different tissues or cell types remains elusive. In this study, we generated an LDL receptor-deficient mouse model with myeloid-specific PXR deficiency (PXR^MyeLDLR^–/–) to elucidate the role of macrophage PXR signaling in atherogenesis. The myeloid PXR deficiency did not affect metabolic phenotypes and plasma lipid profiles, but PXR^MyeLDLR^–/– mice had significantly decreased atherosclerosis at both aortic root and brachiocephalic arteries compared with control littermates. Interestingly, the PXR deletion did not affect macrophage adhesion and migration properties, but reduced lipid accumulation and foam cell formation in the macrophages. PXR deficiency also led to decreased expression of the scavenger receptor CD36 and impaired lipid uptake in macrophages of the PXR^MyeLDLR^–/– mice. Further, RNA-Seq analysis indicated that treatment with a prototypical PXR ligand affects the expression of many atherosclerosis-related genes in macrophages in vitro. These findings reveal a pivotal role of myeloid PXR signaling in atherosclerosis development and suggest that PXR may be a potential therapeutic target in atherosclerosis management.

Kindlins are focal adhesion proteins that regulate integrin activation and outside-in signaling. The kindlin family consists of three members, kindlin-1, -2, and -3. Kindlin-2 is widely expressed in multiple cell types, except those from the hematopoietic lineage. A previous study has reported that the Drosophila Fit1 protein (an ortholog of kindlin-2) prevents abnormal spindle assembly; however, the mechanism remains unknown. Here, we show that kindlin-2 maintains spindle integrity in mitotic human cells. The human neuroblastoma SH-SY5Y cell line expresses only kindlin-2, and we found that when SH-SY5Y cells are depleted of kindlin-2, they exhibit pronounced spindle abnormalities and delayed mitosis. Of note, acetylation of α-tubulin, which maintains microtubule flexibility and stability, was diminished in the kindlin-2–depleted cells. Mechanistically, we found that kindlin-2 maintains α-tubulin acetylation by inhibiting the microtubule-associated deacetylase histone deacetylase 6 (HDAC6) via a signaling pathway involving AKT Ser/Thr kinase (AKT)/glycogen synthase kinase 3β (GSK3β) or paxillin. We also provide evidence that prolonged hypoxia down-regulates kindlin-2 expression, leading to spindle abnormalities not only in the SH-SY5Y cell line, but also cell lines derived from colon and breast tissues. The findings of our study highlight that kindlin-2 regulates mitotic spindle assembly and that this process is perturbed in cancer cells in a hypoxic environment.

Invitation Only Research Event

Event participants

Dr Kori Schake, Resident Scholar and Director of Foreign and Defense Policy Studies, American Enterprise Institute 
Chair: Dr Leslie Vinjamuri, Director, US and Americas Programme

The fish comes steaming, and English is not the only language making sense. Here politics comes with dark green Kale spewing flavor, Kenyans having lunch on the Boulevard, Lakeshore strip, Victoria; Commitment is the idea that momentum cannot disrupt motion, that Committed, one moves forward, Becoming better, Choosing beyond the sound Of Visiting Americans, Prodigal […]

HARRISBURG, Pennsylvania (AP) — A Pennsylvania inmate whose dreadlocks violated a jail’s haircut policy has been released from solitary confinement after more than a year, although his federal lawsuit is still pending. A federal...

Middle East respiratory syndrome (MERS) is an acute viral respiratory tract infection caused by the novel betacoronavirus. Cases have been limited to the Arabian Peninsula and its surrounding countries, and to travellers from the Middle East or their contacts. The clinical spectrum of infection varies from no symptoms or mild respiratory...

Who better to kick off a series on all things health and evidence than the exceptional and erudite Editor-in-Chief of The BMJ, Dr Fiona Godlee. In this episode, Fiona chats to Ray about the BMJ's ongoing and often controversial campaigns to change medicine - and broader society - for the better. She also looks to a future that addresses the...

A ‘Peace of Paradise’ garden has been created in George Headley Primary School, which is positively affecting behavioural change in students. The garden was created by students, teachers, and members of the community for the 2019 Trees for Peace...

As the global battle against the deadly COVID-19 disease wages on, with each country’s government, healthcare industry, and general public playing its part in defeating this new and relatively unknown enemy, two seemingly unlikely foot soldiers...

Reduced storage of dietary fatty acids (DFAs) in abdominal adipose tissues with enhanced cardiac partitioning has been shown in subjects with type 2 diabetes (T2D) and prediabetes. We measured DFA metabolism and organ partitioning using positron emission tomography with oral and intravenous long-chain fatty acid and glucose tracers during a standard liquid meal in 12 obese subjects with T2D before and 8–12 days after bariatric surgery (sleeve gastrectomy or sleeve gastrectomy and biliopancreatic diversion with duodenal switch). Bariatric surgery reduced cardiac DFA uptake from a median (standard uptake value [SUV]) 1.75 (interquartile range 1.39–2.57) before to 1.09 (1.04–1.53) after surgery (P = 0.01) and systemic DFA spillover from 56.7 mmol before to 24.7 mmol over 6 h after meal intake after surgery (P = 0.01), with a significant increase in intra-abdominal adipose tissue DFA uptake from 0.15 (0.04–0.31] before to 0.49 (0.20–0.59) SUV after surgery (P = 0.008). Hepatic insulin resistance was significantly reduced in close association with increased DFA storage in intra-abdominal adipose tissues (r = –0.79, P = 0.05) and reduced DFA spillover (r = 0.76, P = 0.01). We conclude that bariatric surgery in subjects with T2D rapidly reduces cardiac DFA partitioning and hepatic insulin resistance at least in part through increased intra-abdominal DFA storage and reduced spillover.

With Greg Holland now signed, will he be the closer or is that still going to be Archie Bradley? Beat reporter Steve Gilbert answers this question and more from fans as Spring Training approaches.

OBJECTIVE

Diabetes is a rapidly growing health problem in low- and middle-income countries (LMICs), but empirical data on its prevalence and relationship to socioeconomic status are scarce. We estimated diabetes prevalence and the subset with undiagnosed diabetes in 29 LMICs and evaluated the relationship of education, household wealth, and BMI with diabetes risk.

Gary F Lewis
Apr 1, 1996; 19:390-393
Symposium On Insulin Resistance

A class action lawsuit alleging that a Florida dental practice sent unsolicited text messages in violation of the Telephone Consumer Protection Act was filed in the U.S. District Court for the Southern District of Florida Jan. 6.

The deadline for abstracts for the upcoming National Summit on Smokeless Tobacco Prevention is Feb. 29.

The deadline for submission of abstracts for the FDI World Dental Congress is March 25.

Noting that we’re living through a time of uncertainty and it’s normal to feel stressed and anxious, the Center for Professional Success today posted free resources on stress management to help dentists navigate this time of uncertainty amid the COVID-19 pandemic.

The deadline for dental offices to install amalgam separators remains intact but the Environmental Protection Agency announced March 26 that it will be initiating “a new temporary enforcement discretion policy” during the COVID-19 pandemic.

The U.S. Department of Labor said April 28 that it is extending the Employee Retirement Income Security Act of 1974 filing deadlines for certain notice and disclosure requirements in the wake of the COVID-19 pandemic.

In the face of economic challenges, the ADA has released two online guides relating to third-party payment programs available at ADA.org/virus that are intended to help smooth the path of reopening practices: Handling Contract Negotiations and Handling Eligibility Verification

OBJECTIVE

To identify sleep duration trajectories from early to middle adulthood and their associations with incident type 2 diabetes.

OBJECTIVE

Preanalytical processing of blood samples can affect plasma glucose measurement because on-going glycolysis by cells prior to centrifugation can lower its concentration. In June 2017, ACT Pathology changed the processing of oral glucose tolerance test (OGTT) blood samples for pregnant women from a delayed to an early centrifugation protocol. The effect of this change on the rate of gestational diabetes mellitus (GDM) diagnosis was determined.

This guest post is written by Angela Peterson who writes on the topic of Online Psychology Degrees and can be emailed at angela_peterson@rediffmail.com

It’s not easy raising a child, and when he or she is affected by a severe disorder or disease, you have a greater challenge ahead of you. You have to put in extra effort, energy and thought into your child’s development and progress, one aspect of which includes their education. Some parents of children with special needs may be tempted to overprotect by keeping them in cloistered environments and limiting their interaction with the outside world. This usually only hampers the child instead of helping them. If you’re a parent with a child who has special needs, here’s some strategies:

* Understand your child: Some children may be able to express themselves while others are limited because of their disability. Whatever the case, understand your child and know that they have a mind of their own even if they are unable to speak it. Instead of forcing your will on them, get to know what they wish to do and cater to their needs as much as possible as long as it does not cause them any harm.

* Be patient: It’s a tough task, but you need to have an enormous amount of patience with your child. You need to condition yourself to be patient through practice and experience, otherwise you and your child will be subject to a great deal of stress.

* Decide on their education: There are many options for providing education to your special needs child, so look for what is available in your area. If you plan to homeschool, you will need to do some research before you’re up to the task. Many feel that it’s better to let the professionals handle this task who are trained and more experienced. Also, your child gets to mingle with other children and interact with them on a regular basis, which is very important to his or her social development.

*Think about inclusive classrooms: Parents often want their special needs children to attend regular schools. Learn about inclusive classrooms and determine if it is a good fit for your child. Consider if your child is up to the task of being educated with general education children and if he/she can cope with the curriculum in such classrooms. Although teachers in inclusive classrooms are trained to deal with children with special needs, there may be times when your child could be bullied or teased by the other kids for not being like them. Take all these facts into consideration before you decide on an inclusive classroom for your child.


Children with special needs need all the help and support they can get from parents and teachers, and it’s up to you to decide on the best form of education for them.

As the population of gray wolves expands across the northern United States, researchers are finding a surprising side-effect: Their presence appears to lead to a reduction in the coyote population.

The Internal Revenue Service said Wednesday is the last day for Americans to provide their direct deposit information to receive their stimulus checks directly to their bank accounts.

Google's homepage features arcade classic "Pac-Man" in the latest Doodle.

This event hosted by MPI Europe and the Research Unit of the Expert Council of German Foundations on Integration and Migration featured a discussion of research into legal migration pathways for work and training for low- and middle-skilled migrants.

The Houston metro area, home to 1.6 million immigrants, is diverse and rapidly growing. This report sketches the area's immigrant population, examining top origin countries, key socioeconomic measures, and more. It also explores how Hurricane Harvey affected the immigrant population, and how national policy changes under the Trump administration are being felt locally, including by DACA recipients and asylum seekers.

Marking the release of two research reports that highlight promising, effective approaches to teaching and learning for Dual Language Learners in multilingual, multicultural classrooms, report authors present their findings on this webinar and discuss key implications for policy and practice.

BRUSSELS — While the European Union has called on Member States to expand channels for foreign workers as a way to meet labour market needs and potentially tackle spontaneous migration, they have struggled to deliver on this pledge. To date, policies have focused more on attracting high-skilled workers, but less attention has been paid to admission of low- or middle-skilled nationals. Policymakers would do well not to overestimate the potential of legal channels to reduce irregular migration.

This recipe was featured on Foodie Tuesday, a weekly segment with Raf Epstein on Drive, 774 ABC Melbourne, 3:30 PM, courtesy of Neil Perry. Neil's new book is "Spice Temple."

2 tablespoons sesame oil 2 teaspoons garlic, minced 1 cup shredded carrots 1 cup cabbage, thinly sliced 1 red capsicum, thinly sliced 1 green chilli, sliced 3 large zucchini, spiralled into noodles 2 large chicken breasts, cooked & shredded Toppings 1/2 cup cashew nuts, chopped spring onion Satay sauce 1/2 cup peanut butter 1/3 cup honey 1/3 cup soy sauce 2 tablespoons sesame oil 2 tablespoons rice vinegar 2 teaspoons fresh ginger, minced 1 tablespoon sweet chilli sauce

This recipe features on Foodie Tuesday, a weekly segment on 774 Drive with Raf Epstein, 3.30PM, courtesy of David Hall of Pure South Dining

This recipe features on Foodie Tuesday, a weekly segment on 774 Drive with Raf Epstein, 3.30PM, shared by Hetty McKinnon, founder of Surry Hills community kitchen Arthur Street Kitchen and author of new cookbook 'Neighbourhood'.

Fresh and easy for summer!