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Bouygues Telecom Entreprises sécurise les flottes mobiles de ses clients avec IBM
aufeminin.com a choisi la solution de Bouygues Telecom Entreprises pour sa simplicité d’utilisation et sa sécurité
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C&E Spotlight: On-Demand Mobile Fueling—Enforcing Existing Regulations and Evaluating Future Needs
Andrew Klein, Principle with AS Klein Engineering, and Lynne Kilpatrick, Fire Marshal in Sunnyvale, CA led an education session on ‘On-Demand Mobile Fueling; Enforcing Existing Regulations and Evaluating Future Needs” at NFPA Conference &
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Demobilizing buildings under construction, alteration or demolition during COVID-19 construction shutdown
COVID-19 is having an immediate and drastic impact on the construction industry with job sites being abandoned and workers being furloughed. A byproduct of these unprecedented pandemic-related changes has been the demobilization of
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Buzzirk Mobile and Global Verge Compensation Plan - Can You Really Make Some Money?
A close look at the Buzzirk Mobile and Global Verge Compensation Plan. Also a chance to see if this business can really deliver the goods and make you money.
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How to Make a Mobile-Friendly Website: Responsive Design in CSS
Find out how you can make your website mobile-ready by simply modifying its Cascading Style Sheets (CSS).
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[Updated] Free Mobile-Friendly Layout Wizard: now creates 1, 2, 3 column websites
For the sake of completeness (and also because a visitor requested it), the Layout Wizard has been updated to support one column websites as well. As a result, it can now create one, two and three column websites (depending on which you prefer). The generated web page is mobile-friendly and completely customizable. There are no advertisements, and nothing you enter into the Wizard is recorded anywhere. And it's free.
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How to Rotate an Image on a Website When Viewed on a Mobile Phone (CSS)
In response to a visitor's query, this article deals with how you can turn an image on its side when a web page is viewed on a mobile phone.
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Geographic Mobility in America: Evidence from Cell Phone Data -- by M. Keith Chen, Devin G. Pope
Traveling beyond the immediate surroundings of one’s residence can lead to greater exposure to new ideas and information, jobs, and greater transmission of disease. In this paper, we document the geographic mobility of individuals in the U.S., and how this mobility varies across U.S. cities, regions, and income classes. Using geolocation data for ~1.7 million smartphone users over a 10-month period, we compute different measures of mobility, including the total distance traveled, the median daily distance traveled, the maximum distance traveled from one’s home, and the number of unique haunts visited. We find large differences across cities and income groups. For example, people in New York travel 38% fewer total kilometers and visit 14% fewer block-sized areas than people in Atlanta. And, individuals in the bottom income quartile travel 12% less overall and visit 13% fewer total locations than the top income quartile.
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Bring on the e-scooters: A Bird executive explains how New York City can smartly and safely welcome the micromobility devices
Electric scooters are coming to New York and, with a little planning and preparation, they can safely thrive here. To understand how, it helps to start with some context.
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Hoodlums in the ’hood: Where mobsters lived in South Florida
Some of the most infamous mobsters lived in South Florida neighborhoods we call home today, from Miami to Hollywood to Boca Raton.
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Pistol-whipping Russian mobster explodes at prosecutor at Brooklyn sentencing: ‘I can’t listen to these lies!’
Aleksey Tsvetkov, 40, blew up while an Assistant U.S. Attorney recited his criminal history during his sentencing hearing in Brooklyn Federal Court on racketeering charges..
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Legendary mobster Sonny Franzese dead at 103
The renowned tough guy did his prison time without ever turning on his mob associates following a 1967 conviction that was widely considered both inside and outside organized crime as a set-up.
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SEE IT: 15-year-old girl ‘traumatized’ after being beaten and robbed by teen mob in Brooklyn
The teen victim was chased to the corner of Utica Ave. and Sterling Place around 4:10 p.m. Thursday before being knocked to the ground. Video then shows a horde of teens descending upon her.
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3 Reasons Why A Mobile-Friendly Website Design Is Essential
Online advertisers, logged off organizations, mentors, and creators are listening to all the more habitually about the need to guarantee that you have a mobile-friendly site plan. Basically, this implies that your site should naturally and powerfully conform to whichever gadget is being utilized to view the site, whether this is a cell phone, a tablet, or a desktop PC. Alterably conforming implies that the peruser does not need to make conformities physically; its done naturally.
A variable influencing this ...
The post 3 Reasons Why A Mobile-Friendly Website Design Is Essential appeared first on RSS Feed Converter.
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Mobile Marketing: How to Convert the Mobile Visitor
Digital marketing is having a moment — and it’s a mobile one. For months, digital marketers have been readying their sites for mobile traffic page by page and #Mobilegeddon has come to define the current zeitgeist. According to SMX Speaker and WordStream Content Marketing Specialist Margot da Cunha, this has been a long time coming.
“Everyone’s been preaching the importance of having a robust mobile marketing strategy for the past seven years or so, and although we all know this, ...
The post Mobile Marketing: How to Convert the Mobile Visitor appeared first on RSS Feed Converter.
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RepeatServer.com gets a mobile-friendly overhaul
RepeatServer.com now allows you to update your RSS feeds, etc, from your smart phones and tablets
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USC's Isaiah Mobley finding his stride after rough start to college career
Isaiah Mobley has learned to deal with adversity since arriving at USC as one of the top college basketball recruits in the nation.
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John 'Sonny' Franzese, powerful mob boss who hung out with Frank Sinatra, dies at 103
Alleged to be a prolific killer, Franzese was finally released from prison when he was 100
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Rap videos, virtual running club, bookmobile: Teachers go above and beyond amid pandemic
Join IndyStar and #ThankATeacher during Teacher Appreciation Week. These are some educators that are making the best of a bad situation.
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Orange Extends Services with Interactive TV and Mobile Apps
Orange Slovensko the leading telco operator on the market uses the nangu.TV Media Platform for IPTV and OTT delivery. "With the growing demand for interactive television and more viewing possibilities, Orange sought a proven solution to bring to the market," says Product Manager at Orange, Martin Hainzl.
Orange offers their customers TV with value added features, which gives them more options and comfort than classic live TV. The VoD selection stores 50 movie titles, accessible on multiple screens: TV, PC, Smartphone or tablet. The TV Archive allows playback of content up to 7 days in the past. Customers can utilize the time shift feature to browse content already aired and watch it at their leisure with pause, play and star t over commands. They have flexibility in watching television on the go with the newly released applications for both iOS and Android devices. The nangu.TV solution allows operators to stay ahead of competition by giving cutomers the chance to be in control of how they watch TV.
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From Concept to Design: How Developers Create Today’s Most Popular Mobile Games
In the past five years, mobile games have exploded in popularity. With the advent of Apple’s App Store, mobile app developers have jumped on the opportunity to create mobile games from scratch on the most popular devices in the world. What Makes a Mobile Game Go Viral? Why is it that some mobile games become […]
The post From Concept to Design: How Developers Create Today’s Most Popular Mobile Games appeared first on SpyreStudios.
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oscon: Mobile UX Design & Development for Apps - learn to craft an app that’s functional and fun to use http://t.co/L8kTLaxbYH #oscon #tutorial
oscon: Mobile UX Design & Development for Apps - learn to craft an app that’s functional and fun to use http://t.co/L8kTLaxbYH #oscon #tutorial
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AT#409 - Travel to Mobile, Alabama
Hear about travel to Mobile, Alabama as the Amateur Traveler talks to Carla Rountree from theinconsistentnomad.com about her home state. There are beautiful beaches. It is an area that was founded in the early 1700s so there is lots of culture, lots of history and it is even the area where Mardi Gras actually started in the USA.
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Leaders need to mobilize change-ready workforces
Rita J. King, co-director and EVP for business development at Science House, recently conducted a series of interviews with business leaders, exploring the challenges and hurdles companies face in evolving business landscapes. In this interview, King chats with Jen Bruno, SVP of culture and human capital at LPL Financial, about mobilizing a change-ready workforce, leadership […]
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Article: Mobile Apps, Influencer Marketing Top Fraud Targets for 2018
Michael Tiffany, co-founder and president of ad verification and fraud prevention firm White Ops, discusses the next evolution of fraudulent practices for 2018.
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Why We Need a Transatlantic Charter for Data Security and Mobility
28 June 2017
Dr Christopher Smart
Former Associate Fellow, US and the Americas Programme2017-06-23-TsystemsData.jpg
Data centre for T-Systems, a subsidiary of Deutsche Telekom. Photo by: Thomas Trutschel/Photothek/Getty Images
While trade and tax remain at the heart of the difficult economic conversations between Europe and the US, a new issue has emerged as a potential source of even greater friction: data.
Growth in the traditional global trade in goods and services has levelled off, but cross-border data flows continue to expand rapidly and the challenges of developing policies that protect privacy, security and innovation are already tremendous. For example, data analytics are driving dramatic productivity gains in industry, particularly for large and complex installations whose safety and efficiency will increasingly depend on flows of those data across jurisdictions. Meanwhile, ‘fintech’ (financial technology) start-ups and large banks alike are testing new modes of accumulating, analysing and deploying customer data to provide less expensive services and manage the risk profile of their businesses.
The rules that govern the collection, transmission and storage of data are perhaps one of the more surprising controversies in the transatlantic relationship. Similar liberal democracies with similar geostrategic interests might be expected to approach the handling of personal, corporate and government data in more or less the same way. And yet the US and its key European partners have struck different balances in the trade-offs between national security and citizens’ rights, between freedom of expression and personal privacy, and between free enterprise and market regulation.
While the US debate on the use of data has often been framed around the trade-off between national security and personal privacy, Europeans often face an even more complex set of concerns that include worries that their digital and technology firms lag behind dominant US competitors. The political and regulatory uncertainty helps neither side, and leaves transatlantic companies struggling to comply with uncertain and conflicting rules in different jurisdictions.
This makes more determined efforts by US and European policymakers to agree basic principles that will guide the usage and protection of personal and commercial data all the more important. While common regulations or even greater alignment among regulators seem out of reach, a ‘Transatlantic Charter for Data Security and Mobility’ would provide a set of principles for more specific rules amid political landscapes and technological developments that are evolving rapidly. It could also provide the basis for firms, whether in manufacturing or financial services or health care, to draft their own voluntary standards on how they protect data even as they develop new algorithms that improve productivity, safety and customer satisfaction.
Embarrassing leaks, careful denials and endless lawsuits will continue to shape the awkward efforts of policymakers to find common ground around issues like cyberespionage, defence of common networks and the sharing of personal data with law enforcement. Cyberattacks with the aim of disrupting government operations or influencing election campaigns will add still further pressures. These will all serve as a noisy backdrop to a related but separate debate over how commercial firms should exploit the opportunities of global networks and ‘big data’ analytics while protecting national interests and privacy.
Yet, setting common guidelines for commercial data transmission and storage remains crucial both to protect the goods and services that already depend on sophisticated data-gathering and analysis, and to support the next generation of productivity gains and business opportunities.
Global firms yearn for clarity and predictability as they organize themselves to make the most of the data revolution. Neither is likely to become a reality soon. The EU’s new General Data Protection Regulation will take effect in 2018, but its implementation will inevitably be coloured by the fact that American firms currently dominate the information technology business. Last year’s ‘Privacy Shield’ agreement between the US and the EU renews the permission for firms with transatlantic business interests to transfer data, subject to compliance with basic standards of protection, but the agreement remains vulnerable to European court challenges. Britain’s decision to leave the EU adds a further complication, as it establishes its own set of data protection rules that may not easily align with either European or US requirements. Meanwhile, the World Trade Organization continues to debate new rules for digital trade, even as markets like China, Russia and Brazil make up their own.
If this ‘Transatlantic Charter for Data Security and Mobility’ were adopted bilaterally, say as part of the annual reviews of the US–EU Privacy Shield agreement, it could form the basis for broader cooperation on these issues, helping to drive progress in the G7 and G20 and ultimately perhaps in trade agreements under the WTO. It would hardly secure complete alignment on these questions, but it could help establish the framework for a debate that all too often lurches to extremes and risks damaging a fundamental alliance for global stability – along with a fundamental driver of 21st-century economic progress.
To comment on this article, please contact Chatham House Feedback
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Supporting the US Economy by Improving the Mobility of High-skilled Labour Across the Atlantic
27 September 2017
US policymakers should give special consideration to a more open immigration policy for highly skilled professionals from the EU. This would ultimately benefit the US economy.
2017-09-25-labour-mobility-us-economy.jpg
Businessman on bicycle passing skyline of La Defense business district in Paris, France. Photo: Getty Images.
Summary
- The United States and the European Union are deeply integrated economically in terms of movement of goods, services and capital across the Atlantic, but this is not matched by the mobility of labour. Freer movement of high-skilled workers across the Atlantic has a potentially critical role to play in maintaining and strengthening the bilateral economic relationship.
- Both the US and EU seek to attract high-skilled labour through the use of temporary visa programmes. Various routes are available for highly skilled workers from the EU to temporarily work in the US (for instance, through the H-1B visa for foreign nationals in ‘specialty occupations’, as well as other visa categories for treaty traders and investors, intra-company transferees, and international students seeking work authorization in the US before or after graduation). The main ways for highly skilled workers from the US to temporarily work in EU member states are through EU-wide schemes that apply in 25 out of the 28 member states (for holders of EU Blue Cards or intra-company transferees); or via member states’ parallel national schemes.
- The experiences of US and EU employers and workers under the US H-1B programme and the EU’s Blue Card scheme differ greatly. The EU Blue Card scheme avoids many of the drawbacks of the H-1B visa. It does not have an annual cap on the number of visas issued. It also grants greater autonomy to the worker by not requiring the employer to sponsor long-term residence, by providing greater flexibility to switch employment, and by having a longer grace period for visa-holders to find new employment after dismissal.
- The US visa system hampers America’s economic growth. Restrictive policies such as an annual limit on the number of H-1B visas issued, and the associated uncertainty for employees and employers, hinder the ability of US companies to expand and innovate. The complex and costly visa application process is a particular burden for small and medium-sized enterprises. Problems around the timely availability of visas frustrate investors both from the US and from abroad (including from the EU). European firms face difficulties in acquiring visas for intra-company transferees, and not all EU member states have access to the treaty trader and treaty investor visa categories. At times, this impedes foreign direct investment and restricts US job creation. In addition, current policies hinder the economy’s retention of EU and other graduates of US universities. This is of particular concern given that skilled graduates have a critical role to play in addressing the US’s growing shortage of workers in the science, technology, engineering and mathematics (STEM) fields.
- Given the comparability of US and EU wages and labour markets, US concerns about foreign workers ‘stealing’ their jobs or depressing wages generally do not apply to EU citizens. On the contrary, a more open immigration policy for high-skilled workers – in particular for EU citizens – would benefit the US economy.
- Efforts to reform visa systems for high-skilled labour are under way in both the US and EU. In order to facilitate the movement of highly skilled workers across the Atlantic, this research paper recommends (1) creating a special visa for highly skilled EU citizens to work temporarily in the US; (2) extending the availability of treaty trader and investor visas to all EU member states; and (3) increasing efforts to eliminate fraud and abuse in the H-1B system. These measures could potentially help to create more investment, jobs and economic growth in the US.
Department/project
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Up in smoke? Global tobacco advocacy and local mobilization in Africa
4 September 2019 , Volume 95, Number 5
Even though most African states have signed and ratified the Framework Convention on Tobacco Control (FCTC), a global treaty to limit tobacco use, African states have been slow to pass and implement tobacco control policies like regulations on sales, smoke-free environments and taxes. This article examines how the ineffectiveness of local tobacco-control advocacy contributes to this suboptimal outcome. It asserts that the disconnect between the global tobacco-control advocacy network and local advocates shapes this ineffectiveness. With funding and direction predominately from the Bloomberg Initiative, local advocates emulate the funders' goal of achieving quick, measurable policy results. Their reliance on the network drives African advocates to strive to pass legislation, even in difficult political climates, and to remake their agendas when funders change their priorities. They also emulate the network's focus on evidence-based arguments that stress epidemiological data and biomedical interventions, even when this issue frame does not resonate with policy-makers. Financial dependence can draw local advocates into expectations about patronage politics, undermine their ability to make principled arguments, and lead them to downplay the ways that their home country's socioeconomic and cultural contexts affect tobacco use and control. Based on key informant interviews with African advocates, media analysis and the case-studies of Ghana and Tanzania, the article broadens the study of philanthropy in global health, it adds an African perspective to the literature on global health advocacy, and it deepens knowledge on power dynamics between external funders and local actors in the realms of health and development.
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Putting the auto in automobile
It may be hard to accept but it.s likely that we.d all be much safer in autonomous vehicles driven by computers, not humans. Annually more than 30,000 Americans die in car crashes, almost all due to human error. Autonomous vehicles will communicate position and speed to each other and avoid potential collisions-without the possibility of dozing off or road rage. There are still many legal (and insurance) issues to resolve, but researchers who are revving up the development of autonomous vehicles are relying on geometry for recognizing and tracking objects, probability to assess risk, and logic to prove that systems will perform as required. The advent of autonomous vehicles will bring in new systems to manage traffic as well, for example, at automated intersections. Cars will communicate to intersection-managing computers and secure reservations to pass through. In a matter of milliseconds, the computers will use trigonometry and differential equations to simulate vehicles. paths through the intersection and grant entry as long as there is no conflict with other vehicles. paths. Waiting won.t be completely eliminated but will be substantially reduced, as will the fuel--and patience--currently wasted. Although the intersection at the left might look wild, experiments indicate that because vehicles would follow precise paths, such intersections will be much safer and more efficient than the ones we drive through now.
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CBD Joint Press Release: Mobilizing society to support biodiversity: As Countdown 2010 initiative closes, local coordinated actions show way to solving the global biodiversity crisis.
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CBD Communiqué: World Association of Zoos and Aquariums mobilized for the United Nations Decade on Biodiversity
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CBD News: Parties to the Convention on Biological Diversity (CBD) wrapped up a weeklong meeting on implementation with recommendations on, among others, resource mobilization, technical and scientific cooperation, poverty eradication and sustainable devel
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CBD News: To support the mobilisation and alignment of technical and financial resources for priority capacity-building needs, IPBES is developing a prototype Matchmaking Facility. This Facility aims to promote and facilitate dialogue and cooperation amon
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CBD News: On 12 April, Sir David Attenborough joins the head of the UN's Convention on Biological Diversity and a panel from government, business and civil society to discuss how to mobilise global action to tackle what is said to be the greatest thre
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CBD News: The film highlights the importance of nature in tackling climate change, calling for the need to protect, restore and fund nature and mobilizing attention to scale nature-based solutions.
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Evaluation and Evolution of Diabetes Mobile Applications: Key Factors for Health Care Professionals Seeking to Guide Patients
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Going Mobile With Diabetes Support: A Randomized Study of a Text Message-Based Personalized Behavioral Intervention for Type 2 Diabetes Self-Care
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MoBay residents flock COVID ‘giveaway truck’
Despite being placed under strict restrictions and COVID-19 curfew measures, shoppers, commuters, motorists, and vendors in Montego Bay got a feel of Christmas on Wednesday, when they were showered with items as part of the COVID-19 giveaway by an...
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MaxQuant software for ion mobility enhanced shotgun proteomics
Nikita Prianichnikov
Mar 10, 2020; 0:TIR119.001720v1-mcp.TIR119.001720
Technological Innovation and Resources
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Mobilizing Multinational Military Operations in Africa: Quick Fixes or Sustainable Solutions?
Research Event
25 October 2019 - 9:30am to 11:15am
Chatham House | 10 St James's Square | London | SW1Y 4LE
Event participants
Professor Tony Chafer, University of Portsmouth
Professor Gordon Cumming, Cardiff University
Dr Roel van der Velde, Cardiff University
Ahmed Soliman, Research Fellow, Horn of Africa, Chatham House
Dr Elisa Lopez Lucia, Université Libre de Bruxelles; University of Portsmouth
Chair: Janet Adama Mohammed, West Africa Programme Director, Conciliation Resources
Peacekeeping missions which have sought to address evolving forms of conflict and instability on the African continent – led by the United Nations, African Union and European Union – have frequently been overstretched.
Across regions including the Sahel, the Horn and West Africa, the issues of violent extremism and criminality – often set against a backdrop of collapsing or severely weakened central states – have led to the mobilisation of a diverse set of new collective responses.
These include notable African-led efforts such as AMISOM in Somalia or more recently the G5 Sahel, where France have played a pivotal role in initiating new and more ad hoc approaches to coalition-building.
As existing multinational missions in Africa continue to evolve on the ground and while new collective opportunities increasingly present themselves, it is critical for policymakers to understand how far such efforts reflect meaningful long-term solutions to the challenges of conflict and insecurity.
At this roundtable event, participants will reflect on how such missions become mobilised and legitimised, the extent to which they can be defined as ‘new’, and whether they represent a truly sustainable means to tackle the issue of conflict in Africa.
This roundtable is held in partnership with Cardiff University and the University of Portsmouth and is supported by the Leverhulme Trust.
Department/project
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Central & Eastern Europe and Africa Engagement: Labour Mobility and Policy in East Africa
Research Event
15 January 2020 - 10:00am to 12:30pm
Nairobi, Kenya
Strengthened links between the states of sub-Saharan Africa (SSA) and Central and Eastern Europe (CEE) are emerging marked by growth in diplomatic representation, trade and economic ties and supporting networks.
Against this backdrop, labour migration within and from the CEE and East Africa sub-regions are a key policy area with significant potential for shared learning and cooperation. For both regions, migration trends in recent years have evolved as a result of a diverse range of interactions among public, private and civil society actors and at local, national, regional and international levels. Unpacking such interactions and their political and geographical specificities is essential to effective engagement and cooperation within and between the regions on issues of labour migration and their management.
This roundtable brainstorming workshop will provide a platform for stakeholders based in East Africa to discuss the way in which different actors and agencies in the region influence and shape labour migration processes and policy responses.
This event is supported by the Robert Bosch Stiftung.
Event attributes
Chatham House RuleDepartment/project
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MaxQuant software for ion mobility enhanced shotgun proteomics [Technological Innovation and Resources]
Ion mobility can add a dimension to LC-MS based shotgun proteomics which has the potential to boost proteome coverage, quantification accuracy and dynamic range. Required for this is suitable software that extracts the information contained in the four-dimensional (4D) data space spanned by m/z, retention time, ion mobility and signal intensity. Here we describe the ion mobility enhanced MaxQuant software, which utilizes the added data dimension. It offers an end to end computational workflow for the identification and quantification of peptides and proteins in LC-IMS-MS/MS shotgun proteomics data. We apply it to trapped ion mobility spectrometry (TIMS) coupled to a quadrupole time-of-flight (QTOF) analyzer. A highly parallelizable 4D feature detection algorithm extracts peaks which are assembled to isotope patterns. Masses are recalibrated with a non-linear m/z, retention time, ion mobility and signal intensity dependent model, based on peptides from the sample. A new matching between runs (MBR) algorithm that utilizes collisional cross section (CCS) values of MS1 features in the matching process significantly gains specificity from the extra dimension. Prerequisite for using CCS values in MBR is a relative alignment of the ion mobility values between the runs. The missing value problem in protein quantification over many samples is greatly reduced by CCS aware MBR.MS1 level label-free quantification is also implemented which proves to be highly precise and accurate on a benchmark dataset with known ground truth. MaxQuant for LC-IMS-MS/MS is part of the basic MaxQuant release and can be downloaded from http://maxquant.org.
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Adipose Triglyceride Lipase is a Key Lipase for the Mobilization of Lipid Droplets in Human Beta Cells and Critical for the Maintenance of Syntaxin1a Level in Beta Cells
Lipid droplets (LDs) are frequently increased when excessive lipid accumulation leads to cellular dysfunction. Distinct from mouse beta cells, LDs are prominent in human beta cells, however, the regulation of LD mobilization (lipolysis) in human beta cells remains unclear. We found that glucose increases lipolysis in non-diabetic human islets, but not in type 2 diabetic (T2D) islets, indicating dysregulation of lipolysis in T2D islets. Silencing adipose triglyceride lipase (ATGL) in human pseudoislets (shATGL) increased triglycerides, and the number and size of LDs indicating that ATGL is the principal lipase in human beta cells. In shATGL pseudoislets, biphasic glucose-stimulated insulin secretion (GSIS) and insulin secretion to IBMX and KCl were all reduced without altering oxygen consumption rate compared with scramble control. Like human islets, INS1 cells showed visible LDs, glucose responsive lipolysis, and impairment of GSIS after ATGL silencing. ATGL deficient INS1 cells and human pseudoislets showed reduced Stx1a, a key SNARE component. Proteasomal degradation of Stx1a was accelerated likely through reduced palmitoylation in ATGL deficient INS1 cells. Therefore, ATGL is responsible for LD mobilization in human beta cells and supports insulin secretion by stabilizing Stx1a. The dysregulated lipolysis may contribute to LD accumulation and beta cell dysfunction in T2D islets.
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Adipose Triglyceride Lipase is a Key Lipase for the Mobilization of Lipid Droplets in Human Beta Cells and Critical for the Maintenance of Syntaxin1a Level in Beta Cells
Lipid droplets (LDs) are frequently increased when excessive lipid accumulation leads to cellular dysfunction. Distinct from mouse beta cells, LDs are prominent in human beta cells, however, the regulation of LD mobilization (lipolysis) in human beta cells remains unclear. We found that glucose increases lipolysis in non-diabetic human islets, but not in type 2 diabetic (T2D) islets, indicating dysregulation of lipolysis in T2D islets. Silencing adipose triglyceride lipase (ATGL) in human pseudoislets (shATGL) increased triglycerides, and the number and size of LDs indicating that ATGL is the principal lipase in human beta cells. In shATGL pseudoislets, biphasic glucose-stimulated insulin secretion (GSIS) and insulin secretion to IBMX and KCl were all reduced without altering oxygen consumption rate compared with scramble control. Like human islets, INS1 cells showed visible LDs, glucose responsive lipolysis, and impairment of GSIS after ATGL silencing. ATGL deficient INS1 cells and human pseudoislets showed reduced Stx1a, a key SNARE component. Proteasomal degradation of Stx1a was accelerated likely through reduced palmitoylation in ATGL deficient INS1 cells. Therefore, ATGL is responsible for LD mobilization in human beta cells and supports insulin secretion by stabilizing Stx1a. The dysregulated lipolysis may contribute to LD accumulation and beta cell dysfunction in T2D islets.
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Pharmacologic PPAR-{gamma} Activation Reprograms Bone Marrow Macrophages and Partially Rescues HSPC Mobilization in Human and Murine Diabetes
Mobilization of hematopoietic stem/progenitor cells (HSPCs) from the bone marrow (BM) is impaired in diabetes. Excess oncostatin M (OSM) produced by M1 macrophages in the diabetic BM signals through p66Shc to induce Cxcl12 in stromal cells and retain HSPCs. BM adipocytes are another source of CXCL12 that blunts mobilization. We tested a strategy of pharmacologic macrophage reprogramming to rescue HSPC mobilization. In vitro, PPAR- activation with pioglitazone switched macrophages from M1 to M2, reduced Osm expression, and prevented transcellular induction of Cxcl12. In diabetic mice, pioglitazone treatment downregulated Osm, p66Shc and Cxcl12 in the hematopoietic BM, restored the effects of granulocyte-colony stimulation factor (G-CSF), and partially rescued HSPC mobilization, but it increased BM adipocytes. Osm deletion recapitulated the effects of pioglitazone on adipogenesis, which was p66Shc-independent, and double knockout of Osm and p66Shc completely rescued HSPC mobilization. In the absence of OSM, BM adipocytes produced less CXCL12, being arguably devoid of HSPC-retaining activity, whereas pioglitazone failed to downregulate Cxcl12 in BM adipocytes. In diabetic patients under pioglitazone therapy, HSPC mobilization after G-CSF was partially rescued. In summary, pioglitazone reprogrammed BM macrophages and suppressed OSM signaling, but sustained Cxcl12 expression by BM adipocytes could limit full recovery of HSPC mobilization.