Previous studies have shown that sphingosine kinase interacting protein (SKIP) inhibits sphingosine kinase (SK) function in fibroblasts. SK phosphorylates sphingosine producing the potent signaling molecule sphingosine-1-phosphate (S1P). SKIP gene (SPHKAP) expression is silenced by hypermethylation of its promoter in acute myeloid leukemia (AML). However, why SKIP activity is silenced in primary AML cells is unclear. Here, we investigated the consequences of SKIP down-regulation in AML primary cells and the effects of SKIP re-expression in leukemic cell lines. Using targeted ultra-HPLC-tandem MS (UPLC-MS/MS), we measured sphingolipids (including S1P and ceramides) in AML and control cells. Primary AML cells had significantly lower SK activity and intracellular S1P concentrations than control cells, and SKIP-transfected leukemia cell lines exhibited increased SK activity. These findings show that SKIP re-expression enhances SK activity in leukemia cells. Furthermore, other bioactive sphingolipids such as ceramide were also down-regulated in primary AML cells. Of note, SKIP re-expression in leukemia cells increased ceramide levels 2-fold, inactivated the key signaling protein extracellular signal-regulated kinase, and increased apoptosis following serum deprivation or chemotherapy. These results indicate that SKIP down-regulation in AML reduces SK activity and ceramide levels, an effect that ultimately inhibits apoptosis in leukemia cells. The findings of our study contrast with previous results indicating that SKIP inhibits SK function in fibroblasts and therefore challenge the notion that SKIP always inhibits SK activity.

The recent economic downturn has dealt a severe blow to many employees. However, for Shiu Yin-ming and Poon Man-kit, the crisis has brought them skill-upgrading opportunities.

Miss Shiu has over 30 years’ experience in the retail industry. Her last job was a salesperson at a lighting store. Struck by the competition with online stores and a series of protests, the shop closed in October last year and left her unemployed.

“I have got no choice. Many people in Hong Kong have mortgage burdens. It is the most worrying part. And it is frightening to see my account balance drop,” she said.

Miss Shiu spent several months trying to get a job but failed.

“Of course I was frustrated. Perhaps the employers think that young people are more hard-working. It is difficult for middle-aged people like me to get a job. It hurt my confidence and I hesitated to keep going."

Seeing the demand in the healthcare industry, Miss Shiu decided to swap careers. She joined the Love Upgrading Special Scheme and enrolled in the Foundation Certificate in Care-related Support Worker Training.

The course covered basic pathology and healthcare skills. It also arranged recruitment from the Hospital Authority in class. Miss Shiu said the special course helped her to find a job and she will soon work at a nursing home.

“It is like an admission ticket. During an interview at a nursing home, the interviewer asked how I would change a nappy for an elderly person. I answered what I had learnt from the course. Moreover, as I have not participated in an interview after so many years of work, the interview skills that I have learnt from the course have geared me up,” she said.

Better prospects

Young newcomers to the job market are also affected by the economic downturn.

Mr Poon has been engaged in casual work in the catering industry. The 19-year-old said there used to be plenty of casual job opportunities on career websites, but that is no longer the case. He has been underemployed in recent months and feels his family just see him as someone who is not in education, employment, or training.

“The full-time waiters have not got much work to do, and each of them is assigned to be responsible for a few positions. So, the restaurant does not need extra casual manpower. My relatives look down on me like I am a neet,” he said.

Mr Poon has enrolled in the Foundation Certificate in Barista Training to gain experience in different positions in the industry.

"Many coffee shops and hotels need people to make latte art. I think the course will help me get a job more easily. I plan to further enroll in other courses relating to pastry-making," he added.

Skills upgrade

The Love Upgrading Special Scheme, launched in last October, provides free training to employees affected by the recent economic downturn to upgrade their skills. The courses are conducted in full-time or part-time mode and offer special allowances.

According to the Employees Retraining Board, as of the end of March, more than 12,200 people have applied for the scheme. About one-third of them are aged between 50 to 59.

The applicants mainly come from the catering, retail, social and personal services industries.

The most popular course is the Foundation Certificate in Care-related Support Worker Training, followed by courses related to baker and pastry cook, barista and security training.

Employees Retraining Board Executive Director Byron Ng said the 66 courses under the scheme were specially selected.

“We want to help those employees in the hard-hit industries like tourism, catering, retail, hotel, construction, etc. Also, we want to provide courses in industries which demand heavy labour during this period, such as healthcare and innovative technology.”

The scheme does not impose any restrictions on the trainees’ industry and educational attainment.

“We hope to encourage all unemployed or underemployed employees, including those who are highly educated, and take these chances to upgrade their own skills so they can re-enter the market smoothly,” Mr Ng said.

He added that those who have completed a full-time vocational skills course will get a follow-up service that includes three months of employment.

The second phase of the scheme will be launched in July, and the monthly maximum allowance is expected to increase from $4,000 to $5,800.

(JAMA Network) This randomized clinical trial looked at the effect of a face-aging mobile app on daily sunscreen use and other skin protection among teens in Brazil. Selfies of students were altered to show UV effects on their future faces and shown to their class, accompanied by information about sun protection. Reducing UV exposure in children and adolescents is important because of the increased risk of skin cancer with cumulative UV exposure and sunburns early in life.

Previous studies have shown that sphingosine kinase interacting protein (SKIP) inhibits sphingosine kinase (SK) function in fibroblasts. SK phosphorylates sphingosine producing the potent signaling molecule sphingosine-1-phosphate (S1P). SKIP gene (SPHKAP) expression is silenced by hypermethylation of its promoter in acute myeloid leukemia (AML). However, why SKIP activity is silenced in primary AML cells is unclear. Here, we investigated the consequences of SKIP down-regulation in AML primary cells and the effects of SKIP re-expression in leukemic cell lines. Using targeted ultra-HPLC-tandem MS (UPLC-MS/MS), we measured sphingolipids (including S1P and ceramides) in AML and control cells. Primary AML cells had significantly lower SK activity and intracellular S1P concentrations than control cells, and SKIP-transfected leukemia cell lines exhibited increased SK activity. These findings show that SKIP re-expression enhances SK activity in leukemia cells. Furthermore, other bioactive sphingolipids such as ceramide were also down-regulated in primary AML cells. Of note, SKIP re-expression in leukemia cells increased ceramide levels 2-fold, inactivated the key signaling protein extracellular signal-regulated kinase, and increased apoptosis following serum deprivation or chemotherapy. These results indicate that SKIP down-regulation in AML reduces SK activity and ceramide levels, an effect that ultimately inhibits apoptosis in leukemia cells. The findings of our study contrast with previous results indicating that SKIP inhibits SK function in fibroblasts and therefore challenge the notion that SKIP always inhibits SK activity.

Jeroen van Smeden
Apr 7, 2020; 0:jlr.RA120000639v1-jlr.RA120000639
Research Articles

It's a pop culture episode this week as we do a deep dive into dystopian fiction. Scott Carey is your host as he chats to Dominic Preston and Tamlin Magee about the best novels, films, TV shows and video games set in dystopian universes.

We talk about how the world is closer to fiction than ever before, and how this impacts the way we think about fictional dystopias, and end on a positive note to discuss our favourite utopian fiction too.

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Individuals with Netherton syndrome (NTS) have increased serine protease activity, which strongly impacts the barrier function of the skin epidermis and leads to skin inflammation. Here, we investigated how serine protease activity in NTS correlates with changes in the stratum corneum ceramides, which are crucial components of the skin barrier. We examined two key enzymes involved in epidermal ceramide biosynthesis, glucocerebrosidase (GBA) and acid-sphingomyelinase (ASM). We compared in situ expression levels and activities of GBA and ASM between NTS patients and controls and correlated the expression and activities with i) stratum corneum ceramide profiles, ii) in situ serine protease activity, and iii) clinical presentation of patients. Using activity-based probe labeling, we visualized and localized active, epidermal GBA, and a newly developed in situ zymography method enabled us to visualize and localize active ASM. Reduction in active GBA in NTS patients coincided with increased ASM activity, particularly in areas with increased serine protease activity. NTS patients with scaly erythroderma exhibited more pronounced anomalies in GBA and ASM activities than patients with ichthyosis linearis circumflexa. They also displayed a stronger increase in stratum corneum ceramides processed via ASM. We conclude that changes in the localization of active GBA and ASM correlate with i) altered stratum corneum ceramide composition in NTS patients, ii) local serine protease activity, and iii) the clinical manifestation of NTS. 

Ceramides (Cers) with ultralong (~32-carbon) chains and -esterified linoleic acid, composing a subclass called omega-O-acylceramides (acylCers), are indispensable components of the skin barrier. Normal barriers typically contain acylCer concentrations of ~10 mol%; diminished concentrations, along with altered or missing long periodicity lamellar phase (LPP), and increased permeability accompany an array of skin disorders, including atopic dermatitis, psoriasis, and ichthyoses. We developed model membranes to investigate the effects of the acylCer structure and concentration on skin lipid organization and permeability. The model membrane systems contained six to nine Cer subclasses as well as fatty acids, cholesterol, and cholesterol sulfate; acylCer content—namely, acylCers containing sphingosine (Cer EOS), dihydrosphingosine (Cer EOdS), and phytosphingosine (Cer EOP) ranged from zero to 30 mol%. Systems with normal physiologic concentrations of acylCer mixture mimicked the permeability and nanostructure of human skin lipids (with regard to LPP, chain order, and lateral packing). The models also showed that the sphingoid base in acylCer significantly affects the membrane architecture and permeability and that Cer EOP, notably, is a weaker barrier component than Cer EOS and Cer EOdS. Membranes with diminished or missing acylCers displayed some of the hallmarks of diseased skin lipid barriers (i.e., lack of LPP, less ordered lipids, less orthorhombic chain packing, and increased permeability). These results could inform the rational design of new and improved strategies for the barrier-targeted treatment of skin diseases.

Frank Robinson's tenure as Giants manager was short but significant. He and his teams provided hope and promise when both were in short supply around Candlestick Park.

A TB infection can take two forms, active and latent. Active disease is transmissible, and causes the damage to the lungs which makes TB one of the biggest killers in the world. In the latent form, the bacteria Mycobacterium tuberculosis is quiescent and can stay that way for years until it becomes active and causes those clinical signs. Testing...

One of the best catchers in baseball was available all winter in J.T. Realmuto, and the Reds were very much one of the teams in hot pursuit in trade talks with the Marlins. But on Thursday, it was the Phillies who acquired Realmuto from Miami.

Beat reporter Mark Sheldon answers questions about David Bell's managing style, free agents and who will play center field.

She’s what you’d term the consummate creative – through the sensory ‘dry land tourist’ tales of her ‘Right Roun Di Corna’ blog to the pieces in her JadeLauren eyewear brand, Lauren Campbell is colouring the world with beauty, life, and bomb...

In an effort to help develop their players on and off the field, the D-backs have added a mental skills department to their baseball operations staff.

They've talked in small groups. They've talked in larger groups. The front office has discussed it. It's a topic that kept manager Torey Lovullo up at night at times. What in the world happened to the D-backs last September when they watched the National League West Division lead slip away during an 8-19 finish?

A report release and presentation of first-ever U.S. estimates on the actual economic costs of skill underutilization for immigrants, their families, and the U.S. economy, in terms of forgone earnings and unrealized federal, state, and local taxes.

Although in many countries immigrants fill labor gaps in fields such as agriculture and construction, few legal migration pathways exist for low-skilled workers. As states meet to negotiate a Global Compact for Safe, Orderly, and Regular Migration, this policy brief takes stock of the channels available for such workers to move legally and take up work abroad, highlighting promising practices and policy gaps.

As the final phase of preparations for the historic adoption of a Global Compact for Safe, Orderly, and Regular Migration approaches, this webinar explores two central objectives of the compact: enhancing the availability and flexibility of pathways for regular migration, and investing in skills development. 

As the final phase of preparations for the historic adoption of a Global Compact for Safe, Orderly, and Regular Migration approaches, this webinar explores two central objectives of the compact: enhancing the availability and flexibility of pathways for regular migration, and investing in skills development.

This report analyzes the evolution of Chinese emigration from the 1970s, when market-oriented reforms began reducing barriers to movement beyond the country's borders, to the present day. High-skilled and high-value emigration is rising fast. Despite liberalized exit controls, low-skilled labor migration is stagnant as a result of complicated and expensive recruitment procedures.

This report by MPI and the Asian Development Bank lays out a realistic roadmap toward freer movement among skilled professionals within the ASEAN Economic Community (AEC), encouraging cooperation among ASEAN Member States in recognizing foreign qualifications and making government investments in training and educations systems that prepare workers in accordance with common standards.

While partnerships to facilitate skilled migration have had mixed success in the past, the Global Compact for Migration is advancing a new approach that may change this. This policy brief compares this new partnership model with the traditional one, highlighting the questions policymakers will need to answer if they are to encourage mobility, sustain employer engagement, and see development benefits in countries of origin.

Amid aging populations and the growth of chronic diseases, the demand for skilled health-care professionals is on the rise in the United States, Canada, and Mexico. This report explores the policy implications, benefits, and challenges of harmonizing nursing qualifications in the region, suggesting that a more collaborative approach could result in greater supply and quality of nurses.

Blood clots, skin rashes and other lesions might be among the symptoms some people experience with COVID-19, according to new research released Thursday.

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.

Economists project a shortage of 5 million U.S. workers with postsecondary education and training by 2020. Yet 2 million immigrant college graduates in the United States are either unemployed or work in jobs that require no more than a high school degree. How can this skill underutilization, known as "brain waste," be remedied? MPI asked the experts, and this report summarizes their discussion and recommendations.

This webinar discusses the first-ever profile of the 30 million immigrant-origin adults in the United States who lack a postsecondary credential such as a college degree, apprenticeship certificate, or occupational license. The researchers discuss their findings and policy implications with leading experts.

U.S. debates about immigration from Mexico often center on the low skilled, but this analysis shows a population in change. Nearly one in five Mexican immigrants arriving between 2013-17 had a college degree, compared to slightly more than 1 in 20 during the 1996-2000 period. Mexicans now make up the fourth-largest group of highly skilled immigrants. This fact sheet explores their characteristics at U.S. and Texas levels.

Originally published in June 1899

-- Read more on ScientificAmerican.com

Across the United States, nearly 2 million immigrants with college degrees are unemployed or stuck in low-skilled jobs. This skill underutilization, known as “brain waste,” varies significantly by state. These fact sheets offer a profile of these highly skilled immigrants and estimate their forgone earnings and resulting unrealized tax receipts in eight states: California, Florida, Michigan, New York, Ohio, Oregon, Texas, and Washington.

Nearly 2 million college-educated immigrants in the United States, more than half coming with academic and professional credentials, are unable to fully utilize their professional skills and instead are stuck in low-skilled work or are unemployed. This report explores a range of programs and policies that are providing cutting-edge career navigation, relicensing, gap filling, and job search assistance to remedy this brain waste.

This webinar discusses the first-ever profile of the 30 million immigrant-origin adults in the United States who lack a postsecondary credential and offers analysis of the significant payoff credentials could bring in terms of workforce participation and wages.

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.

4 salmon fillets, skin on (175g per portion) 2 tbs soy sauce 1 tbs rice wine vinegar 1 tbs olive oil 1 clove garlic, minced 1 tbs ginger, mined 1 small red chilli 1 lime, juiced

Salmon with a twist.

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

As the threat of COVID-19 continues, infectious disease expert and TED Fellow Adam Kucharski answers five key questions about the novel coronavirus, providing necessary perspective on its transmission, how governments have responded and what might need to change about our social behavior to end the pandemic. (This video is excerpted from a 70-minute interview between Kucharski and head of TED Chris Anderson. Listen to the full interview at http://go.ted.com/adamkucharski. Recorded March 11, 2020)

There's a simple and powerful way to confront the world's most pressing crises, says women's rights activist Yifat Susskind: think like a mother. As she puts it: "When you think like a mother, you prioritize the needs of the many, not the whims of the few." Follow along as she shares moving stories of people around the world who embody this mindset -- and shows how it can also help you see beyond suffering and act to build a better world.

Leaders in some districts say remote teaching will now be a skill they will build even more in their existing teacher corps. Others are more skeptical.

The state’s supreme court ended a yearslong fight over K-12 funding earlier this summer, but in districts across the state the battles have continued and tensions remain.

An introduction to the group that was established by Dina Davis, with only six members who email examples of their current work to the rest of the group for review and feedback. Includes biographical details and examples of the work of each author.

The National Agreement for Skills and Workforce Development (NASWD) was agreed by the Australian, State and Territory governments in 2009 and updated in 2012. The NASWD sets out goals for skills attainment by Australians through the vocational education and training (VET) system and commitments to reforms to ensure that the system is accessible, produces high quality services and operates efficiently. This study will assess progress made by governments against the NASWD, and whether the agreement is still an effective long-term framework for government policy and cooperation.

Concerned that schools don't notice or nurture business skills, nonprofits are using the humble lemonade stand to foster entrepreneurship.

Stuttgart : F. Enke, 1894.

Jena : G. Fischer, 1891.

London : Adlard, 1904.