New T cell therapy protects immunodeficient patients

Scientists at Technische Universitat Munchen (TUM), together with colleagues at Frankfurt, Wurzburg and Gottingen, have discovered a new method to protect patients against viruses following bone marrow transplants. 

Immune system cells are created from stem cells in the bone marrow. In diseases affecting the bone marrow, such as leukemia, degenerate cells must be destroyed using radiation or chemotherapy.

Stem cells from a healthy donor are required to replace the cells of the hematopoietic system following treatment. However, a temporary weakening of the immune system can leave patients vulnerable to infections that would not normally pose a threat.

One such agent is the cytomegalovirus (CMV), which does not cause problems in healthy human beings as specific immune cells keep the infection at bay. However, in patients with weakened defences, it can cause serious damage to the lungs or liver.

The research involved the transfer of T cells that can recognise and kill specific pathogens. The team isolated T cells from the blood of healthy donor mice and directed them against molecular elements of a bacterial species which normally causes severe infections in animals.

These cells were given to other mice, which had undergone a genetic modification so they could no longer produce immune cells of their own.  

The recipient mice were treated with bacteria after the transfer and were found to have effective immune protection, preventing them from becoming ill. 

"The most astonishing result was that the offspring cells of just one transferred donor cell were enough to completely protect the animals," first author Dr Christian Stemberger explained.

A trial was then carried out on human patients who had to undergo stem cell transplants due to a congenital immunodeficiency and leukemia, and who had contracted CMV.

T cells specifically programmed to target the CMV virus were isolated and transferred from a donor. After only a few weeks, the virus-specific cells proliferated and the number of viruses in the blood dropped.

A clinical study will now be carried out to examine the potential of the identified T cells. The scientists aim to develop innovative cell therapies using recent results and cell products created at a special TUM facility.

HR Information

HR to raise technology investment

A new survey of HR departments reveals many firms are looking to strike a balance between people, process and technology.

Towers Watson's 2014 HR Service Delivery and Technology Survey shows one in three companies are set to boost their spending on HR technology in the coming year compared with the previous 12 months.

Some 23 per cent plan to raise their spending by as much as ten per cent, while only 15 per cent plan to spend less on HR technology.

The focus here is on new functionality such as HR portals, talent management solutions, mobile access services and leading software-as-a -service systems such as Workday.

HR data and analytics, portals and payroll figure in many organisations' investment plans, with one-third of respondents expecting to spend more in the coming year.

In addition, one in three companies plan to make changes to their HR structure during the next 12 months. 

The survey of 1,048 organisations around the world shows that streamlining business processes was the number one initiative for business functions for the second year in a row.

More than half (55 per cent) of those surveyed reported reengineering key HR processes over the past 18 months, while around half (49 per cent) improved line managers' people management capabilities.

Business process reengineering and strategic decision-making are expected to feature prominently in efforts to ensure the HR function remains focused, efficient and effective.

Towers Watson suggests the trend for balance is due to a shift in streamlining business processes and a commitment to running the HR function like a business, with an effective mix of strategic perspective and operational discipline. 

Mike DiClaudio, global leader of Towers Watson's HR Service Delivery practice, said: "Companies are realising the value that consumer-grade technology brings to HR and are willing to make smart investments that can grow and evolve with the business. 

"It also appears that companies are splitting their investments between core HR systems such as talent management and payroll, and next-generation technology including HR data and analytics, and integrated talent management systems."


Type 1 diabetes reversal ‘could one day benefit humans’

Researchers have succeeded in reversing type 1 diabetes in mice and their efforts could help to combat the disease in humans.

Type 1 diabetes currently affects five per cent of all people with diabetes, according to the American Diabetes Association. It is usually diagnosed in children and young adults.

The incidence of the disease has increased since the mid-20th century and this could be due to under-stimulation of innate immune systems which trigger autoimmunity in children and young adults.

Individuals with type 1 diabetes do not produce enough insulin, which is central to glucose metabolism. While there is no cure for the disease, it can be controlled with insulin therapy.

Previous studies have shown that non-obese diabetic mice have defects in innate immune cells and that TLR4, a toll-like receptor, plays a protective role in preventing type 1 diabetes.

Researchers at the University of Cincinnati reversed new onset diabetes in a high percentage of newly diabetic non-obese mice using an agonistic monoclonal antibody, UT18, to boost the activity of TLR4.

"The cause of this reversal is a preservation of the endocrine pancreatic beta cells that produce insulin," explained professor William Ridgway. "These cells are preserved from the autoimmune attack which is the hallmark of type 1 diabetes."

Timing is key to reversing type 1 diabetes in mice – the disease needs to be caught at its onset, which is typically within a very short time window. This is longer in humans but is still a relatively short period from new onset to end-stage type 1 diabetes.

The new approach differs from conventional methods as the therapies in mice do not directly interact with T-cells.

Rather than targeting the adaptive immune system, Professor Ridgway's method targets the innate immune system, focusing on a receptor that is found mostly on the innate immune cells, such as dendritic cells.

"This same molecular TLR4 pathway operates in humans in many similar ways; though there are some differences, it is possible this new pathway of targeting the immune system could be tested in humans," the professor said.

HR Information

Auto-enrolment is many firms’ ‘biggest challenge’

A new report has revealed many employers view auto-enrolment as the biggest challenge their organisation will face over the coming years.

Auto-Enrolment: Expectations versus Reality, commissioned by Buzzacott Employee Solutions and Meridian West, states that four in ten employers have such a view of auto-enrolment, HR Magazine reports.

Those who have been through the process found it more arduous than expected, the study reveals, with 34 per cent saying it is more time-consuming than they thought it would be.

A different attitude prevails among those who have yet to reach their staging date, however, with 97 per cent confident they will be able to make the changes in good time.

Companies that are yet to reach their staging date need to "take a holistic approach" to auto-enrolment if they want to make it work, according to Amanda Francis, a managing partner at Buzzacott.

Timing is a crucial factor in the successful roll-out of auto-enrolment, the report suggests. Some 77 per cent of companies which have passed their staging date started planning less than 12 months in advance – but many wish they had done so sooner.

According to Richard Phelps, head of Barclays Corporate & Employer Solutions, many small and medium-sized enterprises (SMEs) are underestimating the scale of the auto-enrolment task

"It is thought that to date only two per cent of UK companies have successfully completed the auto-enrolment process," he said. 

"We are at a critical point as SMEs now start reaching their staging dates in large numbers. Reports suggest that many companies are unaware of their statutory obligations."

Barclays and Standard Life are offering support for smaller companies who are yet to reach their staging date, with the next deadline set for July 1st.

The Pensions Regulator recommends employers allow at least 12 months before their staging date to prepare for auto-enrolment.

There is a guide available on the regulator's website to ensure companies are well-prepared for the changes and there is also a tool available for creating an auto-enrolment action plan.


Cancer drug raises levels of vascular-protective gene

An existing drug that is used to treat cancer patients has been found to be effective in protecting people from vascular clots. 

Bortezomib (Velcade), which is used to treat multiple myeloma, was approved for use by the US Food and Drug Association in 2012. As well as attacking cancer cells, it has been found to help prevent clot development common to many forms of the disease.

The anti-thrombotic effects of bortezomib are determined by KLF2, part of a family of Kruppel-like factors – master regulators of vascular health. These factors prevent clot formation in the body's major blood vessels.

Previous work by the researchers at Case Western Reserve University revealed that Kruppel-like factors function as nodal regulators of vascular health. This led them to surmise that bortezomib protects against thrombosis by increasing KLF levels.

Lalitha Nayak, an assistant professor of medicine, decided to test the hypothesis in the laboratory. She showed that bortezomib treatment rendered normal mice resistant to clot formation.

Next, she demonstrated that the drug specifically and potently induced KLF2 levels. Finally, she confirmed KLF2's importance by administering bortezomib to mice missing the KLF2 gene. In these animals, the drug did not have the effect of protecting them from thrombosis.

"This taught us how important KLF2 is for the ability of bortezomib to protect against thrombosis," professor Nayak said.

The results of the study could alter the management of thrombosis in patients who have a predisposition to clot formation, particularly where present treatments are ineffective.

Antiphospholipid antibody syndrome (APLS) is one such condition. Patients with the disorder have an increased risk for blood clots in both arteries and veins. It often affects young women, and there is no effective antithrombotic strategy for this group of patients.

Bortezomib protects against thrombosis and does not increase bleeding, making this drug a potential treatment alternative for APLS patients.

"Vascular clots are the number one cause of death and disability worldwide," professor Nayak said. "Our studies show that increasing KLF2 levels provides a favorable thromboprotective effect."

HR Information

Employers ‘could face flexible working application surge’

Employers could face a surge in flexible working applications when the new legislation comes into effect later in the year.

A new survey conducted by YouGov reveals 26 per cent of British workers (excluding sole traders) are likely to request flexible working arrangements, HR review reports.

Some 69 per cent of the working population has never made a flexible working request, with 13 per cent of these reluctant to do so because of the financial implications and nearly a quarter (22 per cent) believing their request would be unlikely to be accepted.

However, attitudes could change when the new legislation comes into force. All employees with a minimum of 28 weeks' service will be able to request flexible working as of June 30th 2014, whereas previously only employees with children under 17 or with caring responsibilities were able to change their working patterns.

The employees most likely to request flexible working are 18-24 year-olds, with 31 per cent of this group considering making a request. Women (30 per cent) are more likely to request flexible working than men (22 per cent).

Croner, a Wolters Kluwer company providing information and consultancy to HR, health & safety and business professionals, commissioned the survey of 2,328 Britons.

Richard Smith, head of employment law at Croner, said: "For SMEs, flexible working will not be the easiest policy to implement, particularly if there is sudden rush of applicants this July. However, once the trust and change of mind set has been established the rewards of a flexible work force will become clear."

The research suggests there are significant business benefits to be had from implementing flexible working arrangements.

Some 27 per cent of those surveyed whose businesses allowed flexible working said it provided a boost to productivity, while 28 per cent said it reduced sickness and absence.

However, 16 per cent of respondents and 19 per cent among the 45-54 age group said it could raise tensions in the workplace.


Scientists explain link between stress and heart disease

Researchers have uncovered a possible explanation for the observation that stress, emotional shock, or overexertion may trigger heart attacks in vulnerable people.

Hormones released during such events may cause bacterial biofilms on arterial walls to disperse and this could allow plaque deposits to rupture into the bloodstream.

"Our hypothesis fitted with the observation that heart attack and stroke often occur following an event where elevated levels of catecholamine hormones are released into the blood and tissues, such as occurs during sudden emotional shock or stress, sudden exertion or over-exertion" said Professor David Davies of Binghamton University, New York, an author on the study.

The research team isolated and cultured different species of bacteria from diseased carotid arteries that had been removed from patients with atherosclerosis.

They found multiple bacterial species living in the walls of every atherosclerotic (plaque-covered) carotid artery tested.

Biofilms contain communities of microbes that are resistant to antibiotic treatment and clearance by the immune system. 

When they receive certain molecular signals they disperse and release enzymes that break down the scaffolding that maintain the bacteria within the biofilm. These enzymes could dissolve the nearby tissues that prevent the arterial plaque deposit from rupturing into the bloodstream.

An experiment was conducted to test the theory by adding norepinephrine, at a level that would be found in the body following stress or exertion, to biofilms formed on the inner walls of silicone tubing. 

Professor Davies said at least one species of bacteria was able to undergo a biofilm dispersion response when exposed to norepinephrine.

The dispersal of a biofilm could trigger the sudden release of the surrounding arterial plaque and lead to a heart attack.

Managing bacteria within an arterial plaque lesion may therefore be as important as managing cholesterol, the research suggests.

Almost 160,000 people in the UK died of cardiovascular disease in 2011 and 74,000 of these deaths were caused by coronary heart disease, making it the country's biggest killer.


Longer telomeres linked to increased risk of brain cancers

New research led by scientists at UC San Francisco has revealed a link between common gene variants that lead to longer telomeres and an increased risk of developing deadly brain cancers known as gliomas.

Variants in two telomere-related genes known as TERT and TERC are respectively carried by 51 per cent and 72 per cent of the general population.

Telomeres are the caps on chromosome ends thought by many scientists to confer health by protecting cells from ageing.

It is thought that the benefits conferred by these variants in terms of improved cellular robustness outweigh the increased risk of developing gliomas, which are invariably fatal but relatively rare.

A massive genomic analysis of 40,000 individuals conducted at the University of Leicester found that shorter telomeres were associated with a significantly increased risk of cardiovascular disease.

The first phase of the new study involved analysing genome-wide data from 1,644 glioma patients and 7,736 healthy control individuals, including some who took part in The Cancer Genome Atlas project sponsored by the National Cancer Institute and National Human Genome Research Institute.

This confirmed the link between TERT and gliomas established in previous research and identified TERC as a glioma risk factor for the first time.

As both genes were used to regulate the action of telomerase, the enzyme that maintains telomere length, the research team analysed the Leicester data and found the two variants associated with glioma risk were also linked with greater telomere length.

Much previous research has linked longer telomeres to better health. However, as cancer cells promote their longevity by maintaining telomere length, many drug companies have searched for drugs to specifically target and block telomerase in tumors in the hopes that cancer cells will accumulate genetic damage and die.

TERT variants are also thought to play a role in lung, prostate, testicular and breast cancers, and TERC variants in leukemia, colon cancer and multiple myeloma. The research thus has a potentially much broader relevance than the glioma-related study.

HR Information

Candidate availability falls ‘at sharpest rate since 1997’

New data reveals the number of applicants available for jobs has fallen at its sharpest rate for 16 years, even as the number of positions continues to grow.

The Recruitment and Employment Confederation's (REC) Report on Jobs, a comprehensive survey of employment trends compiled in conjunction with KPMG, finds that the availability of candidates to fill permanent positions continued to fall during May.

Temporary and contract staff availability also decreased markedly, dropping at a slightly slower rate than April's 13-year record.

The number of vacancies continued to grow, however, despite easing to a five-month low. Permanent vacancies grew faster than temporary or contract roles.

Partly as a result of the increasing scarcity of available candidates, the rate of growth in salaries for permanent positions remained considerable during May.

The Midlands witnessed the strongest rise in permanent placements during May, with the slowest increase recorded in London.

Temporary billings growth was fastest in the Midlands, with the south also enjoying significant increases. There were robust rates of expansion in both London and the north.

Demand for staff in the private sector was significantly higher than in the public sector, the data suggests, with demand for permanent positions growing at a faster rate than for temporary ones in both sectors.

REC chief executive officer Kevin Green said: "The creation of these jobs, combined with the return of job fluidity, is creating a dynamic labour market. However the big issue remains that employers are finding it hard to find the talent and skills they need, yet ONS figures show that we still have 2.2 million unemployed people in the UK."

Mr Green added that the skills shortage has a bearing on the political debate surrounding immigration and the government should reform the visa system to ensure UK businesses are able to grow. He said this would create more opportunities for young people and more chances for career progression.

The greatest demand for staff was experienced in the accounting and financial sector, with engineering dropping to second place despite recording robust expansion.


Research identifies gene involved in Parkinson’s disease

A team of researchers at the University of California Los Angeles (UCLA) has identified a new gene involved in Parkinson's disease, potentially providing a target for drugs that could treat or cure the disorder.

Parkinson's disease involves the gradual breakdown and death of multiple neurons in the brain, leading to movement impairments, such as tremor, rigidity, slowness in movement and difficulty walking. Depression, anxiety, sleeping difficulties and dementia can also occur as a result of the illness.

Dr Ming Guo, the study team leader, associate professor of neurology and pharmacology and a practicing neurologist at UCLA, has worked on a number of studies investigating the genetic origins of the disease.

Dr Guo's team was one of two groups which found that two genes involved in inherited cases of Parkinson's disease – PTEN-induced putative kinase 1 (PINK1) and PARKIN – are also responsible for maintaining the health of mitochondria, which provide energy for the cell and are important in maintaining brain health. Mutations in these genes lead to early onset Parkinson's disease.

When these genes are working properly, they help maintain the shape of healthy mitochondria and eliminate damaged ones. Parkinson's disease can result from the accumulation of unhealthy or damaged mitochondria in neurons and muscles.

The new study found that a gene known as MUL1 (also known as MULAN and MAPL) plays an important role in mediating the pathology of the PINK1 and PARKIN.

Experiments on fruit flies and mice found that providing an extra amount of MUL1 ameliorates the mitochondrial damage due to mutated PINK/PARKIN, while inhibiting MUL1 makes the damage worse.

The team also found that removing MUL1 from mouse neurons of the PARKIN disease model leads to unhealthy mitochondria and degeneration of the neurons.

"We are very excited about this finding," said Dr Guo. "There are several implications to this work, including that MUL1 appears to be a very promising drug target and that it may constitute a new pathway regulating the quality of mitochondria."