Mice lacking the fat hormone leptin or the ability to respond to it become morbidly obese and severely diabetic - not to mention downright sluggish. Now, a new study in the June Cell Metabolism shows that blood sugar control in those animals can be completely restored by returning leptin sensitivity to a single class of neurons in the brain, which account for only a small fraction of those that normally carry the hormone receptors.

"Just the receptors in this little group of neurons are sufficient to do the job," said Christian Bjorbaek of Harvard Medical School.

What's more, animals with leptin receptors only in the so-called pro-opiomelanocortin (POMC) neurons spontaneously increase their physical activity levels despite the fact that they remain profoundly obese. While understanding exactly how the POMC neurons act on other organs remains a future challenge, the discovery suggests that drugs designed to tap into the pathway - turning up or down the dial, so to speak - might have benefit for those with severe diabetes and obesity, according to the researchers.

Such drugs might even encourage obese individuals to get moving. "This gives us the opportunity to search for drugs that might induce the desire or will to voluntarily exercise," Bjorbaek said.

Leptin was first identified 15 years ago and made famous for its ability to curb appetite and lead to weight loss. It is known to play a pivotal role in energy balance through its effects on the central nervous system, specifically by acting on a hypothalamic brain region known as the arcuate nucleus (ARC). The ARC contains two types of leptin-responsive neurons, the POMC neurons, which cause a loss of appetite, and the so-called Agouti-related peptide (AgRP) neurons, which do the opposite.

Studies had also revealed a role for leptin in blood sugar control and activity level, also via effects on the ARC. However, scientists still didn't know which neurons were responsible, until now.

When the researchers restored leptin receptor activity in POMC neurons of otherwise leptin-resistant, obese, and diabetic mice, the animals began eating about 30 percent fewer calories and lost a modest amount of weight. Remarkably, the researchers report, their blood sugar levels returned to normal independently of any change in their eating habits or weight. The animals also doubled their activity levels.

Whether this particular bunch of neurons also plays a similarly important role in animals that are lean remains uncertain, Bjorbaek said. "It may be that in the context of severe obesity and diabetes, these neurons do something they don't normally do," he said. But, he added, even if that were the case, it may not matter when it comes to its potential as a therapeutic target.

Achieving a world first, scientists in China have induced cells from pigs to become pluripotent stem cells, which like embryonic stem cells are able to develop into any cell of the body.

The study, which is to published early June in the newly launched Journal of Molecular Cell Biology, was the work of principal investigator Dr Lei Xiao, who leads the stem cell lab at the Shanghai Institute of Biochemistry and Cell Biology, and colleagues.

This is the first time anyone in the world has made pluripotent stem cells from somatic cells (as opposed to germline cells such as sperm and eggs) from an ungulate (an animal that has hooves).

The researchers hope this opens the door to making human disease models, engineering animals as sources of organs for transplant into humans, and developing pigs that are resistant to diseases like swine flu.

Quoted in a separate statement, Xiao said:

"Pig pluripotent stem cells would be useful in a number of ways, such as precisely engineering transgenic animals for organ transplantation therapies."

"The pig species is significantly similar to humans in its form and function, and the organ dimensions are largely similar to human organs," added Xiao.

Xiao and colleagues took cells from the ears and bone marrow of pigs and using transcription factors introduced by a virus they reprogrammed them and coaxed them to develop into colonies of induced pluripotent stem cells (iPS cells) which are very similar to embryonic stem cells, regarded as the "gold standard" of stem cell research.

Further tests showed that like embryonic stem cells, the new iPS pig cells were capable of differentiating into the types of cells that form the endoderm, mesoderm and ectoderm layers of an embryo.

Working with iPS cells in this way also gives information that should make it easier to develop embryonic stem cells (ES cells) from pig or other ungulate embryos, said the researchers.

"We could use embryonic stem cells or induced stem cells to modify the immune-related genes in the pig to make the pig organ compatible to the human immune system," explained Xiao, adding that the pigs could then be used as organ donors for human patients without their immune system having an adverse reaction.

Another application could be to create models for human diseases, for many of them are caused by a disorder of gene expression.

"We could modify the pig gene in the stem cells and generate pigs carrying the same gene disorder so that they would have a similar syndrome to that seen in human patients," explained Xiao, adding that it would then be possible to use the pig model to develop treatments.

And another use could be to breed gene-modified pigs with resistance to diseases like swine flu.

"We would do this by first, finding a gene that has anti-swine flu activity, or inhibits the proliferation of the swine flu virus; second, we can introduce this gene to the pig via pluripotent stem cells, a process known as gene knock-in," said Xiao.

Another way they could make pigs resistant to swine flu would be to knock out the pig cell membrane receptor that the virus uses to gain access to cells. Doing this would stop the virus invading cells and using their contents to replicate itself.

"We could knock out this receptor in the pig via gene targeting in the pig induced pluripotent stem cell," explained Xiao.

There could also be applications to farming, not only by helping to breed healthier and more disease resistant pigs, but also by improving the way that pigs grow.

There is a frenzied push by mental health providers--almost all of whom have financial ties to psychotropic drug manufacturers--to persuade government to adopt a policy of screening teenagers and women for depression.

The women being targeted at this juncture are vulnerable: they are either pregnant or have just given birth to a child. In both cases, both mother and infant are at risk of being harmed by pharmacological interventions.

The problem with mental screening starts with the fact that the method for mental screening is an unreliable suggestive questionnaire which is noted for its high rate (84%) for misidentifying normal teens as having mental disorders.

The diagnostic tools used by psychiatrists remain subjective and unscientific. And, overwhelmingly, the "therapeutic" interventions prescribed are dangerous psychotropic drugs that have often aggravated an emotional problem. Indeed, antidepressants increase the risk of suicide--as these drugs' warning labels indicate.

Schools should not be turned into medical fishing terminals; it is devastating for any child to be labeled as having a mental illness as such a label opens the child to a life of stigmatization, discrimination and undesirable status.

When the "diagnosis" is false, a crime has been committed: who will assume responsibility for such a child's derailed life and shattered dream of becoming President?

The proponents of screening are disingenuous as they pretend that non-pharmacological therapies are widely available--they are not, especially for the non-wealthy.

Paroxysmal nocturnal hemoglobinuria (PNH) cells are present in the majority of patients with myelodysplastic syndromes (MDS), aplastic anemia (AA), and other bone marrow failure syndromes (BMF), according to interim results from 5,285 patients enrolled in the EXPLORE trial. EXPLORE (EXamination of PNH, by Level Of CD59 on REd and white blood cells) is the first large multicenter study to determine the frequency of PNH cells in these patient populations using a central laboratory conducting a high sensitivity test for PNH cells. The findings from EXPLORE will be presented tomorrow at the 45th Annual Meeting of the American Society of Clinical Oncology (ASCO). The EXPLORE trial was sponsored by Alexion Pharmaceuticals, Inc. (Nasdaq:ALXN).

PNH cells are defined as blood stem cells lacking certain proteins, known as GPI-anchored proteins, which include proteins that ordinarily protect blood cells from destruction by complement, a component of the normal immune system. The lack of these complement inhibitors results in the hemolysis (red blood cell destruction) that characterizes PNH, an ultra-rare, debilitating and life-threatening disease.

"The true prevalence of PNH cells in patients with a number of bone marrow failure syndromes has been unclear due to variability in PNH testing. Interim results from the EXPLORE trial show that PNH cells are common in these patients," said Azra Raza, M.D., Director, MDS Program, St. Vincent's Comprehensive Cancer Center, New York. "These results show that high sensitivity testing may help physicians detect undiagnosed PNH in patients with bone marrow failure disorders, and identify those patients with bone marrow failure who may be more likely to respond to immunosuppressive therapy."

Interim results from the EXPLORE trial are based on 5,285 patients with evidence of bone marrow failure, including 4,433 with MDS, 451 with AA, and 351 with other bone marrow failure syndromes (including patients with more than one diagnosis). To eliminate variability in the detection and reporting of PNH cell populations, a central laboratory employed a commercially available high-sensitivity flow cytometry test to identify GPI anchor-deficient PNH red blood cells and white blood cells, resulting in 0.01% sensitivity. Interim results are as follows:

- PNH cells were present in 70% of patients with AA, 55% of patients with MDS, and 55% of patients with other BMF syndromes when tested at a sensitivity of 0.01% PNH cells.

- PNH clones of clinical significance (≥1% of white blood cells) were found in 25% of patients with AA (113 of 451), 1% of patients with MDS (54 of 4,433) and 5% of patients with other BMF syndromes (16 of 351).

- Among patients with PNH clones of clinical significance, elevated levels of hemolysis, or red blood cell destruction, were evident in 38% of patients with AA, 44% of patients with MDS, and 69% of patients with other BMF syndromes. In PNH, excessive hemolysis can lead to thrombosis, pulmonary hypertension, kidney failure, pain and fatigue in affected patients.

- Most patients who tested positive had smaller populations of PNH cells (< 1% of white blood cells), demonstrating the need to test patients using flow cytometry with sufficiently high sensitivity capable of detecting these abnormal cells.

- PNH cells were identified in patients with all subtypes of MDS as well as in patients with both severe and non-severe aplastic anemia, supporting the clinical importance of testing all MDS and AA patients.