Discovery of cell memory mechanism

AUG 22, 2013- The cells in our bodies can divide as often as once every 24 hours, creating a new, identical copy. DNA binding proteins called transcription factors are required for maintaining cell identity. They ensure that daughter cells have the same function as their mother cell, so that for example muscle cells can contract or pancreatic cells can produce insulin. However, each time a cell divides the specific binding pattern of the transcription factors is erased and has to be restored in both mother and daughter cells. Previously it was unknown how this process works, but now scientists at Karolinska Institute have discovered the importance of particular protein rings encircling the DNA and how these function as the cell's memory.

The DNA in human cells is translated into a multitude of proteins required for a cell to function. When, where and how proteins are expressed is determined by regulatory DNA sequences and a group of proteins, known as transcription factors, that bind to these DNA sequences. Each cell type can be distinguished based on its transcription factors, and a cell can in certain cases be directly converted from one type to another, simply by changing the expression of one or more transcription factors. It is critical that the pattern of transcription factor binding in the genome be maintained. During each cell division, the transcription factors are removed from DNA and must find their way back to the right spot after the cell has divided. Despite many years of intense research, no general mechanism has been discovered which would explain how this is achieved.

 Jussi Taipale, professor at Karolinska Institute and the University of Helsinki,is behind the discovery.

 The scientist found that a large protein complex called cohesin is positioned as a ring around the two DNA strands that are formed when a cell divides, marking virtually all the places on the DNA where transcription factors were bound. Cohesin encircles the DNA strand as a ring does around a piece of string, and the protein complexes that replicate DNA can pass through the ring without displacing it. Since the two new DNA strands are caught in the ring, only one cohesin is needed to mark the two, thereby helping the transcription factors to find their original binding region on both DNA strands.                                                                                                                                                                  

Transcription factors play a pivotal role in many illnesses, including cancer as well as many hereditary diseases. The discovery that virtually all regulatory DNA sequences bind to cohesin may also end up having more direct consequences for patients with cancer or hereditary diseases. Cohesin would function as an indicator of which DNA sequences might contain disease-causing mutations.

A new biomarker for chronic stress: Hair Cortisol

AUG 22, 2013-   Cortisol is a well-known stress hormone and until recently, we have only been able to understand how stressed a person has been for about the past 20 minutes or the past day. Now, with about 100 strands of hair clipped from the scalp, we can get a biological indicator of stress over the past three months. Since hair growth approximately 1 cm per month, with 3 cms, we capture cortisol retrospectively, so we can measure "chronic" or accumulated stress.This study was conducted by the University of Massachusetts, Boston campus, in which they included students, staff, and community members.

                                     CORTISOL

 Furthermore, this research examines potential differences in biological and perceived stress by racial/ethnic identity, SES, sex and age. We obtained domain-specific indices of stress (i.e. personal perceived stress, chaos in the home and neighborhood assessments) and examined associations between CORT, subjective stress and health indicators [blood pressure and waist-to-hip ratio (WHR)]. Finally, we also investigated the interactions of well-known factors associated with health disparities: racial/ethnic identity and SES with both hair CORT and the perceived stress indices as the dependent variables.

It has been found through research that the highest cortisol levels in males, the group aged 18-22 (the entire sample was 18-66 yrs.), and those who identified as an ethnic minority. Critically, we also found perceived stress was positively related to hair cortisol. Specifically, when an individual was higher across several domains of stress (e.g., stress at home, stress in their neighborhood); this was associated with higher secretion of the stress hormone. One important interpretation of this is that perceiving something as stressful, whether happening or not, can be just as meaningful on our biological reactions to stress.

An unanticipated finding was that hair cortisol levels were higher for minorities in the higher socioeconomic status (SES). Much of the literature examining the SES/health gradient posits that better health is associated with higher objective and subjective status. However, there is related evidence that minority members may not always be conferred this benefit. One interpretation is that minorities in higher SES experience greater, albeit more subtle discrimination. Researchers suggest that in high SES, race becomes more salient, along with greater instances of misunderstanding cultural differences and awkwardness during interactions.

Interestingly, CORT was associated with only one of the other biomarkers of stress, higher systolic blood pressure. Waist and WHR were not significantly associated with CORT in these data. This was unexpected, since WHR is a well-known indicator of allostatic load and has been positively associated with CORT in other research (e.g.Manenschijn, et al., 2011). The relationship between CORT and health risk indicators needs further investigation. It is not yet known whether CORT will be consistently associated with chronic health issues and reliably predictive of chronic diseases associated with allostatic load.

Since hair grows approximately 1 cm per month, capturing 3 cms of hair (about 75-100 strands) can give us a retrospective window of stress levels for the past 3 months, rather than moments or days. Hair cortisol is a promising measure of cumulative or long term stress stress. And chronic stress is quickly becoming recognized as the mediator for multiple psychological and physical health outcomes

Vitamin D Deficiency May Raise Allergy and Asthma Risk in Obese Children, Teens

august 21, 2013 —One reason why obese children and teenagers are more likely to have hard-to-control asthma and allergies may be vitamin D deficiency, a new study finds. 

The increased risk for asthma and allergies, and for more severe cases of allergic disease, in overweight and obese adolescents has not previously been understood," said Candace Percival, MD, lead investigator and a pediatric endocrinology fellow at Walter Reed National Military Medical Center, Bethesda, MD. "However, past research has shown that vitamin D is important for a normal immune system and that vitamin D deficiency is common in obese individuals."

The study, conducted in 86 subjects ages 10 to 18 years, aimed to determine whether vitamin D deficiency plays a role in the increased allergy risk in youth with excess weight.

Fifty-four study subjects were overweight or obese, as determined by their body mass index (BMI) being at or above the 85th percentile for their age and sex on growth charts. The remaining 32 subjects had a healthy weight. For each subject, the researchers calculated the BMI standard deviation, called the BMI Z-score. All subjects had a vitamin D blood test called serum 25-hydroxyvitamin D, and all obese subjects were vitamin D insufficient, Percival said.

She and her team also measured levels of certain hormones called adipokines that originate in fat cells. Specifically, they assessed leptin and adiponectin, which laboratory and animal studies have shown change with obesity, with leptin becoming elevated and adiponectin decreasing. They evaluated whether these two hormones correlate with vitamin D levels and, in some subjects, with the body's allergy signaling pathways -- biochemical measures of allergic disease.

A subgroup of 39 subjects (19 with overweight or obesity and 20 with a healthy weight) underwent blood tests to measure their levels of immunoglobulin E (IgE), which is one of the main players in allergic reactions. Of these 39 subjects, 36 (17 overweight/obese and 19 healthy-weight) also underwent measurements of chemical messengers called cytokines that contribute to allergy and asthma, specifically interleukins (IL) 4, 6, 10 and 13 and interferon-gamma.

The investigators found significant correlations between the severity of the subjects' obesity, the adipokine levels and some biochemical measures of allergic disease. As expected, the higher the BMI Z-score was (indicating greater obesity), the higher the level of leptin and the lower the levels of adiponectin and vitamin D, the authors reported. Obese subjects also had increased levels of IgE, IL-6 and IL-13. However, Percival said, "the relationship between the BMI-Z score and the adipokines and markers of allergic disease seemed to depend on the vitamin D deficiency seen in the more obese patients, leading us to conclude that the increased risk for allergy in obesity may be mediated by vitamin D to some degree."