Jung-Hyun Lee, Sung Gyun Kang (Korean Ocean Research and Development Institute, and University of Science and Technology, Korea) and coworkers have found a microorganism which grows at 80 degrees Celsius, and uses formate to synthesize both hydrogen and adenosine triphosphate (energy) molecules, in oxygen-deprived conditions. This news feature was written on September 17, 2010.... Read more »
The biggest utility of NMR spectroscopy in drug discovery is in assessing three things; whether a particular ligand binds to a protein, what site on the protein it binds, and what parts of the ligand interact with the protein. Over the last few years a powerful technique named ‘SAR by NMR’ has emerged which is now widely used in ligand screening. In this technique, changes in the resonances of ligand and protein protons are observed to pinpoint the ligand binding site and corresponding residues. Generally when a ligand binds to a protein, both its and the protein’s rotational correlation time decreases; the result is a broadening of signals in the spectrum which can be used to detect ligand binding. One of the most effective methods in this general area is Saturation Transfer Difference (STD) spectroscopy. As the name indicates, it hinges on the transfer of magnetization between protein and ligand; the resulting decrease in intensity of ligand signals can provide valuable information about proximity of ligand protons with specific protein residues.But these kinds of techniques suffer from some drawbacks. One straightforward drawback is that signals from protein and ligand may simply overlap. Secondly, the broadening may be so much as to virtually make the signals disappear. Thirdly from a practical perspective, it is hard to get sufficient amounts of N15-labeled protein (usually obtained by growing bacteria on a N15-rich source and then purifying the proteins of interest).To circumvent some of these problems, a team at Abbott Laboratories has come up with a neat and relatively simple method which they call ‘labeled ligand displacement’. The method involves synthesizing a protein-binding probe that has been selectively labeled with C13. Protein binding broadens and diminishes the signals of this probe. However, when a high-affinity ligand is then added, it displaces the probe and we get recovery of the C13 signals. The authors illustrate this paradigm with several proteins of pharmaceutical interest, including heat-shock protein and carbonic anhydrase.The method is relatively simple. For one thing, using a commercially available C13-labeled building block for synthesizing a ligand is easier than obtaining a N15-labeled protein. The biggest merit of the method though is the fact that it hinges on C13 signals very specific to the probe; thus there is no complicating overlap of signals. And finally, the ligand seems to be general enough to be applied to any protein. Only time will tell how much it is utilized, but for now it seems like a neat addition to the arsenal of NMR methods for studying protein-ligand interactions.Swann, S., Song, D., Sun, C., Hajduk, P., & Petros, A. (2010). Labeled Ligand Displacement: Extending NMR-Based Screening of Protein Targets ACS Medicinal Chemistry Letters, 1 (6), 295-299 DOI: 10.1021/ml1000849... Read more »
Swann, S., Song, D., Sun, C., Hajduk, P., & Petros, A. (2010) Labeled Ligand Displacement: Extending NMR-Based Screening of Protein Targets. ACS Medicinal Chemistry Letters, 1(6), 295-299. DOI: 10.1021/ml1000849
Earlier this week I wrote about some of the exciting polaritons in semiconductors. And just a few days later, there is another intriguing paper on this topic out. Something that I speculate(!) might lead to new types of quantum computers. But to recapitulate, polaritons are object that form when light interacts with electronic excitations. What I [...]... Read more »
Lagoudakis, K., Pietka, B., Wouters, M., André, R., & Deveaud-Plédran, B. (2010) Coherent Oscillations in an Exciton-Polariton Josephson Junction. Physical Review Letters, 105(12). DOI: 10.1103/PhysRevLett.105.120403
There are three neutrino species in the standard model, hereafter refereed to as 1, 2, and 3, that we know have mass from atmospheric and solar neutrino oscillation experiments. Furthermore, data from these experiments put constraints on the mass-splittings between these three neutrinos. From atmospheric experiments we know the mass differences between 2 and 3 is |M223| ~ 1.4x10-3 eV2 and from
... Read more »
Jimenez, R., Kitching, T., Peña-Garay, C., & Verde, L. (2010) Can we measure the neutrino mass hierarchy in the sky?. Journal of Cosmology and Astroparticle Physics, 2010(05), 35-35. DOI: 10.1088/1475-7516/2010/05/035
Here's an interesting paper that was just published in Cancer Research that describes some factors driving acquired resistance to MET inhibition with small molecules. MET inhibitors have gained a lot of attention recently (see Comoglio et al's review in the...... Read more »
Cepero, V., Sierra, J., Corso, S., Ghiso, E., Casorzo, L., Perera, T., Comoglio, P., & Giordano, S. (2010) MET and KRAS Gene Amplification Mediates Acquired Resistance to MET Tyrosine Kinase Inhibitors. Cancer Research. DOI: 10.1158/0008-5472.CAN-10-0436
Comoglio, P., Giordano, S., & Trusolino, L. (2008) Drug development of MET inhibitors: targeting oncogene addiction and expedience. Nature Reviews Drug Discovery, 7(6), 504-516. DOI: 10.1038/nrd2530
Sea Otters are turning up dead in central California. In 2007, 11 sea otters were recovered from Monterrey Bay. Over the last three years, dead otters washing up on beaches has reached a record high?
What could be causing all these otter deaths? Are there new predators in the area? Is there some kind of disease? [...]... Read more »
Miller, M., Kudela, R., Mekebri, A., Crane, D., Oates, S., Tinker, M., Staedler, M., Miller, W., Toy-Choutka, S., Dominik, C.... (2010) Evidence for a Novel Marine Harmful Algal Bloom: Cyanotoxin (Microcystin) Transfer from Land to Sea Otters. PLoS ONE, 5(9). DOI: 10.1371/journal.pone.0012576
Child sexual abuse in the Catholic Church: Revisiting the rotten apples explanation From Criminal Justice and Behavior The Pope’s first state visit to Britain this week has fuelled controversy, not least due to his recent comments expressing his “great sadness” over revelations of widespread abuse of children by Catholic priests, saying ”authorities in the church have [...]... Read more »
White, M., & Terry, K. (2008) Child Sexual Abuse in the Catholic Church: Revisiting the Rotten Apples Explanation. Criminal Justice and Behavior, 35(5), 658-678. DOI: 10.1177/0093854808314470
If all that you knew about paleontology came from headlines alone, you could be excused for thinking that the science consists of little more than naming one obscure creature after another. There are a few petrified celebrities which can draw sustained attention – Tyrannosaurus and Triceratops foremost among them – but, in general, it seems [...]... Read more »
Gingerich, P., Franzen, J., Habersetzer, J., Hurum, J., & Smith, B. (2010) Darwinius masillae is a Haplorhine — Reply to Williams et al. (2010). Journal of Human Evolution. DOI: 10.1016/j.jhevol.2010.07.013
Franzen JL, Gingerich PD, Habersetzer J, Hurum JH, von Koenigswald W, & Smith BH. (2009) Complete primate skeleton from the Middle Eocene of Messel in Germany: morphology and paleobiology. PloS one, 4(5). PMID: 19492084
Seiffert, E., Perry, J., Simons, E., & Boyer, D. (2009) Convergent evolution of anthropoid-like adaptations in Eocene adapiform primates. Nature, 461(7267), 1118-1121. DOI: 10.1038/nature08429
Williams BA, Kay RF, Christopher Kirk E, & Ross CF. (2010) Darwinius masillae is a strepsirrhine-a reply to Franzen et al. (2009). Journal of human evolution. PMID: 20188396
“Overfishing” is a term associated with resource depletion, extinction, and human greed. While the definition of overfishing is technically a subjective measure (How much fishing is too much?), it has been widely accepted to mean catching more of an aquatic … Continue reading →... Read more »
Vetemaa, M., Eschbaum, R., Albert, A., Saks, L., Verliin, A., Jurgens, K., Kesler, M., Hubel, K., Hannesson, R., & Saat, T. (2010) Changes in fish stocks in an Estonian estuary: overfishing by cormorants?. ICES Journal of Marine Science. DOI: 10.1093/icesjms/fsq113
Astrophysics is not only a complicated discipline, but it’s becoming more and more esoteric, so much so that there seems to be an entire genre of deriving "groundbreaking papers" from obscure numerology, and the scientific community took a while to catch up with the Bogdanov brothers’ papers and show them to be just the sort [...]... Read more »
Measuring diversity in the fossil record can be a tricky task. Short of inventing time travel, there will be always be some uncertainty about how many species of dinosaur existed at any one place and time, and as we learn more about the fossil record it may turn out that what we once thought to [...]... Read more »
Quandaries such as those involving stealing a drug to save a spouse's life or whether or not to have an abortion have historically dominated the study of the development of moral thinking. The predominant research programs in psychology today use dilemmas in which one choice is deontologically correct (it is wrong to rotate a lever that will divert a train and kill one person instead of five), and the other is consequentially correct (kill one person if it will save five others).
Read the rest of this post... | Read the comments on this post...... Read more »
It sounds like a science fiction movie: a blind man wearing sunglasses licks a plastic lollipop and can suddenly see. This device, however, exists today. The Brain Port—a contraption comprised of a tiny video camera attached to a pair of sunglasses linked to a plastic “lollipop”—is enabling the blind to see . . . with [...]... Read more »
Sampaio, E. (2001) Brain plasticity: 'visual' acuity of blind persons via the tongue. Brain Research, 908(2), 204-207. DOI: 10.1016/S0006-8993(01)02667-1
It sounds like a science fiction movie: a blind man wearing sunglasses licks a plastic lollipop and can suddenly see. This device, however, exists today. The Brain Port—a contraption comprised of a tiny video camera attached to a pair of sunglasses linked to a plastic “lollipop”—is enabling the blind to see . . . with their tongues.... Read more »
Sampaio, E. (2001) Brain plasticity: 'visual' acuity of blind persons via the tongue. Brain Research, 908(2), 204-207. DOI: 10.1016/S0006-8993(01)02667-1
by Isobel in Promega Connections
I know that results in mice do not always translate to humans. I know that. I know that clinical trials can take years and that there are many hurdles between the first promising result in an animal model and the actual development of some form of treatment. Nevertheless I could not stifle a surge of [...]... Read more »
Boyd TD, Bennett SP, Mori T, Governatori N, Runfeldt M, Norden M, Padmanabhan J, Neame P, Wefes I, Sanchez-Ramos J.... (2010) GM-CSF upregulated in rheumatoid arthritis reverses cognitive impairment and amyloidosis in Alzheimer mice. Journal of Alzheimer's disease : JAD, 21(2), 507-18. PMID: 20555144
For as long as I have been in pain research (and long before I ever even thought about pain research) the topic of mechanically-gated ion channels has been a huge deal. The reasons are simple: 1) We obtain information about … Continue reading →... Read more »
Coste, B., Mathur, J., Schmidt, M., Earley, T., Ranade, S., Petrus, M., Dubin, A., & Patapoutian, A. (2010) Piezo1 and Piezo2 Are Essential Components of Distinct Mechanically Activated Cation Channels. Science. DOI: 10.1126/science.1193270
by Peter Janiszewski, Ph.D. in Obesity Panacea
So what have we learned thus far?
1. About a third of obese individuals fail to exhibit the metabolic complications commonly attributed to excess weight.
2. These same individuals also seem to be at the same relative risk of diabetes and cardiovascular disease as equally healthy, but lean individuals.
3. Nevertheless, despite being metabolically healthy, some evidence suggests that excess weight may put such obese individuals at risk for early mortality due to other, non-metabolic, factors.
4. This latter point would imply that all obese individuals should be encouraged to lose weight, despite their metabolic health. This, in fact, is in line with guidelines developed by leading health authorities which currently recommend weight reduction as the primary treatment strategy for all obese patients, regardless of metabolic health. However, as we learned yesterday, weight loss via caloric restriction among metabolically healthy obese may actually result in a deterioration in insulin sensitivity, thereby increasing risk of developing type-2 diabetes.
Now, as most of you know, when a completely counter-intuitive finding like this comes along, where even the study authors fail to come up with a plausible mechanism, it is up to other researchers to follow up with additional research to either corroborate or refute this original finding.
Because I am personally drawn to paradoxical and counterintuitive findings in science, I was very intrigued by the findings of Karelis and colleagues and decided to follow up their study, but include a few variations:
a) Since the study of Karelis et al. only used female subjects, we wanted to ensure this wasn’t due to a gender effect and thus included both men and women.
b) Additionally, to test the possibility that their finding was driven only by modality of weight loss (caloric restriction, in their case) we employed a number of weight loss interventions (diet alone, exercise alone, and the combination of diet and exercise).
c) Finally, while the original study only looked at insulin sensitivity, we decided to assess changes in other variables of interest (body composition, blood lipids, glucose and insulin levels, etc.).
In our study, which has just been published in the prestigious journal, Diabetes Care, a total of 63 metabolically-healthy obese men and women and 43 metabolically-unhealthy obese men and women participated in 3-6 months of exercise and/or diet weight-loss intervention.
And what did we find?
First, body weight, waist circumference, and total and abdominal fat mass were significantly reduced in all subjects – regardless of gender, modality of weight loss, and metabolic status.
Second, in contrast to the findings of Karelis et al., insulin sensitivity IMPROVED after weight loss in both the metabolically-healthy (by about 20%) and metabolically-unhealthy obese individuals. However, the improvement was greater in the metabolically-unhealthy subjects. See figure below.
Importantly, this improvement was similar across all weight loss modalities. In other words, dietary caloric restriction did not have a unique negative effect on insulin sensitivity.
Finally, while the metabolically-unhealthy obese individuals also showed improvement in numerous other outcomes (triglycerides, fasting glucose and insulin, HDL-cholesterol, and total cholesterol), a reduction in fasting insulin was the only other metabolic improvement among the metabolically-healthy obese. This latter finding is not surprising given the normal baseline levels of most metabolic risk factors among metabolically-healthy obese individuals. That is, since they were healthy to begin with – they can only get so much healthier after weight loss (ceiling effect).
Thus, we found no evidence of deterioration in metabolic profile among metabolically-obese individuals who lost weight via a lifestyle intervention.
While limited health care resources dictate the need to prioritize high-risk obese individuals for aggressive treatment, to imply that obese individuals who are metabolically healthy should not lose weight may not be the most appropriate public health message. Such a public health message may be particularly misguided at a time when the prevalence of obesity continues to increase, despite a greater public awareness of the benefits of weight loss. In this context, our findings reinforce current recommendations which suggest that all obese individuals should be encouraged to lose 5-10% body weight.
Although a fair number of obese individuals may have a perfect metabolic profile, it appears they may still experience negative consequences of their excess weight. Furthermore, weight loss achieved via lifestyle intervention appears to still bring about some metabolic benefit among previously healthy obese individuals (it certainly doesn’t seem to harm health). Given the numerous non-metabolic benefits of weight loss (mobility, joint problems, psychological status, sexual function, etc.), all obese individuals have something to gain from a modest 5-10% weight loss.
Have a wonderful weekend,
References and Further Reading:
Janiszewski, P., & Ross, R. (2010). Effects of Weight Loss Among Metabolically Healthy Obese Men and Women Diabetes Care, 33 (9), 1957-1959 DOI: 10.2337/dc10-0547
... Read more »
Janiszewski, P., & Ross, R. (2010) Effects of Weight Loss Among Metabolically Healthy Obese Men and Women. Diabetes Care, 33(9), 1957-1959. DOI: 10.2337/dc10-0547
This was a follow up to a nationwide survey of GPs in Scotland completed in 2000. They used a similar questionnaire to the original study and sent it to a random sample of one in four Scottish GPs (n=1065). After a poor initial response they sent an abbreviated questionnaire on the key areas from the [...]... Read more »
Matheson C, Porteous T, van Teijlingen E, & Bond C. (2010) Management of drug misuse: an 8-year follow-up survey of Scottish GPs. The British journal of general practice : the journal of the Royal College of General Practitioners, 60(576), 517-20. PMID: 20594442
Glucosamine and chondroitin do not work in alleviating the pain of osteoarthritis (of hip or knee), other than perhaps as an expensive placebo that sufferers who do gain some relief daren’t stop paying for. A new meta analysis of 10 trials amounting to 3803 patients has been carried out. On a 10 cm visual analogue [...]... Read more »
Wandel, S., Juni, P., Tendal, B., Nuesch, E., Villiger, P., Welton, N., Reichenbach, S., & Trelle, S. (2010) Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis. BMJ, 341(sep16 2). DOI: 10.1136/bmj.c4675
Predation is a key driver of biological systems over both ecological and evolutionary timescales. Thus, to understand our role as Homo sapiens within this evolutionary framework we must look to the animal kingdom to find our place. This is important for anyone following an evolutionary eating plan as it gives our species an ecological context, which we can consider when making choices about our lifestyle and diet. In the latest edition of Behavioral Ecology, Shultz & Finlayson utilised a range of studies on vertebrate predators to establish the relationship between prey behavioral and ecological characteristics, and predator diet composition at the population level. Although this focuses on non-human species it is easy to extrapolate information from this data and find our place within the animal kingdom.... Read more »
Shultz, S., & Finlayson, L. (2010) Large body and small brain and group sizes are associated with predator preferences for mammalian prey. Behavioral Ecology, 21(5), 1073-1079. DOI: 10.1093/beheco/arq108
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