Friday, January 31, 2014

3D microscopy

A 3D window into living cells, no dye required

January 27, 2014

A new 3D imaging technique for live cells uses a conventional microscope to capture image slices throughout the depth of the cell, then computationally renders them into one three-dimensional image. The technique uses no dyes or chemicals, allowing researchers to observe cells in their natural state. (Credit: University of Illinois)

University of Illinois researchers have developed a new imaging technique that needs no dyes or other chemicals, yet renders high-resolution, three-dimensional, quantitative imagery of cells and their internal structures using conventional microscopes and white light.

Called white-light diffraction tomography (WDT), the imaging technique opens a window into the life of a cell without disturbing it and could allow cellular biologists unprecedented insight into cellular processes, drug effects and stem cell differentiation.

The team, led by electrical and computer engineeringand bioengineering professor Gabriel Popescu, published their results in the journal Nature Photonics./.../

Perception

Where and when the brain recognizes, categorizes an object

January 28, 2014

MIT researchers combined fMRI and MEG data to reveal which parts of the brain are active shortly after an image is seen. At around 60 milliseconds, only early visual cortex in the back of the brain was active (image at left). Then, activity spread to brain regions involved in later visual processing until the inferior temporal cortex was activated (image at right). This brain region represents complex shapes and categories of objects. (Credit: Radoslaw Martin Cichy, Dimitrios Pantazis, Aude Oliva)

MIT researchers scanned individuals’ brains as they looked at different images and were able to pinpoint, to the millisecond, when the brain recognizes and categorizes an object, and where these processes occur.

“This method gives you a visualization of ‘when’ and ‘where’ at the same time. It’s a window into processes happening at the millisecond and millimeter scale,” saysAude Oliva, a principal research scientist in MIT’sComputer Science and Artificial Intelligence Laboratory(CSAIL).

Oliva is the senior author of a paper describing the findings in the Jan. 26 issue of Nature Neuroscience. Lead author of the paper is CSAIL postdoc Radoslaw Cichy. Dimitrios Pantazis, a research scientist at MIT’sMcGovern Institute for Brain Research, is also an author of the paper./.../

Interplanetary dust

Interplanetary dust particles carry water and organics

Mars had liquid water 4 billion years ago

January 29, 2014

Interplanetary dust particles carry water generated with hydrogen solar wind + oxygen from silicate mineral grains (credit: John Bradley)

Interplanetary dust particles could be delivering water and organics to the Earth and other terrestrial planets scientists have found.

Interplanetary dust — dust that has come from comets, asteroids, and leftover debris from the birth of the solar system — continually rains down on the Earth and other Solar System bodies.

These particles are bombarded by the solar wind, predominately hydrogen ions. This ion bombardment knocks the atoms out of order in the silicate mineral crystal and leaves behind oxygen that is more available to react with hydrogen to create water molecules.

“It is a thrilling possibility that this influx of dust has acted as a continuous rainfall of little reaction vessels containing both the water and organics needed for the eventual origin of life on Earth and possibly Mars,” said Hope Ishii, new Associate Researcher in the Hawaiʻi Institute of Geophysics and Planetology (HIGP) at the University of Hawaiʻi and co-author of the study./.../

strategic planning/decision making/multitasking

A brain area unique to humans is linked to strategic planning/decision making/multitasking

January 30, 2014

Image shows in red an area of the frontal cortex of the brain that appears to be uniquely human (credit: Oxford University)

Oxford University researchers have identified a specific area of the human brain that appears to be unlike anything in the brains of some of our closest relatives.

MRI imaging of 25 adult volunteers was used to identify key components in the area of the human brain called the ventrolateral frontal cortex, and how these components were connected up with other brain areas. The results were then compared with equivalent MRI data from 25 macaque monkeys.

The ventrolateral frontal cortex area of the brain is involved in many of the highest aspects of cognition and language, and is only present in humans and other primates./.../

Synthetic magnetic monopoles

Physicists create synthetic magnetic monopoles

May lead to entirely new materials, such as superconductors

January 30, 2014

Artist illustration of the synthetic magnetic monopole (credit: Heikka Valja)

Nearly 85 years after pioneering theoretical physicist Paul Dirac predicted the possibility of their existence, scientists have created, identified and photographed synthetic magnetic monopoles.

The groundbreaking accomplishment, described by a paper in Nature, paves the way for the detection of the particles in nature, which would be a revolutionary development comparable to the discovery of the electron, according to the scientists.

“The creation of a synthetic magnetic monopole should provide us with unprecedented insight into aspects of the natural magnetic monopole — if indeed it exists,” said Amherst College Physics Professor David S. Hall.

fisetin

Natural plant compound prevents Alzheimer’s disease in mice

January 30, 2014

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Fisetin reduces (right) astrocytic reactivity in the brains of Alzheimer’s disease mice. Scale bar: 10 microns. (Credit: Antonio Currais et al./Aging Cell)

A daily dose of fisetin, an antioxidant chemical that’s found in fruits and vegetables from strawberries to cucumbers, appears to stop memory loss that accompanies Alzheimer’s disease in mice, scientists at the Salk Institute for Biological Studies have discovered.

In experiments on mice that normally develop Alzheimer’s symptoms less than a year after birth, a daily dose of the compound prevented the progressive memory and learning impairments.

The drug, however, did not alter the formation of amyloid plaques in the brain, accumulations of proteins that are commonly blamed for Alzheimer’s disease. The new finding suggests a way to treat Alzheimer’s symptoms independently of targeting amyloid plaques.

“We had already shown that in normal animals, fisetin can improve memory,” says Pamela Maher, a senior staff scientist in Salk’s Cellular Neurobiology Laboratory who led the new study. “What we showed here is that it also can have an effect on animals prone to Alzheimer’s.”

More than a decade ago, Maher discovered that fisetin helps protect neurons in the brain from the effects of aging. She and her colleagues have since — in both isolated cell cultures and mouse studies — probed how the compound has both antioxidant and anti-inflammatory effects on cells in the brain. Most recently, they found that fisetin turns on a cellular pathway known to be involved in memory.

“What we realized is that fisetin has a number of properties that we thought might be beneficial when it comes to Alzheimer’s,” says Maher.

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The fisetin protective mode of action (credit: Antonio Currais et al./Aging Cell)

The experiments

So Maher — who works with Dave Schubert, the head of the Cellular Neurobiology Lab — turned to a strain of mice that have mutations in two genes linked to Alzheimer’s disease. The researchers took a subset of these mice and, when they were only three months old, began adding fisetin to their food.

As the mice aged, the researchers tested their memory and learning skills with water mazes. By nine months of age, mice that hadn’t received fisetin began performing more poorly in the mazes. Mice that had gotten a daily dose of the compound, however, performed as well as normal mice, at both nine months and a year old.

“Even as the disease would have been progressing, the fisetin was able to continue preventing symptoms,” Maher says.

In collaboration with scientists at the University of California, San Diego, Maher’s team next tested the levels of different molecules in the brains of mice that had received doses of fisetin and those that hadn’t. In mice with Alzheimer’s symptoms, they found, pathways involved in cellular inflammation were turned on. In the animals that had taken fisetin, those pathways were dampened and anti-inflammatory molecules were present instead.

One protein in particular — known as p35 — was blocked from being cleaved into a shorter version when fisetin was taken. The shortened version of p35 is known to turn on and off many other molecular pathways. The results were published December 17, 2013, in the journal Aging Cell.

Next steps

Next, Maher’s team hopes to understand more of the molecular details on how fisetin affects memory, including whether there are targets other than p35.

“It may be that compounds like this that have more than one target are most effective at treating Alzheimer’s disease,” says Maher, “because it’s a complex disease where there are a lot of things going wrong.”

They also aim to develop new studies to look at how the timing of fisetin doses affect its influence on Alzheimer’s.

“The model that we used here was a preventive model,” explains Maher. “We started the mice on the drugs before they had any memory loss. But obviously human patients don’t go to the doctor until they are already having memory problems.” So the next step in moving the discovery toward the clinic, she says, is to test whether fisetin can reverse declines in memory once they have already appeared.

The work was supported by grants from the Alzheimer’s Association, Paul Slavik, the National Institutes of Health, the Alzheimer’s Drug Discovery Foundation, and the George E. Hewitt Foundation.

Abstract of Aging Cell paper

Alzheimer’s disease (AD) is the most common type of dementia. It is the only one of the top ten causes of death in the USA for which prevention strategies have not been developed. Although AD has traditionally been associated with the deposition of amyloid β plaques and tau tangles, it is becoming increasingly clear that it involves disruptions in multiple cellular systems. Therefore, it is unlikely that hitting a single target will result in significant benefits to patients with AD. An alternative approach is to identify molecules that have multiple biological activities that are relevant to the disease. Fisetin is a small, orally active molecule which can act on many of the target pathways implicated in AD. We show here that oral administration of fisetin to APPswe/PS1dE9 double transgenic AD mice from 3 to 12 months of age prevents the development of learning and memory deficits. This correlates with an increase in ERK phosphorylation along with a decrease in protein carbonylation, a marker of oxidative stress. Importantly, fisetin also reduces the levels of the cyclin-dependent kinase 5 (Cdk5) activator p35 cleavage product, p25, in both control and AD brains. Elevated levels of p25 relative to p35 cause dysregulation of Cdk5 activity leading to neuroinflammation and neurodegeneration. These fisetin-dependent changes correlate with additional anti-inflammatory effects, including alterations in global eicosanoid synthesis, and the maintenance of markers of synaptic function in the AD mice. Together, these results suggest that fisetin may provide a new approach to the treatment of AD.

REFERENCES:

Antonio Currais et al., Modulation of p25 and inflammatory pathways by fisetin maintains cognitive function in Alzheimer's disease transgenic mice, Aging Cell, 2013, DOI: 10.1111/acel.12185

Tuesday, January 28, 2014

DDT and Alzheimer

Alzheimer's Risk Tied to Banned Pesticide

Published: Jan 27, 2014

By John Gever, Deputy Managing Editor, MedPage Today

Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania

Exposure to the notorious pesticide DDT may play a role in development of Alzheimer's disease, a small case-control study suggested.

Levels of dichlorodiphenyldichloroethylene (DDE), the main metabolite of DDT, averaged 2.64 ng/mg in serum (SE 0.35) in 86 individuals diagnosed with Alzheimer's disease, compared with 0.69 ng/mg (SE 0.1) in 79 controls (P<0 .001="" a="" according="" href="http://eohsi.rutgers.edu/content/directory?profile=84" nbsp="" style="color: #008be8; outline-style: none; text-decoration: none;" target="_blank" to="">Jason R. Richardson, PhD

, of Rutgers Robert Wood Johnson Medical School in Piscataway, N.J., and colleagues.

Looked at another way, those study participants in the highest tertile of serum DDE level had quadruple the risk of carrying an Alzheimer's disease diagnosis (odds ratio 4.18, 95% CI 2.54-5.82 versus the lowest tertile), the researchers reported online in JAMA Neurology.

Mean scores on the 30-point Mini-Mental State Examination (MMSE) were lower by 1.605 points (95% CI 0.114-3.095) in the highest versus lower tertiles of serum DDE, Richardson and colleagues also found.

And, they identified a potential mechanism whereby DDT/DDE exposure may promote development of Alzheimer's disease. In vitro experiments with human neuroblastoma cells showed that exposure to either chemical boosted secretion of amyloid precursor protein -- the parent of beta-amyloid protein. Beta-amyloid plaques in the brain are a major hallmark of Alzheimer's disease.

Although DDT was banned in the U.S. in 1972, Richardson and colleagues noted, it is still in use elsewhere in the world. Americans may continue to be exposed to the pesticide through imported foods. Moreover, it is very long-lived in the environment, and exposure to contaminated soils may be another route of continuing exposure.

The researchers cited findings from recent federal surveys that found 75% to 80% of participants had measurable levels of DDE in serum.

Other researchers not involved in the study cautioned that it was small, preliminary, and not designed to establish causality. Huntington Potter, PhD, of the University of Colorado School of Medicine in Aurora, told MedPage Today that it was essentially "a pilot study."

But Potter, as well as authors of an accompanying editorial in JAMA Neurology, noted that it was important for suggesting a specific environmental factor that may contribute to Alzheimer's disease risk -- something that has long been hypothesized but with few specific clues for where to look.

"Richardson and colleagues have provided both a wake-up call to explore environmental influences and pointed us to a first area to assess -- pesticides, which have already been implicated in other human illnesses," wrote Steven DeKosky, MD, of the University of Virginia in Charlottesville, and Sam Gandy, MD, PhD, of the Mount Sinai Alzheimer's Disease Research Center in New York City, in the editorial.

For example, last year a meta-analysis found that pesticide exposure was a significant risk factor for Parkinson's disease.

For the study, Richardson and colleagues recruited two cohorts of participants, one at the University of Texas Southwestern Medical Center in Dallas and the other at Emory University in Atlanta, from 2002 to 2008. Blood samples were drawn and the investigators decided by consensus, on the basis of published diagnostic criteria, whether participants had Alzheimer's disease or were cognitive normal.

One finding that tended to reinforce the connection between DDE levels and Alzheimer's disease risk was that participants with high levels and the APOE4 genotype -- well known to dramatically increase the risk of Alzheimer's disease risk -- showed an exaggerated decrease in MMSE scores relative to those with low DDE levels.

The mean difference in MMSE score between the first and third tertiles of serum DDE was -1.70 (95% CI minus 0.11-minus 3.29) among those with the APOE4 genotype, versus -0.53 (95% CI minus 0.43-minus 0.62) for those with APOE2/3 genotypes (P=0.04 for interaction).

A weakness in the study identified by the editorialists as well as Potter was that, when the two study cohorts were analyzed separately, the association of DDE with Alzheimer's disease risk was not statistically significant in either. It became significant only when the data were pooled.

Consequently, Potter said, the results should be considered preliminary. He noted as well that noncausal explanations for the association can't be ruled out.

For example, he said, individuals with Alzheimer's disease may simply be more rapid metabolizers of DDT, such that their DDE levels are higher even though their exposure to DDT is not.

DeKosky and Gandy argued that more resources should be directed to uncovering environmental factors that promote Alzheimer's disease, because it appears "less likely" that undiscovered genetic factors will have "new and powerful effects" on the risk.

"The time has arrived to direct resources toward the formation of collaborative teams of epidemiologists, toxicologists, geneticists, and dementia researchers," they wrote, with collaborations among the various NIH institutes and other public and private partners.

The study was funded by the NIH.

Study authors declared they had no relevant financial interests.

DeKosky reported relationships with AstraZeneca, Merck, Elan/Wyeth, Novartis, Lilly, Janssen, Helicon, Genzyme, Baxter, and Pfizer. Gandy reported relationships with Baxter, Polyphenolics, Amicus, Janssen, DiaGenic, and Cerora.

Comment

Primary source: JAMA Neurology
Source reference: Richardson J, et al "Elevated serum pesticide levels and risk for Alzheimer disease" JAMA Neurol 2014; DOI: 10.1001/jamaneurol.2013.6030.

Additional source: JAMA Neurology
Source reference:DeKosky S, et al "Environmental exposures and the risk for Alzheimer disease: Can we identify the smoking guns?" JAMA Neurol 2014; DOI: 10.1001/jamaneurol.2013.6031.

Bicho preguiça - Sloth

The Sloth’s Busy Inner Life

By NICHOLAS WADEJAN. 27, 2014

A three-toed juvenile sloth in Costa Rica. iStock

Flu

Why Is This Year's Flu So Dangerous for Young Adults?

Here's what you need to know.

—By Kiera Butler

| Mon Jan. 27, 2014 6:38 AM GMT

You've probably heard by now that this year's flu season is a bad one. Below is a guide to the viruses that are going around now, plus a refresher on flu basics.

Is the flu widespread where I live?
Probably:

Centers for Disease Control and Prevention

How many people have died so far this year?
Twenty-eight children have died so far. The Centers for Disease Control and Prevention does not keep track of adult deaths. That's because states are not required to report flu deaths to the CDC. Older adults often die of flu complications or secondary infections rather than the flu itself, so tracking flu deaths is not an exact science. That said, in California, the death toll is currently at 146, including 95 people under the age of 65. At this time last year, just 9 Californians under 65 had died of the flu, and by the end of the season, a total of 106 people had died./.../

Drogadição

27 de janeiro de 2014 | N° 17686

ARTIGOS

Viagens, por Themis Groisman Lopes*

Um novo ano se iniciou e, com ele, sucedem-se as crises e mazelas em nosso mundo. Entre elas, existem algumas de fundamental importância, para as quais nossa atenção deve ser redobrada. São as viagens de desastrosas consequências, cujos passageiros são os usuários das drogas ilícitas, no caso: maconha, cocaína e crack. Ainda que a primeira tenha sido liberada em alguns países e Estados americanos, independentemente de seus não bem provados efeitos terapêuticos, sabe-se que seu consumo crônico acarreta problemas de motivação comportamental.

Ela age nos circuitos cerebrais provocando alterações cognitivas. Onde foi liberada, seu consumo aumentou assustadoramente. Quanto às outras duas, são notórios e comprovados cientificamente os sérios danos que causam. Inclusive com riscos de morte.

São casos de saúde pública e como tais devem ser tratados. Os usuários são doentes que necessitam de atendimento especializado. As políticas governamentais em relação ao assunto são dirigidas para a internação compulsória dos usuários, o que, para a maioria dos estudiosos do assunto, não resolve. Só é indicada quando existem riscos para o paciente ou para outrem.

É básico, em qualquer terapia, estudar a fundo a origem da problemática. O fácil acesso aos produtos, a miséria e os transtornos preexistentes são considerados fatores de risco. No entanto, restringir-se à simplificação desses não levará à sua solução. Faz-se mister que sejam pesquisadas as causas que levam as pessoas ao uso das drogas, quase como uma forma de sobrevivência. A personalidade prévia de cada um, bem como a genética da compulsividade, são elementos quase sempre presentes. Deve ser feito um levantamento psicológico de cada usuário. Em geral, são jovens carentes, de famílias desintegradas, que procuram nas drogas uma fuga para a falta de afeto e cuidados.

O Brasil é grande demais para se dizer que foi vencido pelo crack. Segundo o Dr. Paulo de Argollo Mendes, presidente do Sindicato Médico do Rio Grande do Sul, 80% dos usuários manifestam vontade de serem tratados. Então, o fundamental é como podem ser tratados. Existem os Centros de Assistência Psicossocial (CAPs), onde os drogados são atendidos. O problema é a falta de recursos disponíveis nesses centros para o atendimento global. Deve haver uma equipe de saúde multidisciplinar que se dedique a atender os usuários e suas famílias. A participação das últimas é fundamental. É bem mais confortável para uma mãe ou um pai que acorrenta o filho para afastá-lo das drogas participar com ele dos programas de ajuda mútua.

Existe, em São Paulo, o projeto Amar-Gen (o gene do amor), formado por um grupo de profissionais da saúde e artistas que trabalham com espetáculos teatrais, procurando cooptar pacientes para participarem. Atuam em hospitais, vão às casas dos pacientes e recrutam jovens em praças públicas, para ocupá-los, não simplesmente para fazer uma “limpeza” das vias urbanas.

Somado a medidas terapêuticas, com assistência psicológica e medicação, deve haver um empenho geral do governo, destinando mais recursos para os centros de reabilitação, bem como uma mobilização da sociedade como um todo, na luta para recuperar pessoas, que, na maioria, pedem muito pouco: atenção e carinho. Se medidas assim forem tomadas, posso garantir que esta será uma ótima viagem.

*PSIQUIATRA

Monday, January 27, 2014

Phylosophy and Science

Why Scientists Should Study Philosophy

published by Theral Timpson on Sun, 01/26/2014 - 23:50

Since the first human genome was sequenced, there has been disappointment in and with the life science community over the fact that we haven’t figured out more of the big biology problems. Cancer, for instance. Oh, there’s been rapid technological progress. Illumina announced this year that the human genome that cost $3 billion to sequence originally can now be done for the cost of a root canal, or $1,000.

So why the disappointment? Why were scientific expectations so high? /.../

Sunday, January 26, 2014

Reutilização de Marca-Passo

Há poucos dias O cirurgião Fernando Lucchese esteve no programa do Lauro discutindo sobre transplantes cardíacos. Não consegui assistir mas pelos comentário foi muito apreciado. Quando soube aproveitei para fazer uma pergunta sobre reutilização de MP porque a família de um amigo recém falecido tentou oferecer o aparelho que ainda deveria ter no mínimo cinco anos de utilidade, não o estava conseguindo por "barreira legal".

Enviei a seguinte pergunta: gostaria de saber se existe algum motivo real de risco para reutilização do aparelho já que se pode reutilizar um coração inteiro natural. Porque não o MP? Abraço AA

Dr. Lucchese ou não leu minha pergunta ou não quis responder, mas tive a atenção do do Cidio

Cidio Halperin (friends with Fernando Antônio Lucchese) also commented onFernando Antônio Lucchese's status.

Cidio Halperin Caro Dr Aloyzio Cechella Achutti Apesar da legislação brasileira não permitir, diversos estudos http://tinyurl.com/n9hf6br mostram que o reuso é uma alternativa viável, desde que cuidados adequados sejam tomados. Logo escreverei um post sobre o assunto no www.foradoponto.com . Abs

Reuse of Pacemakers

circ.ahajournals.org

Background—In developing economies, there are patients in whom pacemaker implantation is delayed because they cannot afford one. Reused devices have been a solution. To address concerns about safety, a cohort of consecutive patients implanted with a reused pacemaker was compared with a control group...