Date:
July 30, 2018

Source:
University of Cologne

Summary:
Observations made with ESO’s Very Large Telescope have for the first time clearly revealed the effects of Einstein’s general relativity on the motion of a star passing through the extreme gravitational field very close to the supermassive black hole in the center of the Milky Way. This long-sought result represents the climax of a 26-year-long observation campaign using ESO’s telescopes in Chile.

 

Observations made with ESO’s Very Large Telescope have for the first time revealed the effects predicted by Einstein’s general relativity on the motion of a star passing through the extreme gravitational field near the supermassive black hole in the center of the Milky Way. This long-sought result represents the climax of a 26-year-long observation campaign using ESO’s telescopes in Chile.
Credit: European Space Observatory

 

 

Obscured by thick clouds of absorbing dust, the closest supermassive black hole to the Earth lies 26,000 light years away at the centre of the Milky Way. This gravity monster, which has a mass four million times that of the Sun, is surrounded by a small group of stars orbiting at high speed. This extreme environment — the strongest gravitational field in our galaxy — makes it the perfect place to test gravitational physics, particularly Einstein’s general theory of relativity.

New infrared observations from the exquisitely sensitive GRAVITY, NACO and SINFONI instruments on ESO’s Very Large Telescope (VLT) have now allowed astronomers to follow one of these stars, called S2, as it passed very close to the black hole during May 2018 at a speed in excess of 25 million kilometres per hour — three percent of the speed of light — and at a distance of less than 20 billion kilometres.

These extremely delicate measurements were made by an international team led by Reinhard Genzel of the Max Planck Institute for extraterrestrial physics (MPE) in Garching, Germany, in conjunction with collaborators around the world. The observations form the culmination of a 26-year series of ever more precise observations of the centre of the Milky Way using ESO instruments. ‘This is the second time that we have observed the close passage of S2 around the black hole in our galactic centre. But this time, because of much improved instrumentation, we were able to observe the star with unprecedented resolution’, explains Genzel. ‘We have been preparing intensely for this event over several years, as we wanted to make the most of this unique opportunity to observe general relativistic effects.’

The new measurements clearly reveal an effect called gravitational redshift. Light from the star is stretched to longer wavelengths by the very strong gravitational field of the black hole. And the stretch in wavelength of light from S2 agrees precisely with that predicted by Einstein’s theory of general relativity. This is the first time that this deviation from the predictions of simpler Newtonian gravity has been observed in the motion of a star around a supermassive black hole. The team used SINFONI to measure the motion of S2 towards and away from Earth and the GRAVITY interferometric instrument to make extraordinarily precise measurements of the position of S2 in order to define the shape of its orbit. GRAVITY creates such sharp images that it can reveal the motion of the star from night to night as it passes close to the black hole — 26,000 light years from Earth.

‘Our first observations of S2, about two years ago, already showed that we would have the ideal black hole laboratory’, adds Frank Eisenhauer (MPE), Co-Principal Investigator of the GRAVITY instrument. ‘During the close passage, we managed not only to precisely follow the star on its orbit, we could even detect the faint glow around the black hole on most of the images.’ By combining the position and velocity measurements from SINFONI and GRAVITY, as well as previous observations using other instruments, the team could compare them to the predictions of Newtonian gravity, general relativity and other theories of gravity. As expected, the new results are inconsistent with Newtonian predictions and in excellent agreement with the predictions of general relativity. More than one hundred years after he published his paper setting out the equations of general relativity, Einstein has been proved right once more.

The hardware contribution of the Institute of Physics I of the University of Cologne was the development and construction of the two spectrometers of GRAVITY. The spectrometers analyse the wavelength of the observed stellar light and convert the received photons into electronic signals. ‘GRAVITY is a technological challenge. However, after more than two decades of astrophysical research on the high velocity stars in the Galactic Centre and on the development of astronomical instrumentation, the effort has been rewarded with an excellent result in experimental physics’, says Andreas Eckhart from the University of Cologne.

Continuing observations are expected to reveal another relativistic effect later in the year — a small rotation of the star’s orbit, known as Schwarzschild precession — as S2 moves away from the black hole.

Story Source:

Materials provided by University of CologneNote: Content may be edited for style and length.


Journal Reference:

  1. R. Abuter, A. Amorim, N. Anugu, M. Bauböck, M. Benisty, J. P. Berger, N. Blind, H. Bonnet, W. Brandner, A. Buron, C. Collin, F. Chapron, Y. Clénet, V. Coudé du Foresto, P. T. de Zeeuw, C. Deen, F. Delplancke-Ströbele, R. Dembet, J. Dexter, G. Duvert, A. Eckart, F. Eisenhauer, G. Finger, N. M. Förster Schreiber, P. Fédou, P. Garcia, R. Garcia Lopez, F. Gao, E. Gendron, R. Genzel, S. Gillessen, P. Gordo, M. Habibi, X. Haubois, M. Haug, F. Haußmann, Th. Henning, S. Hippler, M. Horrobin, Z. Hubert, N. Hubin, A. Jimenez Rosales, L. Jochum, L. Jocou, A. Kaufer, S. Kellner, S. Kendrew, P. Kervella, Y. Kok, M. Kulas, S. Lacour, V. Lapeyrère, B. Lazareff, J.-B. Le Bouquin, P. Léna, M. Lippa, R. Lenzen, A. Mérand, E. Müler, U. Neumann, T. Ott, L. Palanca, T. Paumard, L. Pasquini, K. Perraut, G. Perrin, O. Pfuhl, P. M. Plewa, S. Rabien, A. Ramírez, J. Ramos, C. Rau, G. Rodríguez-Coira, R.-R. Rohloff, G. Rousset, J. Sanchez-Bermudez, S. Scheithauer, M. Schöller, N. Schuler, J. Spyromilio, O. Straub, C. Straubmeier, E. Sturm, L. J. Tacconi, K. R. W. Tristram, F. Vincent, S. von Fellenberg, I. Wank, I. Waisberg, F. Widmann, E. Wieprecht, M. Wiest, E. Wiezorrek, J. Woillez, S. Yazici, D. Ziegler, G. Zins. Detection of the gravitational redshift in the orbit of the star S2 near the Galactic centre massive black holeAstronomy & Astrophysics, 2018; 615: L15 DOI: 10.1051/0004-6361/201833718

 

Source: University of Cologne. “Einstein’s general relativity confirmed near black hole.” ScienceDaily. ScienceDaily, 30 July 2018. <www.sciencedaily.com/releases/2018/07/180730090158.htm>.

Target Health’s Mary Shatzoff on FDA Panel

 

At the invitation of Office of Antimicrobial Products (CDER), Mary Shatzoff, Senior Director of Regulatory Affairs at Target Health, will be a speaker at the FDA workshop entitled: “Development of Non-Traditional Therapies for Bacterial Infections.” The purpose of this public workshop is to discuss the general development considerations of non-traditional therapies, including pre-clinical development, early clinical studies, and the design and evaluation of safety and efficacy in phase 3 clinical trials. This workshop will be held on August 21, 2018 from 8:30 to 4:30, and on August 22, 2018 from 8:30 to 12. This public workshop will also be available via a webcast.

 

For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 165). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website.

 

 

Joyce Hays, Founder and Editor in Chief of On Target

Jules Mitchel, Editor

 

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Circadian Rhythms

Overview of biological circadian clock in humans. Biological clock affects the daily rhythm of many physiological processes. This diagram depicts the circadian patterns typical of someone who rises early in morning, eats lunch around noon, and sleeps at night (10 p.m.). Although circadian rhythms tend to be synchronized with cycles of light and dark, other factors – such as ambient temperature, meal times, stress and exercise – can influence the timing as well.

 

Graphic credit: NoNameGYassineMrabetTalk fixed by Addicted04 – The work was done with Inkscape by YassineMrabet. Informations were provided from “The Body Clock Guide to Better Health“ by Michael Smolensky and Lynne Lamberg; Henry Holt and Company, Publishers (2000). Landscape was sampled from Open Clip Art Library (Ryan, Public domain). Vitruvian Man and the clock were sampled from Image:P human body.svg (GNU licence) and Image:Nuvola apps clock.png, respectively., CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=3017148

 

 

A circadian rhythm is any biological process that displays an endogenous, entrainable oscillation of about 24 1) ___. These 24-hour rhythms are driven by a circadian clock, and they have been widely observed in plants, animals, fungi, and cyanobacteria. The term circadian comes from the Latin circa, meaning “around“ (or “approximately“), and diem, meaning 2) ___. The formal study of biological temporal rhythms, such as daily, tidal, weekly, seasonal, and annual rhythms, is called chronobiology. Processes with 24-hour oscillations are more generally called diurnal rhythms; strictly speaking, they should not be called circadian rhythms unless their endogenous nature is confirmed. Although circadian rhythms are endogenous (“built-in“, self-sustained), they are adjusted (entrained) to the local environment by external cues called zeitgebers (from German, “time giver“), which include light, temperature and redox cycles. In medical science, an abnormal circadian rhythm in humans is known as circadian3) ___ disorder.

 

To produce the near 24 h rhythm in mammals requires a complex mechanism involving clock genes, clock proteins, phosphorylation of proteins, dimerization of proteins and subsequent degradation, and nuclear receptors. An internal 4) ___ also allows the multiple biochemical and physiological rhythms within the body to be aligned appropriately to each other. The activity of organs such as the stomach, liver, small intestine and pancreas and the blood supply to these organs need internal synchronization, and a clock can provide this co-ordination. To date, up to 20 genes and their protein products have been linked to the generation of circadian rhythms. At the heart of the molecular clock is a negative feedback loop, which in a very simplified description consists of the following sequence of events: clock genes are transcribed and their mRNAs are translated into proteins; the 5) ___ interact to form complexes, which move from the cytoplasm into the nucleus, where the transcription of the clock genes is inhibited; the inhibitory clock protein complexes are then degraded, and the core clock genes are once more free to make their mRNA and hence fresh protein, and so the cycle continues. This negative feedback loop generates a near 24 h rhythm of protein production and degradation, which encodes the biological day.

 

Although chronobiologists commonly study rhythms in constant conditions, organisms live in the cycling world of day and night. The two chief entraining stimuli that synchronize the endogenous clock with the exogenous temporal environment are 6) ___ and temperature. With the cloning of the Drosophila per gene, which encodes a novel protein of unknown function, the central question in clock research immediately became, “how can this gene product generate a circadian rhythm?“ Negative feedback loops had been suspected to underlie the circadian clock, and several observations on per suggested that it might fit into such a loop. per mRNA abundance showed a circadian oscillation that was followed, with a lag of ~4 h, by oscillations in PER protein. As PER protein accumulated, per mRNA declined in abundance. This suggested a simple autoregulatory negative feedback 7) ___: the clock gene is transcribed and the transcript is translated into a protein that accumulates in the nucleus to inhibit further transcription. Degradation of both mRNA and protein relieves this inhibition, and the cycle renews. This simple model has largely withstood the test of time, although it has increased in complexity.

 

There are at least two interlocked feedback loops that include both positive and negative feedback. Positive components promote the transcription of negative components, and negative components play a dual role, blocking their own expression as well as increasing the expression of positive components, which interlocks the loops to create a robust sustained oscillation. This paradigm of interlocked transcriptional/translational feedback loops underpins the molecular mechanisms of the circadian clock in all eukaryotes studied to date. However, the combination of components recruited to form the clock varies among organisms; the fungal clock is quite distinct from the animal clock, although fly and mouse clocks are fairly similar. It is also clear that cyanobacteria provide a stunning exception to the essential ubiquity of transcriptional regulation in clock function, as a temperature-compensated circadian rhythm can be reconstituted in vitro with three Synechococcus proteins and ATP. Although we can safely conclude that the paradigm of interlocked feedback loops constituting a circadian oscillator is conserved in plants, not all the components have yet been identified, and the mechanistic details of almost every step are only incompletely understood. After so much effort and progress, almost all questions remain only incompletely answered and, effectively, all questions remain! Moreover, the field is now expanding its view from the purely reductionist goal of identifying the oscillator itself to a consideration of the evolutionary and ecological consequences of variation in clock function, so a host of new questions are being considered. It is exhilarating to consider what a retrospective view a decade from now will reveal.

 

Oxidative stress seems to have a circadian rhythm connection. The toxic effects of oxygen were first appreciated in 1954 with Gershman’s free-radical theory, suggesting that oxygen toxicity may happen due to partially reduced forms of oxygen. Commoner et al., in the same year, suggested the presence of free radicals in a variety of biological materials. These new ideas triggered a surge of scientific research into the idea that although a necessary part of life, oxygen may not always be beneficial. The cell has evolved an intricate web of energy synthesis and signaling mechanisms that are dependent on oxygen and its more reactive forms, reactive oxygen species (ROS). Intense research has been done on ROS, their beneficial and detrimental effects on the organism, as well as the efforts mounted by the cell to counteract them. Interestingly, many of these efforts, including the production of antioxidants and protective enzymes, have been reported to be regulated by a biological clock or expressed in rhythmic fashions. The circadian clock system confers daily anticipatory physiological processes with the ability to be reset by environmental cues. This “circadian adaptation system“ (CAS), driven by cell-autonomous molecular clocks, orchestrates various rhythmic physiological processes in the entire 8) ___. Hence, the dysfunction of these clocks exacerbates various diseases, which may partially be due to the impairment of protective pathways. If this is the case, how does the CAS respond to cell injury stresses that are critical in maintaining health and life by evoking protective pathways?

 

A short nap during the day does not affect circadian rhythms. Timing of medical treatment in coordination with the body clock, chronotherapeutics, may significantly increase efficacy and reduce drug toxicity or adverse reactions. A number of studies have concluded that a short period of sleep during the day, a power-nap, does not have any measurable effect on normal circadian rhythms but can decrease stress and improve productivity.

 

Health problems can result from a disturbance to the circadian rhythm. 9) ___ rhythms also play a part in the reticular activating system, which is crucial for maintaining a state of consciousness. A reversal in the sleep – wake cycle may be a sign or complication of uremia, azotemia or acute renal failure. Studies have shown that light has a direct effect on human health because of the way it influences the circadian rhythms. A great deal more research is needed to determine the interactions between biological clocks, human health and disease.

 

In 2017, the Nobel Prize in Physiology or Medicine was awarded to Jeffrey C. Hall, Michael Rosbash and Michael W. Young “for their discoveries of molecular mechanisms controlling the circadian rhythm“ in fruit 10) ___.

 

ANSWERS: 1) hours; 2) “day”; 3) rhythm; 4) clock; 5) proteins; 6) light; 7) loop; 8) body; 9) Circadian; 10) flies

 

The Biological Clock

A mosaic of Hippocrates on the floor of the Asclepieion of Kos, with Asklepius in the middle, 2nd-3rd century.Photo credit: This file is licensed under the Creative Commons Attribution-Share Alike 2.5 Generic license. Wikipedia Commons

 

 

Hippocratic medicine was humble and passive. The therapeutic approach was based on the healing power of nature. “If we could give every individual the right amount of nourishment and exercise, not too little and not too much, we would have found the safest way to health”. Hippocrates, 460 BCE.

 

The earth rotates on its axis every 24 hours, with the result that any position on the earth’s surface alternately faces toward or away from the sun -day and night. That the metabolism, physiology, and behavior of most organisms changes profoundly between day and night is obvious to even the most casual observer. These biological oscillations are apparent as diurnal rhythms. It is less obvious that most organisms have the innate ability to measure time. Indeed, most organisms do not simply respond to sunrise but, rather, anticipate the dawn and adjust their biology accordingly. When deprived of exogenous time cues, many of these diurnal rhythms persist, indicating their generation by an endogenous biological circadian clock. Until recently, the molecular mechanisms by which organisms functioned in this fourth dimension, time, remained mysterious. However, over the last 30 or so years, the powerful approaches of molecular genetics have revealed the molecular underpinnings of a cellular circadian clockwork as complicated and as beautiful as the wonderful chronometers developed in the 18th century.

 

CHARACTERISTICS OF CIRCADIAN RHYTHMS

 

Circadian rhythms are the subset of biological rhythms with period, defined as the time to complete one cycle of~24 hours. This defining characteristic inspired Franz Halberg in 1959 to coin the term circadian, from the Latin words “circa“ (about) and “dies“ (day). A second defining attribute of circadian rhythms is that they are endogenously generated and self-sustaining, so they persist under constant environmental conditions, typically constant light (or dark) and constant temperature. Under these controlled conditions, the organism is deprived of external time cues, and the free-running period of ~24 h is observed. A third characteristic of all circadian rhythms is temperature compensation; the period remains relatively constant over a range of ambient temperatures. This is thought to be one facet of a general mechanism that buffers the clock against changes in cellular metabolism.

 

The first writings, at least in the western canon, to recognize diurnal rhythms come from the fourth century BCE. Androsthenes described the observation of daily leaf movements of the tamarind tree, Tamarindus indicus, that were observed on the island of Tylos (now Bahrein) in the Persian Gulf during the marches of Alexander the Great. There was no suggestion that the endogenous origin of these rhythms was suspected at the time, and it took more than two millennia for this to be experimentally tested. The scientific literature on circadian rhythms began in 1729 when the French astronomer de Mairan reported that the daily leaf movements of the sensitive heliotrope plant (probably Mimosa pudica) persisted in constant darkness, demonstrating their endogenous origin. Presciently, de Mairan suggested that these rhythms were related to the sleep rhythms of bedridden humans. It took 30 years before de Mairan’s observations were independently repeated. These studies excluded temperature variation as a possible zeitgeber driving the leaf movement rhythms.

 

The observation of a circadian or diurnal process in humans is mentioned in Chinese medical texts dated to around the 13th century, including the Noon and Midnight Manual and the Mnemonic Rhyme to Aid in the Selection of Acu-points According to the Diurnal Cycle, the Day of the Month and the Season of the Year. As early as 1880, Charles and Francis Darwin suggested the heritability of circadian rhythms, as opposed to the imprinting of a 24-hour period by exposure to diurnal cycles during development. This was initially explored in the 1930s by two strategies. In one, plants or animals were raised in constant conditions for multiple generations. One of the most grueling among such studies demonstrated the retention of stable rhythms among fruit flies reared in constant conditions for 700 generations. In a second strategy, seedlings or animals were exposed to cycles that differed from 24 hour in an effort to imprint novel periods; such studies could sometimes impose the novel period length during the novel cycles, but upon release into continuous conditions, the endogenous circadian period was restored. The inheritance of period length among progeny from crosses of parents with distinct period lengths was first reported in Phaseolus; hybrids had period length intermediates between those of the parents. In 1896, Patrick and Gilbert observed that during a prolonged period of sleep deprivation, sleepiness increases and decreases with a period of approximately 24 hours. In 1918, J.S. Szymanski showed that animals are capable of maintaining 24-hour activity patterns in the absence of external cues such as light and changes in temperature. In the early 20th century, circadian rhythms were noticed in the rhythmic feeding times of bees. Extensive experiments were done by Auguste Forel, Ingeborg Beling, and Oskar Wahl to see whether this rhythm was due to an endogenous clock. The existence of circadian rhythm was independently discovered in the fruit fly Drosophila melanogaster in 1935 by two German zoologists, Hans Kalmus and Erwin Bunning.In 1954, an important experiment was reported by Colin Pittendrigh who showed that eclosion (the process of pupa turning into adult) in D. pseudoobscura was a circadian behavior. He demonstrated that temperature played a vital role in eclosion rhythm, the period of eclosion was delayed but not stopped when temperature was decreased. It was an indication that circadian rhythm was controlled by an internal biological clock. The term circadian was coined by Franz Halberg in 1959. Genetic analysis identifying components of circadian clocks began in the 1970s. Although now it seems axiomatic that circadian clocks are composed of the products of genes, just how this might be so was the source of considerable controversy. It was argued that forward genetic efforts would be fruitless because clocks were sufficiently complex to reasonably be expected to exhibit polygenic inheritance and would not yield easily to standard genetic approaches. However, mutations conferring altered period length were identified and characterized in the fruit fly Drosophila melanogaster, the green alga Chlamydomonas reinhardtii, and the filamentous fungus N. crassa. It took more than a decade to clone the first clock gene, the Drosophila period (per) gene, and another 5 years to clone the second, the Neurospora frequency gene. However, the decade of the 1990s saw rapid progress toward the identification of clock components and the elucidation of oscillator mechanisms central to the circadian clock in a number of organisms, most notably Drosophila, Neurospora, and mice.

 

Ron Konopka and Seymour Benzer identified the first clock mutant in Drosophila in 1971 and called it “period“ (per) gene, the first discovered genetic determinant of behavioral rhythmicity per gene was isolated in 1984 by two teams of researchers. In 1977, the International Committee on Nomenclature of the International Society for Chronobiology formally adopted the definition, which states:

 

Circadian: relating to biologic variations or rhythms with a frequency of 1 cycle in 24 + 4 h; circa (about, approximately) and dies (day or 24 h). Note: term describes rhythms with an about 24-h cycle length, whether they are frequency-synchronized with (acceptable) or are desynchronized or free-running from the local environmental time scale, with periods of slightly yet consistently different from 24-h.

 

Joseph Takahashi discovered the first mammalian circadian clock mutation using mice in 1994. However, recent studies show that deletion of clock does not lead to a behavioral phenotype (the animals still have normal circadian rhythms), which questions its importance in rhythm generation. Konopka, Jeffrey Hall, Michael Roshbash and their team showed that per locus is the center of the circadian rhythm, and that loss of per stops circadian activity. At the same time, Michael W. Young’s team reported similar effects of per, and that the gene covers 7.1-kilobase (kb) interval on the X chromosome and encodes a 4.5-kb poly(A)+ RNA. They went on to discover the key genes and neurones in Drosophila circadian system, for which Hall, Rosbash and Young received the Nobel Prize in Physiology or Medicine 2017. Sources: nih.gov; Wikipedia

 

Protein Affected By Rare Parkinson’s Mutation May Lurk Behind Many Cases

 

Parkinson’s disease (PD) is a neurodegenerative disorder that affects predominately dopamine-producing (“dopaminergic“) neurons in a specific area of the brain called substantia nigra. Symptoms generally develop slowly over years. The progression of symptoms is often a bit different from one person to another due to the diversity of the disease. People with PD may experience: tremor (mainly at rest and described as pill rolling tremor in hands), bradykinesia (slowness of movement), limb rigidity, and gait/balance problems.

 

Mutations in the gene LRRK2 have been linked to about 3% of PD cases. Now, according to an article published in Science Translational Medicine (25 July 2018), evidence has been found that the activity of LRRK2 protein might be affected in many more patients with PD, even when the LRRK2 gene itself is not mutated. More than 10 years ago, researchers linked mutations in the LRRK2 gene with an increased risk for developing PD. The observed mutations produce a version of LRRK2 protein that behaves abnormally and is much more active than it would be normally. Despite its importance in PD, the very small amount of normal LRRK2 protein in nerve cells made it difficult to study. In the current study, the authors developed a new method for observing LRRK2 cells that made them glow fluorescently only when LRRK2 was in its activated state. The authors also used detection of fluorescent signals to demonstrate loss of binding of an inhibitor protein to LRRK2 when LRRK2 was activated.

 

For the study, the authors looked first at postmortem brain tissue from PD patients who did not have mutations in LRRK2. Compared to healthy individuals of similar ages, there was a striking increase in LRRK2 activity in the dopamine-containing neurons of the substantia nigra, the area of the brain most affected in PD. This suggested that increased LRRK2 activity could be a common feature of the disease. To get a closer look at how LRRK2 activity is related to Parkinson’s disease. The authors next turned to rodent models of the disorder. The sensitivity of their new technique allowed for the direct study of LRRK2 activity, which until now could not be done. By injecting rodents with the environmental toxin rotenone and studying the effect on LRRK2, the authors linked increased LRRK2 activity with the accumulation of alpha-synuclein, a process that leads to the formation of Lewy bodies in the brain, a hallmark of Parkinson’s disease. In another model of the disease, where synuclein was present in much higher amounts than normal, LRRK2 activity was increased. In contrast, when the animals were treated with a drug that blocks LRRK2 activity, the accumulation of alpha-synuclein and Lewy body formation were both prevented. Finally, additional links were found between LRRK2 activity and the potentially damaging consequences of PD. The authors also observed that reactive oxygen species (ROS), compounds that can interact and affect other components within cells, were increased in the brains of both rodent models. ROS were seen to increase the activity of LRRK2, and when ROS production was blocked, LRRK2 activation was not observed.

 

According to the authors, the findings suggest that both genetic and environmental causes of PD can be tied back to the activity of LRRK2 protein. The authors added that this is important, because it suggests that the drugs being developed for patients with the LRRK2 mutation, which represent a very small percentage of the affected population, could benefit a much greater number of people with the disease.

 

More Information:

 

PD Information Page

Patient and Caregiver Information

NINDS NIH

 

Next-Generation ALS Drug Silences Inherited Form of the Disease in Animal Models

 

Amyotrophic-Lateral-Sclerosis (ALS) destroys motor neurons responsible for activating muscles, causing patients to rapidly lose muscle strength and their ability to speak, swallow, move, and breathe. Most die within three to five years of symptom onset. Previous studies suggested that a gene therapy drug, called an antisense oligonucleotide, could be used to treat a form of ALS caused by mutations in the gene superoxide dismutase 1 (SOD1). These drugs turned off SOD1 by latching onto versions the gene encoded in messenger RNA (mRNA), tagging them for disposal and preventing SOD1 protein production.

 

According to an article published in the Journal of Clinical Investigation (25 July 2018), a study in the rodent delayed the onset of ALS after injection of a second-generation drug designed to silence the gene, SOD1. The results suggest the newer version of the drug may be effective at treating an inherited form of the disease caused by mutations in SOD1.

 

Using rats and mice genetically modified to carry normal or disease-mutant versions of human SOD1, the authors discovered that newer versions of the drug may be more effective at treating ALS than the earlier one that had been tested in a phase 1 clinical trial. For instance, injections of the newer versions were more efficient at reducing normal, human SOD1 mRNA levels in rats and mice and they helped rats, genetically modified to carry a disease-causing mutation in SOD1, live much longer than previous versions of the drug. Injections of the new drugs also delayed the age at which mice carrying a disease-mutant SOD1 gene had trouble balancing on a rotating rod and appeared to prevent muscle weakness and loss of connections between nerves and muscles, suggesting it could treat the muscle activation problems caused by ALS. These and other results were the basis for a current phase 1 clinical trial testing the next generation drug in ALS patients (NCT02623699).

 

FDA Approves Magnetic Device System for Guiding Sentinel Lymph Node Biopsies in Certain Patients with Breast Cancer

 

Sentinel lymph nodes are the first lymph nodes to which cancer cells are most likely to spread from a primary tumor. For patients with breast cancer, testing the sentinel lymph nodes indicates whether the cancer has spread from the breast. A sentinel lymph node biopsy is used to identify, remove and examine lymph nodes to determine whether cancer cells are present.

 

The FDA has approved a magnetic device system for guiding lymph node biopsies in patients with breast cancer undergoing mastectomy. The Magtrace and Sentimag Magnetic Localization System (Sentimag System) uses magnetic detection during sentinel lymph node biopsy procedures to identify specific lymph nodes, known as sentinel lymph nodes, for surgical removal. Currently, a sentinel lymph node biopsy is performed after injection of radioactive materials and/or blue dye. This currently approved system offers patients undergoing mastectomy an option for their sentinel lymph biopsy procedure that does not require the injection of radioactive materials. A negative sentinel lymph node biopsy result suggests that cancer has not spread to nearby lymph nodes. A positive result may indicate that cancer is present in the sentinel lymph node and may be present in other nearby lymph nodes and, possibly, other organs. This information can help a doctor determine the stage of the cancer and develop an appropriate treatment plan.

 

The Sentimag System uses magnetic materials to guide the sentinel lymph node biopsy procedure. The system is comprised of a sensitive magnetic sensing probe and base unit designed to detect small amounts of Magtrace, the magnetic tracer drug that is injected into breast tissue. The Magtrace particles travel to lymph nodes and become physically trapped in them, facilitating magnetic detection of the lymph nodes. Following the injection of Magtrace, the Sentimag probe is applied to the patients’ skin in areas closest to the tumor site containing the lymph nodes. The sensing of the magnetic particles is indicated by changes in audio and visual alerts from the base unit, enabling the surgeon to move the hand-held probe around the area of the lymph nodes, and locate the sentinel lymph node or nodes (if there are more than one). The surgeon then makes a small incision and removes the node, which is checked by a pathologist for the presence of cancer cells.

 

The FDA evaluated data from a trial of 147 patients with breast cancer to compare the Sentimag System to the control method of injecting patients with blue dye and radioactive materials together and using a gamma probe to identify the sentinel lymph node. Patients were administered both methods to compare lymph node detection rates. The lymph node detection rate for the Sentimag System was 94.3% while the control method detection rate was 93.5%. Overall, 98.0% of patients had the same detection rate with both the Sentimag System and the control method. The most common reported adverse events, included breast discoloration, which is reported to disappear after three months in patients who underwent mastectomy, cardiac disorder (bradycardia) and potential allergic reaction to the magnetic materials. The Sentimag System is contraindicated in any patient with hypersensitivity to iron oxide or dextran compounds It is also not recommended for patients with iron overload disease or with a metal implant in the axilla or in the chest.

 

Magtrace may travel to regions away from the injection site such as liver or spleen, if injected directly into the bloodstream. In such cases the presence of Magtrace may cause image artifacts during Magnetic Resonance Imaging (MRI). Magtrace residues have not been reported to produce artifacts affecting imaging in X-ray, positron emission tomography (PET) scans, computed tomography (CT) scans, PET/CT scans or ultrasound studies.

 

The FDA reviewed the Sentimag System application using a coordinated, cross-agency approach. The clinical review was conducted by the FDA’s CDRH in consultation with the Center for Drug Evaluation and Research and with support from the FDA’s Oncology Center of Excellence, while all other aspects of review and the final product approval determination was conducted by the FDA’s CDRH.

 

The FDA granted approval of the Sentimag System to Endomagnetics Inc.

 

Kale Salad with Mushrooms, Dried Cranberries and Pomegranate Arils

This is a beautiful tasty salad, if I do say so myself. It’s easy to make. Give it a try; it’ll be worth it. ©Joyce Hays, Target Health Inc.

 

Ingredients

6 cups kale, sliced or pulled into bite size, tough stems removed

2 cloves garlic, sliced or chopped

1/2 cup pine nuts, toasted

1/2 cup sunflower seeds, toasted

2 eggs (hard boil, then use whites only, chopped)

2 Tablespoons extra virgin olive oil

1 large onion, well chopped

1 and 1/2 cups mushrooms, sliced or chopped

2 Tablespoons red wine vinegar

2 teaspoons Dijon mustard

1 Tablespoon artificial bacon (optional)

1 pinch black pepper

1 pinch salt

3/4 cup dried cranberries

1/2 cup fresh pomegranate arils

 

I’ve experimented many times with kale salads. Forget the anchovies that you see above. Adding those, did not work out well. ©Joyce Hays, Target Health Inc.

 

Directions

1. Get out the bowl you will serve the salad in.

2. Do all of your chopping, grinding, slicing first.

 

Chopping the hardboiled egg whites. ©Joyce Hays, Target Health Inc.

 

3. Wash kale three times. Drain three times. Pat dry with paper towel before slicing. Kale grows in sandy soil and has tiny bits of grit on the leaves. Terrible to serve a beautiful salad, only to feel your teeth crunch down on even one grain of sand.

4. Pull the leaves off the stems (throw stems away) into bite size pieces, but not too small and put leaves into salad serving bowl.

 

These kale leaves were rinsed three times, drained, patted dry, then allowed to air. About to be added to the egg whites in the salad bowl. ©Joyce Hays, Target Health Inc.

 

5. Put the chopped egg whites into the salad bowl and toss with kale.

 

After chopping the egg whites, they were thrown into the salad serving bowl. ©Joyce Hays, Target Health Inc.

 

6. Get out a skillet. You’re going to make a warm dressing now, over medium heat. Add the olive oil, onion, garlic, stir for 2 minutes.

7. Add the sliced or chopped mushrooms, combine all ingredients and cook while stirring for another 2 minutes, or until mushrooms have softened.

 

Above is the warmed mixture, set aside to cool off. The above iteration of my kale salad experiments, had black beans and seeded, well chopped jalapenos, which worked well, if you want to give them a try. ©Joyce Hays, Target Health Inc.

 

Mushroom mixture is added to the kale and egg whites. ©Joyce Hays, Target Health Inc.

 

After the kale is tossed with the mushroom mixture and the egg whites, here is what it looks like. ©Joyce Hays, Target Health Inc.

 

Dried cranberries added. ©Joyce Hays, Target Health Inc.

 

Pomegranate arils added. ©Joyce Hays, Target Health Inc.

 

Here, the mustard is being added to the red wine vinegar, and stirred well before being added to the salad which is ready to be served. ©Joyce Hays, Target Health Inc.

 

8. Remove skillet from heat and let it cool down. While dressing is cooling, add the mustard, 1  pinch of black pepper, artificial bacon if using, and mix it in well. Let dressing cool more, before you add the vinegar. Another option is to serve the salad with warm dressing and it will be equally delicious.

9. Toss the salad well so that all surfaces of the kale are covered with the dressing.

10. Sprinkle over top of salad the dried cranberries and arils and bring to the table a delicious and beautiful salad. At the table, give one last toss so that the cranberries and arils get tossed with everything else.

 

Enjoy!

 

Tossed again at the table and ready to serve. Easy, healthy, light and delicious. ©Joyce Hays, Target Health Inc.

 

A single refreshing serving of the kale salad. Best with a light wine, white, rose or sparkling. ©Joyce Hays, Target Health Inc.

 

We’re raising our glasses and toasting our readers: Have the best August of your lives! We’ll be back after our long Labor Day weekend in September. ©Joyce Hays, Target Health Inc .

 

Have a great August everyone!

 

Bon Appetit!

 

Date:
July 26, 2018

Source:
University of Edinburgh

Summary:
Forests in tropical regions could soon become a source of greenhouse gases, contributing to global warming and hampering efforts to meet the main goal in the Paris Agreement of 2015.

 

Forests in tropical regions, such as this forest in Trinidad, could soon become a source of greenhouse gases, contributing to global warming rather than helping to counteract it, according to research led by the University of Edinburgh
Credit: Ed Mitchard

 

 

Forests in tropical regions could soon become a source of greenhouse gases, contributing to global warming rather than helping to counteract it, according to research.

Loss of trees to agriculture or livestock in tropical regions and the impact of climate change is limiting the forests’ ability to absorb carbon dioxide, a study shows.

This could make it impossible to meet the main goal in the Paris Agreement of 2015, which seeks to limit the global temperature rise to 2C compared with pre-industrial levels.

Researchers estimate that tropical forests currently take in as much carbon from the atmosphere through growth as they generate through deforestation — the loss of forest to commercial activities — and degradation — the removal of trees for timber or fuel.

Tropical forests are at risk of becoming a major source of emissions in coming decades as climate change accelerates and deforestation continues, driven by agriculture, animal grazing and mining in South America, Asia and Africa.

Loss of forest to deforestation and degradation, mainly in tropical regions, accounts for about one-fifth of recent human-made greenhouse gas emissions, scientists say. Currently, an equivalent amount of CO2 is absorbed by the remaining forests. This is aided by increased levels of carbon in the atmosphere, which makes it easier for trees to grow.

If deforestation and degradation were to stop and forests allowed to recover, they would once again help to absorb significant greenhouse gas emissions, researchers add.

It is hard to predict the fate of tropical forests under current conditions, scientists say. Climate change will cause higher temperatures and droughts, killing more trees, but at the same time higher levels of carbon dioxide in the atmosphere will aid tree growth.

Predicting the outcome could be helped by more field experiments and by countries sharing their data, to take advantage of observations from forthcoming satellites.

The study, published in Nature, was supported by the Natural Environment Research Council and the UK Space Agency.

Dr Ed Mitchard of the University of Edinburgh’s School of GeoSciences, who led the study, said: “Predicting how tropical forests will affect climate is a complex challenge — we do not know how climate will affect forests, nor if countries will meet their commitments to safeguard them. Worryingly, research indicates that forests could soon stop counteracting warming, and instead become a major source of greenhouse gas.”

Story Source:

Materials provided by University of EdinburghNote: Content may be edited for style and length.


Journal Reference:

  1. Edward T. A. Mitchard. The tropical forest carbon cycle and climate changeNature, 2018; 559 (7715): 527 DOI: 10.1038/s41586-018-0300-2

 

Source: University of Edinburgh. “Tropical forests may soon hinder, not help, climate change effort.” ScienceDaily. ScienceDaily, 26 July 2018. <www.sciencedaily.com/releases/2018/07/180726085806.htm>.

Date:
July 24, 2018

Source:
American Institute of Biological Sciences

Summary:
Scientists highlight ecological harm that could result from the construction of a wall along the US-Mexico border.

 

Amidst increased tensions over the US-Mexico border, a multinational group of over 2500 scientists have endorsed an article cautioning that a hardened barrier may produce devastating ecological effects while hampering binational conservation efforts. In the BioScience Viewpoint , a group led by Robert Peters, William J. Ripple, and Jennifer R. B. Miller call attention to ecological disturbances that could affect hundreds of terrestrial and aquatic species, notably including the Mexican gray wolf and Sonoran pronghorn.

The authors argue that the border wall will harm wildlife populations by fragmenting, degrading, and eliminating existing habitat, as well as by blocking species migration. “Our analysis shows that the border bisects the geographic ranges of 1506 native terrestrial and freshwater animal (n = 1077) and plant (n = 429) species,” say the authors, noting that the number includes 62 species already listed as Critically Endangered, Endangered, or Vulnerable by the International Union for Conservation of Nature.

Further, the authors express concern that as a result of the 2005 Real ID Act, construction could proceed “without the necessary depth of environmental impact analysis, development of less-damaging alternative strategies, postconstruction environmental monitoring, mitigation, public input, and pursuit of legal remedies.” Compounding the issue of forgone legal protections, Peters and colleagues warn that a border wall could threaten ongoing research and conservation programs, including those in binational habitat corridors and the 18% of borderlands that contain environmentally protected lands.

To mitigate the effects of the proposed wall, the authors make several urgent recommendations to the United States Congress and Department of Homeland Security; these include following existing environmental laws, taking action to mitigate ecological harm, and forgoing physical barriers in particularly sensitive areas. The article` also calls for the government to encourage scientific research in the borderlands, to inform and assist environmental evaluation and mitigation efforts. The authors conclude that “national security can and must be pursued with an approach that preserves our natural heritage.”

Story Source:

Materials provided by American Institute of Biological SciencesNote: Content may be edited for style and length.


Journal Reference:

  1. Robert Peters, William J. Ripple, Christopher Wolf, Matthew Moskwik, Gerardo Carreón-Arroyo, Gerardo Ceballos, Ana Córdova, Rodolfo Dirzo, Paul R. Ehrlich, Aaron D. Flesch, Rurik List, Thomas E. Lovejoy, Reed F. Noss, Jesús Pacheco, José K. Sarukhán, Michael E. Soulé, Edward O. Wilson, Jennifer R. B. Miller, and 2500 signatory scientists. Nature Divided, Scientists United: U.S.-Mexico Border Wall Threatens Biodiversity and Binational ConservationBioScience, 2018 DOI: 10.1093/biosci/biy063

 

Source: American Institute of Biological Sciences. “Scientists warn that proposed US-Mexico border wall threatens biodiversity, conservation.” ScienceDaily. ScienceDaily, 24 July 2018. <www.sciencedaily.com/releases/2018/07/180724120901.htm>.

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