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Pathol Res Pract. 2012 Jul 15;208(7):377-81. doi: 10.1016/j.prp.2012.04.006. Epub 2012 Jun 8.
The influence of physical activity in the progression of experimental lung cancer in mice
Renato Batista Paceli 1, Rodrigo Nunes Cal, Carlos Henrique Ferreira dos Santos, José Antonio Cordeiro, Cassiano Merussi Neiva, Kazuo Kawano Nagamine, Patrícia Maluf Cury
- PMID: 22683274
- DOI: 10.1016/j.prp.2012.04.006
Impact_Fator-wise_Top100Science_Journals
GRUPO_AF1 – GROUP AFA1 – Aerobic Physical Activity – Atividade Física Aeróbia – ´´My´´ Dissertation – Faculty of Medicine of Sao Jose do Rio Preto
GRUPO AFAN 1 – GROUP AFAN1 – Anaerobic Physical Activity – Atividade Física Anaeróbia – ´´My´´ Dissertation – Faculty of Medicine of Sao Jose do Rio Preto
GRUPO_AF2 – GROUP AFA2 – Aerobic Physical Activity – Atividade Física Aeróbia – ´´My´´ Dissertation – Faculty of Medicine of Sao Jose do Rio Preto
GRUPO AFAN 2 – GROUP AFAN 2 – Anaerobic Physical Activity – Atividade Física Anaeróbia – ´´My´´ Dissertation – Faculty of Medicine of Sao Jose do Rio Preto
Slides – mestrado – ´´My´´ Dissertation – Faculty of Medicine of Sao Jose do Rio Preto
CARCINÓGENO DMBA EM MODELOS EXPERIMENTAIS
DMBA CARCINOGEN IN EXPERIMENTAL MODELS
Avaliação da influência da atividade física aeróbia e anaeróbia na progressão do câncer de pulmão experimental – Summary – Resumo – ´´My´´ Dissertation – Faculty of Medicine of Sao Jose do Rio Preto
Abstract
Lung cancer is one of the most incident neoplasms in the world, representing the main cause of mortality for cancer. Many epidemiologic studies have suggested that physical activity may reduce the risk of lung cancer, other works evaluate the effectiveness of the use of the physical activity in the suppression, remission and reduction of the recurrence of tumors. The aim of this study was to evaluate the effects of aerobic and anaerobic physical activity in the development and the progression of lung cancer. Lung tumors were induced with a dose of 3mg of urethane/kg, in 67 male Balb – C type mice, divided in three groups: group 1_24 mice treated with urethane and without physical activity; group 2_25 mice with urethane and subjected to aerobic swimming free exercise; group 3_18 mice with urethane, subjected to anaerobic swimming exercise with gradual loading 5-20% of body weight. All the animals were sacrificed after 20 weeks, and lung lesions were analyzed. The median number of lesions (nodules and hyperplasia) was 3.0 for group 1, 2.0 for group 2 and 1.5-3 (p=0.052). When comparing only the presence or absence of lesion, there was a decrease in the number of lesions in group 3 as compared with group 1 (p=0.03) but not in relation to group 2. There were no metastases or other changes in other organs. The anaerobic physical activity, but not aerobic, diminishes the incidence of experimental lung tumors.
Copyright © 2012 Elsevier GmbH. All rights reserved.
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Cutting-edge CRISPR gene editing appears safe in three cancer patients
By Jennifer Couzin-FrankelFeb. 6, 2020 , 2:00 PM
Launching a new chapter in the fast-moving cancer immunotherapy field, scientists have blended two cutting-edge approaches: CRISPR, which edits DNA, and T cell therapy, in which sentries of the immune system are exploited to destroy tumors. Two women and one man, all in their 60s—one with sarcoma and two with the blood cancer multiple myeloma—received CRISPR-altered versions of their own cells last year, researchers report online in Science this week.
For these pioneers, the benefits were limited: One has since died, and the disease has worsened in the others. But the clinical trial, which underwent years of regulatory scrutiny, wasn’t designed to try to cure cancer, says Carl June, a cancer researcher at the University of Pennsylvania (UPenn) who co-led the work. Rather, its goal was to show that the strategy appeared feasible and safe.
By that measure, scientists agree, it succeeded. “This is a Rubicon that has been decisively crossed,” says Fyodor Urnov, a genome editor at the University of California (UC), Berkeley. The study, he says, the first of its kind in the United States, answers “questions that have frankly haunted the field.”
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The researchers used CRISPR alongside another strategy that incorporates new DNA into immune cells. June’s team helped pioneer that strategy in 2010, when it added DNA to T cells from three men with chronic leukemia and returned those cells to the patients. The results were remarkable: Two men are still alive and healthy today. Others were testing the same approach, called CAR-T cell therapy—after the inserted chimeric antigen receptor gene that helps the infused T cells latch onto and destroy cancer cells with a specific protein on their surface. Two CAR-T cell therapies are now approved for patients with leukemia and lymphoma.
But with time, the therapy’s limitations have come into focus. Not every cancer patient is helped, and even those who are can suffer a relapse, says Edward Stadtmauer, who treats blood cancers at UPenn and co-led the new study. And solid tumors like those in the brain and pancreas have proved tough to treat.
Using CRISPR to knock out selected genes while also adding DNA, it was hoped, might make T cells even more powerful and persistent. But CRISPR brought its own uncertainties. Lab studies have revealed “off-target” effects, in which unintended DNA gets modified. No one knew whether T cells with sliced and diced genes could even survive in the human body. Last year, Vertex Pharmaceuticals and CRISPR Therapeutics announced that two patients treated for inherited blood diseases with CRISPR-edited cells were doing well. But details were sparse.
June, Stadtmauer, and their colleagues began by hunting for patients whose tumors produced a protein called NY-ESO-1, a target for the gene the researchers would add to their T cells. The patients also needed to carry a specific version of human leukocyte antigen, an immune gene complex that could help the infused T cells flourish. The four patients who qualified were all extremely ill, as is the norm for such a novel therapy. A woman with multiple myeloma had undergone three bone marrow transplants. Another, in her late 30s with sarcoma, became too sick to treat while her cells were being prepped in the lab, a process that takes 4 to 6 weeks. She entered hospice care and died.
To try to rev up the patients’ T cells against their disease, the scientists used CRISPR to knock out two genes that encode what’s known as the T cell receptor. The group also crippled a third gene, for a protein called PD-1. PD-1 puts the brakes on immune responses, and eliminating its effects, June’s team theorized, might enrich the T cells’ powers. Then, they inserted the gene for a different T cell receptor that would target NY-ESO-1.
Intensive monitoring of the patients, including blood draws to study their altered T cells, confirmed that CRISPR had left some off-target changes. But they were few, and the number of cells with these unintended DNA changes faded over time. Encouragingly, the CRISPR-edited cells persisted at least 9 months—versus about 2 months in comparable CAR-T cell therapy studies. Imaging showed “beautiful, healthy T cells,” June says, that in lab studies beat back cancer months after they’d been infused.
But in patients, outcomes were modest. The best response was in the sarcoma patient, whose primary tumor shrank, though his cancer later progressed. “It wasn’t like you turned off those genes and those T cells started doing things that were amazing,” says Antoni Ribas, an oncologist at UC Los Angeles. Ribas, June, and others offer potential reasons, including the small number of patients treated, possible limitations of NY-ESO-1 as a target—selected in part for its safety record—and the failure to knock out all three genes in many of the cells.
Some of the authors are working with companies to commercialize the method. But much experimentation lies ahead. “This whole area is just teeming with different ideas,” Stadtmauer says. A handful of other trials, including several in China, are offering CRISPR-modified cells to patients with cancer or other diseases. A company called PACT Pharma, which Ribas helped found, is running a trial that uses CRISPR to target gene mutations within solid tumors.
What June’s group offers is “a needed start” for giving patients CRISPR-edited T cells, Ribas says. From now on, he adds, “It’s going to be easier—because they did it first.”Posted in:
doi:10.1126/science.abb1990

Jennifer Couzin-Frankel
Staff Writer
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A.I. translation tool sheds light on the secret language of mice
By Luke DormehlFebruary 19, 2020
Ever wanted to know what animals are saying? Neuroscientists at the University of Delaware have taken a big leap forward in decoding the sounds made by one particular animal in a way that takes us a whole lot closer than anyone has gotten so far. The animal in question? The humble mouse.
To study mouse vocalizations, the team gathered data as groups of four mice — two males and two females — interacted. They interacted for five hours at a time in a chamber that was kitted out with eight microphones and a video camera. In total, the researchers recorded encounters between a total of 44 mice. Starting with the enormous amounts of ensuing video and audio data, the researchers then used machine learning A.I. to develop a system that’s able to connect specific sounds with distinct animal behaviors. In short, it could work out which mouse was squeaking, where, and in what scenario.
“To link mouse vocalizations to specific actions, we needed multiple technological advances,” University of Delaware neuroscientist Joshua Neunuebel told Digital Trends. “First, we needed to be able to assign specific vocalizations to individual mice that were socially interacting. To do this, we developed a sound source localization system that simultaneously recorded mouse ultrasonic vocalizations on eight different microphones, as well as the position of the mice with a video camera.”
The combination of microphones and camera allowed the team to estimate the location of where a particular vocal signal was emitted and then assign the signal to a specific mouse. Once they were able to assign vocalizations to specific animals, the team used an unsupervised learning algorithm that groups items with similar features to categorize them. Finally, they used a tool called JAABA, the Janelia Automatic Animal Behavior Annotator, to automatically extract specific social behaviors with high fidelity.
“It’s not necessarily a translational tool per se, but it’s a tool that helps us interpret mouse social behaviors,” Neunuebel said. “However, this being said, mice are good models for understanding the neural basis of social behavior, which may ultimately shed light upon how the brain circuitry of humans is functioning.”
The work is the subject of two new papers published in the journals Nature Neuroscience and Scientific Reports. Both papers report on different aspects of the work on how communication shapes social behavior and the neural networks that encode this information.
As Neunuebel says, they haven’t developed a full-fledged human-to-mouse translation tool. Nonetheless, this work — alongside similar research into communications of animals like dolphins — certainly brings us closer to understanding the subtleties of animal chat.
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CERN Accelerating science

News News Topic: Knowledge sharing
How particle physics could prevent financial fraud
A new collaboration agreement sees CERN data analytics used to help protect commodity and financial markets from fraud
20 FEBRUARY, 2020
Every day, commodity markets trade millions of food ingredients and more, so detecting fraud can be challenging. A new collaboration agreement between CERN, the Commodity Risk Management Expertise Center (CORMEC) and Wageningen University & Research (WUR) will now use advanced data analytics from particle physics to help protect commodity and financial markets from fraud. The insights gained could be used by governments and regulators to improve market stability.
During a visit to CERN, WUR economics professor Joost Pennings realised the similarities between the billions of particle collisions in CERN’s Large Hadron Collider and the high-speed trading on commodity futures markets. Most transactions, or collisions, show no anomalies. But when they do, this may lead to new ground-breaking insights for both economists and physicists.
Hence this new collaboration plans to combat fluctuations in markets caused by anomalies, by combining the unique commodity and financial market data and understanding from CORMEC and WUR with CERN’s ROOT data analysis expertise and techniques.
“We see that ROOT, CERN’s scientific big data analytics framework, has the potential to be a game changer for finance data analytics. It’s exciting that ROOT can serve society also outside its core domain of high-energy physics.”
– Dr Axel Naumann, CERN senior applied physicist and ROOT project leader
This collaboration will use data analytics to diagnose manipulation in commodity and financial markets. This should enable regulators to create safer and more stable environments for trading, leading to improved regulation and market integrity. The research may also lead to new diagnostic tools for predicting financial instability, which will indirectly help risk management.
The three-year knowledge-transfer project is named HighLo (High Energy Physics Tools in Limit Order Book Analysis) and is supported by the Province of Limburg in the Netherlands. The first results are expected at the end of 2020.Find out more on the CERN Knowledge Transfer websiteKnowledge transfer
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CERN Accelerating science

News News Topic: Knowledge sharing
How particle physics could prevent financial fraud
A new collaboration agreement sees CERN data analytics used to help protect commodity and financial markets from fraud
20 FEBRUARY, 2020
Every day, commodity markets trade millions of food ingredients and more, so detecting fraud can be challenging. A new collaboration agreement between CERN, the Commodity Risk Management Expertise Center (CORMEC) and Wageningen University & Research (WUR) will now use advanced data analytics from particle physics to help protect commodity and financial markets from fraud. The insights gained could be used by governments and regulators to improve market stability.
During a visit to CERN, WUR economics professor Joost Pennings realised the similarities between the billions of particle collisions in CERN’s Large Hadron Collider and the high-speed trading on commodity futures markets. Most transactions, or collisions, show no anomalies. But when they do, this may lead to new ground-breaking insights for both economists and physicists.
Hence this new collaboration plans to combat fluctuations in markets caused by anomalies, by combining the unique commodity and financial market data and understanding from CORMEC and WUR with CERN’s ROOT data analysis expertise and techniques.
“We see that ROOT, CERN’s scientific big data analytics framework, has the potential to be a game changer for finance data analytics. It’s exciting that ROOT can serve society also outside its core domain of high-energy physics.”
– Dr Axel Naumann, CERN senior applied physicist and ROOT project leader
This collaboration will use data analytics to diagnose manipulation in commodity and financial markets. This should enable regulators to create safer and more stable environments for trading, leading to improved regulation and market integrity. The research may also lead to new diagnostic tools for predicting financial instability, which will indirectly help risk management.
The three-year knowledge-transfer project is named HighLo (High Energy Physics Tools in Limit Order Book Analysis) and is supported by the Province of Limburg in the Netherlands. The first results are expected at the end of 2020.Find out more on the CERN Knowledge Transfer websiteKnowledge transfer
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Physiological discoveries abound within NASA samples
News and Views
Elizabeth Keller
NASA Ames Research Center, CA, USA
Ryan Scott
NASA Ames Research Center, CA, USA

Before humans risked their lives launching into space aboard the Vostok Program and Mercury Project, various organisms were flown to determine if it was possible for life to survive spaceflight. For decades, NASA, along with international partners, have continued sending biological experiments to space. Potential biological hazards from spaceflight include decreased gravity, increased exposure to radiation, altered light-dark cycles, and loads experienced during launch and landing. It is imperative to understand the basic science and health risks associated with spaceflight, along with developing countermeasures, as humanity ventures back to the Moon, and then to Mars and beyond.
NASA Ames Research Center houses an Institutional Scientific Collection (ISC) of spaceflight biological specimens and tissues. Through NASA’s Biospecimen Sharing Program (BSP), the samples in this biological repository are available for request by all researchers, including those based outside the United States.

A number of newly identified biological knowledge gaps and astronaut health risks have emerged from extended exposure to microgravity from long-duration missions. Of particular concern to NASA is the loss of visual acuity, which a significant number of astronauts have unexpectedly experienced. NASA is keen on getting researchers to work on elucidating the underlying cause(s) of this issue. In an effort to further the research progress on this topic, the NASA BSP coordinated the sharing of mouse eyes from the STS-133 Shuttle mission. The study led by Susana Zanello1 conducted histological examinations of the mouse eyes from post-flight days 1, 5 and 7. Gene expression analysis suggested that reversible molecular damage occurs in the retina of mice exposed to the spaceflight environment, and that protective cellular pathways are induced in the retina and optic nerve in response to these changes. While correlation of research findings in the mouse tissues to human astronauts presents a set of challenges, the mouse model is an excellent way to characterise underlying changes at the cellular and molecular levels that are simply not available with the human crew.
The costly effort of sending organisms into space makes space-flown biological specimens a rare and valuable resource. Quite often, when life science samples are retrieved from completed missions, there are surplus tissues which remain unused by the Principal Investigators and collaborators. In this scenario the tissues are harvested, preserved, and archived in the NASA ISC at the Ames Research Center to ensure the maximum scientific return from space missions in the belief that new discoveries can be made from the samples.
An important recent finding was made possible by the study of what would have previously been considered waste: rodent fecal pellets. Through NASA’s BSP, Martha Vitaterna, from Northwestern University obtained mouse fecal pellets from a 37-day mission aboard the International Space Station and examined them for the effects of spaceflight on gastrointestinal microbiota2. Findings from previous studies have demonstrated a change in the gut microbial diversity and community structure during spaceflight, but it was unclear what the functional relevance of those microbiome changes were. Using 16S rRNA gene amplicon sequencing, Vitaterna and her team profiled the microbiome of the fecal samples. They then compared the microbiome changes to other relevant datasets and integrated the gut microbiome data with publicly available transcriptomic data in the liver of the same animals for a systems-level analysis. Observations from her analyses shed light on the specific environmental factors that contributed to a robust effect on the gut microbiome during spaceflight, with important implications for mammalian metabolism.
Available tissues for physiology research
The NASA ISC at Ames Research Center currently stores over 32,000 specimens. Most come from Shuttle and International Space Station flight investigations, but also included in the collection are ground-based specimens from spaceflight-model experiments. Tissues are predominantly from mice and rats, though samples are also available from bacteria and quail. The specimens include tissues from many systems including musculoskeletal, neurosensory, reproductive, respiratory, circulatory, and digestive. The samples are stored at -80°C, -20°C, or +4°C, depending on the fixative used. Detailed metadata are available for all samples. Historically, these tissues have been used for a wide range of analyses, including histology, genomics, and transcriptomics. The NASA Ames Life Sciences Data Archive (ALSDA) has been shipping samples to investigators since 1995.
How to request tissues from the NASA ISC
Tissue requests are initiated by submitting an online Biospecimen or Data Request. If the requested tissues are available, the requestor will be sent instructions for submission of a short proposal. Visit the NASA ISC website for more information: nasa.gov/ames/research/space-biosciences/isc-bsp Contact the ALSDA team: arc-dl-alsda@mail.nasa.gov
References
- Zanello SB et al. (2013). Spaceflight effects and molecular responses in the mouse eye: observations after shuttle mission STS-133. Gravitational and Space Research 1(1), 29 – 46.
- Jiang P et al. (2019). Reproducible changes in the gut microbiome suggest a shift in microbial and host metabolism during spaceflight. Microbiome 7(1), 113. DOI: 10.1186/s40168-019-0724-4
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