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Scientists were able to turn pro-inflammatory cells into anti-inflammatory cells
Thermoregulation control in the brain
Different Sensory Pathways Engaged in Feeling and Responding to External Temperature
To maintain the body at an appropriate temperature despite changes in the environment, there are a number of physiological and behavioral responses that can be adopted, such as shivering or moving into or out of direct sunlight. Although these responses are well understood, there is still a lack of understanding of the nerve and brain pathways that control them.
Researchers at the Department of Integrative Physiology at Nagoya University Graduate School of Medicine have boosted our knowledge of sensing external temperature and responding to it to maintain body temperature, known as “thermoregulation,” by disabling parts of the brain in rats and then observing the animals’ choices of a comfortable environmental temperature. The new findings, recently published in Scientific Reports, could also help us understand conditions in which these regulatory systems go awry, such as heatstroke.
The team built on earlier studies that suggested the involvement of two brain/neural sensory pathways in thermoregulation, namely, the spinothalamocortical (STC) pathway and the lateral parabrachial nucleus-hypothalamus preoptic area (LPB-POA) pathway. They injected toxic substances into parts of the brain involved in each of these pathways to disable them, and then investigated how this influenced the “feeling” of temperature changes and responses to such changes.
“We tested the thermal responses of rats using an arrangement with two floor plates of different temperatures,” Takaki Yahiro says. “In control conditions, the rats preferred to stay on the 28°C plate, rather than the 15°C or 38°C one.” He adds, “When we injected a toxin into part of the brain involved in the STC pathway, surprisingly, we found that the rats still showed this temperature preference, even though they had lost their ability to ‘feel’ temperature in the primary somatosensory cortex.”
However, when part of the LPB pathway was instead disabled by injecting another toxin, the rats no longer tried to avoid the hot and cold plates. Measuring their body temperature also revealed that their brains had warmed up to a hyperthermic state when they had been on a warm plate, showing that the body’s ability to regulate its core temperature had been damaged.
“These findings show the different functions of these two sensory pathways in ‘feeling’ external temperature changes and in actually responding to these changes behaviorally,” Kazuhiro Nakamura says. “We can now pursue a much better understanding of the circuits that control thermal comfort and how these help the temperature of the body to be maintained.”
The team hopes to build on this work by obtaining detailed findings on the specific groups of neurons involved in the pathways and on the involvement of emotion-related parts of the brain in thermoregulation and the behavior of seeking thermal comfort.
ABOUT THIS NEUROSCIENCE RESEARCH ARTICLE
Funding: Funding provided by Ministry of Education, Culture, Sports, Science and Technology of Japan, Japan Science and Technology Agency, Hori Science and Art Foundation, Takeda Science Foundation, and others.
Source: Koomi Sung – Nagoya University
Image Source: NeuroscienceNews.com image is credited to Kazuhiro Nakamura.
Original Research: Full open access research for “The lateral parabrachial nucleus, but not the thalamus, mediates thermosensory pathways for behavioural thermoregulation” by Takaki Yahiro, Naoya Kataoka, Yoshiko Nakamura & Kazuhiro Nakamura in Scientific Reports. Published online July 10 2017 doi:10.1038/s41598-017-05327-8
CITE THIS NEUROSCIENCENEWS.COM ARTICLE
Nagoya University “Different Sensory Pathways Engaged in Feeling and Responding to External Temperature.” NeuroscienceNews. NeuroscienceNews, 3 August 2017.
<temperature-sensory-pathways-7231/>.
<temperature-sensory-pathways-7231/>.
Abstract
The lateral parabrachial nucleus, but not the thalamus, mediates thermosensory pathways for behavioural thermoregulation
Thermoregulatory behaviour, such as migration to a comfortable thermal environment, is a representative innate animal behaviour and facilitates effective autonomic regulation of body temperature with a reduced cost of resources. Here we determine the central thermosensory ascending pathway that transmits information on environmental temperature from cutaneous thermoreceptors to elicit thermoregulatory behaviour. To examine the contribution of the spinothalamocortical pathway, which is known to mediate thermosensory transmission for perception of skin temperature, we lesioned thalamic regions mediating this pathway in rats. Thalamic-lesioned rats showed compromised electroencephalographic responses in the primary somatosensory cortex to changes in skin temperature, indicating functional ablation of the spinothalamocortical pathway. However, these lesioned rats subjected to a two-floor innocuous thermal plate preference test displayed intact heat- and cold-avoidance thermoregulatory behaviours. We then examined the involvement of the lateral parabrachial nucleus (LPB), which mediates cutaneous thermosensory signaling to the thermoregulatory center for autonomic thermoregulation. Inactivation of neurons in the LPB eliminated both heat- and cold-avoidance thermoregulatory behaviours and ablated heat defense. These results demonstrate that the LPB, but not the thalamus, mediates the cutaneous thermosensory neural signaling required for behavioural thermoregulation, contributing to understanding of the central circuit that generates thermal comfort and discomfort underlying thermoregulatory behaviours.
“The lateral parabrachial nucleus, but not the thalamus, mediates thermosensory pathways for behavioural thermoregulation” by Takaki Yahiro, Naoya Kataoka, Yoshiko Nakamura & Kazuhiro Nakamura in Scientific Reports. Published online July 10 2017 doi:10.1038/s41598-017-05327-8
Scientists were able to turn pro-inflammatory cells into anti-inflammatory cells
Summary: According to a Nature study, researchers developed a method to reprogram specific T cells in the immune system. Scientists were able to turn pro-inflammatory cells into anti-inflammatory cells, and vice versa, to boost or suppress the immune system. Researchers believe their findings could have significant impact on developing treatments for autoimmune diseases.
Source: Gladstone Institute.
The discovery could improve treatments for autoimmune diseases and cancer.
When the immune system is imbalanced, either due to overly-active cells or cells that suppress its function, it causes a wide range of diseases, from psoriasis to cancer. By manipulating the function of certain immune cells, called T cells, researchers could help restore the system’s balance and create new treatments to target these diseases.
Scientists at the Gladstone Institutes revealed, for the first time, a method to reprogram specific T cells. More precisely, they discovered how to turn pro-inflammatory cells that boost the immune system into anti-inflammatory cells that suppress it, and vice versa.
The researchers studied two types of cells called effector T cells, which activate the immune system to defend our body against different pathogens, and regulatory T cells, which help control the immune system and prevent it from attacking healthy parts of its environment.
“Our findings could have a significant impact on the treatment of autoimmune diseases, as well as on stem cell and immuno-oncology therapies,” said Gladstone Senior Investigator Sheng Ding, PhD, who is also a professor of pharmaceutical chemistry at the University of California, San Francisco.
By drawing on their expertise in drug discovery, Ding’s team identified a small-molecule drug that can successfully reprogram effector T cells into regulatory T cells. Their study, published in the renowned journal Nature, describes in detail a metabolic mechanism that helps convert one cell type into another.
This new approach to reprogram T cells could have several medical applications. For instance, in autoimmune disease, effector T cells are overly activated and cause damage to body. Converting these cells into regulatory T cells could help reduce the hyperactivity and return balance to the immune system, thus treating the root of the disease.
In addition, the study could improve therapies using stem cells. At least in theory, producing regulatory T cells could promote immune tolerance and prevent the body from rejecting newly-transplanted cells.
“Our work could also contribute to ongoing efforts in immuno-oncology and the treatment of cancer,” explained Tao Xu, postdoctoral scholar in Ding’s laboratory and first author of the study. “This type of therapy doesn’t target the cancer directly, but rather works on activating the immune system so it can recognize cancer cells and attack them.”
Many cancers take control of regulatory T cells to suppress the immune system, creating an environment where tumors can grow without being detected. In such cases, the team’s findings could be used to transform regulatory T cells into effector T cells to strengthen the immune system so it can better recognize and destroy cancer cells.
ABOUT THIS NEUROSCIENCE RESEARCH ARTICLE
Funding: The research was supported by the Gladstone Institutes.
Other authors of this study include Katerina Akassoglou, Kai Liu, Min Xie, Jae Kyu Ryu, Ke Li, Tianhua Ma, Haixia Wang, Saiyong Zhu, Nan Cao, and Yu Zhang from Gladstone; Edward M. Driggers, Kelly M. Stewart, and Dongwei Zhu from Agios Pharmaceuticals; and Chen Dong, Xiaohu Wang, and Lu Ni from Tsinghua University in China.
Source: Julie Langelier – Gladstone Institute
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Abstract for “Metabolic control of TH17 and induced Treg cell balance by an epigenetic mechanism” by Tao Xu, Kelly M. Stewart, Xiaohu Wang, Kai Liu, Min Xie, Jae Kyu Ryu, Ke Li, Tianhua Ma, Haixia Wang, Lu Ni, Saiyong Zhu, Nan Cao, Dongwei Zhu, Yu Zhang, Katerina Akassoglou, Chen Dong, Edward M. Driggers & Sheng Ding in Nature. Published online August 2 2017 doi:10.1038/nature23475
CITE THIS NEUROSCIENCENEWS.COM ARTICLE
Gladstone Institute “How to Reprogram Cells in Our Immune System.” NeuroscienceNews. NeuroscienceNews, 3 August 2017.
<http://neurosciencenews.com/immune-system-reprogramming-7232/>.
<http://neurosciencenews.com/immune-system-reprogramming-7232/>.
Abstract
The cell non-autonomous function of ATG-18 is essential for neuroendocrine regulation of Caenorhabditis elegans lifespan
Metabolism has been shown to integrate with epigenetics and transcription to modulate cell fate and function. Beyond meeting the bioenergetic and biosynthetic demands of T-cell differentiation whether metabolism might control T-cell fate by an epigenetic mechanism is unclear. Here, through the discovery and mechanistic characterization of a small molecule, (aminooxy)acetic acid, that reprograms the differentiation of T helper 17 (TH17) cells towards induced regulatory T (iTreg) cells, we show that increased transamination, mainly catalysed by GOT1, leads to increased levels of 2-hydroxyglutarate in differentiating TH17 cells. The accumulation of 2-hydroxyglutarate resulted in hypermethylation of the Foxp3 gene locus and inhibited Foxp3 transcription, which is essential for fate determination towards TH17 cells. Inhibition of the conversion of glutamate to α-ketoglutaric acid prevented the production of 2-hydroxyglutarate, reduced methylation of the Foxp3 gene locus, and increased Foxp3 expression. This consequently blocked the differentiation of TH17 cells by antagonizing the function of transcription factor RORγt and promoted polarization into iTreg cells. Selective inhibition of GOT1 with (aminooxy)acetic acid ameliorated experimental autoimmune encephalomyelitis in a therapeutic mouse model by regulating the balance between TH17 and iTreg cells. Targeting a glutamate-dependent metabolic pathway thus represents a new strategy for developing therapeutic agents against TH17-mediated autoimmune diseases.
“Metabolic control of TH17 and induced Treg cell balance by an epigenetic mechanism” by Tao Xu, Kelly M. Stewart, Xiaohu Wang, Kai Liu, Min Xie, Jae Kyu Ryu, Ke Li, Tianhua Ma, Haixia Wang, Lu Ni, Saiyong Zhu, Nan Cao, Dongwei Zhu, Yu Zhang, Katerina Akassoglou, Chen Dong, Edward M. Driggers & Sheng Ding in Nature. Published online August 2 2017 doi:10.1038/nature23475
Washington Post evening edition
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Healthy red blood cells for oxygen delivery, preventing heart failure
Healthy red blood cells for oxygen delivery, preventing heart failure
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Oxygen delivery is facilitated by healthy red blood cells made every 120 days - The following helps in ensuring healthy red blood cells:
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Exercise
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De-stress , avoiding too much stress
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Avoidance of alcohol
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Avoidance of toxic medications/drugs
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Carotenoids
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Whole foods rich in iron, copper, Vitamin B complex (all Bs), Vitamin C, Vitamin D, folate
- Erythropoietin, also known as EPO, hematopoietin or hemopoietin, is a hormone produced in the kidneys that controls red blood cell production (erythropoiesis) which can be sourced naturally from:
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Echinacea
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Astragalus
Beetroot juice
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Spirulina
Dietary protein
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Arachidonic acid
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Cobalt
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Portulaca oleracea L.
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Rhodiola (Salidroside)
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Rehmannia (Catalpol)
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Emodin
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Altitude training
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Sauna
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Diabetes and Carotenoids: High serum carotenoids associated with lower metabolic risks
Diabetes and Carotenoids: High serum carotenoids associated with lower metabolic risks
High serum carotenoids associated with lower risk for the metabolic syndrome and its components among Japanese subjects: Mikkabi cohort study.
Sugiura M1, Nakamura M2, Ogawa K1, Ikoma Y1, Yano M1.
Author information
Abstract
Recent epidemiological studies show the association of carotenoids with the metabolic syndrome (MetS), but thorough longitudinal cohort studies regarding this association have not been well conducted. The objective of this study was to investigate longitudinally whether serum carotenoids are associated with the risk of developing the MetS and its components in Japanese subjects. We conducted a follow-up study on 1073 men and women aged 30-79 years at the baseline from the Mikkabi prospective cohort study. Those who participated in the baseline and completed follow-up surveys were examined longitudinally. Over the 10-year period, 910 subjects (295 men and 615 women) took part in the follow-up survey at least once. Over a mean follow-up period of 7·8 (sd 2·9) years, thirty-six men and thirty-one women developed new MetS. After adjustments for confounders, the hazard ratio (HR) for the MetS in the highest tertile of serum β-carotene against the lowest tertile was 0·47 (95 % CI 0·23, 0·95). On the other hand, significantly lower risks for dyslipidaemia were observed in the highest tertiles of serum α- and β-carotene and β-cryptoxanthin (HR 0·66; 95 % CI 0·46, 0·96; HR, 0·54; 95 % CI 0·37, 0·79; and HR 0·66; 95 % CI 0·44, 0·99, respectively). Other significant associations between the risks for obesity, high blood pressure and hyperglycaemia with serum carotenoids were not observed. Our results further support the hypothesis that eating a diet rich in carotenoids might help prevent the development of the MetS and its complications in Japanese subjects.
KEYWORDS:
Antioxidants; Carotenoids: Metabolic syndrome; HR; Longitudinal studies: Cohort studies; MetS; hazard ratio; metabolic syndrome
California drug makers are using their monopoly power
California drug makers are using their monopoly power
California drug makers are using their monopoly power against the people of California. Right now, these corporations have free rein to hike up drug prices at a moment’s notice and keep drug purchasing data secret, leaving Californians in the dark.
Sen. Hernandez has introduced Senate Bill 17, which will hold drug makers accountable by demanding greater transparency. This bill has already made it through the state Senate, and the Assembly is considering the measure right now.
Senate Bill 17 will:
- Require drug makers to publish data about purchasing trends, including drug prescription and pricing data.
- Prevent drug companies from dramatically raising prices without warning by requiring drug companies to give 60 days’ notice to purchasers before making major increases to drug prices.
- Require health insurance companies to disclose what portion of premiums go towards prescription drugs.
This legislation will empower purchasers to make cost-effective health care decisions based off newly-available information pharmaceutical companies have to provide. With more transparency, SB 17 will help keep costs down for Californians.
Act Now: Write your state assemblymember and urge them to support Senate Bill 17.
| ACT NOW >> |
Thanks for taking a stand,
http://sign.actiontaker.org/Support-Senate-Bill-17
— NextGen America
Bay area events this week
A Palo Alto pooch stuck at a home construction site was rescued by firefighters on July 26. Mele, a mixed poodle and chow chow, was found by her owner at a rear corner of a Tennyson Avenue lot, steps away from a 10- to 12-feet-deep hole where a house once stood. Three firefighters who responded to the scene made their way across a narrow pathway to the anxious dog, who they secured on a leash and brought back to stable ground. The owner suspected Mele likely escaped from her backyard through a loose wooden panel on the fence and found herself on the neighboring property.
TOP STORIESfrom the Palo Alto Weekly and the Palo Alto Online staff
Brock Turner judge hires Trump consultant
Aaron Persky, the Santa Clara County judge facing a recall measure in the wake of his controversial … (Thursday, 9:40 AM)
Heidelberg wants to be Palo Alto’s ‘sister city’
Heidelberg, a city of gothic churches, a sprawling castle and Germany’s oldest university and librar… (Thursday, 8:35 AM)
City Council set to approve new shuttle plan
Palo Alto’s effort to expand and re-invigorate its small shuttle program could speed ahead later thi… (Wednesday, 4:29 PM)
Air district board supports Paris climate accord
The Bay Area Air Quality Management District’s board of directors voted Wednesday to support the Par… (Thursday, 8:45 AM)
HOT PICKSMust-see events recommended by our A&E editors
Music: SJW Jazz Institute Showcase
This mini-festival of jazz includes musicians of all ages and from all over the world. In four convenient venues, audiences can hear dozens of instrumentalists and vocalists performing everything from cool jazz to bebop, and from standards to original songs. All are participants in Stanford Jazz Workshop’s Jazz Institute, tonight, Aug. 3, 7-9 p.m. at Dinkelspiel Auditorium, 471 Lagunita Drive, Stanford. Go to stanfordjazz.org.
Reading Series: Story Is the Thing
Story Is the Thing is an evening of storytelling with seven Bay Area authors reading on the theme “Forbidden Places.” Readers include Joan Frank, Lucy Jane Bledsoe, Ethel Rohan, Elaine Ray, Fyza Parviz, Ron Chapman and Nicola Maye Goldberg. Wine, cheese and cupcakes will be served at 7:15 p.m., tonight, Aug. 3, 7:15-9 p.m. at Kepler’s Books, 1010 El Camino Real, Menlo Park. Go to keplers.org.
Theater: ‘Lord of the Flies’
A Theatre Near U presents William Golding’s raw and terrifying classic, “Lord of the Flies.” The play follows a group of boys marooned on an idyllic island, as they shed their cultured upbringings and descend into brutal savagery, tonight, Aug. 3, 7:30 p.m. at The Pear Theatre, 1110 La Avenida, Mountain View. Go to atheatrenearu.org.
Concert: SJW All-Star Jam
This concert will feature renowned artists in jazz, performing in combinations familiar and unfamiliar, while delivering performances of intensity, passion and excitement, tomorrow, Aug. 4, 8-10 p.m. at Dinkelspiel Auditorium, 471 Lagunita Drive, Stanford. Go to stanfordjazz.org.
Food & Drink: Eat, Drink & Be Techie
Friday Nights @CHM offers a whole new way to experience the Computer History Museum this summer in partnership with Off the Grid. Enjoy seven food trucks, CHM exhibits with new extended hours and live music, tomorrow, Aug. 4, 5 p.m. at the Computer History Museum, 1401 N Shoreline Blvd., Mountain View. Go to computerhistory.org.
Play: Autumn Dance
Autumn Dance, written and directed by Shabnam Tolouei, follows three tormented Iranian women experiencing exile, even while living in their own country. The play allows the audience to be transported from Tehran to Paris to uncover the connection between these three women. All three roles are played by Shabnam Tolouei, an award-winning actress, playwright and director, tomorrow, Aug. 4, 7:30 p.m. at Bing Concert Hall, 327 Lasuen St., Stanford. Go tolive.stanford.edu.
Sharapova withdraws from the Bank of the West Classic
Maria Sharapova, based on doctor’s advice, has withdrawn from the Bank of the West Classic on Wedn… (Wednesday, 4:59 PM)
A portable line judge that settles tennis disputes
Gregoire Gentil is a rabid tennis fan but his love of the sport had little to do with his latest inv… (Thursday, 12:26 AM)
Steffens remains in contention for NCAA Woman of the Year
Stanford grad Maggie Steffens is one of the 145 candidates, of 543, who remain in contention for the… (Wednesday, 6:45 PM)
Menlo College bulks up on track and field athletes
Menlo College Cross Country and Track and Field coach Dan Noel has put the finishing touches on the … (Wednesday, 6:57 PM)
SPORTS SCORES
Mens Crew: World Junior Championship , Results
Womens Tennis: Bank of the West Classic , Order of Play
Womens Beach volleyball: World Championship , Results
Girls Diving: USA Championship , Results
Boys Diving: USA Championship , Results
SPORTS CALENDAR
Womens Tennis: Bellis vs. Cepede Royg at Bank of the West Classic, 11 a.m. today
Mens Swimming: Locals in finals at U.S. Open Championships , 2 p.m. today
Womens Swimming: Locals in finals at U.S. Open Championships , 2 p.m. today
Mens Swimming: Locals at Futures Championships, 4 p.m. today
Womens Swimming: Locals at Futures Championships, 4 p.m. today
• PASportsOnline.com Home Page
TOWN SQUAREPalo Alto’s online gathering place
FAA report looks to change noisy SFO-arrivals path
A new flight path that would reduce noise over Palo Alto and surrounding cities is being developed b…
Brick-and-mortar retailers face steep challenges
Downtown Palo Alto stores are struggling with high costs, difficulties in finding employees who will…
A&E PAGE
Don’t take phone or Internet service away from poor people
Sign the petition: Don’t take phone or Internet service away from poor people.
Republicans just don’t know how to stop. As if attacking healthcare, immigration, affirmative action, and transgender rights weren’t enough, the GOP is now going after poor people’s access to phone and Internet service.
This week, Republican Representative Austin Scott introduced the “End Taxpayer Funded Cell Phone Act,” which targets Lifeline—a crucial program that provides telephone, cell phone, and Internet subsidies to low-income Americans.
This bill would cut off funding for cell phone and Internet, and “restore” Lifeline’s services to only fund landline telephones. Sign now if you agree that Lifeline should continue to fund landline phones, cell phones, and Internet service.
Reducing Lifeline’s services is unacceptable. Lifeline makes landline phones, cell phones, and Internet accessible for poor, disabled, and elderly people. Taking those services away would be cruel.
In solidarity,
Sarah Hogg, Daily Kos
Esther Dello Buono, artist San Jose CA
<blockquote class=”instagram-media” data-instgrm-captioned data-instgrm-version=”7″ style=” background:#FFF; border:0; border-radius:3px; box-shadow:0 0 1px 0 rgba(0,0,0,0.5),0 1px 10px 0 rgba(0,0,0,0.15); margin: 1px; max-width:658px; padding:0; width:99.375%; width:-webkit-calc(100% – 2px); width:calc(100% – 2px);”>
<p style=” margin:8px 0 0 0; padding:0 4px;”> <a href=”https://www.instagram.com/p/BVnpfhzlxPP/” style=” color:#000; font-family:Arial,sans-serif; font-size:14px; font-style:normal; font-weight:normal; line-height:17px; text-decoration:none; word-wrap:break-word;” target=”_blank”>Some spring colors for the summer 🌿🌸🐝 #watercolor #softpastels #natureart #watercolorflowers #beesandbutterflies #watercolorflorals</a></p> <p style=” color:#c9c8cd; font-family:Arial,sans-serif; font-size:14px; line-height:17px; margin-bottom:0; margin-top:8px; overflow:hidden; padding:8px 0 7px; text-align:center; text-overflow:ellipsis; white-space:nowrap;”>A post shared by Esther Dello Buono (@e.philomena_) on <time style=” font-family:Arial,sans-serif; font-size:14px; line-height:17px;” datetime=”2017-06-21T23:08:28+00:00″>Jun 21, 2017 at 4:08pm PDT</time></p></div></blockquote>
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