Researchers: Derrick C. Wan, MD, FACS and Arash Momeni, MD, FACS

DURHAM, N.C. (PRWEB) December 03, 2019

A new study released today in STEM CELLS outlines how fat grafting which previous studies have shown can reduce and even reverse fibrosis (scar tissue) buildup also improves the range of motion of the affected limb. The study, conducted by researchers at Stanford University School of Medicine, was conducted on mice.

The tumor-destroying capabilities of radiation therapy can be a life saver for a person suffering from cancer. But its a therapy that has several unwanted side effects, too, including causing substantial damage not just to cancerous cells, but any healthy tissue in its path. Over time, fibrosis builds up in the treated area which, in the case of an arm, shoulder, or leg, for example, can lead to painful contractures that significantly limit extensibility and negatively impact the persons quality of life.

The Stanford team irradiated the right hind legs of subject mice, which resulted in chronic fibrosis and limb contracture. Four weeks later, the irradiated limbs of one group of the mice were injected with fat enriched with stromal vascular cells (SVCs). These potent cells already naturally exist in fat, but supplementation of fat with additional SVCs enhances its regenerative capabilities. A second group was injected with fat only, a third group with saline and a fourth group received no injections, for comparison. The animals ability to extend their limb was then measured at baseline and every two weeks for a 12-week period. At the end of the 12 weeks, the hind limb skin underwent histological analysis and biomechanical strength testing.

Each animal showed significant reduction in its limb extension ability due to the radiation, but this was progressively rescued by fat grafting, reported corresponding author Derrick C. Wan, M.D., FACS. Fat grafting also reduced skin stiffness and reversed the radiation-induced histological changes in the skin.

The greatest benefits were found in mice injected with fat enriched with SVCs, Dr. Wan added. SVCs are easily obtained through liposuction and can be coaxed into different tissue types, where they can support neovascularization, replace cells and repair injured issue.

Our study showed the ability of fat to improve mobility as well as vascularity and appearance, he continued. We think this holds enormous clinical potential especially given that adipose tissue is abundant and can be easily collected from the patients themselves and underscores an attractive approach to address challenging soft tissue fibrosis in patients following radiation therapy.

Furthermore, said co-author and world-renowned breast reconstructive expert Arash Momeni, M.D., FACS, Our observations are potentially translatable to a variety of challenging clinical scenarios. Being able to reverse radiation-induced effects holds promise to substantially improve clinical outcomes in implant-based as well as autologous breast reconstruction. The study findings are indeed encouraging as they could offer patients novel treatment modalities for debility clinical conditions.

Excessive scarring is a challenging problem that is associated with a variety of clinical conditions, such as burn injuries, tendon lacerations, etc. The potential to improve outcomes based on treatment modalities derived from our research is indeed exciting, Dr. Momeni added.

"Skin and soft tissue scarring and fibrosis are well-established problems after radiation. The current study, showing that human fat grafting can normalize the collagen networks and improve tissue elasticity in immune deficient mice, provides molecular evidence for how fat grafting functions, said Dr. Jan Nolta, Editor-in-Chief of STEM CELLS. The studies indicate that, with the appropriate regulatory approvals, autologous fat grafting could potentially also help human patients recover from radiation-induced tissue fibrosis.

The full article, Fat grafting rescues radiation-induced joint contracture, can be accessed at https://stemcellsjournals.onlinelibrary.wiley.com/doi/full/10.1002/stem.3115.

About the Journal: STEM CELLS, a peer reviewed journal published monthly, provides a forum for prompt publication of original investigative papers and concise reviews. The journal covers all aspects of stem cells: embryonic stem cells/induced pluripotent stem cells; tissue-specific stem cells; cancer stem cells; the stem cell niche; stem cell epigenetics, genomics and proteomics; and translational and clinical research. STEM CELLS is co-published by AlphaMed Press and Wiley.

About AlphaMed Press: Established in 1983, AlphaMed Press with offices in Durham, NC, San Francisco, CA, and Belfast, Northern Ireland, publishes three internationally renowned peer-reviewed journals with globally recognized editorial boards dedicated to advancing knowledge and education in their focused disciplines. STEM CELLS (http://www.StemCells.com) is the world's first journal devoted to this fast paced field of research. THE ONCOLOGIST (http://www.TheOncologist.com) is devoted to community and hospital-based oncologists and physicians entrusted with cancer patient care. STEM CELLS TRANSLATIONAL MEDICINE (http://www.StemCellsTM.com) is dedicated to significantly advancing the clinical utilization of stem cell molecular and cellular biology. By bridging stem cell research and clinical trials, SCTM will help move applications of these critical investigations closer to accepted best practices.

About Wiley: Wiley, a global company, helps people and organizations develop the skills and knowledge they need to succeed. Our online scientific, technical, medical and scholarly journals, combined with our digital learning, assessment and certification solutions, help universities, learned societies, businesses, governments and individuals increase the academic and professional impact of their work. For more than 200 years, we have delivered consistent performance to our stakeholders. The company's website can be accessed at http://www.wiley.com.

Share article on social media or email:

Read this article:
Fat grafting improves range of motion in limbs damaged by radiation therapy - PR Web

Innate Pharma SA (Euronext Paris: IPH ISIN: FR0010331421; Nasdaq: IPHA) today announced its certification as a great work place by the independent institute, Great Place to Work, a global authority on workplace culture, employee experience and leadership behaviors. This recognition was based extensively on ratings provided by Innate Pharma's employees in an anonymous survey that assessed perspectives on leadership, organizational culture and trust.

We are very proud to have obtained the Great Place to Work certification, which acknowledges a high-performing and collaborative culture that attracts, engages and develops its employees," said Mondher Mahjoubi, Chief Executive Officer of Innate Pharma. In the highly competitive biotech industry, our success depends on our ability to foster a positive company culture. Its rewarding to see the time, resources and energy weve committed around collaborating, listening and communicating to employees, reflected in our high levels of employee engagement and recognized by this external validation.

Eighty-six percent of employees participated in the Great Place to Work survey process. Managerial practices, collaborative spirit, working conditions and commitment to the company were identified as main strengths of the company.

"Congratulations to Innate Pharma for being one of the Great Place to Work 2019 certified companies. This innovative company, with a strong social mission, has succeeded in getting employees to support its corporate culture and mission. As such, 90 percent of employees say they are proud to tell others that they are working for Innate Pharma. Thus, the Great Place to Work project, led by the company's highest level of management, contributes to making it a great place to work, said Patrick Dumoulin, President of Great Place to Work France.

About Great Place to Work

Great Place to Work is the global authority on workplace culture.Since 1992, they have surveyed more than 100 million employees around the world and used those deep insights to define what makes a great workplace: trust. Their unparalleled benchmark data is used to recognize Great Place to Work-Certified companies and the Best Workplaces in the US and more than 60 countries, including the 100 Best Companies to Work For and World's Best list published annually in Fortune. Everything they do is driven by the mission to build a better world by helping every organization become a Great Place to Work For All. To learn more, visit greatplacetowork.com.

About Innate Pharma:

Innate Pharma S.A. is a commercial stage oncology-focused biotech company dedicated to improving treatment and clinical outcomes for patients through therapeutic antibodies that harness the immune system to fight cancer.

Innate Pharmas commercial-stage product, Lumoxiti, in-licensed from AstraZeneca in the US, EU and Switzerland, was approved by the FDA in September 2018. Lumoxiti is a first-in class specialty oncology product for hairy cell leukemia. Innate Pharmas broad pipeline of antibodies includes several potentially first-in-class clinical and preclinical candidates in cancers with high unmet medical need.

Innate has been a pioneer in the understanding of natural killer cell biology and has expanded its expertise in the tumor microenvironment and tumor-antigens, as well as antibody engineering. This innovative approach has resulted in a diversified proprietary portfolio and major alliances with leaders in the biopharmaceutical industry including Bristol-Myers Squibb, Novo Nordisk A/S, Sanofi, and a multi-products collaboration with AstraZeneca.

Based in Marseille, France, Innate Pharma is listed on Euronext Paris and Nasdaq in the US.

Learn more about Innate Pharma at http://www.innate-pharma.com

Information about Innate Pharma shares:

Disclaimer:

This press release contains certain forward-looking statements, including those within the meaning of the Private Securities Litigation Reform Act of 1995.The use of certain words, including believe, potential, expect and will and similar expressions, is intended to identify forward-looking statements.Although the company believes its expectations are based on reasonable assumptions, these forward-looking statements are subject to numerous risks and uncertainties, which could cause actual results to differ materially from those anticipated. These risks and uncertainties include, among other things, the uncertainties inherent in research and development, including related to safety, progression of and results from its ongoing and planned clinical trials and preclinical studies, review and approvals by regulatory authorities of its product candidates, the Companys commercialization efforts and the Companys continued ability to raise capital to fund its development.For an additional discussion of risks and uncertainties which could cause the company's actual results, financial condition, performance or achievements to differ from those contained in the forward-looking statements, please refer to the Risk Factors (Facteurs de Risque") section of the Universal Registration Document filed with the French Financial Markets Authority (AMF), which is available on the AMF website http://www.amf-france.org or on Innate Pharmas website, and public filings and reports filed with the U.S. Securities and Exchange Commission (SEC), including the Companys final prospectus dated October 16, 2019, and subsequent filings and reports filed with the AMF or SEC, or otherwise made public, by the Company.

This press release and the information contained herein do not constitute an offer to sell or a solicitation of an offer to buy or subscribe to shares in Innate Pharma in any country.

For additional information, please contact:

Read this article:
Innate Pharma Certified as a Great Place to Work - GlobeNewswire

November 25, 2019

The air, earth and water of our planet are pulsating with living things. Within it, a vast and diverse web of life exists, about which almost nothing is known. This is the world of flagellates, tiny organisms that persist in staggering numbers in many diverse ecosystems around the world.

According to Jeremy Wideman, a researcher at theBiodesign Center for Mechanisms in Evolutionat Arizona State University, we have a great deal to learn from these delicate and wildly varied creatures. Among other surprises, flagellates could provide valuable clues about a shadowy event that may have occurred 1.5-2 billion years ago (no one is really sure of the timing) with the arrival of a new type of cell. The graphic shows a tree of life for complex forms known as Eukaryotes that arose mysteriously around 1.2-2 billion years ago from a progenitor known as LECA (for Last Eukaryote Common Ancestor.) ASU researcher Jeremy Wideman and his colleagues used a new method to sequence mitochondrial DNA for around 100 species of flagellates tiny aquatic organisms that populate many branches of the tree. These are seen on the graphic as red dots marking the particular lineages these flagellates belong to. Graphic by Shireen Dooling Download Full Image

Known as LECALast Eukaryote Common Ancestor, it was a sort of primal egg out of which the astonishing profusion of complex life from flagellate organisms, fungi and plants, to insects, zebra and humans exploded and spread over the Earth.

In new research appearing today in the journalNature Microbiology, Wideman and his many international colleagues, including Proferssor Thomas Richards at the University of Exeter, describe a new method for investigating the genomes of eukaryotic flagellate organisms, which have been notoriously tricky to pinpoint and sequence.

Specifically, they explored samples of mitochondrial DNA, sequencing around 100 such genomes for previously undocumented flagellates. The new technique could help scientists like Wideman begin to fill in the largely blank region of the eukaryotic puzzle, where flagellate life flourishes.

Wideman, originally a traditional cell biologist, became frustrated with the many unaddressed questions in the field, recently joining the emerging discipline of evolutionary cell biology. This rapidly advancing research area uses cells as fundamental units for the study of evolutionary processes and imports concepts from evolutionary biology to better understand how cells work.

I'm literally a cell biologist that wants to know more about things we know nothing about, he said.

Evolutionary cell biology is a profoundly transdisciplinary endeavor, fusing evolutionary theory, genomics and cell biology with quantitative branches of biochemistry, biophysics and population genetics.

Jeremy Wideman is a researcher in the Biodesign Center for Mechanisms in Evolution and the School of Life Sciences at Arizona State University.

Flagellates include many parasites implicated in human disease, from the intestinal bug Giardia to more damaging trypanosomes and leishmania. Flagellates also perform more benevolent tasks. As the major consumers of bacteria and other protists in aquatic ecosystems, they help ensure the recycling of limiting nutrients.

Single-celled eukaryotic organisms, which include flagellates, constitute the overwhelming majority of eukaryotic diversity, vastly outpacing the more familiar multicellular plants, animals and fungi. Despite their importance and ubiquity across the globe, flagellates are, as Wideman stresses, an almost entirely unknown inhabitant of the living world and one of the most enigmatic. When viewed under a microscope, their often science fiction-like appearance is markedly distinct from the kinds of eukaryotic cells commonly described in biology textbooks. Their emergence from comparatively rudimentary prokaryotes marks the most momentous transition in the history of life on earth.

Novel lineages of heterotrophic flagellates are being discovered at an alarming rate, Wideman said. In the last two years, two kingdom level lineages have been discovered, meaning lineages that have been evolving independently of animals and fungi for over a billion years.

Nevertheless, researchers have barely scratched the surface of this astonishing diversity and new methods must be brought to bear to speed up the quest.

Any drop of pond, lake or ocean water is likely to contain many flagellates, but separating them from a multitude of nonflagellates and accurately reading their genomes by conventional means has been slow and painstaking work. Only a minute fraction of extant flagellates have known genomic sequences and its even possible that the overwhelming majority have never actually been seen. According to Wideman, flagellate life forms represent the "dark matter" of the eukaryotic universe.

HeterotrophicHeterotrophs are organisms that cannot synthesize their own food, relying instead on other organisms for nutrition. flagellates are the target, Wideman said. They're not a lineage. They're many, many lineages that are from all over the tree of life. LECA, the Last Eukaryotic Common Ancestor, was a heterotrophic flagellate, which means that every major lineage (of eukaryotes) evolved from some sort of heterotrophic flagellate.

To access the elusive flagellate mitochondrial DNA, the researchers exploited a feature common to all flagellates and from which they take their name the existence of flagella, which, unlike in animal sperm are on the front of cells and are often used to pull them forward like a microscopic breast stroke but are also involved in sensation, feeding, and perhaps other as-yet unknown functions.

Flagella are rich in a particular protein known as tubulin. The new method for identifying flagellates and distinguishing them from their aquatic neighbors primarily algae and bacteria capitalizes on this fact by applying a selective stain to flagella-bearing organisms, activated by their high tubulin content. (Algal cells are naturally marked by their chloroplasts, which the flagellates of interest in the new study lack.)

Samples of sea water collected in 2014 off the coast of California provided a test case. Using the technique, the researchers gathered a windfall of mitochondrial sequence data, significantly expanding the catalog of flagellates identified by molecular means. Indeed, they doubled the existing mitochondrial DNA library for flagellate organisms.

We got many, many different kinds of organisms. So it was a very rich sample and very few were identical, Wideman said.

Apart from the mystery of lifes origin, the puzzle of where eukaryotes came from and how the LECA event transpired is the most important and vexing unanswered question in all of biology. (It has been dubbed theblack holeat the heart of the living world.)

Correctly establishing the sequence of events underlying the crucial innovations within eukaryotes, from whence all complex life sprang, will take much more research in unexplored regions of the existing eukaryotic domain, particularly, the flagellates. Wideman believes the rapid advance of techniques for identifying and sequencing these organisms, such as the one outlined in the new study, offer hope such questions may one day find answers.

This project was supported by a Gordon and Betty Moore foundation grant (GBMF3307) to 597 TAR, AES, AZW and PJK, and a Philip Leverhulme Award (PLP-2014-147) to TAR. Field sampling was 598 supported by the David and Lucile Packard Foundation and GBMF3788 to AZW. TAR and AM are 599 supported by Royal Society University Research Fellowships. JGW was supported by the European 600 Molecular Biology Organization Long-term Fellowship (ALTF 761-2014) co-funded by European 601 Commission (EMBOCOFUND2012, GA-2012-600394) support from Marie Curie Actions and a College for 602 Life Sciences Fellowship at the Wissenschaftskolleg zu Berlin. RRM is supported by CONICYT FONDECYT 603 11170748. FM is supported by Genome Canada.

Continue reading here:
Aquatic microorganisms offer important window on the history of life - Arizona State University

Cell biology has very particular characteristics. During the last decade, researchers and scientists have astounded us with their discoveries in bioprinting and regenerative medicine, proving that a great deal of what happens at the lab is basically knowing and understanding cells. These microscopic structures are the foundation of most projects where cells are patterned to grow into mature tissues, interacting with other cells and non-cellular components of their local environment, such as the extracellular matrix and nutrient sources.

But there have been a few challenges along the way, basically: how to keep the cells alive, what materials to use for cells to live in, and keeping up with the requirements of micro parts in the production sector as well as in academic and industrial research. And that is a big part of bioprinting. Tissue growth and the behavior of cells can be controlled and investigated particularly well by embedding the cells in a delicate 3D framework, yet some methods are very imprecise or only allow a very short time window in which the cells can be processed without being damaged. Moreover, the materials used must be cell-friendly during and after the process, restricting the variety of possible materials, which includes biocompatible synthetic and natural polymers. Now a new high-resolution bioprinting process developed at Vienna University of Technology (TU Wien), in Austria, ensures living cells can be integrated into fine structures created in a 3D printer extremely fast.

Thanks to a special bioink and 3D printing system, cells can be embedded in a 3D matrix printed with micrometer precision, at a printing speed of one meter per second. This high-resolution bioprinting process with completely new materials allows the fabrication of structures and surface textures mimicking the microenvironment of cells.

The behavior of a cell depends crucially on the mechanical, chemical and geometric properties of its environment, said Aleksandr Ovsianikov, head of the 3D Printing and Biofabrication research group at the Institute of Materials Science and Technology at TU Wien. The structures in which the cells are embedded must be permeable to nutrients so that the cells can survive and multiply. But it is also important whether the structures are stiff or flexible and whether they are stable or degrade over time.

The high-resolution 3D printing technology and the materials are being commercialized by UpNano GmbH, a spin-off company of TU Wien. The ultrafast high-resolution 3D printing system called NanoOne is based on multiphoton lithography and combines the precision of two-photon polymerization. UpNano claims that their patented process enables the batch production of microparts with the highest resolution and complexity in the market, enabling the economic production of polymer parts from micro to mesoscale. The biocompatible process in combination with optimized materials facilitates cell, tissue, and biofabrication. Meaning that the living cells of choice can be mixed into the material and printed directly or seeded on sterile, pre-fabricated scaffold structures.

NanoOne 3D printing system

In order to achieve an extremely high resolution, two-photon polymerization methods have been used at TU Wien for years. This method uses a chemical reaction that is only initiated when a molecule of the material simultaneously absorbs two photons of the laser beam. According to the institute, this is only possible where the laser beam has a particularly high intensity. At these points, the substance hardens, while it remains liquid everywhere else. Therefore, this two-photon method is best suited to produce extremely fine structures with high precision.

However, these high-resolution techniques usually have the disadvantage of being very slowoften in the range of micrometers or a few millimeters per second. At TU Wien, however, cell-friendly materials can be processed at a speed of more than one meter per second, and they claim that only if the entire process can be completed within a few hours there is a good chance of the cells surviving and developing further.

Aleksandr Ovsianikov

According to Ovsianikov, printing microscopically fine 3D objects is no longer a problem today, however, the use of living cells presents science with completely new challenges: until now, there has simply been a lack of suitable chemical substances. You need liquids or gels that solidify precisely where you illuminate them with a focused laser beam. However, these materials must not be harmful to the cells, and the whole process has to happen extremely quickly.

UpNanos high-performance two-photon materials are engineered and optimized to utilize the full potential of the NanoOne printing system. In addition to UpBio, the hydrogel material for biological applications and bioprinting, UpNano offers photopolymers (UpPhoto) and sol-gel hybrid materials (UpSol). Living cells of choice can be mixed into the material and printed directly, and cells embedded in an UpBio matrix can be used for 3D in vitro cell tests, which gain increasing importance in cell culture, tissue regeneration and pharmaceutical research.

Our method provides many possibilities to adapt to the environment of the cells. Depending on how the structure is built, it can be made stiffer or softer. Even fine, continuous gradients are possible. In this way, we can define exactly how the structure should look in order to allow the desired kind of cell growth and cell migration. The laser intensity can also be used to determine how easily the structure will be degraded over time.

Ovsianikov is convinced that this is an important step forward for cell research: Using these 3D scaffolds, it is possible to investigate the behavior of cells with previously unattainable accuracy. It is possible to study the spread of diseases, and if stem cells are used, it is even possible to produce tailor-made tissue in this way.

The research project is an international and interdisciplinary cooperation in which three different institutes of the TU Vienna were involved: Ovsianikovs research group was responsible for the printing technology itself, the Institute of Applied Synthetic Chemistry at TU Wien developed fast and cell-friendly photoinitiators (the substances that initiate the hardening process when illuminated) and TU Wiens Institute of Lightweight Structures and Structural Biomechanics analyzed the mechanical properties of the printed structures.

Cells spreading in a 3D scaffold. From left to right: week 1, week 3 week 5. Top: 3D setup, bottom: one layer only.

The advantages of the NanoOne high-resolution printing system enable the additive manufacturing of polymeric microparts in research, science, and industry, with achievable part sizes, ranging from micro to mesoscale, with structure details in a submicrometer range and throughput of the system that opens up a universe of application possibilities. Considering that UpNano is a very new company, founded in 2018, we can expect researchers to come up with some very interesting solutions in a universe of applications.

Join the discussion of this and other 3D printing topics at3DPrintBoard.com.

Go here to read the rest:
UpNano: Forging Ahead in Microfabrication With Two-Photon Polymerization - 3DPrint.com

Researchers from Bengaluru have made an important discovery of the mechanism used by TB bacteria to tolerate TB drugs, which necessitates longer treatment of six-nine months. They have also demonstrated that a drug combination that prevents the bacteria from inducing this mechanism leads to almost complete clearance of the bacteria from the mice lungs in just two months of therapy. If further studies and trials show similar results, a shorter treatment regimen might be sufficient to treat drug-sensitive TB.

The common notion is that only the non-replicating or slowly metabolising TB bacteria become tolerant to anti-TB drugs. But the team led by Amit Singh from the Department of Microbiology and Cell Biology, and Centre for Infectious Disease Research at the Indian Institute of Science (IISc) found a fraction of the bacteria inside the macrophages was able to tolerate anti-TB drugs even when actively multiplying.

The researchers found that using an already approved anti-malaria drug chloroquine in combination with a TB drug isoniazid can almost clear all the bacteria from the lungs of mice and guinea pigs in just eight weeks. In addition, the drug combination also reduces the chances of TB relapse. The results were published in the journal Science Translational Medicine.

Reducing the pH to make it acidic is the first-line of defence by macrophages when infected with pathogens. But the researchers found that instead of controlling the TB bacteria, the mildly acidic pH was actually facilitating a fraction of the bacteria to continue multiplying and develop drug tolerance.

We used a biosensor which we had developed a few years ago to see the amount of oxidative stress inside the TB bacteria during infection. We found that anti-TB drugs induce oxidative stress to kill bacteria inside macrophages. However, the drug tolerant bacteria have a remarkable ability to counter oxidative stress, says Prof. Singh. The bacteria used the acidic pH of macrophages as a cue to specifically increase its capacity to deal with oxidative stress. Also, the drug-tolerant bacteria induce efflux pumps to expel antibiotics as an additional mechanism to reduce antibiotic efficacy.

The drug-tolerant bacteria were found in macrophages that were more acidic (pH 5.8) while the drug-sensitive bacteria were seen in macrophages that were less acidic (pH 6.6).

We hypothesised that reverting the pH within macrophages to its normal state could probably make the bacteria sensitive to antibiotics, Prof. Singh says. The chloroquine drug does just that it neutralises the pH within the macrophages. This prevented the bacteria from inducing the mechanism to protect themselves from oxidative stress. So no drug-tolerant TB bacteria emerged. Once the pH is neutralised, the isoniazid drug was able to eradicate TB from animals.

While the two-month treatment was able to completely sterilise mouse lungs, a near-complete eradication was observed from the lungs of guinea pigs. The combination was shown to reduce TB bacteria load in both mice and guinea pigs, says Richa Mishra from IISc and the first author of the paper.

In the case of in vitro studies using cell lines and mice macrophages, the ability of the combination drug therapy to reduce TB load was found to be three- to fivefold higher than when treated only with TB drugs. Reduction in bacteria load was more when we combined chloroquine with isoniazid, says Mishra. We observed threefold reduction when we combined chloroquine with rifampicin and fivefold reduction when we used chloroquine-isoniazid combination.

To determine TB relapse following treatment, mice infected with TB were completely rid of bacteria using the drug combination. Eight weeks later, the immune system of mice was suppressed using a drug. While all the five mice treated with only isoniazid relapsed with high bacterial load, three of the five mice treated with the combination drug showed very little presence of bacteria. This shows that the drug combination reduces the chances of TB relapse, says Mishra.

The work was carried out in collaboration with researchers from Bengalurus National Centre for Biological Sciences and Foundation for Neglected Disease Research.

You have reached your limit for free articles this month.

Register to The Hindu for free and get unlimited access for 30 days.

Find mobile-friendly version of articles from the day's newspaper in one easy-to-read list.

Enjoy reading as many articles as you wish without any limitations.

A select list of articles that match your interests and tastes.

Move smoothly between articles as our pages load instantly.

A one-stop-shop for seeing the latest updates, and managing your preferences.

We brief you on the latest and most important developments, three times a day.

*Our Digital Subscription plans do not currently include the e-paper ,crossword, iPhone, iPad mobile applications and print. Our plans enhance your reading experience.

View post:
Combination therapy using malaria drug quickly clears TB - The Hindu

This picture shows a spirited flying Taiwan Blue Magpie displaying a full array of flight feathers in action. Credit: Shao Huan Lang

If you took a careful look at the feathers on a chicken, youd find many different forms within the same birdeven within a single feather. The diversity of feather shapes and functions expands vastly when you consider the feathers of birds ranging from ostriches to penguins to hummingbirds. Now, researchers reporting in the journal Cell on November 27, 2019, have taken a multidisciplinary approach to understanding how all those feathers get made.

We always wonder how birds can fly and in different ways, says corresponding author Cheng-Ming Chuong of the University of Southern California, Los Angeles. Some soar like eagles, while others require rapid flapping of wings like hummingbirds. Some birds, including ostriches and penguins, dont fly at all.

This picture shows a the asymmetric vane and tapering main shaft of a single flight feather from a goshawk. Credit: Hao Howard Wu and Wen Tau Juan

Such differences in flight styles are largely due to the characteristics of their flight feathers, Chuong adds. We wanted to learn how flight feathers are made so we can understand nature better and learn principles of bioinspired architecture.

In the new study, the researchers put together a multidisciplinary team to look at feathers in many different ways, from their biophysical properties to the underlying molecular biology that allows their formation from stem cells in the skin. They examined the feathers of flightless ostriches, short-distance flying chickens, soaring ducks and eagles, and high-frequency flying sparrows. They studied the extremes by including hummingbirds and penguins. To better understand how feathers have evolved and changed over evolutionary time, the team also looked to feathers that are nearly 100 million years old, found embedded and preserved in amber in Myanmar.

Based on their findings, the researchers explain that feathers modular structure allowed birds to adapt over evolutionary time, helping them to succeed in the many different environments in which birds live today. Their structure also allows for the specialization of feathers in different parts of an individual birds body.

The flight feather is made of two highly adaptable architectural modules: the central shaft, or rachis, and the peripheral vane. The rachis is a composite beam made of a porous medulla that keeps feathers light surrounded by a rigid cortex that adds strength. Their studies show that these two components of the rachis allow for highly flexible designs that enabled to fly or otherwise get around in different ways. The researchers also revealed the underlying molecular signals, including Bmp and Ski, that guide the development of those design features.

Attached to the rachis is the feather vane. The vane is the part of the feather made up of many soft barbs that zip together. The researchers report that the vane develops using principles akin to paper cutting. As such, a single epithelial sheet produces a series of diverse, branched designs with individual barbs, each bearing many tiny hooklets that hold the vane together into a plane using a Velcro-like mechanism. Their studies show that gradients in another signaling pathway (Wnt2b) play an important role in the formation of those barbs.

To look back in time, the researchers studied recently discovered amber fossils, allowing them to explore delicate, three-dimensional feather structures. Their studies show that ancient feathers had the same basic architecture but with more primitive characteristics. For instance, adjacent barbs formed the vane with overlapping barbules, without the Velcro-like, hooklet mechanism found in living birds.

Weve learned how a simple skin can be transformed into a feather, how a prototypic feather structure can be transformed into downy, contour, or flight feathers, and how a flight feather can be modulated to adapt to different flight modes required for different living environments, Chuong says. In every corner and at different morphological scales, we were amazed at how the elegant adaption of the prototype architecture can help different birds to adapt to different new environments.

The researchers say that, in addition to helping to understand how birds have adapted over time, they hope these bioinspired architectural principles theyve uncovered can be useful in future technology design. They note that composite materials of the future could contribute toward the construction of light but robust flying drones, durable and resilient wind turbines, or better medical implants and prosthetic devices.

Team co-leader and biophysicist Wen Tau Juan of the Integrative Stem Cell Center of China Medical University Hospital, Taiwan, has already begun to explore the application of feather-inspired architectural principles in bio-material design. The team also hopes to learn even more about the molecular signals that allow the formation of such complex feather structures from epidermal stem cells that all start out the same.

###

Reference: The Making of a Flight Feather: Bio-architectural Principles and Adaptation by Wei-Ling Chang, Hao Wu, Yu-Kun Chiu, Shuo Wang, Ting-Xin Jiang, Zhong-Lai Luo, Yen-Cheng Lin, Ang Li, Jui-Ting Hsu, Heng-Li Huang, How-Jen Gu, Tse-Yu Lin, Shun-Min Yang, Tsung-Tse Lee, Yung-Chi Lai, Mingxing Lei, Ming-You Shie, Cheng-Te Yao, Yi-Wen Chen, J.C. Tsai, Shyh-Jou Shieh, Yeu-Kuang Hwu, Hsu-Chen Cheng, Pin-Chi Tang, Shih-Chieh Hung, Chih-Feng Chen, Michael Habib, Randall B. Widelitz, Ping Wu, Wen-Tau Juan and Cheng-Ming Chuong, 27 November 2019, Cell.DOI: 10.1016/j.cell.2019.11.008

This work was supported by the ISCC, CMUH, Taiwan, the Drug Development Center, CMU, Higher Education Sprout Project, Ministry of Education (HESP-MOE), and grants from the National Institutes of Health, Ministry of Science and Technology, Taiwan, iEGG/Avian Genetic Resource/ABC supported by HESP-MOE, the Human Frontier Science Program, the National Natural Science Foundation of China, NSFC, Academia Sinica Research Program on Nanoscience and Nanotechnology, Top Notch Project, NCKU, and a University Advancement grant by MOE, Taiwan.

Go here to see the original:
How Flight Feathers Evolved: Study of Chickens, Ostriches, Penguins, Ducks and Eagles - SciTechDaily

An intrinsically photosensitive retinal ganglion cell (ipRGC) as it would appear if you looked at a mouses retina through the pupil. The white arrows point to the many different types of cells it networks with: other subtypes of ipRGC cell (red, blue and green) and retinal cells that are not ipRGCs (red). The white bar is 50 micrometers long, approximately the diameter of a human hair. (Image by Franklin Caval-Holme)

November 30, 2019 - ByRobert Sanders- By the second trimester, long before a babys eyes can see images, they can detect light.

But the light-sensitive cells in the developing retina the thin sheet of brain-like tissue at the back of the eye were thought to be simple on-off switches, presumably there to set up the 24-hour, day-night rhythms parents hope their baby will follow.

University of California, Berkeley, scientists have now found evidence that these simple cells actually talk to one another as part of an interconnected network that gives the retina more light sensitivity than once thought, and that may enhance the influence of light on behavior and brain development in unsuspected ways.

In the developing eye, perhaps 3% of ganglion cells the cells in the retina that send messages through the optic nerve into the brain are sensitive to light and, to date, researchers have found about six different subtypes that communicate with various places in the brain. Some talk to the suprachiasmatic nucleus to tune our internal clock to the day-night cycle. Others send signals to the area that makes our pupils constrict in bright light.

But others connect with surprising areas: the perihabenula, which regulates mood, and the amygdala, which deals with emotions.

In mice and monkeys, recent evidence suggests that these ganglion cells also talk with one another through electrical connections called gap junctions, implying much more complexity in immature rodent and primate eyes than imagined.

Given the variety of these ganglion cells and that they project to many different parts of the brain, it makes me wonder whether they play a role in how the retina connects up to the brain, said Marla Feller, a UC Berkeley professor of molecular and cell biology and senior author of a paper that appeared this month in the journalCurrent Biology. Maybe not for visual circuits, but for non-vision behaviors. Not only the pupillary light reflex and circadian rhythms, but possibly explaining problems like light-induced migraines, or why light therapy works for depression.

The cells, called intrinsically photosensitive retinal ganglion cells (ipRGCs), were discovered only 10 years ago, surprising those like Feller who had been studying the developing retina for nearly 20 years. She played a major role, along with her mentor, Carla Shatz of Stanford University, in showing that spontaneous electrical activity in the eye during development so-called retinal waves is critical for setting up the correct brain networks to process images later on.

Hence her interest in the ipRGCs that seemed to function in parallel with spontaneous retinal waves in the developing retina.

We thought they (mouse pups and the human fetus) were blind at this point in development, said Feller, the Paul Licht Distinguished Professor in Biological Sciences and a member of UC Berkeleys Helen Wills Neuroscience Institute. We thought that the ganglion cells were there in the developing eye, that they are connected to the brain, but that they were not really connected to much of the rest of the retina, at that point. Now, it turns out they are connected to each other, which was a surprising thing.

UC Berkeley graduate student Franklin Caval-Holme combined two-photon calcium imaging, whole-cell electrical recording, pharmacology and anatomical techniques to show that the six types of ipRGCs in the newborn mouse retina link up electrically, via gap junctions, to form a retinal network that the researchers found not only detects light, but responds to the intensity of the light, which can vary nearly a billionfold.

Gap junction circuits were critical for light sensitivity in some ipRGC subtypes, but not others, providing a potential avenue to determine which ipRGC subtypes provide the signal for specific non-visual behaviors that light evokes.

Aversion to light, which pups develop very early, is intensity-dependent, suggesting that these neural circuits could be involved in light-aversion behavior, Caval-Holme said. We dont know which of these ipRGC subtypes in the neonatal retina actually contributes to the behavior, so it will be very interesting to see what role all these different subtypes have.

The researchers also found evidence that the circuit tunes itself in a way that could adapt to the intensity of light, which probably has an important role in development, Feller said.

In the past, people demonstrated that these light-sensitive cells are important for things like the development of the blood vessels in the retina and light entrainment of circadian rhythms, but those were kind of a light on/light off response, where you need some light or no light, she said. This seems to argue that they are actually trying to code for many different intensities of light, encoding much more information than people had previously thought.

The research was supported by the National Institutes of Health.

More:
UC Scientists Say Babies In The Womb May See More Than We Thought - Sierra Sun Times

Scientists have cracked a cell mechanism that drives tumor formation in most types of cancer. This finding could lead to much-needed new therapies for cancer, including the hard-to-treat triple-negative breast cancer. Scientists have zoomed in on a cellular mechanism that stabilizes a tumor-driving protein. Disrupting it may lead to new therapies.

The discovery concerns the molecular activity of the suppressor protein p53. This protein sits inside the nucleus of the cell and protects the cells DNA from stress. It has acquired the nickname guardian of the genome for this reason.

However, mutated forms of p53, which are common in cancer, behave differently than regular p53. Instead of protecting the cell, they can take on oncogenic, or tumor-promoting, properties and become active drivers of cancer.

Previous studies had already shown that p53 mutations are more stable than their nonmutant counterparts and can accumulate until they eclipse them in the nucleus. However, the mechanism behind the stability of p53 mutations remained unclear.

Now, researchers from the School of Medicine and Public Health at the University of Wisconsin-Madison have unpicked the stabilizing mechanism, and they suggest that it offers a promising target for new treatments. Their findings in the journal Nature Cell Biology.

The stabilizing process involves two molecules: the enzyme PIPK1-alpha and its lipid messenger PIP2. Between them, they appear to regulate the function of p53.

Although p53 is one of the most commonly mutated genes in cancer, says co-lead researcher and study author Vincent L. Cryns, who is a professor of medicine, we still do not have any drugs that specifically target p53.

The p53 protein protects the genome in several ways. Inside the nucleus, it binds to DNA. When ultraviolet light, radiation, chemicals, or other agents inflict damage on DNA, p53 to repair the damage or instruct the cell to self-destruct.

If the decision is to repair the DNA, p53 triggers other genes to start this process. If the DNA is beyond repair, p53 stops the cell from dividing and sends a signal to begin apoptosis, which is a type of programmed cell death.

In this way, nonmutant p53 prevents cells with damaged DNA from dividing and potentially growing into cancerous tumors.

However, many mutant forms of p53 involve a change to a single building block, or amino acid, in the protein molecule, which prevents it from stopping the replication of cells with damaged DNA.

Using a range of cell cultures, the team behind the new study discovered that the PIPK1-alpha enzyme links up with p53 to make PIP2 when cells become stressed due to DNA damage or another cause.

PIP2 also binds strongly to p53 and causes the protein to associate with small heat shock proteins. It is this association with heat shock proteins that stabilizes mutant p53 and allows it to promote cancer.

Small heat shock proteins are really good at stabilizing proteins, Prof. Cryns explains.

In our case, their binding to mutant p53 likely facilitates its cancer-promoting actions, something we are actively exploring, he adds.

The scientists were surprised to find PIPK1-alpha and PIP2 in the nucleus of cells, as these two molecules tend to occur only in cell walls.

They also found that disrupting the PIP2 pathway prevented the accumulation of mutant p53, effectively stopping it from promoting tumor development.

The team suggests that getting rid of mutant p53 could be a powerful way to fight cancers in which it is the key driver.

This could be a promising route for discovering drugs to treat triple negative , an aggressive type which, by its nature, for drugs to target.

The researchers are already trawling for compounds that block PIPK1-alpha and could become candidate drugs for the treatment of tumors with mutant p53.

Our discovery of this new molecular complex points to several different ways to target p53 for destruction, including blocking [PIPK1-alpha] or other molecules that bind to p53.

Prof. Vincent L. Cryns

See original here:
Medical News Today: How destroying a tumor promoter could lead to new cancer treatments - Stock Daily Dish

Creating innovative tools and high-tech systems for life science researchers around the globe has turned up some fascinating new companies in the last few years; and with Europe currently housing over 35% of biotechnology companies worldwide, we can expect some enticing new discoveries to come. Sweden is certainly not lagging behind, with a buoyant environment for university researchers and students, as well as being known as one of the so-called ideal places to hatch startups, one company is quickly breaking new ground. Founded in 2012 as a spin-off from Chalmers University of Technology, Fluicell is a publicly-traded biotech company providing platforms to investigate cell behavior like never before. Using open-volume microfluidics, they wanr to revolutionize how cells are bioprinted.

Fluicell CEO Victoire Viannay

As a further development to their existing product portfolio, the company has developed a unique high-resolution bioprinting technology in both 2D and 3D called Biopixlar, capable of creating complex tissue-like structures where positioning of individual cells can be controlled from a gamepad, just like you would a videogame. Their original approach is part of a more market-oriented strategy, which brings revolutionary technology straight to the fingertips of users. To get a better sense of what the company is trying to accomplish, 3DPrint.com spoke to Victoire Viannay, Fluicells CEO since 2017.

Since microfluidics is so complex we are trying to create very easy to use platforms for our clients in the life sciences. Our original idea with the Biopixlar was: how to make the system easy to use and fun? So now you can see that we have even incorporated the gamepad, which is a way of creating an easy to use interface, said Viannay.

Biopixlar uses microfluidics which allows for better control of the material at a micro level due to the precision of a pump or microfluidic tube when it comes to directing the flow of biomaterial to actual printing execution. Having such a precise control at the microlevel, systems naturally scale up to the macrolevel and result in high-resolution prints. Additionally, the technology allows the creation of multi-material prints for bioprinting purposes, with users being able to create the materials within the printer technology itself, avoiding the need for laboratory fabrication of the material. A microfluidic chamber can control the mixing of various materials in house. Resulting in a 3D printed structure that is immediately complete without having to deal with gels or scaffolds.

We want to be as true as possible to the science, so it is important for us to protect the landscape, and for that we have a good internal team for harnessing and developing knowledge, knowing that we need to have both invention and method patents.

Fluicell currently has three products on the market, and are now looking actively for partners for the Biopixlar in both Europe and the United States. The research tools Biopen and Dynaflow, allow researchers to investigate the effects of drugs on individual cells at a unique level of detail, as part of their mission to redefine the approach to cell biology, and drug discovery by providing miniaturized instrumentation for single-cell investigations. The company holds a strong IP and patent position with four approved patents in the estate.

Since 2012, the company has moved from Chalmers and established their own laboratories just a few minutes away from the campus, in Gothenburg. There they have commercialized a product portfolio to study single cells, (primarily in the field of drug development), gone public, and launched Biopixlar. Funded by Almi Invest, a local early-stage investor, their aim now is to keep providing innovative tools redefining approaches within cell biology, bioprinting, and secondary drug screening and discovery.

When the company was created we started at Chalmers, but at some point we thought we had to become more independent from the university, so we came up with our own facilities and discovery team, people who work on tissue and disease models in house so that we can do primary research ourselves and the discovery aspects as a way of helping potential clients discover applications which could benefit their needs. We have this both as a demonstration, and also as a contract research organization (CRO) service.

With 20 employees, the company is looking to become the next Swedish bioprinting success, after another company born out of the same city as Fluicell, began selling their popular bioprinters and bioinks, thats Erik Gatenholms CELLINK, now a global big player in biotech. Actually, Viannay claims that Sweden is a great country to start a company, just behind the captivating and successful landscape in the United States.

Sweden is very supportive of new companies. The whole country is built upon innovation, proving that its people were never afraid to try out new things, so it should be the same with bioprinting. Right now there is a very good landscape to work on our projects and i really think that Sweden is ready to support more bioprinting initiatives, suggested Viannay, who is originally French and moved to Sweden after meeting her husband. She has proved to be a great match for the company because of her strong background in law. With a PhD in the field from the Universit Paris II Panthon/Assas and over more than 10 years of experience in labor laws, human resources and legal management, particularly in the field of scientific research, her incorporation came in at just the right time. Her knowledge came in handy during the companys IPO in early 2018.

Two lab experts at Fluicell using the gamepad to control the Biopixlar system

Fluicell has a good growth model based on market penetration, acquiring new geographic areas and expansion and market diversification. So it has worked very well for us while growing the company, next we would be interested in being a profitable company that is very well recognized in the world thanks to our products, which began with the Biopen, and had great traction among our customers. For our Biopixlar technology we would like to further target other areas, such as regenerative medicine, moving towards building tissues and taking it outside of pure research and development by using it to develop something that can go into regenerative or therapeutic medicine.

Join the discussion of this and other 3D printing topics at3DPrintBoard.com.

Read more:
Fluicell is Preparing to be the Next Big Player in Swedens Bioprinting Field - 3DPrint.com

Researchers have discovered the existence of tendon stem cells, which could lead to improvements in treating tendon injuries, avoiding surgery.

New research has revealed the existence of tendon stem cells which could potentially be harnessed to improve tendon recovery after an injury and perhaps even avoid surgery.

The research was led by Chen-Ming Fan at the Carnegie Institution of Science, US.

Once tendons are injured, they rarely fully recover, which can result in limited mobility and require long-term pain management or even surgery. This is due to fibrous scars, which disrupt the tissue structure of the tendon.

This image shows the Patellar tendon 30 days after an injury. The red marks newly discovered tendon stem cells that have self-renewed and are layered over green marked, original tendon cells. During regeneration, some tendon stem cells differentiate to make newly regenerated tendon cells a process during which they transition into a yellow-orange colour. The blue indicates cellular nuclei (credit: Tyler Harvey).

Fan, along with Carnegies Tyler Harvey and Sara Flamenco, revealed all of the cell types present in the Patellar tendon, found below the kneecap, including previously undefined tendon stem cells.

Because tendon injuries rarely heal completely, it was thought that tendon stem cells might not exist, said lead author Harvey. Many searched for them to no avail, but our work defined them for the first time.

The teams research showed that both fibrous scar tissue cells and tendon stem cells originate in the same space the protective cells that surround a tendon. Moreover, these tendon stem cells are part of a competitive system with precursors of fibrous scars, which explains why tendon healing is such a challenge.

It was thought that tendon stem cells might not exist but our work defined them for the first time

The team demonstrated that both tendon stem cells and scar tissue precursor cells are stimulated into action by a protein called platelet-derived growth factor-A. When tendon stem cells are altered so that they do not respond to this growth factor, then only scar tissue and no new tendon cells form after an injury.

Tendon stem cells exist, but they must outcompete the scar tissue precursors in order to prevent the formation of difficult, fibrous scars, Fan explained. Finding a therapeutic way to block the scar-forming cells and enhance the tendon stem cells could be a game-changer when it comes to treating tendon injuries.

The research was published in Nature Cell Biology.

View original post here:
Tendon stem cell discovery could lead to improvements in injury recovery - Drug Target Review