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Genetics

Hemp Genetics CEO: Stable THC Levels Will Come With Breeding Innovation (OPINION) – Greenhouse Grower

Photo Courtesy Chuck Zimmerman/AgWired.com

Society at-large is literally bursting at the seams with interest in hemp and CBD, and the traditional, John Deere-tractor-and-a-bag-of-GMO-seed segment of the agriculture world has not been spared.

You can jump on your Google machine and pull up report after report of long-downtrodden ag regions known for legacy production of tobacco and cotton and other commoditized, low value crops turning acres over to hemp in large numbers. The Carolinas are a hotbed for this type of thing, from what were hearing anyways.

But really its happening all over the countryside, and its not going to stop anytime soon, not with the most conservative estimates pitting an acre of high-CBD hemp biomass fetching anywhere from $250 to $500 at market (after accounting for production costs, the bulk of which are to pay expensive hand labor crews to harvest the plants).

Comparably, soy farmers that have the benefit of large scale, mechanized planting and harvesting equipment were making around $160 per acre average on their crop back in 2012, whereas today they are reportedly taking a $20 an acre loss on average on production.

Thats largely the result of the market-depressing 2019 commodities Trade Wars, which has many farmers looking to hemp as a way to get themselves and the family farm out of the roller coaster international trade market and its wild fluctuations.

And lets not even mention the horrible spring planting season this past year for most commodity crops, where a ton of acres didnt even get planted and remained fallow for all of 2019.

Its all a long way of making the point that, you cant really blame a lot of these farmers for looking to hemp to change their fortunes. Farming is, after all, a business at the end of the day.

But, I digress. Lets get to the point of this article:

Long the gathering place for corn, soybean, sorghum, and other large-scale, commercial crop breeders and researchers working both for and with the multinational seed companies, this year the American Seed Trade Association (ASTA) held a Hemp and Seed Opportunities & Challenges session at the groups annual winter meeting in downtown Chicago, IL.

Those in attendance that mid-December afternoon report there was lots of interest in the session. I was mostly interested in hearing what one featured speaker, New West Genetics CEO Wendy Mosher, had to say to the group, which I found a recording of on ag media veterans Chuck and Cindy Zimmermans AgWired site (Thanks, Chuck and Cindy!).

The reason seeing Moshers name on the agenda peaked my interest: Growers weve come to know in this space have reported the genetics in hemp (and legal cannabis) as uneven performing at best, often generally unreliable for the marketed phenotypes promised and, at worst, either non-germinating or non-compliant on the 0.3% THC content requirement established in USDAs now-infamous Interim Final Rulemaking.

As CEO Mosher herself, an expert in the field, pointed out in her address to ASTA, theres just so little replicated, independent breeding data on all of these genetic varieties and crosses and hybrid strains of cannabis sativa she describes the current hemp breeding world as still in the 1950s compared to other technologically advanced ag seed segments like corn and soy.

Anyways, the reason I was interested in hearing from Mosher is I had heard of her outfit, New West Genetics, before. The name kept coming up in conversations with growers and in web searches as we did our preliminary homework on the genetic side of the hemp market.

New West is notable in the hemp genetics game and should be on any prospective hemp growers radar for many reasons, perhaps chiefly among them having the first US-bred commercial variety of hemp (NWG ELITE) to be earn classification as a certified variety by the Association of Seed Certifying Agencies (AOSCA). I would also add that theyve assembled a top-notch team of traditional and non-traditional breeding expertise, which you can check out here. Im no grower myself, but if I were, these are the type of genetics providers Id look to work with.

The hemp seed breeder CEO started off her address to ASTA with a plea for more participation from the ag seed industry, saying hemp breeding desperately needs the seed industries expertise and professionalism.

We need the seed industry to be participating so we can keep things as optimized as we can, she added.

Currently, she says, her group New West Genetics is focused on creating mechanized, stable varieties for the modern hemp market, which is pretty much exclusively for the flower and processing market, with some modest demand (for the grain).

With CBD based-products projected to be a $1.8 billion industry by 2022, and consumers becoming more aware of the high Omega 3 to low Omega 6 ratios in hemp Mosher says its the closest ratio to fish oil found in a plant-based formulation the hemp market seems like it is here to stay for the foreseeable future, and opportunity for farmers on both the flower and the grain side abound.

Mosher had one particular point that I found fascinating, mostly because it debunked one of the long-held beliefs I had come to take as fact, that the THC percentage levels of finished hemp flower were the direct result of environmental factors like heat stress, light, climate, etc.

All of the research that we have done thus far, and, again, its initial, but all of it has proven the exact opposite, Mosher says. Weve found that the genetics are controlling a little over 80% of the traits of the cannabinoids, as opposed to something like yield which is more 50-50. This is great news, because with well-bred seed we can create stable THC content across regions. And, of course, CBD (levels) as well.

Mosher also says New West has uncovered in its research trials from 2019 that some of the major commercial varieties on the market are not compliant (with the 0.3% THC requirement).

Yet, there is good news on the breeding side as well.

We want to find a balance between the two markets (flower and grain) and make mechanically harvestable varieties that are also enhanced for CBD, she says. And youre going to see enhanced CBD varieties that are diaceous next year, in 2020. Weve got them coming to market, weve just got to bulk up (the numbers).

New West is perhaps unlike some others Ive encountered in the industry in that the group is not actively lobbying for a loosening of the 0.3% THC or lower requirement in the IFR, or asking for an allowance of up to 1% THC as has become common during the USDA comment period, which was recently extended to Jan. 30.

While Mosher admits the requirement is the greatest risk for producers, from our perspective, she believes it can be managed and even conquered consistently by sourcing certified, replicated genetics.

Right now the way it (testing) works is you estimate about a 20-30 day window from maturity and you start to test for THC content, starting weekly and then as you see the THC content start to climb you start testing more frequently so you can catch it before it crosses the threshold, she explains. We see that as a result of using non-compliant genetics, but everyone in the industry sees it a little differently.

The consequences of missing that (0.3%) window is severe, because if it happens your crop cannot enter the stream of commerce, she adds. This hasnt been a huge deal up until this point because before the IFR not everybody was being tested, right? Now, they want every plot tested so its becoming more and more of a risk to not use compliant, proven genetics.

In concluding her address to ASTA, Mosher stressed the need for a mechanized harvesting solution so growers can more economically harvest the crop, as well as a need for more education on the grain side as to using hemp grain and protein in animal feed, bedding, and other sustainable applications.

Matthew J. Grassi is the Technology Editor for Greenhouse Grower and American Vegetable Grower, both Meister Media Worldwide brands. See all author stories here.

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Hemp Genetics CEO: Stable THC Levels Will Come With Breeding Innovation (OPINION) - Greenhouse Grower

Genetics

Genetic Variants Linked to Disparity Between a Persons Internal Gender and Their External Sex – Technology Networks

Some of the first biological evidence of the incongruence transgender individuals experience, because their brain indicates they are one sex and their body another, may have been found in estrogen receptor pathways in the brain of 30 transgender individuals.

Twenty-one variants in 19 genes have been found in estrogen signaling pathways of the brain critical to establishing whether the brain is masculine or feminine, saysDr. J. Graham Theisen, obstetrician/gynecologist and National Institutes of Health Womens Reproductive Health Research Scholar at theMedical College of GeorgiaatAugusta University.

Basically and perhaps counterintuitively these genes are primarily involved in estrogens critical sprinkling of the brain right before or after birth, which is essential to masculinization of the brain.

Variants investigators identified may mean that in natal males (people whose birth sex is male) this critical estrogen exposure doesnt happen or the pathway is altered so the brain does not get masculinized. In natal females, it may mean that estrogen exposure happens when it normally wouldnt, leading to masculinization.

Both could result in an incongruence between a persons internal gender and their external sex. The negative emotional experience associated with this incongruence is called gender dysphoria.

They are experiencing dysphoria because the gender they feel on the inside does not match their external sex, Theisen says. Once someone has a male or female brain, they have it and you are not going to change it. The goal of treatments like hormone therapy and surgery is to help their body more closely match where their brain already is.

It doesnt matter which sex organs you have, its whether estrogen, or androgen, which is converted to estrogen in the brain, masculinizes the brain during this critical period, saysDr. Lawrence C. Layman, chief of the MCG Section of Reproductive Endocrinology, Infertility and Genetics in theDepartment of Obstetrics and Gynecology. We have found variants in genes that are important in some of these different areas of the brain.

These brain pathways are involved in regions of the brain where the number of neurons and how connected the neurons are typically differ between males and females.

They note that while this critical period for masculinizing the brain may seem late, brain development actually continues well after birth and these key pathways and receptors already need to be established when estrogen arrives.

While its too early to definitively say the gene variants in these pathways result in the brain-body incongruence called gender dysphoria, it is interesting that they are in pathways of hormone involvement in the brain and whether it gets exposed to estrogen or not, says Layman.

He and Theisen are co-corresponding authors of the study in the journalScientific Reports.

This is the first study to lay out this framework of sex-specific development as a means to better understand gender identity, Theisen says. We are saying that looking into these pathways is the approach we are going to be taking in the years ahead to explore the genetic contribution to gender dysphoria in humans.

In fact, they already are exploring the pathways further and in a larger number of transgender individuals.

For this study, they looked at the DNA of 13 transgender males, individuals born female and transitioning

to male, and 17 transgender females, born male and transitioning to female. The extensive whole exome analysis, which sequences all the protein-coding regions of a gene (protein expression determines gene and cell function) was performed at the Yale Center for Genome Analysis. The analysis was confirmed by Sanger sequencing, another method used for detecting gene variants.

The variants they found were not present in a group of 88 control exome studies in nontransgender individuals also done at Yale. They also were rare or absent in large control DNA databases.

Reproductive endocrinologist/geneticist Layman says his experience with taking care of transgender patients for about 20 years, made him think there was a biological basis. We certainly think that for the majority of people who are experiencing gender dysphoria there is a biologic component, says Theisen. We want to understand what the genetic component of gender identity is.

While genetics have been suggested as a factor in gender dysphoria, proposed candidate genes to date have not been verified, the investigators say. Most gene or gene variants previously explored have been associated with receptors for androgens, hormones more traditionally thought to play a role in male traits but, like estrogen in males, also are present in females.

MCG investigators and their colleagues decided instead to take what little is known about sex-specific brain development that estrogen bath needed in early life to ensure masculinization of the brain to hone in on potential sites for relevant genetic variances. Extensive DNA testing initially revealed more than 120,000 variants, 21 of which were associated with these estrogen-associated pathways in the brain.

Animal studies have helped identify four areas of the brain with pathways leading to development of a male or female brain, and the investigators focused on those likely also present in humans. Laboratory studies have indicated that disrupting these brain pathways in males and females during this critical period results in cross sex behavior, like female rodents mounting and thrusting and males taking on a more traditional female posture when mating. These cross sex behaviors, which also have been documented in non-human primates, emerge during the natural sex hormone surge of puberty.

While sex specific brain development has not been thoroughly evaluated in humans, as with animals, the effects typically play out most at the time of puberty, a time when sex hormones naturally surge, when the general awareness of our sexuality really begins to awaken and when the complex state of gender dysphoria may become easier for adolescents to articulate, the investigators say. Layman notes that many individuals will report experiencing gender incongruent feelings as early as age 5.

Theisen notes that we all are full of genetic variants, including ones that give us blue eyes versus brown or green, and the majority do not cause disease rather help make us individuals. I think gender is as unique and as varied as every other trait that we have, Theisen says.

The investigators suggest modification of the current system for classifying variants that would not imply that a variant means pathogenic, or disease causing.

Last year, the World Health Organization said that genderincongruenceis not a mental health disorder and six years before thatThe Diagnostic and Statistical Manual of Mental Disorders, replaced gender identity disorder with general dysphoria.

About 0.5 to 1.4% of individuals born male and 0.2 to 0.3 % of individuals born female meet criteria for gender dysphoria. Identical twins are more likely than fraternal twins to both report gender dysphoria.

Gender affirming therapies, like hormone therapies and surgeries along with mental health evaluation and support, help these individuals better align their bodies and brains, the physician-scientists say.

Transgender individuals experience increased rates of discrimination, sexual violence and are at increased risk of depression, substance abuse and attempted suicide. About 26% report use of alcohol or other drugs to help cope; 19% have been denied medical care by a physician or other provider, some report verbal harassment in a medical environment and insurance companies do not consistently cover the cost of gender affirming hormone or surgical therapies.

A problem, the investigators say, is an overall lack of understanding of the biologic basis of gender dysphoria.

While their study of 30 individuals they now have data on more than 30 others appears to be the largest to date, the sample size prompted them to classify the published findings as preliminary.

Reference: Theisen et al. (2019).The Use of Whole Exome Sequencing in a Cohort of Transgender Individuals to Identify Rare Genetic Variants. Scientific Reports.DOI: https://doi.org/10.1038/s41598-019-53500-y.

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Genetic Variants Linked to Disparity Between a Persons Internal Gender and Their External Sex - Technology Networks

Genetics

Genetics researchers target cadmium reduction in cacao – Valley News

The 28th annual International Conference on the Status of Plant and Animal Genome Research took place Jan. 11-15, in San Diego, and the Jan. 12 cacao genomics workshop included a presentation on the attempt to reduce the cadmium content of the bean used for chocolate.

Jim Dunwell of the University of Reading in the United Kingdom addressed the situation including potential solutions in Molecular Genetic Approaches to Reducing Cadmium Accumulation in Cocoa. Dunwell said that the European Union recently implemented a cadmium limit which took effect in January 2019.

During the processing of chocolate, were trying to get rid of cadmium, Dunwell said.

Chocolate is one of the major products with high cadmium levels, and rice grown in China also has high levels of cadmium.

Its something which is not good for anybody, Dunwell said. It accumulates in your body over your life.

The source of cadmium could be natural such as volcanic soils, and the use of phosphate fertilizers, mining activity or industrial pollution can also create cadmium in the soil.

There are hot spots geographically where cacao grown in those areas produce beans that exceed the limit, Dunwell said.

The four nations with the greatest cacao production are in western Africa, where the cadmium levels in the soil are the lowest. Although those four nations account for approximately 72% of the worlds chocolate production, some of the highest-quality chocolate is from South American cacao and many of those areas have cadmium levels which exceed the European Union limit. The initial maximum levels allow for a higher cadmium concentration in darker chocolate but no more than 0.00008%; the lowest maximum level is 0.00001% and the limit for cocoa powder is 0.00006%.

Africa and Asia the range is not too bad, but if you look at the Latin American, South American region the rate is much more, Dunwell said. Its a threat to the livelihoods of particularly sensitive areas of challenged parts of South America.

Efforts have been made to track the source of cadmium in those areas.

Some of them are natural geological sources, Dunwell said.

Other sources are due to fertilizers.

Agriculture in many areas depends on the use of fertilizers, Dunwell said. Certain phosphate fertilizers in parts of the world have high levels of cadmium in them.

The cadmium level in phosphate fertilizers varies depending on the source of the phosphate. Russian phosphate has lower cadmium levels, which creates the political risk that Russia will use that advantage as a bargaining tool.

European agriculture doesnt want to be dependent on Russian fertilizers, Dunwell said.

Some of the research involves adjustment of cadmium levels in the soil.

If you can stop the cadmium from getting into the plant thats probably the best way to start, Dunwell said. Plants dont need cadmium at all.

Biochar binding of the soil is one potential solution.

There is lots of agronomic interest and agronomic activity, but so far it hasnt been proven, Dunwell said.

Adjusting the pH level of soil is complicated by the different levels throughout the world.

Theres a very narrow pH window which you have to calculate, Dunwell said.

A focus on cacao plant rejection of cadmium through the root stock or through transporter genes is part of the research.

If we can do that in the long term, we can put that into a breeding program, Dunwell said. Cadmium comes in as a kind of hitchhiker. There is no cadmium-specific transporter.

Most of the genetic work that has been done in the past uses rice as a model system.

The idea was to identify the region looking at other species, Dunwell said. Rice is the precedent in terms of gene editing.

Cadmium is believed to be transported into the plant through the Natural Resistance-Associated Macrophage Protein transcriptome. Cacao has five NRAMP genes.

Its at one gene that does one thing, Dunwell said.

A mutagenesis process in the research utilizes downregulation of Heavy Metal ATPase genes, and when the HMA gene NtHMA4 is downregulated a reduction of more than thirtyfold is achieved.

Mutagenesis has been used conventionally, Dunwell said.

The NRAMP and HMA genes from were isolated in several accessions which differ in cadmium update.

We looked at variations between the different accessions that we have, Dunwell said.

Variants of different transcriptome length were then spliced. The researchers also used the NRAMP5 gene to transport cadmium from cacao into yeast.

You can test these variants from different cacao accessions, Dunwell said.

The cadmium will have an inhibitory effect on the yeast, Dunwell said. It stops yeast growing, but it allows the uptake of cadmium into yeast.

The purpose of that was for comparison rather than for adding cadmium to yeast, and the experiment confirmed that NRAMP5 encodes a protein capable of cadmium transport.

We know theyre in the right part of the yeast cell, Dunwell said. Were also interested in cadmium isotope variation. Plants can discriminate between these isotopes.

Cadmium in nature has eight isotopes.

We should consider cadmium not as one element but as a series of elements with different isotopes, Dunwell said.

Joe Naiman can be reached by email at jnaiman@reedermedia.com.

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Genetics researchers target cadmium reduction in cacao - Valley News

Physiology

Scientists Reverse Age-Related Thinking Problems in Mice by Tinkering With Immune Cells in Their Brains – Newsweek

Scientists have reversed age-related thinking problems in mice by tinkering with their immune cells, in work they hope could one day help people with Alzheimer's disease and other forms of dementia.

Our cognitive abilities are thought to decline with age because of changes to our brains, such as a decline in grey matter, as well as the potential effects of medications and health problems

The latest study focused on a type of immune cell called group 2 innate lymphoid cells (ILC2s), which help to repair parts of the central nervous system such as the spinal cord.

In the brains of youngtwo to three-month-oldand older18 to 22-month-oldmice, the researchers found ILC2s collected in a part of the brain called the choroid plexus, a specialized brain barrier structure. This sits near the hippocampus, which is key for learning and memory.

In older mice, the team of immunologists and neuroscientists discovered five times as many ILC2s when compared with the younger mice, and that in older mice, these cells were less active.

The team then used a special molecule to reawaken the inactive ILC2s in older mice, and put the animals through a series of tests to see if their cognitive skills had improvedwhich they did.

The scientists also found a collection of ILC2s in the choroid plexus in brain autopsies of humans over than 65-years-old.

Kristen L. Zuloaga of Albany Medical College, co-author of the paper published in the Journal of Experimental Medicine, told Newsweek their study is the first to identify ILC2 cells in the choroid plexus. "We further discovered that these cells accumulate with aging. Strikingly, these aging-associated ILC2s are capable of improving brain physiology and reducing aging-associated cognitive decline," she said.

Zuloaga acknowledged the study was limited because the work was based largely on mouse models, and the team are yet to investigate the immune cells in human patients with neurodegenerative diseases.

However, the team said they were surprised at the findings.

The study's first author, Ivan Ting Hin Fung, of the department of immunology and microbial disease at Albany Medical College, told Newsweek: "Little is known about the roles immune cells play in brain physiology and function and how they influence aging-associated neurodegenerative diseases like Alzheimer's disease."

They hope the study will help with the development of new ways of combating Alzheimer's disease and other forms of dementia that are related to age. Currently, there are no treatments for Alzheimer's disease, which an estimated 5.8 million Americans are living with.

Richard Siow, director of Ageing Research at King's College London in the U.K. who did not work on the study, told Newsweek experts already knew that learning and memory decline with age, along with adaptive immunitywhich in turn makes a person more susceptible to infectious diseases.

"However, this study represents the first demonstration that immune cells can also affect cognitive function in mammals," he said. "The activity of immune cells with aging compensates for decline in adaptive immunity, leading to increased chronic inflammation but this study shows that populations of immune cells with enhanced resilience can combat aging processes."

He stressed that the study was limited because it was largely conducted in mice and "human cognitive ability and mechanisms of age-related brain diseases are very different."

"Further human based studies are necessary to validate these findings. Human tissues were collected from deceased elderly people so not representative of those with earlier stages of cognitive decline," he explained.

Siow said further research exploring ICL2 and the molecule the researchers harnessed will give new insights for the mechanisms of brain aging. This should help the development of strategies to delay the onset of cognitive decline, as well as regenerative therapies to treat brain disease associated with ageing.

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Scientists Reverse Age-Related Thinking Problems in Mice by Tinkering With Immune Cells in Their Brains - Newsweek

Physiology

Gut bacteria linked to muscle function in the colon, says mice study – NutraIngredients.com

Researchers fromCrick University in London and the University of Bern in Switzerland have identified how the contraction and relaxation of muscles in the colon, which is regulated by nerve cells, is influenced by the bacteria in our gut.

The study, published inNature,when such microbes are present, a specific gene called Ahr is activated in intestinal nerves, resulting in healthy contraction and relaxation of the colon. This relationship can be disrupted in cases of intestinal disorders, like irritable bowel syndrome (IBS).

"There is a clear link between the presence of microbes in the colon and the speed at which food moves through the system. If this relationship goes off-kilter it could cause considerable harm," says Yuuki Obata, lead author and postdoc in the Development and Homeostasis of the Nervous System Laboratory at the Crick.

The study help explain how nerve cells sense the microbes in the gut and how they could coordinate their function with other gut tissues.

"Disturbances of intestinal motility are extremely common and cause a lot of suffering in patients after surgical operations or in conditions such as irritable bowel syndrome,"explains Andrew Macpherson, Professor of Medicine and Director of Gastroenterology at the University Hospital of Bern.

"This work provides a foundation to unravel why patients that are colonised with different groups of microbes are susceptible to these intestinal problems."

Brigitta Stockinger, co-lead author and group leader in the AhRimmunity Laboratory at the Crick, adds:"By drawing on different teams at the Crick and internationally with Bern University, we've combined expertise on the gut and how environmental signals from microbiota and diet are passed to cells, to gain understanding of how gut physiology and digestion are affected by these signals."

Vassilis Pachnis, co-lead author and group leader in the Development and Homeostasis of the Nervous System Laboratory at the Crick, adds that this is the first study to demonstrate howAhR is used by intestinal nerve cells to sense the presence of microbes and regulate peristalsis therefore promoting healthy digestion.

He adds: "Inthe future, the use of microbial products that change the activity of AhR in nerve cells could help us alleviate the consequences of abnormal gut peristalsis that is often associated with gastrointestinal diseases."

Source: Nature

Obata, Y., Castao, ., Boeing, S.et al.

"Neuronal programming by microbiota regulates intestinal physiology"

https://doi.org/10.1038/s41586-020-1975-8

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Gut bacteria linked to muscle function in the colon, says mice study - NutraIngredients.com

Physiology

Designer wants to push the limits of human performance in space – AroundtheO

Olivia Echols says her dream job probably doesn't exist yet because it's so futuristic. But the graduate program in sports product design at the University of Oregon Portland is helping her prepare for it.

From 3D body scanning and computer-aided design to physiology and biomechanics, the program gave her a wide range of knowledge and experience in the world of design. Echols graduated in June 2019 and has been working on the Future Design Team at Adidas.

Echols grew up with a love for sewing and making her own clothes, which inspired her to pursue a career in designing apparel. After earning her bachelors degree in apparel design from Oregon State University in 2013, she worked at Nike in technical design and materials innovation for four years.

She decided to go into the sports product design graduate program in order to further develop her skills and shift her career back to design.

I wanted to grow my process and aesthetic and see whats possible, Echols said.

Echols said getting her masters at UO Portland has been invaluable, as shes currently in a design position helping the team at Adidas come up with concepts for items that will reach the market in five to seven years.

Its a different perspective to have gone back to school and now be working again, Echols said. It felt like a reset, and I feel like a stronger designer for it.

The program went beyond apparel and taught Echols and her classmates how to design just about anything for athletes, from footwear and transportation to gloves. They also got to work with the latest technology, including software programs, scanners, 3D printers, laser cutters, vacuum forming machines and more.

Susan Sokolowski, the program director and an associate professor of sports product design, said developing future female and minority design innovation leaders is important to the graduate program, as the sports industry has historically been focused on male leaders and products for men.

Olivia represents the next generation of design innovators. She is an amazing teammate, incredible maker and thinker, Sokolowski said. We support our students to develop their why and point of view of how they can change the industry with new products for untapped markets and users.

For Echols, those physical environments are not limited to Earth.

For her capstone project, Echols designed and produced workout apparel meant for astronauts in space, taking physiology and biomechanics into account. During her spring break last year, she even went to space camp in Houston to learn more about how to design for the way bodies change and perform in space.

The program also gave her opportunities to travel internationally. She and a classmate were selected as finalists in the Woolmark Performance Challenge, a competition for early career designers to develop creative sports products with merino wool. Echols got to travel to London for a workshop at the Woolmark offices.

It was super cool and inspiring, and theres so much going on there, not only in fashion but on the tech side, Echols said. She also got to pitch her ideas to a panel of professionals at a conference in Denver called Outdoor Retailer.

Kiersten Muenchinger, an associate professor of product design in the School of Art + Design, said the graduate program is the only one in the world thats focused on the design and innovation of sports industry products like footwear, apparel and equipment.

Portland is the international hub of design innovation in sports product, Muenchinger said. Both Nike and Columbia Sportswear developed in the Portland area and inspired many international and local brands to follow.

Muenchinger called Echols a leader.

She is comfortable innovating by conducting her own research and applying materials and manufacturing innovations in the areas she researches, Muenchinger said.

Muenchinger said she hopes Echols and the other sports product design students and alumni continue to innovate to help people perform at their peak, in whatever physical environments they encounter.

Echols is inspired to push the boundaries of human performance on Earth and in space.

Its exciting to be entering the industry right now as a woman because I think theres a renewed sense of creating products for women, and Im excited to work at companies with women in leadership roles, she said.

By Emily Lindblom, University Communications

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Designer wants to push the limits of human performance in space - AroundtheO

Physiology

The biology, function, and biomedical applications of exosomes – Science Magazine

Clinical uses of cellular communication

Exosomes are a type of extracellular vesicle that contain constituents (protein, DNA, and RNA) of the cells that secrete them. They are taken up by distant cells, where they can affect cell function and behavior. Intercellular communication through exosomes seems to be involved in the pathogenesis of various disorders, including cancer, neurodegeneration, and inflammatory diseases. In a Review, Kalluri and LeBleu discuss the biogenesis and function of exosomes in disease, highlighting areas where more research is needed. They also discuss the potential clinical applications of exosome profiling for diagnostics and exosome-mediated delivery of therapeutics to target disease cells.

Science, this issue p. eaau6977

All cells, prokaryotes and eukaryotes, release extracellular vesicles (EVs) as part of their normal physiology and during acquired abnormalities. EVs can be broadly divided into two categories, ectosomes and exosomes. Ectosomes are vesicles that pinch off the surface of the plasma membrane via outward budding, and include microvesicles, microparticles, and large vesicles in the size range of ~50 nm to 1 m in diameter. Exosomes are EVs with a size range of ~40 to 160 nm (average ~100 nm) in diameter with an endosomal origin. Sequential invagination of the plasma membrane ultimately results in the formation of multivesicular bodies, which can intersect with other intracellular vesicles and organelles, contributing to diversity in the constituents of exosomes. Depending on the cell of origin, EVs, including exosomes, can contain many constituents of a cell, including DNA, RNA, lipids, metabolites, and cytosolic and cell-surface proteins. The physiological purpose of generating exosomes remains largely unknown and needs investigation. One speculated role is that exosomes likely remove excess and/or unnecessary constituents from cells to maintain cellular homeostasis. Recent studies reviewed here also indicate a functional, targeted, mechanism-driven accumulation of specific cellular components in exosomes, suggesting that they have a role in regulating intercellular communication.

Exosomes are associated with immune responses, viral pathogenicity, pregnancy, cardiovascular diseases, central nervous systemrelated diseases, and cancer progression. Proteins, metabolites, and nucleic acids delivered by exosomes into recipient cells effectively alter their biological response. Such exosome-mediated responses can be disease promoting or restraining. The intrinsic properties of exosomes in regulating complex intracellular pathways has advanced their potential utility in the therapeutic control of many diseases, including neurodegenerative conditions and cancer. Exosomes can be engineered to deliver diverse therapeutic payloads, including short interfering RNAs, antisense oligonucleotides, chemotherapeutic agents, and immune modulators, with an ability to direct their delivery to a desired target. The lipid and protein composition of exosomes can affect their pharmacokinetic properties, and their natural constituents may play a role in enhanced bioavailability and in minimizing adverse reactions. In addition to their therapeutic potential, exosomes also have the potential to aid in disease diagnosis. They have been reported in all biological fluids, and the composition of the complex cargo of exosomes is readily accessible via sampling of biological fluids (liquid biopsies). Exosome-based liquid biopsy highlights their potential utility in diagnosis and determining the prognosis of patients with cancer and other diseases. Disease progression and response to therapy may also be ascertained by a multicomponent analysis of exosomes.

The study of exosomes is an active area of research. Ongoing technological and experimental advances are likely to yield valuable information regarding their heterogeneity and biological function(s), as well as enhance our ability to harness their therapeutic and diagnostic potential. As we develop more standardized purification and analytical procedures for the study of exosomes, this will likely reveal their functional heterogeneity. Nonetheless, functional readouts using EVs enriched for exosomes have already provided new insights into their contribution to various diseases. New genetic mouse models with the ability for de novo or induced generation of cell-specific exosomes in health and disease will likely show the causal role of exosomes in cell-to-cell communication locally and between organs. Whether exosome generation and content change with age needs investigation, and such information could offer new insights into tissue senescence, organ deterioration, and programmed or premature aging. Whether EVs and/or exosomes preceded the first emergence of the single-cell organism on the planet is tempting to speculate, and focused bioelectric and biochemical experiments in the future could reveal their cell-independent biological functions. Single-exosome identification and isolation and cryoelectron microscopy analyses have the potential to substantially improve our understanding of the basic biology of exosomes and their use in applied science and technology. Such knowledge will inform the therapeutic potential of exosomes for various diseases, including cancer and neurodegenerative diseases.

Exosomes are extracellular vesicles generated by all cells and they carry nucleic acids, proteins, lipids, and metabolites. They are mediators of near and long-distance intercellular communication in health and disease and affect various aspects of cell biology.

The study of extracellular vesicles (EVs) has the potential to identify unknown cellular and molecular mechanisms in intercellular communication and in organ homeostasis and disease. Exosomes, with an average diameter of ~100 nanometers, are a subset of EVs. The biogenesis of exosomes involves their origin in endosomes, and subsequent interactions with other intracellular vesicles and organelles generate the final content of the exosomes. Their diverse constituents include nucleic acids, proteins, lipids, amino acids, and metabolites, which can reflect their cell of origin. In various diseases, exosomes offer a window into altered cellular or tissue states, and their detection in biological fluids potentially offers a multicomponent diagnostic readout. The efficient exchange of cellular components through exosomes can inform their applied use in designing exosome-based therapeutics.

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The biology, function, and biomedical applications of exosomes - Science Magazine

Physiology

Aging Technology and Innovation to Take Center Stage at Synapse Summit 2020 – Yahoo Finance

Amir Hadanny, MD, Chief Medical Research Officer of TheSagol Center for Hyperbaric Medicine and Research, todiscuss innovative approaches to aging treatment

TEL AVIV, Israel, Feb. 6, 2020 /PRNewswire/ -- TheSagol Center for Hyperbaric Medicine and ResearchatShamir Medical Center, one of the largest hyperbaric medical centers in the world, today announced that its Chief Medical Research Officer, Amir Hadanny, MD, will participate on a panel discussion at this year's Synapse Summit, entitled, Aging Gracefully: Innovations Improving Life for Millions of Seniors.

The panel, sponsored by the University of South Florida, will discuss new approaches for treating the growing aging population. By the year 2030, all baby boomers will be older than age 65. In 2020, Floridians over the age of 60 will account for more than 25 percent of Florida's population. Dr. Hadanny will discuss the age-related mechanisms for cognitive and physical decline and present new approaches for healthy aging based on ongoing research programs at the Sagol Center. He will discuss the utilization of hyperbaric oxygen therapy and its potential for significant cognitive and physical performance improvements.

"Our technology focuses on improving the aging process through the application of hyperbaric oxygen therapy (HBOT) combined with personalized cognitive and physical training programs," said Dr. Hadanny. "I'm looking forward to discussing our latest research in the fields of aging, neuroscience, physiology and hyperbaric oxygen therapy (HBOT) for the enhancement of cognitive skills, physical performance, increased energy, and enhanced quality of life in healthy aging adults."

Dr. Hadanny is a certified neurosurgeon and hyperbaric physician. He has been researching the impact of HBOT and novel approaches to neurorehabilitation, neuroplasticity and physiology together with Professor Shai Efrati, for over a decade. He has published more than 25 research papers focusing on the effects of HBOT on cognitive and physical performance, with a specific focus on healthy aging adults. Dr. Hadanny earned his MD degree from Tel Aviv University and is finalizing his PhD in Bioinformatics and Machine Learning at Bar Ilan University.

The panel discussion will take place on Tuesday, February 11 from 10:00-10:45 am at Amalie Arena in Tampa, Florida.

Find more information here: https://synapsefl.com/summit.

About the Sagol Center for Hyperbaric Medicine and Research

The Sagol Center for Hyperbaric Medicine and Research at Shamir Medical Center (formerly Assaf Harofeh Medical Center), is a leader in advancing our understanding of the impact of hyperbaric medicine on cognitive and physical function. Serving as one of the largest Hyperbaric centers worldwide, the Sagol Center offers highly advanced large multiplace chambers, treating more than 200 patients daily. Research conducted at the Center has proven that brain rejuvenation is possible across a wide range of neurological pathologies and illnesses.

Media Contact:Nicole GrubnerFinn Partners for The Sagol Center for Hyperbaric Medicine and Research+1-929-222-8011nicole.grubner@finnpartners.com

SOURCE The Sagol Center for Hyperbaric Medicine and Research

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Aging Technology and Innovation to Take Center Stage at Synapse Summit 2020 - Yahoo Finance

Physiology

Beat the heat in poultry production – All about feed

Hot, hotter, heat stress. Climate change with its rising temperatures is increasingly becoming an intense stress factor in animal production. In the summer months, outside temperatures can quickly reach highs of over 35C this means it can get hot in the poultry house.

Modern broiler breeds have a continuously increasing growth rate and feed efficiency, which coincides with a reduced heat tolerance. Housing broilers at high ambient temperatures adversely affects performance, intestinal integrity, immune response, and meat quality. In order to avoid heat-related performance losses, it is advisable to apply some nutritional practices, such as the addition of phytogenic feed additives, alongside other management practices to alleviate the negative consequences of heat stress.

Photo: Delacon

Heat stress is an important environmental challenge for the livestock industry, especially in newly industrialising countries in the (sub)tropics. In the US, the costs of heat stress amount to more than US$160 million per year. The condition of heat stress occurs when animals are unable to lose their body heat due to high ambient temperature in combination with high relative humidity, resulting in unfavourable consequences that range from discomfort to increased mortality. The impact of heat stress depends on several factors including age and genetics, health status, nutritional status, and rearing conditions.

As long as the ambient temperature is lower than the body temperature of the birds, the heat loss from the core to the skin can be increased by radiation by varying the peripheral blood flow. However, if the ambient temperature exceeds the body temperature, the bird loses the ability to give off heat through radiation and the core body temperature increases. Unlike mammals, birds do not have sweat glands hence they are unable to sweat. Birds can lower their body temperature through panting and beak breathing.

Heat stressed animals change their behaviour and physiology to dissipate heat and maintain body temperature. Especially reduced feed intake is one of the first noticeable consequences of heat stress. Commercial broilers are particularly susceptible to heat stress, as their metabolic heat production is relatively high compared to other livestock.

Housing poultry at high ambient temperatures in combination with high humidity not only impairs production performance but also has negative effect on intestinal integrity, immune defence and meat quality. Inside the animals body, heat stress challenges the antioxidant defence systems and reduces the intestinal integrity.

Dry heat or a combination of high temperatures and high humidity causes a variety of behavioural, physiological and immunological changes in poultry. Thus, there are short and long-term negative effects on the immune system, as well as on the welfare, productivity and ultimately health of the animal. The reduction of feed intake is one of the first notable effects of heat stress in poultry. This reduction in feed intake during heat stress accounts for around 90% of the reduced weight gain. In acute stress situations, the synthesis of corticosterone, adrenaline and noradrenaline is also increased, resulting in enhanced muscle activity, increased respiration and blood glucose levels.

These increased plasma cortisol levels stimulate muscle breakdown and lipid peroxidation in muscle tissue, which is reflected in high levels of malondialdehyde (MDA) in the breast muscle of broilers, for example. In addition, the released stress hormones reduce the release of steroids and gonadotropins, resulting in reduced follicular development in hens. Moreover, studies show that the synthesis and release of vitellogenin, which is necessary for the deposition of egg yolk, is suppressed during heat stress. Also, the activity and efficiency of lymphatic organs such as bursa, spleen and thymus are impaired, resulting in impaired immune response in poultry. Furthermore, it has been shown that hyperventilation or panting to dissipate body heat leads to an increased release of CO2, which is necessary for the synthesis of calcium carbonate for egg shell formation. Heat stress has also been shown to increase blood pH and disturb the acid-base balance. This change in the acid-base balance can have negative effects on cardiac muscle activity and bone density.

Further investigations have shown that heat stress also impairs intestinal activity causing increased activity of the gastrointestinal tract, resulting in mild diarrhoea and electrolyte imbalance. Heat stress is also associated with increased lipid peroxidation in the enterocytes: chronic heat stress and associated oxidative stress lead to an overloading of the bodys anti-oxidative mechanisms, thus compromising intestinal integrity. Reactive oxygen species (ROS) also known as free radicals produced during oxidative stress, attack the intestinal mucosal cells and may lead to increased inflammation.

It has also been suggested that heat shock proteins (HSP70, a group of highly conserved protective proteins involved in cell protection and repair) play an essential role in alleviating heat stress by stimulating the activities of antioxidant enzymes and reducing oxidative damage in intestinal mucosal cells during heat stress. As a result, the intestinal epithelia may become increasingly permeable, the digestibility of nutrients decreases and the loss of water from the gut increases. This leaky gut can lead to an increased translocation of bacterial toxins, antigens and bacteria into the bloodstream, triggering the immune system and increasing stress on detoxifying organs especially the liver. As a result, animal performance suffers. But it is not only growth performance that is impacted by heat stress food safety may also be impaired. Due to increased cellular turnover and reduced intestinal integrity, pathogenic bacteria such as Salmonella enteritidis can pass the intestinal barrier and enter the body tissues. This poses a significant risk to food safety and therefore consumer health. However, it has also been suggested that heat shock proteins (HSP70, a group of highly conserved protective proteins involved in cell protection and repair) play an essential role in alleviating heat stress by stimulating the activities of antioxidant enzymes and reducing oxidative damage in intestinal mucosal cells during heat stress.

In addition to the optimisation of feed composition and structure, several (classes of) feed additives have been investigated to mitigate (the consequences of) heat stress. The efficacy of such additives is mainly directed towards their antioxidative effect. Heat stress in particular, induces oxidative processes in enterocytes, as described earlier. Increased amounts of dietary antioxidants, such as a combination of vitamins A and E, are able to reduce lipid peroxidation during heat stress. Furthermore, the addition of vitamin E improves the immune response of heat-stressed broilers.

Moreover, the non-essential amino acid glutamine has also been shown to increase the expression of HSP70 in the jejunal mucosa after acute heat stress, thus protecting it from oxidative stress, in addition to improving growth and meat quality.

Although the effects of nutrient concentration on the heat load of broilers are limited, an increased nutrient concentration of the feed, for example in the form of high-quality pellets, can also reduce the energy necessary for nutrient uptake. In addition, by limiting excess protein and optimising the amino acid profile, the metabolic energy costs associated with excess nitrogen excretion can be minimised. However, the optimal amino acid profile for heat stress conditions is not yet known.

Phytogenic feed additives (PFAs) are a valuable tool to meet current and future challenges in animal production. Many plants (e.g. thyme, oregano) and their active substances show effects that can maintain intestinal integrity and support the antioxidative capacity of the body, especially under heat stress. These mechanisms lead to the maintenance of a normal health status so that the bird can fully exploit its genetic potential.

Many aromatic plants, especially those of the Labiatae family (e.g. rosemary, thyme, oregano and sage), have been extensively studied for their antioxidant and anti-inflammatory properties. For example, thyme oil improved intestinal antioxidant status, reduced MDA content in the enterocytes and improved intestinal integrity. These activities are not only related to the phenolic compounds but also the non-phenolic compounds. These may show considerable anti-oxidative and anti-inflammatory activities by stimulating the detoxification of generated reactive oxygen species during stress. This is via either directly scavenging free radicals or indirectly by upregulating the expression of antioxidant and anti-inflammatory genes resulting in the production of antioxidant enzymes and anti-inflammatory proteins.

Besides limiting the oxidation-inflammation cascade, assorted essential oils have been shown to stimulate heat shock proteins that significantly contribute to the preservation of the intestinal barrier by inducing repair processes and improving cellular defence mechanisms. Moreover, it was shown that assorted pungent substances and essential oils have the ability to enhance the secretion of digestive juices and to stimulate nutrient transport from gut lumen to bloodstream, resulting in improved feed conversion. Additionally, assorted phytogenic ingredients support feed intake and nutrient digestibility and thus maintain high performance even during periods of heat stress.

A phytogenic feed additive (Biostrong Comfort) containing essential oils, flavonoids and pungent substances, spices and saponins has shown to improve the performance of broilers under heat stress conditions (Figure 1). A study conducted on 576 broilers (6 repetitions of 32 birds each; duration 42days) showed an increase in body weight of 5.2%, an increase in feed intake of 2.1%, and a reduction in FCR of 2.0% under cyclic heat stress conditions (8h at 32C, 12h at 26C, plus daily adjustment times; day 1-42 of age).

In terms of improving digestibility and performance even under heat stress, phytogenic feed additives have the potential to become a new generation of feed additives for innovative animal nutrition and welfare. They should be a decisive instrument to counteract heat stress and thus contribute to profitable animal production.

References available upon request

Authors: David Harrington, Special Leader Poultry and Anne Oberdorf, Technical Communications, Delacon

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Beat the heat in poultry production - All about feed

Physiology

The Best Ingredient When Growing A Startup – Thrive Global

I love the term ingredients. It sounds delicious and smooths out the rough sound of technical terms. Growing a startup needs a lot of ingredients, and if youre looking from the entrepreneurs point of view, the list of them should be generous. I mean there are so many ingredients that can set you up for success or failure that a seasoned entrepreneur becomes a complicated dish.

Since my orientation is the mindset, we wont talk about paperwork and bureaucracy. Those are must-haves, unavoidable, fixed stuff. Those are the same for each with country variations of course. But you in your own field in your country will deal with the same steps as others. That wont differentiate you much.

But your mindset will. Because it gives you all those trump cards which can set you apart as a successful company or another failed one.

Going through multiple startups myself and having one right now I must say I went through all those dark roads faced by most of the entrepreneurs. If not all. There are of course several tips and tricks about entrepreneurship and how can you have a promising start.

This time though I want to point out my number one skill Ive learned during all these years that I consider right now the number strength to have as soon as possible; even though if you are young it can be challenging. But if you integrate this into your mindset, youre up to something amazing.

Lets name this power ingredient, the saffron of entrepreneurship. Its called thick skin. Yeep. I cannot imagine anything more important for me now than this. Everything else can be handled if you have your thick skin on.

Because lets see. Any startup is like a complex puzzle, you can see the final picture, but you still need to connect the parts. Right? When you start out you have infinite things to do, handle, overcome. Going through all those initial steps where to your max frustration many are not in your power, you just need to treat them to start the right way.

Then you need to find and blend a team in case youll have employees. Then you need to set up an infrastructure, a rhythm. A complex machine that can work in good order, otherwise, youre just an adventurer, and your startup is a jungle, it can eat you up pretty soon.

Lets name some of the challenges. Shall we?

Your perfect timing for each step faces set back independent of you. Papers are not ready in time, you missed a couple of details no one told you about. Youre envisioning the final part, and yet youre struggling with small details that were never even in your mind.

The road gets longer, and you lose yourself in peculiar tasks. You do have help but, those who are meant to do their part are not involved as you do, so for them, nothing is an emergency. Its not their company. So? You need to step up your personal leadership.

Same with your initial team. Youre dreaming about finding the best people and create a positive picture of everyone you meet. Youll soon find out that finding the right people has nothing to do with CVs, talent, or skill. Its a complex mix that needs to suit you as a person, the entrepreneur.

They need to share the same values; otherwise, theyll become a pain, you know where. Staring over with new employees, learning from your mistakes is not an easy pie. You do it anyway. Some sooner, some delaying the agonizing moment.

All these hustles wear you out, and you get yourself further apart from your dream. They are exhausting. There are moments when you forget why you are doing this. Those are the real struggles of an entrepreneur at the beginning.

Not to mention, since your business is new, no one acknowledges you like a big shot. So youre not important to anyone. And so you face also attitudes, humiliation, secret smiles behind your back. People who dont share your vision doesnt understand it. Youre being ridiculed, many times by your close friends or family. Even your new employees are acting like they are all God. How embarrassing. Right?

You didnt prove anything yet, youre just starting. And seeable improvements are nowhere around in one week, one month or six months. Can you see why many businesses fail before they start?

But thats no wonder because the school doesnt teach you how to become an entrepreneur. If anything, it teaches you the opposite. How to play within the lines, how to comply, when entrepreneurship has nothing to do with any of these.

And so, the thick skin comes into play. I repeat. If you can learn this early in life, you are so much ahead of the vast majority. I can guarantee you this. How to gain think skin.

You need to become your best friend. We all need to rely on someone. But when we start a business many times is no one who can envision 100% percent of what we are up to. Or they dont believe in you, or your plan. It doesnt even matter.

What you need is to erase all those factors out of your control. As many as you can. If you cannot delete the legal steps and everything I said before, you can erase the expectations from others. Dont expect them to sustain you, to help you, to trust you. Just dont. But you also need someone to rely on the right? Yeep. Its you.

So make a commitment to become your best friend and never let yourself down. You can count on yourself. You see the big picture. Youre the most competent one for the job.

Every time when something goes in the wrong direction or someone treats you like youre nothing, turn to your best friend. You. Tell him or her, Hey, chill, they dont see what you see. Nothing that happens right now wont determine the final outcome. You can take it. Its your dream. Make it happen. Who laughs at last laughs harder? Or best revenge success. Or any other motivational quote that inspires you.

If you want my current mindset in such instances, for me any setback gives me 10 times the energy because it makes me stronger. Im like, Ok so this happened. Or, ok, so you do this now to me. Well, thanks. Now I am actually busy to prove you wrong. I dont even care to prove anyone wrong anymore, but sounds powerful. Its about, I have other things to do to lose my time in this situation.

If something is more sensitive or painful, I shake myself, breathe, slow down a bit to relax and think, than go full gear ahead.

Its about the thick skin I grew on the way. You can touch me, but it wont last. I mean, you can still make me feel in a negative way, but that effect can last max 10 minutes in the worst-case scenario. Seriously. You need to do a lot of damage to make me lose myself for more than 10 minutes.

Anyone can do it. Im not Gary Vee to not be touched at all. My education was a bit different, to say it mildly. I still care, but 1% compared to how I cared 20 years ago. And Im working on my zero percent. Ill get there, trust me.

If youre determined to get rid of something or improve in any area, you can with discipline and conscious work. As soon as you feel hit by something, the first thing is to acknowledge it, expose it to yourself, your best friend. Everything exposed loses its power. This is so true. Amazingly true.

So, expose it first consciously. Look at it, analyze it like you have a microscope. Think about it like a foreign object, something that is not you, its an infection you can treat. Ok, this sounds a bit morbid. Its an alien object which altered your optimal state.

Then comes a chit chat with your best friend. Where youre talking about the final goal, vision, missionDo you remember my friend where you wanna go? Youre on the way but still not there. So its normal to face different landscapes. This is one. Just move forward and let this place behind. Go closer to your goal. Noone and nothing can stop you without your will. Make yourself accountable for everything.

This comes with a thick skin package. Because having a thick skin means somehow you created a circumstance where this noise, set back could enter in your plan. Expose it, learn from it, and move forward.

The most powerful method to achieve anything in life, including thick skin, is to be in control of your states. Your state is designed by emotions and physiology. As soon as you can control your emotions and physiology youll control your behavior because the behavior is the ultimate visible part of whats going on inside your mind which translates in emotions and body language.

And depended on your feelings you will act. Once your thick skin is in place, your inner state will be something like chill, cool, under control, under your control. And as you can presume the physiology for such a state is a straight back, heads up or horizontal, slow deep breathing, laser vision into the future.

Another quick and super-efficient way to alter your state in the right direction is to search YouTube about your issue. In 10 minutes with the right video or videos, you should be ready to roll. Ok, if you need more no problem. Youre doing something, youre acting the right way, not letting your state to put you down into a depression.

As long as you keep a state in your life, as powerful it is. So why not shake the bad states as soon as possible and take over with the right states shaping the powerful mindset with that think skin on top which will lead you anywhere, without fail.

Ok. So I hope I gave you the inspiration to boost yourself up and start building your startup without letting anything and anyone to eat up your energy and make you give up.

Its also helpful to know that similar to my story or ideas, you are not alone. Every startup entrepreneur went through a certain kind of hell. Its unavoidable. Unless youre living in a Lala Land in which case professional help is needed.

Otherwise, its just part of the journey. And with thick skin, the journey can even become fun, because this time youre armed with the right mindset, attitude, behavior gaining total control as the final cherry on the pie.

Originally published at platinum-development.ro

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The Best Ingredient When Growing A Startup - Thrive Global