Physical Activity Can Affect Genetic Susceptibility To Weight Gain

By Javierlayus - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=15900701

One often hears the excuse that genes makes someone overweight (note of course that humans have not undergone some sort of rapid genetic change precipitating the obesity epidemic).  It is therefore useful to know that a study has shown that to the extent that genetic differences between people can influence weight gain, that the weight gain can be "diminished by increasing physical activity."  Of course, controlling diet is usually the greatest factor in weight control, even taking genetic differences into account.  Again, genetic differences influencing weight gain have always existed; the skyrocketing expansion of waistlines and BMIs cannot be attributed to genetics as the major factor. Excerpted from the abstract:

Whether change in physical activity over time modifies the genetic susceptibility to long-term weight gain is unknown…In the combined cohorts, 4-year BMI change per 10-risk allele increment was -0.02 kg/m2 among participants with greatest increase in physical activity and 0.24 kg/m2 among those with greatest decrease in physical activity (P[interaction]<0.001), corresponding to 0.01 kg versus 0.63 kg weight changes every 4 years (P[interaction]=0.001). Similar but marginal interactions were observed for the BMI-GRS (P[interaction]=0.045). Our data indicate that the genetic susceptibility to weight gain may be diminished by increasing physical activity.

Alzheimer's Disease-Cancer Link

First described case of Alzheimer's disease. By Unknown - Unknown, Public Domain, https://commons.wikimedia.org/w/index.php?curid=1595297

Sometimes serious diseases have interesting co-morbidities.  Having one disease may increase or decrease your risk of getting the other.  Such co-morbidities exist between some nervous system diseases and some forms of cancer.  Not surprisingly, Alzheimer’s disease and brain cancer are positively linked, which may be due to common changes in immune function affecting brain cells, while Alzheimer’s and lung cancer are negatively associated.  It seems that changes in the mitochondria – “the powerhouse of the cell” – that increase the risk of Alzheimer’s decrease the risk of lung cancer and vice versa.  Studying the mechanisms behind such correlations can lead to new therapies for these diseases.  From the article:

Alzheimer’s disease, lung cancer, and brain cancer—all devastating, all leading public health challenges—have been thought to harbor connections at the molecular level, connections that could explain curious co-morbidities. Specifically, in cases of Alzheimer’s disease, the risk of developing lung cancer is decreased, and the risk of developing glioblastoma, a kind of brain tumor, is increased…

…“A functional analysis of the sets of deregulated genes points to the immune system, up-regulated in both Alzheimer’s disease and glioblastoma, as a potential link between these two diseases,” wrote the article’s author. “Mitochondrial metabolism is regulated oppositely in Alzheimer’s disease and lung cancer, indicating that it may be involved in the inverse co-morbidity between these diseases.”

The authors of the current paper emphasized that they intended to explain previously published findings that overexpressed genes in central nervous system diseases (Alzheimer's disease, Parkinson's disease, and schizophrenia) were underexpressed in cancer (lung, colon, and prostate), and vice versa. Understanding the molecular bases of these processes, the authors suggested, could provide valuable information regarding the study of the causes of each disease and the possible design of new therapeutic strategies (drug repositioning).

Digital Movies In Bacterial DNA

By Credit: Rocky Mountain Laboratories, NIAID, NIH - NIAID: These high-resolution (300 dpi) images may be downloaded directly from this site. All the images, except specified ones from the World Health Organization (WHO), are in the public domain. For the public domain images, there is no copyright, no permission required, and no charge for their use., Public Domain, https://commons.wikimedia.org/w/index.php?curid=104228

Here is a fascinating piece of basic science, in which the gene editing CRISPR system is used to add digital black and white images and a short digital movie into the genome of a bacteria. There are implications here of using live organisms for information storage (bacteria instead of a USB drive?) and the possibilities of using the same principles for gene therapy purposes (e.g., adjusting disease-causing genes). Abstract:

DNA is an excellent medium for archiving data. Recent efforts have illustrated the potential for information storage in DNA using synthesized oligonucleotides assembled in vitro. A relatively unexplored avenue of information storage in DNA is the ability to write information into the genome of a living cell by the addition of nucleotides over time. Using the Cas1-Cas2 integrase, the CRISPR-Cas microbial immune system stores the nucleotide content of invading viruses to confer adaptive immunity. When harnessed, this system has the potential to write arbitrary information into the genome. Here we use the CRISPR-Cas system to encode the pixel values of black and white images and a short movie into the genomes of a population of living bacteria. In doing so, we push the technical limits of this information storage system and optimize strategies to minimize those limitations. We also uncover underlying principles of the CRISPR-Cas adaptation system, including sequence determinants of spacer acquisition that are relevant for understanding both the basic biology of bacterial adaptation and its technological applications. This work demonstrates that this system can capture and stably store practical amounts of real data within the genomes of populations of living cells.

Health Eating And Mortality: Confirming Common Sense

By popsique - Dieta Mediterranea, CC BY-SA 2.0, https://commons.wikimedia.org/w/index.php?curid=1380032

Hopefully, readers of this blog know by now the importance of a healthy diet - emphasizing fruits, vegetables, whole grains, and unsaturated fats. However, it is comforting to have this knowledge, this common sense, legitimized by study.  Thus, read the following abstract about reduced risk of death with healthy diet consumption over time:

BACKGROUND:

Few studies have evaluated the relationship between changes in diet quality over time and the risk of death.

METHODS:

We used Cox proportional-hazards models to calculate adjusted hazard ratios for total and cause-specific mortality among 47,994 women in the Nurses' Health Study and 25,745 men in the Health Professionals Follow-up Study from 1998 through 2010. Changes in diet quality over the preceding 12 years (1986-1998) were assessed with the use of the Alternate Healthy Eating Index-2010 score, the Alternate Mediterranean Diet score, and the Dietary Approaches to Stop Hypertension (DASH) diet score.

RESULTS:

The pooled hazard ratios for all-cause mortality among participants who had the greatest improvement in diet quality (13 to 33% improvement), as compared with those who had a relatively stable diet quality (0 to 3% improvement), in the 12-year period were the following: 0.91 (95% confidence interval [CI], 0.85 to 0.97) according to changes in the Alternate Healthy Eating Index score, 0.84 (95 CI%, 0.78 to 0.91) according to changes in the Alternate Mediterranean Diet score, and 0.89 (95% CI, 0.84 to 0.95) according to changes in the DASH score. A 20-percentile increase in diet scores (indicating an improved quality of diet) was significantly associated with a reduction in total mortality of 8 to 17% with the use of the three diet indexes and a 7 to 15% reduction in the risk of death from cardiovascular disease with the use of the Alternate Healthy Eating Index and Alternate Mediterranean Diet. Among participants who maintained a high-quality diet over a 12-year period, the risk of death from any cause was significantly lower - by 14% (95% CI, 8 to 19) when assessed with the Alternate Healthy Eating Index score, 11% (95% CI, 5 to 18) when assessed with the Alternate Mediterranean Diet score, and 9% (95% CI, 2 to 15) when assessed with the DASH score - than the risk among participants with consistently low diet scores over time.

CONCLUSIONS:

Improved diet quality over 12 years was consistently associated with a decreased risk of death. (Funded by the National Institutes of Health.).

An example of a healthy eating index can be found here.

Mid-July garden

Lettuce in a pot - the only way to keep the lettuce for myself and not feed the rabbits and the groundhog in the backyard

Have you seen flowering garlic - it looks like an alien plant species

Garlic flower up-close but not very personal

My only hydrangea is loaded with flowers

Thyme - this is the second type in my garden; I need to harvest some for a winter tea

Some of the wild flower seeds in my garden created a colorful display

My poor attempt for sustainability: I will have to fight off the zoo in my backyard to keep this squash for myself.

Profusion

These flowers came from the "wild flower seeds for shade" pack

Go to work in search of happiness

 

The picture on the left is that of healthy cells – they communicate with each other (notice how they extend to touch their neighbors), they are large and look strong.  The cells on the right picture are cancer cells of the same tissue – they are smaller, and they tend to not communicate with their neighbors. They also look angry  and isolated in their endeavor to grow faster and faster.

Source: NCI/NIH, https://visuals.nci.nih.gov/details.cfm?imageid=2306, and http://visuals.nci.nih.gov/details.cfm?imageid=2304

I have not written for some time since there is nothing good to report. At work, things are going wrong and people are either evil or dejected, or both! I have not seen even a single truly happy faculty member in years. The problem with this dark plague is that everyone else around the unhappy teachers suffers, including the students.

Next time we are unhappy, we should think about how we impact the atmosphere for everyone around us. Do we want to leave a trail of unhappiness, devastation, negativity and sadness?

I would rather bring some sunshine and inspiration in people’s lives. It is not selfish to intentionally search for happiness. Why not proclaim that the mission of our institutions is the search for happiness? Instead, our missions are usually piles of lofty and empty words that do not amount to anything.

Are you dissatisfied with your place of work? Start a movement – forge a path to an intentional happiness. Start with your connections at the job. There must be a few good people whom you trust – secure good communications with them, establish the foundational network and then expand it.

Here is the first “baby step” to changing your workplace: propose to the few good people a daily meeting of 10-15 minutes. The purpose is to touch base and give support to each other. You will be amazed how much better it is to communicate face-to-face.

My final words are these of a cancer biologist: broken and missing cell communications are a defining characteristic of cancer cells. Just look at the pictures above. Get connected today – do not fall into a malignant state of mind.

Neoantigen Immunotherapy

T cell is the blue one on the right.

By Electron Microscopy Facility at The National Cancer Institute at Frederick (NCI-Frederick) - [1], Public Domain, https://commons.wikimedia.org/w/index.php?curid=407197

The mutations that accumulate in cancer can cause the production of abnormal protein products that could in theory be recognized by the immune system to fight cancer.  This is a field of study in cancer immunotherapy, and today we would like to link to two papers that show some potential advances in this field.  The first one is here. Abstract:

Effective anti-tumour immunity in humans has been associated with the presence of T cells directed at cancer neoantigens, a class of HLA-bound peptides that arise from tumour-specific mutations. They are highly immunogenic because they are not present in normal tissues and hence bypass central thymic tolerance. Although neoantigens were long-envisioned as optimal targets for an anti-tumour immune response, their systematic discovery and evaluation only became feasible with the recent availability of massively parallel sequencing for detection of all coding mutations within tumours, and of machine learning approaches to reliably predict those mutated peptides with high-affinity binding of autologous human leukocyte antigen (HLA) molecules. We hypothesized that vaccination with neoantigens can both expand pre-existing neoantigen-specific T-cell populations and induce a broader repertoire of new T-cell specificities in cancer patients, tipping the intra-tumoural balance in favour of enhanced tumour control. Here we demonstrate the feasibility, safety, and immunogenicity of a vaccine that targets up to 20 predicted personal tumour neoantigens. Vaccine-induced polyfunctional CD4+ and CD8+ T cells targeted 58 (60%) and 15 (16%) of the 97 unique neoantigens used across patients, respectively. These T cells discriminated mutated from wild-type antigens, and in some cases directly recognized autologous tumour. Of six vaccinated patients, four had no recurrence at 25 months after vaccination, while two with recurrent disease were subsequently treated with anti-PD-1 (anti-programmed cell death-1) therapy and experienced complete tumour regression, with expansion of the repertoire of neoantigen-specific T cells. These data provide a strong rationale for further development of this approach, alone and in combination with checkpoint blockade or other immunotherapies.

And here is another paper on the same subject. Abstract:

T cells directed against mutant neo-epitopes drive cancer immunity. However, spontaneous immune recognition of mutations is inefficient. We recently introduced the concept of individualized mutanome vaccines and implemented an RNA-based poly-neo-epitope approach to mobilize immunity against a spectrum of cancer mutations. Here we report the first-in-human application of this concept in melanoma. We set up a process comprising comprehensive identification of individual mutations, computational prediction of neo-epitopes, and design and manufacturing of a vaccine unique for each patient. All patients developed T cell responses against multiple vaccine neo-epitopes at up to high single-digit percentages. Vaccine-induced T cell infiltration and neo-epitope-specific killing of autologous tumour cells were shown in post-vaccination resected metastases from two patients. The cumulative rate of metastatic events was highly significantly reduced after the start of vaccination, resulting in a sustained progression-free survival. Two of the five patients with metastatic disease experienced vaccine-related objective responses. One of these patients had a late relapse owing to outgrowth of β2-microglobulin-deficient melanoma cells as an acquired resistance mechanism. A third patient developed a complete response to vaccination in combination with PD-1 blockade therapy. Our study demonstrates that individual mutations can be exploited, thereby opening a path to personalized immunotherapy for patients with cancer.

Rebuilding The Gallbladder/Common Bile Duct

By from public domain source http://www.pueblo.gsa.gov/cic_text/health/gallstones/digstsys.gif, Public Domain, https://commons.wikimedia.org/w/index.php?curid=56151

Here is another advance in the field of organ/tissue regeneration; human cells were bioengineered in culture and used to repair the gallbladder bile duct in a mouse model.  These are exciting times for regenerative biomedicine. Abstract:

The treatment of common bile duct (CBD) disorders, such as biliary atresia or ischemic strictures, is restricted by the lack of biliary tissue from healthy donors suitable for surgical reconstruction. Here we report a new method for the isolation and propagation of human cholangiocytes from the extrahepatic biliary tree in the form of extrahepatic cholangiocyte organoids (ECOs) for regenerative medicine applications. The resulting ECOs closely resemble primary cholangiocytes in terms of their transcriptomic profile and functional properties. We explore the regenerative potential of these organoids in vivo and demonstrate that ECOs self-organize into bile duct-like tubes expressing biliary markers following transplantation under the kidney capsule of immunocompromised mice. In addition, when seeded on biodegradable scaffolds, ECOs form tissue-like structures retaining biliary characteristics. The resulting bioengineered tissue can reconstruct the gallbladder wall and repair the biliary epithelium following transplantation into a mouse model of injury. Furthermore, bioengineered artificial ducts can replace the native CBD, with no evidence of cholestasis or occlusion of the lumen. In conclusion, ECOs can successfully reconstruct the biliary tree, providing proof of principle for organ regeneration using human primary cholangiocytes expanded in vitro.

Why Not Adjunct Administrators?

At left, is that an academic administrator? 

By http://phil.cdc.gov/PHIL_Images/20031208/87d4bff74e41427cb278526bd9cbe76a/5260_lores.jpg, Public Domain, https://commons.wikimedia.org/w/index.php?curid=776561

Following up on this and also on this, I ask: why not have adjunct administrators?  Well, other people have already written about this.  See this summary:

Rather than fill universities with adjunct instructors, why not replace them with adjunct administrators?

Most of the growth of university costs comes from administrative bloat. Non-faculty staff has grown at more than twice the rate of instructors – you know, the people who are the ostensible reason a university exists. As tenured professors retire, administrators kill those tenure lines and replace them permanently with part timers. Administrators do this so they can gorge on a higher salary while demanding more from the refugee ration-packet salary of academics. Think I am not being generous? Some administrators earn $300,000 a year to fundraise for new football stadium skyboxes. Vice Presidents at the University of Maryland saw their salaries increase by 50 percent between 1998 and 2003, as faculty positions were slashed. All the while adjuncts try to get by with the help of Medicaid or food stamps.

Worse of all, administrators isolate themselves from students behind security doors but meddle more and more in faculty and student lives.

Indeed.  A problem is that hiring and “cost-cutting” decisions are made by administrators themselves. Guess whose positions they have an incentive to protect?

Rent-seeking behavior, anyone?

The same principles apply as to why we have outsourcing and H-1B job replacement for workers, but not for management (or lawyers, economists, politicians, mass media, etc.). Economically, it's always easier for administration (of all types) to focus on the mote in the worker's eye than the beam in their own.

Dismantling academia, part II: the parasites

This post is a sequel of my research on how the U.S. academia is being demolished.

As we have already established, according to major school administrators around the country (including the former president of Stanford University), the major reason for the high college tuition is the overblown salaries of the faculty.

The solution? Remove faculty from the equation – or at least keep them at the bare minimum. Instead of full time faculty with benefits, the higher education institutions should employ adjunct faculty and teaching assistants without benefits.

Whereas these declarations have been made public only recently, the process of switching to adjuncts has been undergoing for decades. The adjunct faculty are now the majority of the higher education instructors in the U.S.

More than 50% of all faculty appointments are part-time.  According the Association of American Association of University Professors: 
 
“This includes positions that may be classified by the institution as adjuncts, part-time lecturers, or graduate assistantships.

Many faculty in so-called “part-time” positions actually teach the equivalent of a full-time course load.

Over one-fifth of part-time appointments are held by graduate student employees, whose chances of obtaining tenure-track positions in the future are increasingly uncertain.

To support themselves, part-time faculty often commute between institutions and prepare courses on a grueling timetable, making enormous sacrifices to maintain interaction with their students.
 
Since faculty classified as part-time are typically paid by the course, without benefits, many college teachers lack access to health insurance and retirement plans” 
 
According to online records, an adjunct professor is paid $3,500 for an entire course. So, why would anyone take on this type of work that is so exacting, requires so much effort and investment of time? 

I just watched a documentary about poverty in America, and one of the featured guys was explaining that as a head busboy he was making approximately $11,000-12,000/year. This income probably does not include tips distributed among the service staff. So, instead of teaching four huge courses in nine months, why not work as a busboy or barista in Starbucks?

It might be that in some places around the country, adjuncts are paid a bit higher for a full load of teaching. Thus, according to this website, the median pay for adjunct professors is $30,000/year; whereas the average salary for all secondary / higher education lecturers / associate / assistant professors is $65,140. Obviously, our administration can save good amount of money by switching to adjunct teachers.

Are there any consequences?

According to online research, this trend damages student learning (the adjuncts do not even have offices in the colleges), faculty governance, and academic freedom (the protection of tenure is gone, so if you are not tenured, and even worse - you are an adjunct, watch your mouth and keep your opinions to yourself).

Meanwhile, no one has tried to compare the salaries of the adjunct educators to these of the administrators. But here they are, I could not find one administrator position that is paid less than $45,000. Most salaries are six figures. 

Most of the administrator positions in the past were created to help faculty fulfill their functions as educators. Today, faculty serve the administrators.  And the administrators are self-propagating.  By the way, these are the defining characteristics of any parasite, look it up in a biology textbook:

"an organism that lives in or on another organism (its host) and benefits by deriving nutrients at the host's expense"