How informative is the mouse for human gut microbiota research?

The pioneering studies on new animal models for gut microbiota research have greatly demonstrated their potential. However, despite the limitations of mouse models, their advantages are numerous and, furthermore, the amount of research and knowledge on mouse gastroenterology, genetics and immunology far surpasses any other model. Murine mouse models provide a range of customizable genotypes and phenotypes far superior to any other model organism. They have thus played a very important role in the emerging gut microbiota research field. Owing to their widespread use in biomedical research, these models are complemented with extensive knowledge on genetic background and deep phenotypic and functional characterization. Moreover, with well-set-up standardized mouse house facilities throughout labs in the world, conducting experiments on mouse models, even germfree ones, can be more easily achieved than with other models.

Each one of the animal models shows some similarity to the physiology of the human digestive system, thus providing useful knowledge from different angles about the gut microbiota in health and disease. It is clear that information obtained from studies using alternative models has diversified our understanding of the mammalian gut microbiota in general and has deepened our knowledge of each model separately. It is, however, important to keep in mind that models always have some degree of dissimilarity with the system modeled. Therefore, results from animal models, including the popular murine ones, are not always translatable to humans and conclusions should be made with caution. In addition, even well-controlled gut microbiota experiments using mouse models show important inter-study variations due to confounding factors in the experimental setup, such as mouse house origin, maternal effects, environmental conditions (food composition, light, stress factors, pathogen infection), genetic backgrounds and in the downstream analysis methods applied.

There have been recent efforts to standardize gut microbiota experiments, for example by establishing standardized microbiota in isobiotic mice that would be shared by institutions involved in gut microbiota research (Hooper et al., 2012). Although these efforts are still in their infancy (Würbel, 2000), they will increase result reproducibility and inter-study comparability, and allow for the healthy growth of the gut microbiota research field.

6 Most Important Health Tests That All Women Must Get Done

Do you exercise an hour daily, eat healthy, and even for a minute don’t think that you would have any underlying health condition? Well ladies, though we all pray you remain hale and hearty always, we want you to rethink this assumption. Certain health check ups are as important as your healthy diet and fitness regime. They help in early detection of diseases, and in getting you their timely cures.

Even though you might not see any symptoms on the surface, it is said that prevention is always better than cure! To help you out, we bring you here a list of few medical tests that every woman must undergo from time to time.

Cervical cancer

Ideally you should undergo a ‘Pap smear’ test first when you turn 21 or within three years of becoming sexually active. Yes, you can get this test done even if you are a virgin, there are no possible side effects. This test should be repeated after every three years. It is usually done to detect cervical cancer, which if detected early, can help in removing abnormal cells from the cervix before they become cancerous. Once you hit 30 you can wait for about five years (if you test negative thrice in a row) before going for another one unless you see any changes in your body.

 

Breast cancer

Usually doctors recommend mammograms, a low dose x-ray to screen the breasts and other tissue around it for cancerous lumps, after the age of 40. But you can start performing a self-exam even in your early 20s and 30s. Although some lumps in your breast can be nonthreatening, this test can help you trace malignant lumps too. But, it all depends on detection, so whether you do a self-test or a medical one, keep a close watch on various symptoms and changes. This way, if the lumps are cancerous they can be prevented from spreading to lymph nodes and brain or lungs.

Skin Test

Melanoma (skin cancer) is the second most life-threatening form of cancer among women, after breast cancer. This is the most common health problem for women in their late 20s or early 30s. If you have a family history of skin cancer, then do visit a dermatologist annually. But, if there has been no prior history, then you can do so semi-annually. This is also known as mole screening. A dermatologist will give a fully body examination, including the skin between your toes, behind your ears and your scalp too. They would check for any forms of suspicious looking moles, freckles and skin growths that might be cancerous in nature.

Heart Disease

Did you know that two-thirds of women who have no prior history of heart problems die of heart diseases? This is to say that even though you don’t have a family history of heart diseases, you still could be at a risk. The secret to keep a check on it is recognising early symptoms, adopting a healthy lifestyle (exercise, quit smoking and sleep well) and undergoing relevant medical tests listed below:

  • Blood pressure
  • Waist circumference
  • Cholesterol
  • Blood glucose levels checked

ECG is recommended if you are on the other side of 50, even if you have no previous history of heart problems in your family. This test helps to monitor heart abnormalities, if any.

 Bone Mineral Density Test

It is important for you to keep a check on the bone mineral density in your body. Especially, women who reach menopause are at a greater risk of having weak bones; and this would increase their risk of getting osteoporosis. You must visit your doctor and discuss if you are at an increased risk of bone deterioration, which comes with age. The most commonly recommended test is DXA or dual energy x-ray absorptiometry. It becomes a must for women above 65 years of age, as with age, bone mineral density reduces and chances of fractures increase. The DXA test will help to measure your bone marrow density and determine risk of osteoporosis.

Ovarian cancer

Most of you would not know, but ovarian cancer is the most common cause of gynaecological cancer deaths. Other than age, family history of ovarian cancer and personal history of breast cancer, endometriosis, post-menopausal hormonal therapy and infertility too are considered contributory factors that increase the risk of ovarian cancer. This risk particularly increases for women between 50 to 75 years of age. Usually during screening, doctors perform a pelvic exam to confirm if the uterus and ovaries show symptoms of cancer or not.

 

So, take an appointment with your doctor who will be in a better position to recommend– depending on your age, family history and other risk factors– the tests you must undergo. And, ladies, do not ignore your health problems or overlook them. Keep a close watch on any slight symptom and change that you see in your body.

Human microbiome research sheds light on psychiatric disease

On the search for gene variants underlying psychopathology, a recent article in the Harvard Review of Psychiatry discusses the lack of success of GWAS and GxE studies to pinpoint genetic determinants of depression. But new findings reveal that our gut microbes are critical players in determining susceptibility to depression, anxiety, and other psychiatric disorders; for example, numerous publications report that antibiotics and probiotics influence CNS disease symptoms. Ongoing studies like the crowd-sourcedAmerican Gut project aim to gather meta-genomic data on microbiome populations – opening new frontiers to study the biological basis of mental illness.

Must Read articles

Wang & Caspar. The role of microbiome in central nervous system disorders. Brain Behav Immun. 2014 May;38:1-12.
Dunn et al. Genetic determinants of depression: recent findings and future directions. Harv Rev Psychiatry 2015 Jan-Feb;23(1):1-18. 2014 May;38:1-12

New Research links childhood stress and psychiatric disease to premature cellular aging

A new study in Biological Psychiatry finds hallmarks of cellular aging in people who have experienced early life stress, depression, anxiety, or substance abuse. The relationship seen between psychopathology and shortened telomeres confirmed earlier reports, and this paper presents the first evidence of altered mitochondrial biogenesis, including increased mtDNA copy number, in people with early life stress, anxiety, or substance use disorders.

Background:Telomere shortening and alterations of mitochondrial biogenesis are involved in cellular aging. Childhood adversity is associated with telomere shortening, and several investigations have shown short telomeres in psychiatric disorders. Recent studies have examined whether mitochondria might be involved in neuropsychiatric conditions; findings are limited and no prior work has examined this in relation to stress exposure.

Methods: Two-hundred ninety healthy adults provided information on childhood parental loss and maltreatment and completed diagnostic interviews. Participants were categorized into four groups based upon the presence or absence of childhood adversity and the presence or absence of lifetime psychopathology (depressive, anxiety, and substance use disorders). Telomere length and mitochondrial DNA (mtDNA) copy number were measured from leukocyte DNA by quantitative polymerase chain reaction.

Results: Childhood adversity and lifetime psychopathology were each associated with shorter telomeres (p < .01) and higher mtDNA copy numbers (p < .001). Significantly higher mtDNA copy numbers and shorter telomeres were seen in individuals with major depression, depressive disorders, and anxiety disorders, as well as those with parental loss and childhood maltreatment. A history of substance disorders was also associated with significantly higher mtDNA copy numbers.

Conclusions: This study provides the first evidence of an alteration of mitochondrial biogenesis with early life stress and with anxiety and substance use disorders. We replicate prior work on telomere length and psychopathology and show that this effect is not secondary to medication use or comorbid medical illness. Finally, we show that early life stress and psychopathology are each associated with these markers of cellular aging.

Tyrka et al. Alterations of Mitochondrial DNA Copy Number and Telomere Length with Early Adversity and Psychopathology. Biological Psychiatry. Article in Press; Published Online: January 16, 2015. DOI: http://dx.doi.org/10.1016/j.biopsych.2014.12.025

A cure for glioma: nanoparticles deliver gene + pro-drug to brain

Biodegradable polymeric nanoparticles have the potential to be safer alternatives to viruses for gene delivery; however, their use has been limited by poor efficacy in vivo. In this work, we synthesize and characterize polymeric gene delivery nanoparticles and evaluate their efficacy for DNA delivery of herpes simplex virus type I thymidine kinase (HSVtk) combined with the prodrug ganciclovir (GCV) in a malignant glioma model. We investigated polymer structure for gene delivery in two rat glioma cell lines, 9L and F98, to discover nanoparticle formulations more effective than the leading commercial reagent Lipofectamine 2000. The lead polymer structure, poly(1,4-butanediol diacrylate-co-4-amino-1-butanol) end-modified with 1-(3-aminopropyl)-4-methylpiperazine, is a poly(β-amino ester) (PBAE) and formed nanoparticles with HSVtk DNA that were 138 ± 4 nm in size and 13 ± 1 mV in zeta potential. These nanoparticles containing HSVtk DNA showed 100% cancer cell killing in vitro in the two glioma cell lines when combined with GCV exposure, while control nanoparticles encoding GFP maintained robust cell viability. For in vivo evaluation, tumor-bearing rats were treated with PBAE/HSVtk infusion via convection-enhanced delivery (CED) in combination with systemic administration of GCV. These treated animals showed a significant benefit in survival (p = 0.0012 vs control). Moreover, following a single CED infusion, labeled PBAE nanoparticles spread completely throughout the tumor. This study highlights a nanomedicine approach that is highly promising for the treatment of malignant glioma.

Abstract Image

Mangraviti et al. Polymeric Nanoparticles for Non-Viral Gene Therapy Extend Brain Tumor Survival In Vivo. ACS Nano. 2015 Feb 24;9(2):1236-49

8 Ways to Celebrate the Ultimate Pi Day: 3.14.15

Every year on March 14, math and science educators and enthusiasts across the globe celebrate the number that represents the ratio of circumference to diameter of a circle with parties, parades, pie eating and number memorization contests.

But this year, on March 14, 2015 (that’s 3-14-15) fans of this irrational number will get more Pi than ever before…and more than they’ll ever see again in their lifetime. That’s because the next two digits in the Pi sequence after 3.14 are 1, and 5.

After this year, we won’t see this many digits of Pi on our calendar again until the year 2115. Making this year’s Pi day the ultimate Pi day.

If you’re looking for fun and engaging ways to celebrate this once in a lifetime occurrence with your students while teaching them about the mystery and excitement of this special number, look no further.

We’ve gathered some of the most useful resources from around the web where you’ll find classroom activities, fun facts, teaching tools, and entire fan clubs dedicated to honoring Pi in all its forms.

From all of us at Ward’s Science, we wish you a happy Ultimate Pi Day, from our science lab to yours!

Here are Eight Ways to Celebrate

  1. See where Pi Day got its start
    The Exploratorium in San Francisco, CA is said to have founded the first Pi Day celebration over 22 years ago, and continues the tradition today with live events, activities, and contests all day long. Visit exploratorium.edu/pi/ for a slew of Pi Day resources and schedule of events.
  2. Memorize one million digits of Pi
    Is your classroom up to the challenge? See how many digits you and your students can memorize and recite back without error – here are the first million digits to study. Think you can beat the current world record set by Chao Lu of China on November 20, 2005 for 67,890 digits in 24 hours and 4 minutes?
  3. Learn a Pi Day Rap Song
    Head to teachpi.org, a self-described one-stop Pi Day shop for teachers and number lovers, to get pumped up for your memorization competition with a Pi Day rap song set to the tune of Eminem’s “Lose Yourself”, along with more songs, Pi games, activities, and an entire community dedicated to sharing their love of Pi.
  4. Read the official National Pi Day Congressional Resolution
    On March 14, 2009, Congress voted in favor of a bill proposing Pi Day as a national holiday. See the full text of the U.S. House Resolution here.
  5. Study the History of Pi
    Learn more about the very first references to Pi in ancient history and texts, and study its chronology through the years.See the history here.
  6. Teach Pi with Storybook Characters
    Captivate student interest with medieval characters and timeless tales that present geometry concepts including Pi, shapes, circumference, and more. Shop titles like Sir Cumference and the Dragon of Pi, and more geometry books from Ward’s Science.
  7. Send a Pi Greeting Card
    There’s no better way to say “Happy Pi Day” from one math lover to another than with this selection of free and customizable online greeting cards.
  8. Don’t forget Einstein!
    Coincidentally, Albert Einstein, the father of modern physics, was born on Pi Day March 14, 1879. Learn more about the life of one of the most influential physicists and mathematicians of the 20th Century.

And if you want to go all out, consider timing your festivities for precisely 9:26 that day.

Gut Microbiota Are Related to Parkinson’s Disease

In Parkinson’s disease (PD), motor symptoms are mainly related to the loss of dopaminergic neurons in the substantia nigra. However, neuropathological changes are much more widespread, involving the autonomic nervous system, olfactory structures, lower brainstem, and cerebral cortex. Extranigral pathology is related to a broad spectrum of non-motor symptoms (NMS) that have been increasingly recognized as an important feature of PD. Gastrointestinal dysfunction, in particular constipation, affects up to 80% of PD patients and may precede the onset of motor symptoms by years. Idiopathic constipation is one of the strongest risk factors for PD. Prolonged intestinal transit time and constipation are associated with neurodegenerative changes in the enteric nervous system (ENS). These changes can be found in earliest stages of PD, sometimes years before motor symptoms appear, and therefore have been suggested as a premotor biomarker. Investigating whether high abundance of Prevotellaceae has protective effects against PD or whether low abundance is rather an indicator of disturbed mucosal barrier function will be important. Although very sensitive, low Prevotellaceae levels alone are not specific for PD. Inclusion of other bacterial families may increase accuracy, and further exploring the potential of fecal microbiome analysis as a biomarker for PD seems worthwhile. Further studies may elucidate the temporal and causal relationships between gut microbiota and PD and the mechanisms involved.

More elaborate study can be found at

Scheperjans_Microbiota_PD_2014_final_online_version.pdf