Humidity > Influenza Virus

Photo, James Gathany Photo credits: CDC

Photo, James Gathany
Photo credits: CDC

Each year in the winter influenza or “flu” season rolls around and this sickness runs rampant throughout the country. This virus, and many in general, are quite scary because of how easily they can be spread through the air ie. via coughing. Researchers of the National Institute for Occupational Safety and Health (NIOSH of the CDC) have recently linked higher humidity and transmission particle size to more inactivation of influenza (and less spread).

Influenza is an RNA virus that affects mammals and birds causing a small scale pandemic every year in the United States. Viruses tend to mutate very quickly, therefore, it is hard to find a single band-aid to blanket cure this bug. Most people can spread the virus between -1 and 6 days after showing symptoms. Airborne transmission is most likely when this virus appears since many people are in closed quarters attempting to stay warm at home with others during winter.

To test the rate at which influenza stays infectious in different humidities, researchers set up coughing and breathing test dummies in an isolated room. The sneezing dummy released about 4.5×103 virus/liter of air into the room, where 4.6% of that virus was seen to be infectious upon discharge. Of that, upwards of 77.2% of the virus retained infectivity at lower relative humidity (7-23%), while only 14.6% retained infectivity at higher relative humidity of 43%. As a grounding point, average in home humidity during winter is just above 20%, while summer humidity indoors is just below 60%.

Next, the rate of loss of infectivity was measured comparing low and moderate humidity (20% and 45%). Within 15 minutes, 52% of the virus’ infective ability was lost at 45% humidity compared to 20% humidity.

Together these two showed more virus lost its ability to infect new people/etc. at higher relative humidities.

Finally, transmission particle size was measured to see if it had bearing on influenza’s spread and infection at differing humidities. Three particle sizes were used, <1 µm, 1-4 µm, and >4 µm. At the two extremes, <1 & >4 µm, 94% infectivity was seen as lost in the first 15 minutes after coughing virus into the air. However, the 1-4 µm range of particles only showed 29% decrease in infectivity of the virus after 15 minutes. All sizes did, however, show increased loss of infectious ability with more time passed.

It seems as though humidity has great bearing on the inactivation/spreading ability of the influenza virus. At higher humidities, 45% +, the influenza virus showed very little strength in infecting new hosts. This was doubly true when the particle size they rode on was really small or really big.

The best way to minimize your chance to get influenza each year without getting a flu shot?…move to a state with really high humidity in the winter.

John D. Noti, Francoise M. Blachere, Cynthia M. McMillen, William G. Lindsley, Michael L. Kashon, Denzil R. Slaughter, Donald H. Beezhold. High Humidity Leads to Loss of Infectious Influenza Virus from Simulated Coughs. PLoS ONE, 2013.


unOC linked to Diabetes relief

GLP-1 effects on different human organs.
Photo credits: Daniel J. Drucker (author of the paper of
DOI: 10.1016/j.cmet.2006.01.004)

Researchers have perhaps found another means by which to manage type 2 diabetes. A group from 九州大学 (Kyushu  University) has shown that addition of uncarboxylated osteocalcin (unOC) stimulates glucagon-like peptide-1 (GLP-1) release and insulin secretion in mice.

GLP-1 is normally released in released into the blood in response to eating, so that insulin can be released and digested glucose can be taken into cells. In those with type-II diabetes, the insulin release pathway is impaired in some way, so insufficient insulin (or no insulin) is produced to promote glucose uptake.

UnOC has shown in previous studies to have an effect on the pancreas directly to stimulate insulin release; therefore, this study wanted to test the indirect effect of unOC on insulin secretion via the GLP-1 pathway.

Using mice, unOC’s effect on GLP-1 secretion was tested. 20 minutes after giving mice unOC orally or intraperitoneally, a maximal rise of 50 pg/mL of serum GLP-1 was seen. However, this significant rise was only seen in mice also given the DPP-IV inhibitor sitgaliptin. This needed to be co-administered because GLP-1 has a very short half life and would breakdown before the effects could be seen.

Extending from this, the insulin levels in mice given unOC were seen as raised as well. With the combination of unOC and sitagliptin, insulin rose (maximally) 0.4 ng/mL. These results were seen administering therapies orally or via intrapineal injection. Administering intravenously gave similar results with significant rises in GLP-1 and insulin sooner (as expected).

This study shows unOC may be a strong therapy for type II diabetes management if given to patients in the pure chemical form, as an additive to food, or the like.

Akiko Mizokami, Yu Yasutake, Jing Gao, Miho Matsuda, Ichiro Takahashi, Hiroshi Takeuchi, Masato Hirata. Osteocalcin Induces Release of Glucagon-Like Peptide-1 and Thereby Stimulates Insulin Secretion in Mice. PLoS ONE, 2013.


A note from me:

Lately my writings have been sluggishly drawn out and without the wherewithal to inspire (not to mention I’ve been posting suuuuuper late). Because of this, I’m taking a week break from blogging. For those that follow: I’ll see you on March 1st. For those that stumbled upon this today: Hopefully you’ll muse my articles, learn some cool stuff, and come back in a week when I pick up again.

See you all seven mornings from now 🙂

Retinal degeneration and blindness, possibly preventable

Photo by Aaron (~Sayn)

Neurodegenerative diseases such as retinitis pigmentosa (RP) currently ravage through the eyes of millions of people worldwide unhindered and untreated. Genetic disorders like these often leave patients blind with no good news from the time of diagnosis. That is likely to change soon as researchers of the Universities of Toronto, Lausanne, Lund, and The Centre of Biomedical Genetics (Amsterdam) found Bmi1 and cyclin-dependent kinases (CDKs) a potential targets to prevent blindness caused by neurodegeneration.

Retinal pigmentosa results from the mutation of around 200 loci or genes leading to the loss of rod and cone photoreceptors. Previous studies showed that neurons prepared to die (due to a neurodegenerative disease) reexpress cell cycle-related proteins like CDKs. Specifically CDK4 and CDK6 activation was seen as involved with neuronal death in these conditions.

Bmi1 to E2F1 cycle

Bmi1 is a polycomb group protein (proteins that silence genes) which inhibits CDK inhibitors. These normally lessen the activity of CDK’s, which inhibit retinoblastoma (Rb) proteins. The Rb proteins down-regulate E2F1, which causes the cell to divide past it’s prime. This little cell cycle here has been shown to be the cause of neurodegeneration in Parkinson’s disease; therefore, researchers are investigating the effects of it in ophthalmological cases.

Rb1 mice (those with induced RP) were first analyzed for their expression of cell cycle markers. Between postnatal day nine (P9) and P12, the amount of CDK4/6 significantly increased in the apoptotic cells of the Rd1 mice. However, almost no CDK4/6 was detected in the wild type mice’s retinal cells.

Because of the higher expression seen, CDK interference was run. An ex vivo (pulled part of the retina out of the mouse to study) assay was performed with retinal explants of Rd1 mice. Using roscovitine (CDK inhibitor) vs. no treatment groups, photoreceptor degeneration was measured. The roscovitine group showed 42% less apoptotic photoreceptors. This meant CDK4/6 were contributing to the loss of photoreceptors.

Consistent with this, inhibited Rb1 was found in Rb1 mice and not wild type mice. This meant E2F proteins were allowed to freely push the cell into apoptotic division. Playing with alleles and expression patterns of E2F1,2,3 in combination, researchers were able to determine ESF1 was more important than E2F2/3 in neurodegeneration. Deleting the gene resulted in slowed, but not stopped photoreceptor degeneration.

Finally, Rd1/Bmi1-/- mice were analyzed vs. Rd1 mice to see the protective effect of removing Bmi1 all together. Respectively, 40% and 90% photoreceptor loss was seen in the mice. Rd1/Bmi1-/- mice lost 50% less photoreceptors than the normal retinitis pigmentosa mice.

Pulling all together, retinal degeneration was significantly slowed and prevented leading to a protection of photoreceptors by inhibition of Bmi1, CDK4/6, and E2F1. Being diagnosed with RP may not be as hopeless any longer. Once therapies are pushed into the clinic using the targets found in this study, RP patients may shrug at their diagnosis rather than shudder.

Dusan Zencak, Karine Schouwey, Danian Chen, Per Ekström, Ellen Tanger, Rod Bremner, Maarten van Lohuizen, Yvan Arsenijevic. Retinal degeneration depends on Bmi1 function and reactivation of cell cycle proteins. Proceedings of the National Academy of Sciences of the United States of America, 2013.

Early cortical pacemaker improves Parkinson’s QoL

Photo Credits: CargoCollective

Parkinson’s disease is currently treated by dopamine agonists followed by deep brain stimulation later in the progression of the disease. However, A group of European researchers suggest deep brain stimulation via brain pacemaker earlier than currently used can improve the quality of life of patients with parkinson’s disease.

Parkinson’s is a neurodegenerative disease that affects mostly those in the upper age of life (> 50 years old), but can affect those as young as 20 if passed through genetics. As less and less dopamine is released by nerves in the brain, chemical messages become weaker and/or non-existent to the point of muscle movement becoming jerky, slow, and rigid. Unwanted shaking deemed ‘tremors’ also may develop. Current treatment is levadopa (a dopamine precursor) or dopamine agonist supplementation followed by (later in the disease) deep brain stimulation (subthalamic nucleus). This is meant to directly stimulate the nerves that are not receiving dopamine as they should.

To test if earlier stimulation than normally initiated could improve parkinson’s patients’ quality of life, a trial with 251 participants with early motor complications who either received normal medical treatment and early neurostimulation or solely normal medical treatment was conducted. The trial lasted two years with patient age averaging 52.

Using the 39 point Parkinson’s Disease Questionnaire, an improvement of 7.8 (average) points was seen in those getting the early stimulation treatment. Those not receiving the early neurostimulation showed an average decrease of 0.2 points at two years (P = 0.002).

The investigation group also showed greater improvement in motor disability (16.4 pt. difference, P <0.001), activities of daily living (6.2 pt. difference, P < 0.001), levodopa-induced motor complications (4.1 pt. difference, P < 0.001), and time without dyskinesia (1.9 hours more, P = 0.01).

Overall the group receiving the early cortical pacemaker for deep brain stimulation showed improvements in their quality of life compared to the group receiving standard medical treatment. Regarding safety however, 17.7% of those with implants had serious adverse events including nonspecific edema. Perhaps these are the risks of the surgery no matter if it comes early on or later in the progression.

This study suggests that deep brain stimulation can be used earlier in the disease progression to significantly improve the quality of life in those with parkinson’s disease.

W.M.M. Schuepbach, J. Rau, K. Knudsen, J. Volkmann, P. Krack, L. Timmermann, T.D. Hälbig, H. Hesekamp, S.M. Navarro, N. Meier, D. Falk, M. Mehdorn, S. Paschen, M. Maarouf, M.T. Barbe, G.R. Fink, A. Kupsch, D. Gruber, G.-H. Schneider, E. Seigneuret, A. Kistner, P. Chaynes, F. Ory-Magne, C. Brefel Courbon, J. Vesper, A. Schnitzler, L. Wojtecki, J.-L. Houeto, B. Bataille, D. Maltête, P. Damier, S. Raoul, F. Sixel-Doering, D. Hellwig, A. Gharabaghi, R. Krüger, M.O. Pinsker, F. Amtage, J.-M. Régis, T. Witjas, S. Thobois, P. Mertens, M. Kloss, A. Hartmann, W.H. Oertel, B. Post, H. Speelman, Y. Agid, C. Schade-Brittinger, and G. Deuschl. Neurostimulation for Parkinson’s Disease with Early Motor Complications. The New England Journal of Medicine, 2013.

Stopping Leukemia’s regeneration and preventing relapse

Photo Credits: Eric V. Grave / Photo Researchers, Inc., ISM/Phototake

Many cancers, and leukemia specifically, are difficult to manage because of the chance of relapse if even a tiny cancerous cell is left behind once treatment stops. Therefore, a hot topic in cancer research is the prevention of cancerous regrowth and metastasis. The ADAR1 enzyme has just been identified as a potential target to block relapse of chronic myeloid leukemia by a team bellwethered by researchers of the University of California, San Diego School of Medicine.

Chronic myeloid leukemia (CML) is a cancer of the white blood cells in which the blood forming tissue of the bone marrow (myeloid tissue) proliferates out of control and causes anemia, easy bruising, decreased ability to fend off infection, fever, and joint pain. To combat this, constant intake of tyrosine kinase inhibitors (TKIs) via chemotherapy is necessary. This works to starve the bulk of the tumor of its energy (ATP) and allow the cells to die. This method is usually long term because the TKIs do not always catch every cancerous cell. Relapse is imminent if treatment stops.

For this reason scientists looked to ADAR1.

This enzyme is expressed during very early development of the fetus to promote blood cell proliferation and protect hematopoietic stem cells from viral attack. Leukemic tumors sequester this enzyme for the protection of their own cells activating ADAR1 when it is not needed. This protects the cancerous white blood cells from chemotherapy and allows for enhanced proliferation of the cells.

Researchers performed a 50% knockdown of ADAR1 in vivo using a murine model to test the effects on CML progenitor cells. The self-renewal rate of the leukemia stem cells was reduced by about 30% by this ADAR1 knockdown test. This confirmed the enzyme’s role in the self renewal of the CML cells.

This puts ADAR1 on the table as a potential drug target for cancer treatment. ADAR1 knockdown in patients receiving tyrosine kinase inhibitors may be what is needed to  kill myeloid leukemia tumors, stop its regeneration, and eradicate the disease from the body for good without the need for perpetual treatment.

Combination treatments get another thumbs up from me if we see this therapy in the clinic soon.

Qingfei Jiang, Leslie A. Crews, Christian L. Barrett, Hye-Jung Chun, Angela C. Court,
Jane M. Isquith, Maria A. Zipeto, Daniel J. Goff, Mark Minden, Anil Sadarangani,
Jessica M. Rusert, Kim-Hien T. Dao, Sheldon R. Morris, Lawrence S. B. Goldstein, Marco A. Marra, Kelly A. Frazer, Catriona H. M. Jamieson. ADAR1 promotes malignant progenitor reprogramming
in chronic myeloid leukemia. PNAS, 2012.

Lower vitamin-D, higher breast cancer risk

Photo credits: Jacek Chabraszewski

No woman ever wants to hear the words “You have breast cancer,” but what if the same woman was told “Breast cancer may develop soon.” instead? Would she be as heart broken? Researchers of the University of California, San Diego (Yea, I spelled out UCSD..waddup?), SDSU, and Heartland Assays (Iowa) discovered that low detectable levels of vitamin D are closely linked with risk of developing breast cancer in young women.

The group found that women who had low serum 25-hydroxyvitamin-D (25(OH)D) three months prior to diagnosis had lower levels of vitamin-D that correlated with their risk of breast cancer. Varied levels prior to this three month period showed no significant link to risk of breast cancer.

25(OH)D is the broken down form of Vitamin D3 that physicians measure for in the blood when detecting vitamin-D concentration.

Vitamin D deficiency has an increasing prevalence in the U.S. as sunscreens with high levels of protection become more popular. Everyday use of such protection blocks UVB, which is needed to make vitamin-D in the body. For this reason, the risk of developing vitamin-D deficiency is higher in late summer/early fall/winter. However, that tangent was just a small aside.

Vitamin-D deficiency has been linked to other types of cancer such as prostate. For this reason, the current study was executed to ascertain the possible link between serum 25(OH)D levels and breast cancer risk.

600 women with breast cancer were matched to 600 control women without breast cancer for this case-control retrospective study. In analysis of 25(OH)D levels of all women, those in the lowest quintile (Q1) of concentration had a three times greater risk of developing breast cancer (Odds ratio: 3.3) than those in the highest quintile (Q5) (Odds ratio: 1.0, p trend = 0.09). However, this association was only seen when levels were low at most 90 days prior to diagnosis.

Because low concentrations showed no significant link greater than 90 days prior to diagnosis, perhaps the tumor is sequestering vitamin-D rapidly during its initial growth. The mechanism of interaction between vitamin D and breast cancer is currently unknown, but further research may reveal a causal relationship between the two. Vitamin-D may be a link to breast cancer prevention, further studies will tell.

For now, this study shows that low pre-diagnostic levels of vitamin-D are significantly associated with higher risk of breast cancer. Abnormal drops in vitamin-D levels may be usable in early detection of breast cancer.

Sharif B. Mohr, Edward D. Gorham, John E. Alcaraz, Christopher I. Kane, Caroline A. Macera, J. Kellogg Parsons, Deborah L. Wingard, Ronald Horst, Cedric F. Garland. Serum 25-hydroxyvitamin D and breast cancer in the military: a case–control study utilizing pre-diagnostic serum. Cancer Causes and Control, 2013.

Dopamine copy-cat to treat Parkinson’s mimic


A Saudi Arabian family was found to have a genetic mutation leading to symptoms similar to parkinson’s disease, but the normal tests for the disease indicated otherwise. Researchers of the University of Toronto found that using a dopamine agonist reversed this parkinsonian condition almost completely.

Of this family, eight children, with a 16 year old as the eldest, were found to have symptoms of brain dopamine-serotonin vesicular transport disease, a VMAT2 deficiency. VMAT2 is a transporter protein that escorts dopamine across the neuronal synapse to its receptor.

Dopamine, in this context, serves as a way for neurons to communicate signals to each other. This was the mechanism breaking down in these children. The children’s symptoms from not having this neurotransmitter transporter were slow walking, difficulty initiating movement, droopy eyelids, audible breathing, dystonia, and other dopamine deficiency signs.

Through analysis of single nucleotide polymorphisms (SNPs pronounces “snips”) a mutation of the SLC18A2 gene was found as the cause of the VMAT2 absence.

To treat, the children were given a compound that activates dopamine receptors, a dopamine agonist, in hopes of making up for the neurotransmitters not hitting their marks. The compound was pramipexole. In less than seven days, improvement was seen. The jerky movements, trouble walking, and accompanying symptoms were almost completely gone after treatment.

The dopamine agonist was shown to nearly reverse all symptoms of the congenital dopamine transporter disease. Dopamine has proven once again how essential it is to the living system.

Jennifer J. Rilstone, Reem A. Alkhater, Berge A. Minassian. Brain Dopamine–Serotonin Vesicular Transport Disease and Its Treatment. The New England Journal of Medicine, 2013.