Life Sciences Commons^™

Longitudinal Transcriptomic Dysregulation In The Peripheral Blood Of Transgenic Huntington’S Disease Monkeys, Jannet Kocerha, Yuhong Liu, David Willoughby, Kumaravel Chidamparam, Joseph Benito, Kate Nelson, Yan Xu, Tim Chi, Heidi Engelhardt, Sean Moran, Shang-Hsun Yang, Shi-Hua Li, Xiao-Jiang Li, Katherine Larkin, Adam Neumann, Heather Banta, Jinjing Yang, Anthony W. S. Chan

Jannet Kocerha

Background: Huntington’s Disease (HD) is a progressive neurodegenerative disorder caused by an expansion in the polyglutamine (polyQ) region of the Huntingtin (HTT) gene. The clinical features of HD are characterized by cognitive, psychological, and motor deficits. Molecular instability, a core component in neurological disease progression, can be comprehensively evaluated through longitudinal transcriptomic profiling. Development of animal models amenable to longitudinal examination enables distinct disease-associated mechanisms to be identified.

Results: Here we report the first longitudinal study of transgenic monkeys with genomic integration of various lengths of the human HTT gene and a range of polyQ repeats. With this unique group …

Advances In Profiling Of Noncoding Rnas In Neurological Disease, Murray J. Cairns, Jannet Kocerha

Jannet Kocerha

No abstract provided.

Expression Of Fused In Sarcoma Mutations In Mice Recapitulates The Neuropathology Of Fus Proteinopathies And Provides Insight Into Disease Pathogenesis, Christophe Verbeeck, Mariely Dejesus-Hernandez, Carolina Ceballos-Diaz, Jannet Kocerha, Todd Golde, Pritam Das, Rosa Rademakers, Dennis W. Dickson, Thomas Kukar

Jannet Kocerha

Background: Mutations in the gene encoding the RNA-binding protein fused in sarcoma (FUS) can cause familial and sporadic amyotrophic lateral sclerosis (ALS) and rarely frontotemproal dementia (FTD). FUS accumulates in neuronal cytoplasmic inclusions (NCIs) in ALS patients with FUS mutations. FUS is also a major pathologic marker for a group of less common forms of frontotemporal lobar degeneration (FTLD), which includes atypical FTLD with ubiquitinated inclusions (aFTLD-U), neuronal intermediate filament inclusion disease (NIFID) and basophilic inclusion body disease (BIBD). These diseases are now called FUS proteinopathies, because they share this disease marker. It is unknown how FUS mutations cause disease …

Endurance Tests Are The Most Reliable Core Stability Related Measurements, Andy Waldhelm, Li Li

Li Li

Purpose: To determine the intra-tester reliability of clinical measurements that assess five components related to core stability: strength, endurance, flexibility, motor control, and function.
Methods: Participants were 15 college-aged males who had not suffered any orthopedic injury in the past year. Core strength measurements included eight isometric tests and a sit-up test. The four core endurance tests were the trunk flexor test, trunk extensor test, and bilateral side bridge tests. Flexibility tests included the sit-and-reach test and active range of the trunk and hip joint motions. Proprioception via passive reposition tests of the hips and a single limb balance test …

The Path To Microrna Therapeutics In Psychiatric And Neurodegenerative Disorders, Anthony W. S. Chan, Jannet Kocerha

Jannet Kocerha

The microRNA (miRNA) class of non-coding RNAs exhibit a diverse range of regulatory roles in neuronal functions that are conserved from lower vertebrates to primates. Disruption of miRNA expression has compellingly been linked to pathogenesis in neuropsychiatric and neurodegenerative disorders, such as schizophrenia, Alzheimer’s disease, and autism. The list of transcript targets governed by a single miRNA provide a molecular paradigm applicable for therapeutic intervention. Indeed, reports have shown that specific manipulation of a miRNA in cell or animal models can significantly alter phenotypes linked with neurological disease. Here, we review how a diverse range of biological systems, including Drosophila, …

Muscular Activity Characteristics Associated With Preparation For Gait Transition, Li Li, Lorna L. Ogden

Li Li

Purpose: The purpose of this study was to investigate lower extremity neuromuscular activity patterns during gait transitions with continuously changing locomotion speeds.
Methods: Muscular activities related to gait transitions (walk to run and run to walk) induced by changing treadmill speed were compared to muscular activities during walk and run at constant speeds. All transition and constant speed conditions were conducted in similar speed range. Surface electromyographic activities of gluteus maximus (GM), rectus femoris (RF), vastus lateralis (VL), biceps femoris long head (BFL), tibialis anterior (TA), gastrocnemius (GA), and soleus (SL) were collected and analyzed. The influences of speed and …

People Can Live Longer By Having More Physical Activity, Li Li

Li Li

We all know being physically active is good for you. But do we know how good? People can live up to 3 years longer, even with as little as 15 min of physical activity a day, according to last October's report by Wen and his colleagues1 at the China Medical University in Taiwan, China.
Many researchers in the field of sport and health sciences know being physically active can bring many benefits to one's life. But this message has sometimes been disseminated using a negative tone. So much so, Bortz2 of California, USA, has coined the word “inactivity” …

Altered Microrna Expression In Frontotemporal Lobar Degeneration With Tdp-43 Pathology Caused By Progranulin Mutations, Jannet Kocerha, Naomi Kouri, Matt Baker, Nicole Finch, Mariely Dejesus-Hernandez, John Gonzalez, Kumaravel Chidamparam, Keith A. Josephs, Bradley F. Boeve, Neill R. Graff-Radford, Julia Crook, Dennis W. Dickson, Rosa Rademakers

Jannet Kocerha

Frontotemporal lobar degeneration (FTLD) is a progressive neurodegenerative disorder that can be triggered through genetic or sporadic mechanisms. MicroRNAs (miRNAs) have become a major therapeutic focus as their pervasive expression and powerful regulatory roles in disease pathogenesis become increasingly apparent. Here we examine the role of miRNAs in FTLD patients with TAR DNA-binding protein 43 pathology (FTLD-TDP) caused by genetic mutations in the progranulin (PGRN) gene.

Results

Using miRNA array profiling, we identified the 20 miRNAs that showed greatest evidence (unadjusted P < 0.05) of dysregulation in frontal cortex of eight FTLD-TDP patients carrying PGRN mutations when compared to 32 FTLD-TDP patients with no apparent genetic abnormalities. Quantitative real-time PCR (qRT-PCR) analyses provided technical validation of the differential expression for 9 of the 20 miRNAs in frontal cortex. Additional qRT-PCR analyses showed that 5 out of 9 miRNAs (miR-922, miR-516a-3p, miR-571, miR-548b-5p, and miR-548c-5p) were also significantly dysregulated (unadjusted P < 0.05) in cerebellar tissue samples of PGRN mutation carriers, consistent with a systemic reduction in PGRN levels. We developed a list of gene targets for the 5 candidate miRNAs and found 18 genes dysregulated in a reported FTLD mRNA study to exhibit anti-correlated miRNA-mRNA patterns in affected cortex and cerebellar tissue. Among the targets is brain-specific angiogenesis inhibitor 3, which was recently identified as an important player in synapse biology.

Conclusions

Our study suggests that miRNAs may contribute to the pathogenesis of FTLD-TDP caused by PGRN mutations and …

Eschar-Associated Spotted Fever Rickettsiosis, Bahia, Brazil, Nanci Silva, Marina Eremeeva, Tatiana Rozental, Guilherme S. Ribeiro, Christopher D. Paddock, Eduardo Antonio G. Ramos, Alexsandra R.M. Favacho, Mitermayer G. Reis, Gregory A. Dasch,, Elba R.S. De Lemos, Albert I. Ko

Marina E. Eremeeva

In Brazil, Brazilian spotted fever was once considered the only tick-borne rickettsial disease. We report eschar-associated rickettsial disease that occurred after a tick bite. The etiologic agent is most related to Rickettsia parkeri, R. africae, and R. sibirica and probably widely distributed from São Paulo to Bahia in the Atlantic Forest.

Emergence Of A Novel Human Ehrlichia-Muris Like Organism In North America – Wisconsin And Minnesota, Bobbi S. Pritt, Lynne M. Sloan, Diep K. Hoang-Johnson, Ulrike G. Munderloh, Susan M. Paskewitz, Kristina M. Mcelroy, Jevon D. Mcfadden, Matthew J. Binnicker, David F. Neitzel, Gongping Liu, William L. Nicholson, Curtis M. Nelson, Joni J. Franson, Scott A. Martin, Scott A. Cunningham, Christopher R. Steward, Kay Bogumill, Mary E. Bjorgaard, Jeffrey P. Davis, Jennifer H. Mcquiston, David M. Warshauer, Mark P. Wilhelm, Robin Patel, Vipul A. Trivedi, Marina Eremeeva

Marina E. Eremeeva

Background: Ehrlichiosis is a clinically important, emerging zoonosis. Only Ehrlichia chaffeensis and E. ewingii have been thought to cause ehrlichiosis in humans in the United States. Patients with suspected ehrlichiosis routinely undergo testing to ensure proper diagnosis and to ascertain the cause.

Methods: We used molecular methods, culturing, and serologic testing to diagnose and ascertain the cause of cases of ehrlichiosis.

Results: On testing, four cases of ehrlichiosis in Minnesota or Wisconsin were found not to be from E. chaffeensis or E. ewingii and instead to be caused by a newly discovered ehrlichia species.

All patients had fever, …

Rocky Mountain Spotted Fever In Panama: A Cluster Description, Maribel Tribaldos, Yamitzel Zaldivar, Sergio Bermudez, Franklyn Samudio, Yaxelis Mendoza, Alexander A. Martinez, Rodrigo Villalobos, Marina Eremeeva, Christopher D. Paddock, Kathleen Page, Rebecca E. Smith, Juan Miguel Pascale

Marina E. Eremeeva

Rocky Mountain spotted fever (RMSF) is a tick-borne infection caused by Rickettsia rickettsii. We report a cluster of fatal cases of RMSF in 2007 in Panama, involving a pregnant woman and two children from the same family. The woman presented with a fever followed by respiratory distress, maculopapular rash, and an eschar at the site from which a tick had been removed. She died four days after disease onset. This is the second published report of an eschar in a patient confirmed by PCR to be infected with R. rickettsii. One month later, the children presented within days of one …

Aflatoxin B1 Albumin Adducts In Plasma And Aflatoxin M1 In Urine Are Associated With Plasma Concentrations Of Vitamins A And E, Francis A. Obuseh, Pauline E. Jolly, Yi Jiang, Faisal M. B. Shuaib, John Waterbor, William O. Ellis, Chandrika J. Piyathilake, Renee A. Desmond, Evans Afriyie-Gyawu, Timothy D. Phillips

Evans Afriyie-Gyawu

Background: Although aflatoxin exposure has been shown to be associated with micronutrient deficiency in animals, there are few investigations on the effects of aflatoxin exposure on micronutrient metabolism in humans.
Objective: To examine the relationship between aflatoxin B1 (AFB1) albumin adducts (AF-ALB) in plasma and the aflatoxin M1 (AFM1) metabolite in urine and plasma concentrations of retinol (vitamin A) and α-tocopherol (vitamin E) in Ghanaians.
Methods: A cross-sectional study of 147 adult participants was conducted. Blood and urine samples were tested for aflatoxin and vitamins A and E levels.
Results: Multivariable analysis showed that participants with high AF-ALB (≥ 0.80 …

Rnai Screen Indicates Widespread Biological Function For Human Natural Antisense Transcripts, Mohammad A. Faghihi, Jannet Kocerha, F. Modarresi, P. G. Engstrom, A. M. Chalk, S. P. Brothers, E. Koesema, G. St. Laurent, Claes Wahlestedt

Jannet Kocerha

Natural antisense transcripts represent a class of regulatory RNA molecules, which are characterized by their complementary sequence to another RNA transcript. Extensive sequencing efforts suggest that natural antisense transcripts are prevalent throughout the mammalian genome; however, their biological significance has not been well defined. We performed a loss-of-function RNA interference (RNAi) screen, which targeted 797 evolutionary conserved antisense transcripts, and found evidence for a regulatory role for a number of natural antisense transcripts. Specifically, we found that natural antisense transcripts for CCPG1 and RAPGEF3 may functionally disrupt signaling pathways and corresponding biological phenotypes, such as cell viability, either independently or …

Striatal Microrna Controls Cocaine Intake Through Creb Signalling, Jonathan A. Hollander, Heh-In Im, Antonio L. Amelio, Jannet Kocerha, Purva Bali, Qun Lu, David Willoughby, Claes Wahlestedt, Michael D. Conkright, Paul J. Kenny

Jannet Kocerha

Cocaine addiction is characterized by a gradual loss of control over drug use, but the molecular mechanisms regulating vulnerability to this process remain unclear. Here we report that microRNA-212 (miR-212) is upregulated in the dorsal striatum of rats with a history of extended access to cocaine. Striatal miR-212 decreases responsiveness to the motivational properties of cocaine by markedly amplifying the stimulatory effects of the drug on cAMP response element binding protein (CREB) signalling. This action occurs through miR-212-enhanced Raf1 activity, resulting in adenylyl cyclase sensitization and increased expression of the essential CREB co-activator TORC (transducer of regulated CREB; also known …

De Novo Truncating Fus Gene Mutation As A Cause Of Sporadic Amyotrophic Lateral Sclerosis, Mariely Dejesus-Hernandez, Jannet Kocerha, Nicole Finch, Richard Crook, Matt Baker, Pamela Desaro, Amelia Johnston, Nicola Rutherford, Aleksandra Wojtas

Jannet Kocerha

Mutations in the gene encoding fused in sarcoma (FUS) were recently identified as a novel cause of amyotrophic lateral sclerosis (ALS), emphasizing the genetic heterogeneity of ALS. We sequenced the genes encoding superoxide dismutase (SOD1), TAR DNA-binding protein 43 (TARDBP) and FUS in 99 sporadic and 17 familial ALS patients ascertained at Mayo Clinic. We identified two novel mutations in FUS in two out of 99 (2.0%) sporadic ALS patients and established the de novo occurrence of one FUS mutation. In familial patients, we identified three (17.6%) SOD1 mutations, while FUS and TARDBP mutations were excluded. The de novo FUS …

The Effect Of Neuragen Pn® On Neuropathic Pain: A Randomized, Double Blind, Placebo Controlled Clinical Trial, Li Li

Li Li

Background: A double blind, randomized, placebo controlled study to evaluate the safety and efficacy of the naturally derived topical oil, "Neuragen PN®" for the treatment of neuropathic pain.

Methods: Sixty participants with plantar cutaneous (foot sole) pain due to all cause peripheral neuropathy were recruited from the community. Each subject was randomly assigned to receive one of two treatments (Neuragen PN® or placebo) per week in a crossover design. The primary outcome measure was acute spontaneous pain level as reported on a visual analog scale.

Results: There was an overall pain reduction for both treatments from pre to post application. …

Contributors To Fatigue Resistance Of The Hamstrings And Quadriceps In Cerebral Palsy, Noelle G. Moreau, Li Li, James P. Geaghan, Diane L. Damiano

Li Li

Background: The purpose of this study was to elucidate relationships between quadriceps and hamstrings voluntary muscle fatigue and upper motor lesion impairments in cerebral palsy in order to gain a better understanding of their contribution to the observed fatigue resistance.