Agmatine reverses pain induced by inflammation, neuropathy, and spinal cord injury

Antagonists of glutamate receptors of the N-methyl-d-aspartate subclass (NMDAR) or inhibitors of nitric oxide synthase (NOS) prevent nervous system plasticity. Inflammatory and neuropathic pain rely on plasticity, presenting a clinical opportunity for the use of NMDAR antagonists and NOS inhibitors in chronic pain. Agmatine (AG), an endogenous neuromodulator present in brain and spinal cord, has both NMDAR antagonist and NOS inhibitor activities. We report here that AG, exogenously administered to rodents, decreased hyperalgesia accompanying inflammation, normalized the mechanical hypersensitivity (allodynia/hyperalgesia) produced by chemical or mechanical nerve injury, and reduced autotomy-like behavior and lesion size after excitotoxic spinal cord injury. AG produced these effects in the absence of antinociceptive effects in acute pain tests. Endogenous AG also was detected in rodent lumbosacral spinal cord in concentrations similar to those previously detected in brain. The evidence suggests a unique antiplasticity and neuroprotective role for AG in processes underlying persistent pain and neuronal injury.

Virus-encoded suppressor of posttranscriptional gene silencing targets a maintenance step in the silencing pathway

Certain plant viruses encode suppressors of posttranscriptional gene silencing (PTGS), an adaptive antiviral defense response that limits virus replication and spread. The tobacco etch potyvirus protein, helper component-proteinase (HC-Pro), suppresses PTGS of silenced transgenes. The effect of HC-Pro on different steps of the silencing pathway was analyzed by using both transient Agrobacterium tumefaciens-based delivery and transgenic systems. HC-Pro inactivated PTGS in plants containing a preexisting silenced β-glucuronidase (GUS) transgene. PTGS in this system was associated with both small RNA molecules (21–26 nt) corresponding to the 3′ proximal region of the transcribed GUS sequence and cytosine methylation of specific sites near the 3′ end of the GUS transgene. Introduction of HC-Pro into these plants resulted in loss of PTGS, loss of small RNAs, and partial loss of methylation. These results suggest that HC-Pro targets a PTGS maintenance (as opposed to an initiation or signaling) component at a point that affects accumulation of small RNAs and methylation of genomic DNA.

New susceptibility locus for rheumatoid arthritis suggested by a genome-wide linkage study

Rheumatoid arthritis (RA), the most common autoimmune disease, is associated in families with other autoimmune diseases, including insulin-dependent diabetes mellitus (IDDM). Its genetic component has been suggested by familial aggregation (λs = 5), twin studies, and segregation analysis. HLA, which is the only susceptibility locus known, has been estimated to account for one-third of this component. The aim of this paper was to identify new RA loci. A genome scan was performed with 114 European Caucasian RA sib pairs from 97 nuclear families. Linkage was significant only for HLA (P < 2.5⋅10−5) and nominal for 19 markers in 14 other regions (P < 0.05). Four of the loci implicated in IDDM potentially overlap with these regions: the putative IDDM6, IDDM9, IDDM13, and DXS998 loci. The first two of these candidate regions, defined in the RA genome scan by the markers D18S68-D18S61-D18S469 (18q22–23) and D3S1267 (3q13), respectively, were studied in 194 additional RA sib pairs from 164 nuclear families. Support for linkage to chromosome 3 only was extended significantly (P = 0.002). The analysis of all 261 families provided a linkage evidence of P = 0.001 and suggested an interaction between this putative RA locus and HLA. This locus could account for 16% of the genetic component of RA. Candidate genes include those coding for CD80 and CD86, molecules involved in antigen-specific T cell recognition. In conclusion, this first genome scan in RA Caucasian families revealed 14 candidate regions, one of which was supported further by the study of a second set of families.

A molecular analysis of dietary diversity for three archaic Native Americans

DNA was extracted from three fecal samples, more than 2,000 years old, from Hinds Cave, Texas. Amplification of human mtDNA sequences showed their affiliation with contemporary Native Americans, while sequences from pronghorn antelope, bighorn sheep, and cottontail rabbit allowed these animals to be identified as part of the diet of these individuals. Furthermore, amplification of chloroplast DNA sequences identified eight different plants as dietary elements. These archaic humans consumed 2–4 different animal species and 4–8 different plant species during a short time period. The success rate for retrieval of DNA from paleofeces is in strong contrast to that from skeletal remains where the success rate is generally low. Thus, human paleofecal remains represent a source of ancient DNA that significantly complements and may in some cases be superior to that from skeletal tissue.

Thrombin induces the release of the Y-box protein dbpB from mRNA: A mechanism of transcriptional activation

We have recently demonstrated that thrombin induces expression of the platelet-derived growth factor B-chain gene in endothelial cells (EC) through activation of the Y-box binding protein DNA-binding protein B (dbpB). We now present evidence that dbpB is activated by a novel mechanism: proteolytic cleavage leading to release from mRNA, nuclear translocation, and induction of thrombin-responsive genes. Cytosolic, full-length dbpB (50 kDa) was rapidly cleaved to a 30-kDa species upon thrombin stimulation of EC. This truncated, “active” dbpB exhibited nuclear localization and binding affinity for the thrombin response element sequence, which is distinct from the Y-box sequence. Oligo(dT) affinity chromatography revealed that cytosolic dbpB from control EC, but not active dbpB from thrombin-treated EC, was bound to mRNA. Latent dbpB immunoprecipitated from cytosolic extracts of control EC was activated by ribonuclease treatment. Furthermore, when EC cytosolic extracts were subjected to Nycodenz gradient centrifugation, latent dbpB fractionated with mRNA, whereas active dbpB fractionated with free proteins. The cytosolic retention domain of dbpB, which we localized to the region 247–267, was proteolytically cleaved during its activation. In contrast to full-length dbpB, truncated dbpB stimulated platelet-derived growth factor B-chain and tissue factor promoter activity by over 5-fold when transiently cotransfected with reporter constructs. These results suggest a novel mode of transcription factor activation in which an agonist causes release from mRNA of a latent transcription factor leading to its transport to the nucleus and its regulation of target gene expression.

Systemic versus cartilage-specific expression of a type II collagen-specific T-cell epitope determines the level of tolerance and susceptibility to arthritis.

Immunization of mice with rat type II collagen (CII), a cartilage-specific protein, leads to development of collagen-induced arthritis (CIA), a model for rheumatoid arthritis. To define the interaction between the immune system and cartilage, we produced two sets of transgenic mice. In the first we point mutated the mouse CII gene to express an earlier defined T-cell epitope, CII-(256-270), present in rat CII. In the second we mutated the mouse type I collagen gene to express the same T-cell epitope. The mice with mutated type I collagen showed no T-cell reactivity to rat CII and were resistant to CIA. Thus, the CII-(256-270) epitope is immunodominant and critical for development of CIA. In contrast, the mice with mutated CII had an intact B-cell response and had T cells which could produce gamma interferon, but not proliferate, in response to CII. They developed CIA, albeit with a reduced incidence. Thus, we conclude that T cells recognize CII derived from endogenous cartilage and are partially tolerized but may still be capable of mediating CIA.

Exploring the Experiences of International Student-Athletes

According to the latest National Collegiate Athletic Association (NCAA) Student Athlete Ethnicity Report, there are 17,653 non-US citizen student-athletes competing in various sports in universities across the country, yet there is very little research to understand their experiences (NCAA, 2010). Previous research has focused on recruitment practices (Bale, 1991; Pierce, Popp, & Meadows, 2011), satisfaction (Trendafilova, Kim, & Hardin, 2010), and adjustment and transitional factors (Pierce, Popp, & Meadows, 2011; Popp, Love, Kim, & Hums, 2010; Ridinger & Pastore, 2000), with a void in examining their overall experiences. Therefore, purpose of this qualitative study was to explore the experiences of international student-athletes in the United States within their athletic department and universities, as well as in the country. Participants were solicited by email, and ultimately six (n = 6) international student-athletes from a Division-I university chose to participate in the study and represented two different countries of origin, Canada and Norway. Participants completed a semi-structured interview, consisting of one broad open-ended question followed by a series of specific follow-up questions. Content analysis revealed that most participants did not consider their experiences different than domestic student-athletes. Challenges shared by most athletes included language barriers, balancing their time, and homesickness. Results also revealed the importance of interpersonal connections, especially with coaches and athletes from the international student-athlete's home country, in ensuring a positive overall experience. Implications of this study are that individuals and professionals working in campus offices associated with international student-athletes should be mindful of their unique roles within the university in order to foster positive experiences and retention.

Performed acculturation at Fort Marion : a case study of Zotom's drawings

This study examines how Native American warriors imprisoned at Fort Marion in St. Augustine, Florida, between 1875 and 1878, used their drawings to perform acculturation. I use the Kiowa warrior Paul Caryl Zotom’s drawings as a case study to demonstrate how the prisoners became methodical and formulaic in their subject matter and artistic style. Euro-American visitors to Fort Marion appreciated particular drawings over others, thereby directing subject matter. Prisoners adopted European artistic standards, thus, connected with their White audience further. Zotom’s embrace of both the subject matter and artistic style that the Euro-American audience appreciated most indicates his desire to demonstrate how successful he and his fellow prisoners were at adopting the white man’s road. I argue that much of the apparent change displayed visually in Zotom’s drawings was performed rather than true acculturation.

Blurring the lines : how Japanese American internment camps re-defined art and religion's relationship

After the Japanese bombed Pearl Harbor during WWII, anyone of Japanese descent living on the West Coast was placed in internment camps scattered throughout the country. Life inside the camps included many different activities to make life as normal as possible. This study will focus on two intersecting day-to-day activities in particular, the practice of religion within the camps, as well as the creation of art. Art created in the camps was influenced by multiple religious traditions. An analysis of artworks created by professional and amateur artists, interviews and an examination of existing scholarship demonstrates that internment camps created a unique environment for the creation of art. The values of internees reflected the seamless coexistence of Christianity, Buddhism and Shinto in internment camp art.

spotlight europe #2013/02-February 2012. Syria: from rebellion to all-out war

The situation in Syria at the beginning of 2013 could hardly be worse. Dead, wounded, refugees, a humanitarian disaster. President Assad is destroying his country and waging war against his own people. Russia and Iran back the regime. The West wants regime change without intervening militarily. The political opposition is now more united but overwhelmed with the situation at hand. The armed resistance, partially dominated by Jihadists, is difficult to size up.

spotlight europe #2013/02-Februar 2013. Syrien-vom aufstand zum krieg = Syria: from rebellion to all-out war

No abstract.

First steps toward harmonized human biomonitoring in Europe : demonstration project to perform human biomonitoring on a European scale

'Reproduced with permission from Environmental Health Perspectives'

JAABA: interactive machine learning for automatic annotation of animal behavior

We present a machine learning-based system for automatically computing interpretable, quantitative measures of animal behavior. Through our interactive system, users encode their intuition about behavior by annotating a small set of video frames. These manual labels are converted into classifiers that can automatically annotate behaviors in screen-scale data sets. Our general-purpose system can create a variety of accurate individual and social behavior classifiers for different organisms, including mice and adult and larval Drosophila.