Anti-Rods/Rings: A Human Model of Drug-Induced Autoantibody Generation

In recent years, autoantibodies targeting subcellular structures described as the rods and rings pattern in HEp-2 ANA have been presented as a unique case of autoantibody generation. These rod and ring structures (RR) are at least partially composed of inosine monophosphate dehydrogenase type 2 (IMPDH2), and their formation can be induced in vitro by several small-molecule inhibitors, including some IMPDH2 inhibitors. Autoantibodies targeting these relatively unknown structures have been almost exclusively observed in hepatitis C virus (HCV) patients who have undergone treatment with pegylated interferon-alpha/ribavirin (IFN/RBV) combination therapy. To date, anti-RR antibodies have not been found in treatment-naive HCV patients or in patients from any other disease groups, with few reported exceptions. Here, we describe recent advances in characterizing the RR structure and the strong association between anti-RR antibody response and HCV patients treated with IFN/RBV, detailing why anti-RR can be considered a human model of drug-induced autoantibody generation

IMP dehydrogenase rod/ring structures in acral melanomas

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Acral lentiginous melanoma (ALM) is a rare subtype of melanoma with aggressive behavior. IMPDH enzyme, involved in de novo GTP biosynthesis, has been reported to assemble into large filamentary structures called rods/rings (RR) or cytoophidium (cellular snakes). RR assembly induces a hyperactive state in IMPDH, usually to supply a high demand for GTP nucleotides, such as in highly proliferative cells. We investigate whether aggressive melanoma tumor cells present IMPDH-based RR structures. Forty-five ALM paraffin-embedded tissue samples and 59 melanocytic nevi were probed with anti-IMPDH2 antibody. Both the rod- and ring-shaped RR could be observed, with higher frequency in ALM. ROC curve analyzing the proportions of RR-positive cells in ALM versus nevi yielded a 0.88 AUC. Using the cutoff of 5.5% RR-positive cells, there was a sensitivity of 80% and specificity of 85% for ALM diagnosis. In ALM, 36 (80%) showed RR frequency above the cutoff, being classified as RR-positive, compared with only 9 (15%) of the nevi (p 4.0mm, compared with only 29% in the RR-low/negative (p = .039). We propose that screening for RR structures in biopsy specimens may be a valuable tool helping differentiate ALM from nevi and accessing tumor malignancy

Nonlinear Dynamics of the Perceived Pitch of Complex Sounds

We apply results from nonlinear dynamics to an old problem in acoustical physics: the mechanism of the perception of the pitch of sounds, especially the sounds known as complex tones that are important for music and speech intelligibility

Effects of Photomixotrophic Conditions on Plants of Eucalyptus Urograndis Propagated in Temporary Immersion Bioreactors

Eucalyptus is one of the crop, which has been investigated with commercial purposes in the world. There are more than 500 species, being the Eucalyptus urograndis one of the most important, because of its intensive use in the production of wood pulp to make papers. The multiplication by means of temporary immersion bioreactors (TIB) is among the present techniques to obtain higher productions of the pulp to satisfy the demands of the market. The effects of the photomixotrophic crop were studies during the elongation of the propagation of shoots in the TIB in order to increase the quality of them. This process consisted of the use of 30 g L-1 combined with two concentration of CO2 (350 and 1200 µmol mol) and two flows of photosynthetic photon flux (PPF= 80 and 250 µmol m-2s-1). The higher percentage of suitable plants were found with the treatment of high PPF (250 µmol m-2 s-1) and 1 200 µmol mol of CO2. The photosynthetic capacity of propagated shoots was of 64% of the adult plants. Also was observed that photomixotrophic conditions reduced the stressed environment that is imposed by the growing in vitro. The catabolic activity in the enzymes of the metabolism of carbon was also reduced, increasing the activity of the Sucrose Phosphate Synthase

The global prevalence of IBS in adults remains elusive due to the heterogeneity of studies: a Rome Foundation working team literature review

Objectives The global prevalence of IBS is difficult to ascertain, particularly in light of the heterogeneity of published epidemiological studies. The aim was to conduct a literature review, by experts from around the world, of community-based studies on IBS prevalence. Design Searches were conducted using predetermined search terms and eligibility criteria, including papers in all languages. Pooled prevalence rates were calculated by combining separate population survey prevalence estimates to generate an overall combined meta-prevalence estimate. The heterogeneity of studies was assessed. Results 1451 papers were returned and 83, including 288 103 participants in 41 countries, met inclusion criteria. The mean prevalence among individual countries ranged from 1.1% in France and Iran to 35.5% in Mexico. There was significant variance in pooled regional prevalence rates ranging from 17.5% (95% CI 16.9% to 18.2%) in Latin America, 9.6% (9.5% to 9.8%) in Asia, 7.1% (8.0% to 8.3%) in North America/Europe/Australia/New Zealand, to 5.8% (5.6% to 6.0%) in the Middle East and Africa. There was a significant degree of heterogeneity with the percentage of residual variation due to heterogeneity at 99.9%. Conclusions The main finding is the extent of methodological variance in the studies reviewed and the degree of heterogeneity among them. Based on this, we concluded that publication of a single pooled global prevalence rate, which is easily calculated, would not be appropriate or contributory. Furthermore, we believe that future studies should focus on regional and cross-cultural differences that are more likely to shed light on pathophysiology

Does Type of Tumor Histology Impact Survival among Patients with Stage IIIB/IV Non-Small Cell Lung Cancer Treated with First-Line Doublet Chemotherapy?

Chemotherapy regimens may have differential efficacy by histology in nonsmall cell lung cancer (NSCLC). We examined the impact of histology on survival of patients (N = 2,644) with stage IIIB/IV NSCLC who received first-line cisplatin/carboplatin plus gemcitabine (C/C+G) and cisplatin/carboplatin plus a taxane (C/C+T) identified retrospectively in the SEER cancer registry (1997–2002). Patients with squamous and nonsquamous cell carcinoma survived 8.5 months and 8.1 months, respectively (P = .018). No statistically significant difference was observed in survival between C/C+G and C/C+T in both histologies. Adjusting for clinical and demographic characteristics, the effect of treatment regimen on survival did not differ by histology (P for interaction = .257). There was no statistically significant difference in hazard of death by histology in both groups. These results contrast the predictive role of histology and improved survival outcomes observed for cisplatin-pemetrexed regimens in advanced nonsquamous NSCLC

The September 2004 stench off the southern Malabar coast - A consequence of holococcolithophore bloom

During the third week of September 2004, particularly on 16th and 17th, an unusual and strong stench was reported from the coast at Kollam and Vizhinjam in Kerala (India). Local dailies reported that over 200 children, mostly below 15 years, complained of nausea, chest pain and short periods of breathlessness because of the stench. Many were hospitalized, but were discharged within a couple of hours. A press report stated that the stench was due to dead fish scattered on the beaches and in the water. The report linked the fish death to oxygen depletion and choking of fish gills. Both were reported to be possibly due to proliferation and eventual putrefaction of a fish-toxic alga Cochlodinium polykreikoides. Information was put up on the web that the bloom was caused by Karenia brevis, a toxic dinoflagellate. It was reported that the stench could be felt up to 5 km inland from the coast. On 20 September 2004, the Government of Kerala requested the National Institute of Oceanography (NIO), Goa to determine the cause of the phenomenon. In response, a team from NIO collected near-shore samples of water on 23 and 26 September off Vizhinjam, Shanghumugham and Kollam. During 3-7 October 2004, RV Sagar Sukti, a coastal research vessel of NIO, was used to collect samples in the waters offshore of Vizhinjam, Veli, Kollam in the depth zones of 20-50 m. The water samples collected on 23 and 26 September from the near-shore spots were analysed for various chemical (dissolved oxygen, hydrogen sulphide, nutrients, and salinity) and biological (microbiological, phytoplankton counting and identification) variables. Data from sea-level records at Cochin Port were also examined to learn about the possible evolution of physical conditions before and after the episode described above. In this preliminary report inferences based on analysis of the data is presented