Vitamin D Receptor and Jak-STAT Signaling Crosstalk Results in Calcitriol-Mediated Increase of Hepatocellular Response to IFN-α.

Recent clinical research suggests a role for vitamin D in the response to IFN-α-based therapy of chronic hepatitis C. Therefore, we aimed to explore the underlying mechanisms in vitro. Huh-7.5 cells harboring subgenomic hepatitis C virus (HCV) replicons or infected with cell culture-derived HCV were exposed to bioactive 1,25-dihydroxyvitamin D3 (calcitriol) with or without IFN-α. In these experiments, calcitriol alone had no effect on the HCV life cycle. However, calcitriol enhanced the inhibitory effect of IFN-α on HCV replication. This effect was based on a calcitriol-mediated increase of IFN-α-induced gene expression. Further mechanistic studies revealed a constitutive inhibitory interaction between the inactive vitamin D receptor (VDR) and Stat1, which was released upon stimulation with calcitriol and IFN-α. As a consequence, IFN-α-induced binding of phosphorylated Stat1 to its DNA target sequences was enhanced by calcitriol. Importantly, and in line with these observations, silencing of the VDR resulted in an enhanced hepatocellular response to IFN-α. Our findings identify the VDR as a novel suppressor of IFN-α-induced signaling through the Jak-STAT pathway.

Developing an Effective Construction Training Program for Hispanic and American Supervisors and Craft Workers, 2007

Hispanics are a large and growing part of the United States workforce. Projections of the U.S. Census Bureau (2001) state that, by the year 2050, Hispanics will account for 25% of the population. For the Midwest in particular, the Hispanic population is expected to increase 35% by the year 2025. The construction industry is expected to experience a greater percentage increase of its Hispanic population, due to the labor-intensive nature of the industry. This study addresses the expected increase of Hispanic workers in the construction industry by testing the best approaches for delivering training to construction crews with Hispanic workers as well as American supervisors and laborers in the state of Iowa. The research methodology consisted of assessing the effects on communication, safety, work environment, and productivity as a result of the integration training. Results show that integration on-site training decreases workers’ desire to move and increases quality of work and productivity. Most importantly, experimental design was used to show the increasing levels of direct construction communication due to the Toolbox Integration Course for Hispanic Workers and American Supervisors (TICHA) designed as part of this project. This study recommends the creation of a quasi-governmental or association program that can offer continuous research and training that can benefit the construction industry as well as society as a whole. The industry involvement in this process is crucial for contractors. Not only do contractors benefit from reduced insurance premiums when workers act safely, but workers with better communication skills are more productive.

Persistent unequal sex ratio in a population of grayling (salmonidae) and possible role of temperature increase.

In some fishes, water chemistry or temperature affects sex determination or creates sex-specific selection pressures. The resulting population sex ratios are hard to predict from laboratory studies if the environmental triggers interact with other factors, whereas in field studies, singular observations of unusual sex ratios may be particularly prone to selective reporting. Long-term monitoring largely avoids these problems. We studied a population of grayling (Thymallus thymallus) in Lake Thun, Switzerland, that has been monitored since 1948. Samples of spawning fish have been caught about 3 times/week around spawning season, and water temperature at the spawning site has been continuously recorded since 1970. We used scale samples collected in different years to determine the average age of spawners (for life-stage specific analyses) and to identify the cohort born in 2003 (an extraordinarily warm year). Recent tissue samples were genotyped on microsatellite markers to test for genetic bottlenecks in the past and to estimate the genetically effective population size (N(e) ). Operational sex ratios changed from approximately 65% males before 1993 to approximately 85% males from 1993 to 2011. Sex ratios correlated with the water temperatures the fish experienced in their first year of life. Sex ratios were best explained by the average temperature juvenile fish experienced during their first summer. Grayling abundance is declining, but we found no evidence of a strong genetic bottleneck that would explain the apparent lack of evolutionary response to the unequal sex ratio. Results of other studies show no evidence of endocrine disruptors in the study area. Our findings suggest temperature affects population sex ratio and thereby contributes to population decline. Persistencia de Proporción de Sexos Desigual en una Población de Tímalos (Salmonidae) y el Posible Papel del Incremento de la Temperatura.

Tandem chimerism as a means to increase protein complexity in the human genome.

The "one-gene, one-protein" rule, coined by Beadle and Tatum, has been fundamental to molecular biology. The rule implies that the genetic complexity of an organism depends essentially on its gene number. The discovery, however, that alternative gene splicing and transcription are widespread phenomena dramatically altered our understanding of the genetic complexity of higher eukaryotic organisms; in these, a limited number of genes may potentially encode a much larger number of proteins. Here we investigate yet another phenomenon that may contribute to generate additional protein diversity. Indeed, by relying on both computational and experimental analysis, we estimate that at least 4%-5% of the tandem gene pairs in the human genome can be eventually transcribed into a single RNA sequence encoding a putative chimeric protein. While the functional significance of most of these chimeric transcripts remains to be determined, we provide strong evidence that this phenomenon does not correspond to mere technical artifacts and that it is a common mechanism with the potential of generating hundreds of additional proteins in the human genome.

May absorbable suture anchors increase the rate of recurrent dislocations after shoulder stabilization?

Introduction: Absorbable anchors are frequently used in shoulder surgery. Mechanisms of absorption induce a local inflammatory reaction. It is not clear if this process may disturb healing of the capsule and ligaments. The purpose of the study was to compare the rate of recurrent dislocation following open shoulder stabilization when using absorbable or non-absorbable suture anchors. Methods: Between 1999 and 2003, 83 open Bankart repairs were performed by the same surgeon. All patients had recurrent traumatic anterior shoulder instability. All had preoperative arthro-MRI or arthro-CT which did not reveal any significant bony Bankart lesion or rotatorcuff tear. Thirty-four patients were treated with absorbable anchors (Panalok®) and sutures (Panacryl®) and 49 with non-absorbable anchors (Mitek GII®) and sutures (Ethibond®). The same surgical technique and rehabilitation protocol were used. The incidence of sports ability and recurrent instability were recorded. We defined instability as true dislocation. Results: Five patients on 34 were lost to follow-up in the absorbable group and 7 on 49 in the non-absorbable group. The mean age of absorbable group was 25 years (range, 17-39 years). At a mean follow-up of 66 months (range, 54-76 months), 86% could resume sports activity. Five patients on 29 (17%) reported recurrent instability and two did need revision surgery. The mean age in non-absorbable group was 28 year (range, 18-47 years). At a mean follow-up of 78 months (range, 49-82 months), 93% could resume sports activity. Three patients on 42 (7%) reported recurrent instability and one did need revision surgery. Conclusion: This clinical study showed a clear tendency to a higher recurrence rate of dislocation when using absorbable suture anchors (17% in absorbable vs 7% in non-absorbable group). It is known that Panacryl® may be responsible for a major local inflammatory response. However, it is still unclear if this could be the failure etiology. Consequently, we prefer to use systematically non-absorbable sutureanchors for shoulder stabilization.

Methods to Increase Durability of Reactive ("D" Cracking) Coarse Aggregate in Portland Cement Concrete, MLR-73-01, 1973

The coarse aggregates used for Portland Cement concrete in southwest Iowa have exhibited a poor serviceability. This early failure is attributed to a characteristic commonly referred as "D" cracking. "D" line cracking is a discolored area of concrete caused by many fine, parallel hairline cracks. "D" line cracking is primarily caused by the movement of water in and through coarse aggregate with a unique pore structure. The presence of the water in the aggregates at the time of freezing causes the "D" cracking to occur and early failure. By making the pore structure less permeable to moisture, it is thought the durability factor of the concrete should increase. By drying the aggregate before mixing and then mixing with the cement, the particles of cement should enter the outer pore structure, and upon hydration make the pore structure less permeable to moisture.

Row Crop Response to Topsoil Restored on Borrow Areas, HR-186, Supplemental Report, 1982

Borrow areas are created where soil is needed to provide fill for construction projects. This research evaluated (1) the changes in row crop productivity resulting from removal of soil for highway construction in Iowa and (2) restoration methods which included: depth of topsoil, subsoil tillage, manure application, and two years of legume growth prior to row cropping. The research was carried out from 1977-1981 at four locations. Corn and soybean y1elds from borrow areas have been below, equal to; and greater than yields from undisturbed, neighboring farmland. Little or no yield increase was noted from restored topsoil at coarse textured sites. At finer textured sites, a marked yield increase of both crops occurred after the addition of 6 inches of topsoil but little added yield increase resulted from restoring 12 inches of topsoil. Subsoil tillage has shown little or no beneficial effect on crop yields. The manure treatment has resulted in a corn yield increase but only in the first year after application.

Row Crop Response to Topsoil Restored on Borrow Areas, HR-186, 1982

Borrow areas are created where soil is needed to provide fill for construction projects. The changes in row-crop productivity resulting from removal of soil for highway construction in Iowa and restoration methods, which included addition to topsoil, subsoil tillage, manure application, and 2 yr of legume growth before row cropping, were evaluated. The research was carried out from 1977 to 1981 at four locations. Corn and soybean yields from borrow areas have been below, equal to, and greater than yields from undisturbed neighboring farmland. Little or no yield increase was noted from restored topsoil at coarse-textured sites. At finer-textured sites, a marked yield increase of both crops occurred after the addition of 6 in. of topsoil but little added yield increase resulted from restoring 12 in. of topsoil. Subsoil tillage has shown little or no beneficial effect on crop yields. The manure treatment has resulted in a corn yield increase but only in the first year after application.

Minor protease inhibitor mutations at baseline do not increase the risk for a virological failure in HIV-1 subtype B infected patients.

BACKGROUND: Minor protease inhibitor (PI) mutations often exist as polymorphisms in HIV-1 sequences from treatment-naïve patients. Previous studies showed that their presence impairs the antiretroviral treatment (ART) response. Evaluating these findings in a larger cohort is essential. METHODS: To study the impact of minor PI mutations on time to viral suppression and time to virological failure, we included patients from the Swiss HIV Cohort Study infected with HIV-1 subtype B who started first-line ART with a PI and two nucleoside reverse transcriptase inhibitors. Cox regression models were performed to compare the outcomes among patients with 0 and ≥ 1 minor PI mutation. Models were adjusted for baseline HIV-1 RNA, CD4 cell count, sex, transmission category, age, ethnicity, year of ART start, the presence of nucleoside reverse transcriptase inhibitor mutations, and stratified for the administered PIs. RESULTS: We included 1199 patients of whom 944 (78.7%) received a boosted PI. Minor PI mutations associated with the administered PI were common: 41.7%, 16.1%, 4.7% and 1.9% had 1, 2, 3 or ≥ 4 mutations, respectively. The time to viral suppression was similar between patients with 0 (reference) and ≥ 1 minor PI mutation (multivariable hazard ratio (HR): 1.1 [95% confidence interval (CI): 1.0-1.3], P = .196). The time to virological failure was also similar (multivariable HR:.9 [95% CI:.5-1.6], P = .765). In addition, the impact of each single minor PI mutation was analyzed separately: none was significantly associated with the treatment outcome. CONCLUSIONS: The presence of minor PI mutations at baseline has no effect on the therapy outcome in HIV infected individuals.

Historical logging, productivity, and structural characteristics of boreal coniferous forests in Norway

Abstract

Improvement of productivity and polysaccharide-protein complex in Agaricus blazei

The objective of this work was to assess the productivity and polysaccharide-protein complex content of Agaricus blazei on rice straw medium, in comparison to conventional sawdust, using four casing soils. The A. blazei strain used was BCRC36814T, purchased from the Food Industry Research and Development Institute, Hsin-Chu, Taiwan. The two media were evaluated as to A. blazei productivity, harvesting time, and production costs. The experimental design used was a randomized complete block, with four replicates. Three local casing soils - Typic Paleudult (CCe), Typic Udorthent (Tq) and Oxyaquic Paleudult (TSp) - were compared to imported peat soil (PS, Saprists, Histosols), used as the control. The productivity of A. blazei using Tq and TSp soil was significantly higher. The TSp casing treatment resulted in earlier harvest by at least 14 to 27 days, when compared to the other treatments. The polysaccharide content in CCe (13.2%) and Tq soils (13.2%) did not differ significantly from the PS (13.4%) and TSp (10.6%) treatments. Local casing soils decreased the production costs of A. blazei cultivation. Composted rice straw can substitute sawdust as the culture medium for A. blazei production with increased yield.

Beneficial bacterial strains on Agaricus blazei cultivation

The objective of this work was to evaluate the effects of six bacterial strains isolated from Agaricus blazei (ABM) on its cultivation. The six strains were characterized as to their effects on the productivity, polysaccharide-protein complex (PSPC), and polysaccharide contents of ABM cultured on sterilized casing soils. Three isolates enhanced ABM mycelium growth. Inoculation of Arthrobacter sp. or Exiguobacterium sp. on sterile peat casing soil resulted in 64% increase in ABM mushroom total fresh matter yield compared to the uninoculated control. Inoculation of Exiguobacterium sp., Microbacterium esteraromaticum or Pseudomonas resinovorans on sterilized loamy casing soil resulted in 62, 95, and 59% increase in ABM mushroom total fresh matter yield, respectively. The PSPC content in ABM increased 7 to 10% in casing soil inoculated with five of the six isolates compared to the uninoculated control. Exiguobacterium sp. inoculated on casing soil resulted in a mushroom-polysaccharide content 15% higher than the control. Moreover, inoculation of five of the six isolates on the casing soil reduced the harvesting time from 10 to 27 days. The evaluated beneficial microbes improve the yield, PSPC, and polysaccharide contents, besides reducing the harvesting time in ABM culture.

Gas exchange rates, plant height, yield components, and productivity of upland rice as affected by plant regulators

The objective of this work was to evaluate gas exchange rates, plant height, yield components, and productivity of upland rice, as affected by type and application time of plant growth regulators. A randomized block design, in a 4x2 factorial arrangement, with four replicates was used. Treatments consisted of three growth regulators (mepiquat chloride, trinexapac-ethyl, and paclobutrazol), besides a control treatment applied at two different phenological stages: early tillering or panicle primordial differentiation. The experiment was performed under sprinkler-irrigated field conditions. Net CO2 assimilation, stomatal conductance, plant transpiration, and water-use efficiency were measured four times in Primavera upland rice cultivar, between booting and milky grain phenophases. Gas exchange rates were neither influenced by growth regulators nor by application time. There was, however, interaction between these factors on the other variables. Application of trinexapac-ethyl at both tillering and differentiation stages reduced plant height and negatively affected yield components and rice productivity. However, paclobutrazol and mepiquat chloride applied at tillering, reduced plant height without affecting rice yield. Mepiquat chloride acted as a growth stimulator when applied at the differentiation stage, and significantly increased plant height, panicle number, and grain yield of upland rice.

BRAIN DAMAGE IN METHYLMALONIC ACIDURIA: 2-METHYLCITRATE LEADS TO AMMONIA INCREASE AND APOPTOSIS

A 3D in vitro model of rat organotypic brain cell cultures in aggregates was used to investigate neurotoxicity mechanisms in methylmalonic aciduria. 1 mM methylmalonate (MMA), 2-methylcitrate (2-MCA) or propionate (PA) were repeatedly added to the culture media at two different time points of the cultures. In cultures treated with 2-MCA, we observed a significant increase of lactate in the medium, consistent with a possible inhibition of Krebs cycle and respiratory chain, as described earlier in the literature. Interestingly, we further observed that 2-MCA induced an important increase in ammonia production with concomitant decrease of glutamine concentrations, which suggests an inhibition of the astrocytic enzyme glutamine synthetase. These previously unreported findings may uncover a pathogenic mechanism in this disease with deleterious effects on early stages of brain development. By immunohistochemistry we could show that 2-MCA substantially increased the number of apoptotic cells. On the cellular level, 2-MCA had a toxic effect (cell swelling and cell death) on glial cells, but not on neurons. Surprisingly, MMA seemed to have a growth stimulating effect on the cultures. We can conclude that 2-MCA was the most toxic metabolite in our model for methylmalonic aciduria inducing ammonia accumulation and massive apoptosis in brain cells.