Effects of Upper-Limit Water Temperatures on the Dispersal of the Asian Clam Corbicula fluminea

Temperature is a determinant environmental variable in metabolic rates of organisms ultimately influencing important physiological and behavioural features. Stressful conditions such as increasing temperature, particularly within high ranges occurring in the summer, have been suggested to induce flotation behaviour in Corbicula fluminea which may be important in dispersal of this invasive species. However, there has been no experimental evidence supporting this hypothesis. It was already proven that C. fluminea drift is supported by a mucilaginous drogue line produced by mucocytes present in the ctenidia. Detailed microscopic examination of changes in these cells and quantification of clam flotation following one, two and three weeks of exposure to 22, 25 and 30°C was carried out so that the effects of increasing water temperatures in dispersal patterns could be discussed. Results show that changes in temperature triggered an acceleration of the mucocytes production and stimulated flotation behaviour, especially following one week of exposure. Dilution of these effects occurred following longer exposure periods. It is possible that these bivalves perceive changing temperature as a stress and respond accordingly in the short-term, and then acclimate to the new environmental conditions. The response patterns suggest that increasing water temperatures could stimulate C. fluminea population expansion.     

Short- and long-term effects of testosterone on diaphragm in castrated and normal male rats

Prezant, David J., Manoj L. Karwa, Helen H. Kim, DianeMaggiore, Virginia Chung, and David E. Valentine. Short- and long-term effects of testosterone on diaphragm in castrated and normalmale rats. J. Appl. Physiol. 82(1):134-143, 1997.The effects of short- and long-term testosteroneabsence or treatment on the diaphragm were studied in castrated andsexually normal male rats. Compared with control rats (untreated normalmales), testosterone absence or treatment did not significantly affect costal weight. In untreated castrated males, there were significant decreases in specific forces, type II fiber cross-sectional area, andmyosin heavy chain (MHC) isoform 2B after 2.5 wk. In castrated malesthat received testosterone, there were significant increases inspecific forces, type II total fiber proportional area, and relativeexpression of all adult diaphragm fast MHC isoforms(MHC-2_all) after 2.5 wk. In normal males thatreceived testosterone, the only significant finding was an increase inMHC-2B after 2.5 wk. Across all groups, there was close correlationbetween increases in maximum tetanic forces and MHC-2_all.Changes in diaphragm function and composition were closely related tochanges in serum testosterone levels at 2.5 wk. The lack of significantchange in diaphragm function at 10 wk occurred despite changes in serumtestosterone levels and diaphragm composition similar to those at 2.5 wk. These findings support our hypothesis that the effects oftestosterone are dependent on basal circulating androgen levels andstudy duration.

     

Comparison of WTC dust size on macrophage inflammatory cytokine release in vivo and in vitro

Background

The WTC collapse exposed over 300,000 people to high concentrations of WTC-PM; particulates up to ∼50 mm were recovered from rescue workers’ lungs. Elevated MDC and GM-CSF independently predicted subsequent lung injury in WTC-PM-exposed workers. Our hypotheses are that components of WTC dust strongly induce GM-CSF and MDC in AM; and that these two risk factors are in separate inflammatory pathways.

Methodology/Principal Findings

Normal adherent AM from 15 subjects without WTC-exposure were incubated in media alone, LPS 40 ng/mL, or suspensions of WTC-PM_10–53 or WTC-PM_2.5 at concentrations of 10, 50 or 100 µg/mL for 24 hours; supernatants assayed for 39 chemokines/cytokines. In addition, sera from WTC-exposed subjects who developed lung injury were assayed for the same cytokines. In the in vitro studies, cytokines formed two clusters with GM-CSF and MDC as a result of PM_10–53 and PM_2.5. GM-CSF clustered with IL-6 and IL-12(p70) at baseline, after exposure to WTC-PM_10–53 and in sera of WTC dust-exposed subjects (n = 70) with WTC lung injury. Similarly, MDC clustered with GRO and MCP-1. WTC-PM_10–53 consistently induced more cytokine release than WTC-PM_2.5 at 100 µg/mL. Individual baseline expression correlated with WTC-PM-induced GM-CSF and MDC.

Conclusions

WTC-PM_10–53 induced a stronger inflammatory response by human AM than WTC-PM_2.5. This large particle exposure may have contributed to the high incidence of lung injury in those exposed to particles at the WTC site. GM-CSF and MDC consistently cluster separately, suggesting a role for differential cytokine release in WTC-PM injury. Subject-specific response to WTC-PM may underlie individual susceptibility to lung injury after irritant dust exposure.     

Organization of the regulatory region of the yeast CYC7 gene: multiple factors are involved in regulation.

Regulation of the CYC7 gene of Saccharomyces cerevisiae, encoding iso-2-cytochrome c, was studied. Expression was induced about 20-fold by heme and derepressed 4- to 8-fold by a shift from glucose medium to one containing a nonfermentable carbon source. Deletion analysis showed that induction by heme depends upon sequences between -250 and -228 (from the coding sequence) and upon the HAP1 activator gene, previously shown to be required for CYC1 expression (L. Guarente et al., Cell 36:503-511, 1984). Thus, HAP1 coordinates expression of CYC7 and CYC1, the two genes encoding isologs of cytochrome c in S. cerevisiae. HAP1-18, a mutant allele of HAP1, which increased CYC7 expression more than 10-fold, also acted through sequences between -250 and -228. In vitro binding studies showed that the HAP1 product binds to these sequences (see also K. Pfeifer, T. Prezant, and L. Guarente, Cell 49:19-28, 1987) and an additional factor binds to distal sequences that lie between -201 and -165. This latter site augmented CYC7 expression in vivo. Derepression of CYC7 expression in a medium containing nonfermentable carbon sources depended upon sequences between -354 and -295. The interplay of these multiple sites and the factors that bind to them are discussed.     

Corrections to the human mitochondrial ribosomal RNA sequences

Two new errors and one consensus change were identified in the human mitochondrial Cambridge consensus sequence. The errors are an A to G substitution at nucleotide 750 in the 12S rRNA gene and a single nucleotide deletion at nt 3107 in the 16S rRNA gene. The consensus change is nt 2706 AG in the 16S rRNA gene.     

PEDF,a pleiotropic WTC-LI biomarker: Machine learning biomarker identification and validation

Biomarkers predict World Trade Center-Lung Injury (WTC-LI); however, there remains unaddressed multicollinearity in our serum cytokines, chemokines, and high-throughput platform datasets used to phenotype WTC-disease. To address this concern, we used automated, machine-learning, high-dimensional data pruning, and validated identified biomarkers. The parent cohort consisted of male, never-smoking firefighters with WTC-LI (FEV_{1, %Pred}< lower limit of normal (LLN); n = 100) and controls (n = 127) and had their biomarkers assessed. Cases and controls (n = 15/group) underwent untargeted metabolomics, then feature selection performed on metabolites, cytokines, chemokines, and clinical data. Cytokines, chemokines, and clinical biomarkers were validated in the non-overlapping parent-cohort via binary logistic regression with 5-fold cross validation. Random forests of metabolites (n = 580), clinical biomarkers (n = 5), and previously assayed cytokines, chemokines (n = 106) identified that the top 5% of biomarkers important to class separation included pigment epithelium-derived factor (PEDF), macrophage derived chemokine (MDC), systolic blood pressure, macrophage inflammatory protein-4 (MIP-4), growth-regulated oncogene protein (GRO), monocyte chemoattractant protein-1 (MCP-1), apolipoprotein-AII (Apo-AII), cell membrane metabolites (sphingolipids, phospholipids), and branched-chain amino acids. Validated models via confounder-adjusted (age on 9/11, BMI, exposure, and pre-9/11 FEV_{1, %Pred}) binary logistic regression had AUC_ROC [0.90(0.84–0.96)]. Decreased PEDF and MIP-4, and increased Apo-AII were associated with increased odds of WTC-LI. Increased GRO, MCP-1, and simultaneously decreased MDC were associated with decreased odds of WTC-LI. In conclusion, automated data pruning identified novel WTC-LI biomarkers; performance was validated in an independent cohort. One biomarker—PEDF, an antiangiogenic agent—is a novel, predictive biomarker of particulate-matter-related lung disease. Other biomarkers—GRO, MCP-1, MDC, MIP-4—reveal immune cell involvement in WTC-LI pathogenesis. Findings of our automated biomarker identification warrant further investigation into these potential pharmacotherapy targets.     

Early Elevation of Serum MMP-3 and MMP-12 Predicts Protection from World Trade Center-Lung Injury in New York City Firefighters: A Nested Case-Control Study

Objective

After 9/11/2001, some Fire Department of New York (FDNY) workers had excessive lung function decline. We hypothesized that early serum matrix metalloproteinases (MMP) expression predicts World Trade Center-Lung Injury (WTC-LI) years later.

Methods

This is a nested case-control analysis of never-smoking male firefighters with normal pre-exposure Forced Expiratory Volume in one second (FEV₁) who had serum drawn up to 155 days post 9/11/2001. Serum MMP-1, 2,3,7,8, 9, 12 and 13 were measured. Cases of WTC-LI (N = 70) were defined as having an FEV1 one standard deviation below the mean (FEV₁≤77%) at subspecialty pulmonary evaluation (SPE) which was performed 32 months (IQR 21–53) post-9/11. Controls (N = 123) were randomly selected. We modeled MMP''s ability as a predictor of cases status with logistic regression adjusted for time to blood draw, exposure intensity, weight gain and pre-9/11 FEV₁.

Results

Each log-increase in MMP-3 and MMP-12 showed reduced odds of developing WTC-LI by 73% and 54% respectively. MMP-3 and MMP-12 consistently clustered together in cases, controls, and the cohort. Increasing time to blood draw significantly and independently increased the risk of WTC-LI.

Conclusions

Elevated serum levels of MMP-3 and MMP-12 reduce the risk of developing WTC-LI. At any level of MMP-3 or 12, increased time to blood draw is associated with a diminished protective effect.