Does egg competition occur in marine broadcast-spawners?

When the availability of sperm limits female reproductive success, competition for sperm, may be an important broker of sexual selection. This is because sperm limitation can increase the variance in female reproductive success, resulting in strong selection on females to compete for limited fertilization opportunities. Sperm limitation is probably common in broadcast-spawning marine invertebrates, making these excellent candidates for investigating scramble competition between broods of eggs and its consequences for female reproductive success. Here, we report our findings from a series of experiments that investigate egg competition in the sessile, broadcast-spawning polychaete Galeolaria caespitosa. We initially tested whether the order in which eggs encounter sperm affects their fertilization success at two ecologically relevant current regimes. We used a split-clutch-split-ejaculate technique to compare the fertilization success of eggs from individual females that had either first access (competition-free treatment) or second access (egg competition treatment) to a batch of sperm. We found that fertilization success depended on the order in which eggs accessed sperm; eggs that were assigned to the competition-free treatment exhibited significantly higher fertilization rates than those assigned to the egg competition treatment at both current speeds. In subsequent experiments we found that prior exposure of sperm to eggs significantly reduced both the quantity and quality of sperm available to fertilize a second clutch of eggs, resulting in reductions in fertilization success at high and low sperm concentrations. These findings suggest that female traits that increase the likelihood of sperm-egg interactions (e.g. egg size) will respond to selection imposed by egg competition.

Icelandic Control Really Is A-Movement: Reply to Bobaljik and Landau

This article discusses the challenges that Bobaljik and Landau (2009) pose to Boeckx and Hornstein`s (2006) movement-based analysis of control in Icelandic. We show in detail that contrary to what Bobaljik and Landau claim, the movement theory of control (with a modification to accommodate quirky Case, a specialty of Icelandic) makes the right empirical cuts regarding the issues they raise, namely, (a) the differences in Case agreement between control and raising constructions, (b) the different patterns of Case transmission (un)available, and (c) the fact that allegedly Case-marked PROs are phonetically null. We argue that rather than being problematic, the data bearing on these issues actually provide independent support to the movement theory of control.

Presence of the metabolic syndrome is associated with reduced adiponectin levels and liver dysfunction in patients with type 2 diabetes

No abstract.

How configurations of binocular disparity determine whether stereoscopic slant or stereoscopic occlusion is seen

A partially occluded contour and a slanted contour may generate identical binocular horizontal disparities. We investigated conditions promoting an occlusion resolution indicated by an illusory contour in depth along the aligned ends of horizontally disparate line sets. For a set of identical oblique lines with a constant width added to one eye's view, strength, depth, and stability of the illusory contour were poor, whereas for oblique lines of alternating orientations the illusory contours were strong, indicating a reliance on vertical size disparities rather than vertical positional disparities in generating perceived occlusion. For horizontal lines, occlusion was seen when the lines were of different lengths and absolute width disparity was invariant across the set. In all line configurations, when the additional length was on the wrong eye to be attributed to differential occlusion, lines appeared slanted consistent with their individual horizontal disparities. This rules out monocular illusory contours as the determining factor.

Expression of the iron regulatory peptide hepcidin is reduced in patients with chronic liver disease

Disturbances in iron metabolism often accompany liver disease in humans and hepatic iron deposition is a frequent finding. Since the peptide hepcidin, a major regulator of body iron homeostasis, is synthesised in the liver, alterations in hepcidin expression could be responsible for these effects. To investigate this possibility, we studied hepcidin expression in liver biopsies from patients with hepatitis C virus (HCV) infection, non-alcoholic fatty liver disease (NAFLD) and hemochromatosis (HC). Total RNA was extracted from the liver tissue of 24 HCV, 17 NASH and 5 HC patients, and 17 liver transplant donors (controls). The levels of mRNA for hepcidin and several other molecules involved in iron metabolism (DMT1, Dcytb, hephaestin, ferroportin, TfR1, TfR2, HFE and HJV) were examined by ribonuclease protection assay and expressed relative to the housekeeping gene GAPDH. The expression of hepcidin was significantly decreased in HCV and NASH patients relative to control liver (109±16 and 200±44 versus 325±26 respectively; P=0.008 and 0.02). We have previously reported similar findings in patients with HC, and this was confirmed in the current analysis (176±21; P=0.003). In both HCV and NAFLD patients the expression of the iron reductase Dcytb and the transferrin binding regulatory molecule TfR2 was also decreased, while the cellular iron exporter ferroportin showed a significant increase. Levels of the mRNA for the iron oxidase hephaestin were lower in HCV patients alone, while expression of the major transferrin binding molecule TfR1 was decreased only in NAFLD patients. Of particular interest was the finding that the expression of HJV (which is mutated in patients with juvenile HC) was significantly increased in NAFLD patients. No changes were seen in the expression of the iron importer DMT1 or the regulatory molecule HFE. Decreased expression of hepcidin in patients with HCV and NAFLD provides an explanation why iron homeostasis could be perturbed in these disorders. Reduced hepcidin levels would increase intestinal iron absorption and iron release from macrophages, which could contribute to hepatic iron accumulation. This in turn could lead to alterations in the expression of various proteins involved in iron transport and its regulation. Indeed most of the changes in the expression of such molecules observed in this study are consistent with this. However, the mechanisms leading to changes in the expression of hepcidin in these diseases remain to be elucidated.

Interferon-gamma is required for killing keratinocytes in vitro and in vivo

Epithelial malignancies are common in immunosuppressed individuals and the general population. However the mechanisms by which the adaptive immune system can eliminate immunogenic epithelial cells remain undefined. The aim of this project was to determine the effector molecules required for induction of apoptosis in murine epidermal keratinocytes (MEKs) in vitro and in vivo. HPV16E7-specific CTL lines and T cell receptor transgenic (E7TCRtg) effector cells were obtained from wild type (wt)-C57 and syngeneic mice rendered functionally inactive for perforin (Pfp), interferon-g (IFN-g) or FasL. CTLs or E7TCRtg spleen cells were co-cultured with primary MEKs in vitro or transferred into skin graft recipients. Inhibition of colony formation and skin graft rejection were used as indicators of T cell:KC interaction. Wt E7-specific CTLs and CTLs deficient in perforin, FasL or IFN-g produced mean reductions in colony formation of 67% (62.4–71.3%), 72% (71.1–72%), 76% (73–78%) and 21.5% (14– 34%) respectively. Wt, perforin deficient or FasL deficient CTLs all induced rejection of skin grafts (wt: 6/12; Pfp: 9/15; FasL: 3/13 survival). Transfer and immunisation of wt E7TCRtg spleen cells induces rejection of 50% of grafts (4/8 survival). In contrast, perforin or IFN-g deficient E7TCRtg failed to induce graft rejection (5/6; 4/4 survival). FasL deficient E7TCRtg induced nonspecific rejection of grafts (E7- 2/6 survival; C57- 4/7 survival). Therefore IFN-g production by CTL is necessary and sufficient in vitro and in vivo to kill epithelial cells which express a nonself antigen. Assessment of immunotherapies directed against epithelial tissues may be more effectively achieved by assaying the amount of IFN-g production by CD8 T cells, and the number and affinity of those cells, in conjunction with quantitation of perforin mediated effects in short term assays.

Detrusor overactivity is associated with downregulation of large-conductance calcium- and voltage-activated potassium channel protein

Chang S, Gomes CM, Hypolite JA, Marx J, Alanzi J, Zderic SA, Malkowicz B, Wein AJ, Chacko S. Detrusor overactivity is associated with downregulation of large-conductance calcium-and voltage-activated potassium channel protein. Am J Physiol Renal Physiol 298: F1416-F1423, 2010. First published April 14, 2010; doi: 10.1152/ajprenal.00595.2009.-Large-conductance voltage-and calcium-activated potassium (BK) channels have been shown to play a role in detrusor overactivity (DO). The goal of this study was to determine whether bladder outlet obstructioninduced DO is associated with downregulation of BK channels and whether BK channels affect myosin light chain 20 (MLC(20)) phosphorylation in detrusor smooth muscle (DSM). Partial bladder outlet obstruction (PBOO) was surgically induced in male New Zealand White rabbits. The rabbit PBOO model shows decreased voided volumes and increased voiding frequency. DSM from PBOO rabbits also show enhanced spontaneous contractions compared with control. Both BK channel alpha- and beta-subunits were significantly decreased in DSM from PBOO rabbits. Immunostaining shows BK beta mainly expressed in DSM, and its expression is much less in PBOO DSM compared with control DSM. Furthermore, a translational study was performed to see whether the finding discovered in the animal model can be translated to human patients. The urodynamic study demonstrates several overactive DSM contractions during the urine-filling stage in benign prostatic hyperplasia (BPH) patients with DO, while DSM is very quiet in BPH patients without DO. DSM biopsies revealed significantly less BK channel expression at both mRNA and protein levels. The degree of downregulation of the BK beta-subunit was greater than that of the BK alpha-subunit, and the downregulation of BK was only associated with DO, not BPH. Finally, the small interference (si) RNA-mediated downregulation of the BK beta-subunit was employed to study the effect of BK depletion on MLC(20) phosphorylation. siRNA-mediated BK channel reduction was associated with an increased MLC(20) phosphorylation level in cultured DSM cells. In summary, PBOO-induced DO is associated with downregulation of BK channel expression in the rabbit model, and this finding can be translated to human BPH patients with DO. Furthermore, downregulation of the BK channel may contribute to DO by increasing the basal level of MLC(20) phosphorylation.

Elevated expression of MeCP2 in cardiac and skeletal tissues is detrimental for normal development

MeCP2 plays a critical role in interpreting epigenetic signatures that command chromatin conformation and regulation of gene transcription. In spite of MeCP2`s ubiquitous expression, its functions have always been considered in the context of brain physiology. In this study, we demonstrate that alterations of the normal pattern of expression of MeCP2 in cardiac and skeletal tissues are detrimental for normal development. Overexpression of MeCP2 in the mouse heart leads to embryonic lethality with cardiac septum hypertrophy and dysregulated expression of MeCP2 in skeletal tissue produces severe malformations. We further show that MeCP2`s expression in the heart is developmentally regulated; further suggesting that it plays a key role in regulating transcriptional programs in non-neural tissues.

Local inflammation is crucial for T cell mediated rejection of skin graft expressing foreign antigen

Most of the skin grafts from (K14hGH.FVB C57BL/6) F1 mice, which express foreign antigen (human growth hormone, hGH) in skin keratinocytes driven by keratin 14 promoter, were spontaneously rejected by syngeneic wild type F1 recipients and hGH-specific immune responses such as antibody and hGHspecific T cells were generated in these recipients. Interestingly, a 2nd F1 hGH-expressing skin graft was rejected by graft primed recipients, but was not rejected from such recipients if CD4+ or CD8+ T cells were depleted prior to the placement of the 2nd graft. Surprisingly, this 2nd graft retained healthy even after CD4+ or CD8+ T cells were allowed to recover so that the animal could reject a freshly placed 3rd F1 hGH-expressing graft. Furthermore, inflammatory response induced by topical treatment with imiquimod could lead to the rejection of some well-healed 2nd grafts. This result indicates that both CD4+ and CD8+ T cells are required for the rejection and the ability of effector T cells to reject a graft is determined by local factors in the graft which are presumably determined by inflammation induced by surgery or imiquimod treatment. Taken together, our results suggest that in addition to CD4+ and CD8+ T cells, local environmental factors induced by inflammation are also crucial for effector T cell functions leading to graft destruction. The understanding of these local factors will lead to more effective immunotherapy for established, epithelial cancer in the future.

Obstructive Sleep Apnea Is Common and Independently Associated With Atrial Fibrillation in Patients With Hypertrophic Cardiomyopathy

Background: Hypertrophic cardiomyopathy (HCM) is associated with arrhythmias and cardiovascular death. Left atrial enlargement and atrial fibrillation (AF) are considered markers for death due to heart failure in patients with HCM. Obstructive sleep apnea (OSA) is independently associated with heart remodeling and arrhythmias in other populations. We hypothesized that OSA is common and is associated with heart remodeling and AF in patients with HCM. Methods: We evaluated 80 consecutive stable patients with a confirmed diagnosis of HCM by sleep questionnaire, blood tests, echocardiography, and sleep study (overnight respiratory monitoring). Results: OSA (apnea-hypopnea index [AHI] > 15 events/h) was present in 32 patients (40%). Patients with OSA were significantly older (56 [41-64] vs 38.5 [30-53] years, P < .001) and presented higher BMI (28.2 +/- 3.5 vs 25.2 +/- 5.2 kg/m(2), P < .01) and increased left atrial diameter (45 [42-52.8] vs 41 [39-47] mm, P = .01) and aorta diameter (34 [30-37] vs 29 [28-32] mm, P < .001), compared with patients without OSA. Stepwise multiple linear regression showed that the AHI (P = .05) and BMI (P = .06) were associated with left atrial diameter. The AHI was the only variable associated with aorta diameter (P = .01). AF was present in 31% vs 6% of patients with and without OSA, respectively (P < .01). OSA (P = .03) and left atrial diameter (P = .03) were the only factors independently associated with AF. Conclusions: OSA is highly prevalent in patients with HCM and it is associated with left atrial and aortic enlargement. OSA is independently associated with AF, a risk factor for cardiovascular death in this population. CHEST 2010; 137(5):1078-1084

Coronary Calcification Is Associated With Lower Bone Formation Rate in CKD Patients Not Yet in Dialysis Treatment

Vascular calcification is a strong prognostic marker of mortality in hemodialysis patients and has been associated with bone metabolism disorders in this population. In earlier stages of chronic kidney disease (CKD), vascular calcification also has been documented. This study evaluated the association between coronary artery calcification (CAC) and bone histomorphometric parameters in CKD predialysis patients assessed by multislice coronary tomography and by undecalcified bone biopsy. CAC was detected in 33 (66%) patients, and their median calcium score was 89.7 (0.4-2299.3 AU). The most frequent bone histologic alterations observed included low trabecular bone volume, increased eroded and osteoclast surfaces, and low bone-formation rate (BFR/BS). Multiple logistic regression analysis, adjusted for age, sex, and diabetes, showed that BFR/BS was independently associated with the presence of coronary calcification [p=.009; odd ratio (OR) = 0.15; 95% confidence interval (Cl) 0.036-0.619] This study showed a high prevalence of CAC in asymptomatic predialysis CKD patients. Also, there was an independent association of low bone formation and CAC in this population. In conclusion, our results provide evidence that low bone-formation rate constitutes another nontraditional risk factor for cardiovascular disease in CKD patients. 2010 American Society for Bone and Mineral Research.