Identification of a mitotic recombination hotspot on chromosome III of the asexual fungus Aspergillus niger and its possible correlation elevated basal transcription

Genetic recombination is an important tool in strain breeding in many organisms. We studied the possibilities of mitotic recombination in strain breeding of the asexual fungus Aspergillus niger. By identifying genes that complemented mapped auxotrophic mutations, the physical map was compared to the genetic map of chromosome III using the genome sequence. In a program to construct a chromosome III-specific marker strain by selecting mitotic crossing-over in diploids, a mitotic recombination hotspot was identified. Analysis of the mitotic recombination hotspot revealed some physical features, elevated basal transcription and a possible correlation with purine stretches

Cardiac oxygen supply is compromised during the night in hypertensive patients

The enhanced heart rate and blood pressure soon after awaking increases cardiac oxygen demand, and has been associated with the high incidence of acute myocardial infarction in the morning. The behavior of cardiac oxygen supply is unknown. We hypothesized that oxygen supply decreases in the morning and to that purpose investigated cardiac oxygen demand and oxygen supply at night and after awaking. We compared hypertensive to normotensive subjects and furthermore assessed whether pressures measured non-invasively and intra-arterially give similar results. Aortic pressure was reconstructed from 24-h intra-brachial and simultaneously obtained non-invasive finger pressure in 14 hypertensives and 8 normotensives. Supply was assessed by Diastolic Time Fraction (DTF, ratio of diastolic and heart period), demand by Rate-Pressure Product (RPP, systolic pressure times heart rate, HR) and supply/demand ratio by Adia/Asys, with Adia and Asys diastolic and systolic areas under the aortic pressure curve. Hypertensives had lower supply by DTF and higher demand by RPP than normotensives during the night. DTF decreased and RPP increased in both groups after awaking. The DTF of hypertensives decreased less becoming similar to the DTF of normotensives in the morning; the RPP remained higher. Adia/Asys followed the pattern of DTF. Findings from invasively and non-invasively determined pressure were similar. The cardiac oxygen supply/demand ratio in hypertensive patients is lower than in normotensives at night. With a smaller night-day differences, the hypertensives’ risk for cardiovascular events may be more evenly spread over the 24 h. This information can be obtained noninvasively

A second generation cervico-vaginal lavage device shows similar performance as its preceding version with respect to DNA yield and HPV DNA results

Contains fulltext : 118480.pdf (publisher's version ) (Open Access)BACKGROUND: Attendance rates of cervical screening programs can be increased by offering HPV self-sampling to non-attendees. Acceptability, DNA yield, lavage volumes and choice of hrHPV test can influence effectiveness of the self-sampling procedures and could therefore play a role in recruiting non-attendees. To increase user-friendliness, a frequently used lavage sampler was modified. In this study, we compared this second generation lavage device with the first generation device within similar birth cohorts. METHODS: Within a large self-sampling cohort-study among non-responders of the Dutch cervical screening program, a subset of 2,644 women received a second generation self-sampling lavage device, while 11,977 women, matched for age and ZIP-code, received the first generation model. The second generation device was different in shape, color, lavage volume, and packaging, in comparison to its first generation model. The Cochran's test was used to compare both devices for hrHPV positivity rate and response rate. To correct for possible heterogeneity between age and ZIP codes in both groups the Breslow-Day test of homogeneity was used. A T-test was utilized to compare DNA yields of the obtained material in both groups. RESULTS: Median DNA yields were 90.4 mug/ml (95% CI 83.2-97.5) and 91.1 mug/ml (95% CI 77.8-104.4, p= 0.726) and hrHPV positivity rates were 8.2% and 6.9% (p= 0.419) per sample self-collected by the second - and the first generation of the device (p= 0.726), respectively. In addition, response rates were comparable for the two models (35.4% versus 34.4%, p= 0.654). CONCLUSIONS: Replacing the first generation self-sampling device by an ergonomically improved, second generation device resulted in equal DNA yields, comparable hrHPV positivity rates and similar response rates. Therefore, it can be concluded that the clinical performance of the first and second generation models are similar. Moreover, participation of non-attendees in cervical cancer screening is probably not predominantly determined by the type of self-collection device

TNK2 preserves epidermal growth factor receptor expression on the cell surface and enhances migration and invasion of human breast cancer cells

Introduction Amplification of the TNK2 gene in primary tumours correlates with poor prognosis. In accordance, TNK2 overexpression was shown to promote invasion of cancer cells - but the mechanism by which TNK2 mediates these effects is unresolved. TNK2 was suggested to regulate Cdc42-driven migration by activation of breast cancer antioestrogen resistance 1 (BCAR1); however, distinct from this effect is evidence for a role of TNK2 in the regulation of epidermal growth factor receptor (EGFR) endocytosis and degradation. In the present study we sought to investigate whether negative targeting of TNK2 by siRNA could be used to inhibit cancer cell invasion, to establish the contribution of its effect on the EGFR and to consequently attempt to resolve the issue of TNK2's mechanism of action. Methods We used siRNA to knockdown expression of TNK2 and its proposed effector BCAR1 in order to analyse the effect of this knockdown on cancer cell behaviour in vitro. We examined morphological changes using phase-contrast microscopy and immunohistochemistry. Functional parameters examined included apoptosis, proliferation, migration and invasion. We also performed flow cytometry analysis to examine EGFR cell surface expression and carried out western blot to examine the total EGFR levels. Results We observed that targeting of TNK2 by siRNA in breast cancer cells resulted in distinct morphological changes characterised by a stellate appearance and an absence of protrusions at membrane edges. These changes were not recapitulated upon siRNA targeting of BCAR1. We thus hypothesised that a component of the effects induced by TNK2 may be independent of BCAR1. Consistent with the idea of an alternative mechanism for TNK2, we observed that TNK2 associates with activated EGFR in breast cancer cells in a TNK2-kinase-independent manner. Furthermore, we demonstrated that TNK2 functions to maintain EGFRs on the cell surface. We could demonstrate that the main functional effect of activating these surface EGFRs in breast cancer cells is stimulation of migration. In accordance, TNK2 silencing by siRNA led to a significant reduction in cell surface EGFR and to a concomitant decrease in the migratory and invasive capacity of breast cancer cells. Conclusion Our data suggest that TNK2 can enhance migration and invasion of breast cancer cells via preservation of EGFR expression, notwithstanding its previously reported signalling via BCAR1, explaining its oncogenic behaviour in vitro and correlation with metastatic human breast cancer in vivo

To Fear is to Gain? The Role of Fear Recognition in Risky Decision Making in TBI Patients and Healthy Controls

Fear is an important emotional reaction that guides decision making in situations of ambiguity or uncertainty. Both recognition of facial expressions of fear and decision making ability can be impaired after traumatic brain injury (TBI), in particular when the frontal lobe is damaged. So far, it has not been investigated how recognition of fear influences risk behavior in healthy subjects and TBI patients. The ability to recognize fear is thought to be related to the ability to experience fear and to use it as a warning signal to guide decision making. We hypothesized that a better ability to recognize fear would be related to a better regulation of risk behavior, with healthy controls outperforming TBI patients. To investigate this, 59 healthy subjects and 49 TBI patients were assessed with a test for emotion recognition (Facial Expression of Emotion: Stimuli and Tests) and a gambling task (Iowa Gambling Task (IGT)). The results showed that, regardless of post traumatic amnesia duration or the presence of frontal lesions, patients were more impaired than healthy controls on both fear recognition and decision making. In both groups, a significant relationship was found between better fear recognition, the development of an advantageous strategy across the IGT and less risk behavior in the last blocks of the IGT. Educational level moderated this relationship in the final block of the IGT. This study has important clinical implications, indicating that impaired decision making and risk behavior after TBI can be preceded by deficits in the processing of fear

Potential advantages of cell administration on the inflammatory response compared to standard ACE inhibitor treatment in experimental myocardial infarction

<p>Abstract</p> <p>Background</p> <p>Bone Marrow (BM) progenitor cells can target the site of myocardial injury, contributing to tissue repair by neovascolarization and/or by a possible direct paracrine effect on the inflammatory cascade. Angiotensin Converting Enzyme inhibitors (ACE-I) are effective in reducing mortality and preventing left ventricular (LV) function deterioration after myocardial infarction.</p> <p>Methods</p> <p>We investigated the short term effects of BM mononuclear cells (BMMNCs) therapy on the pro-inflammatory cytokines (pro-CKs) and on LV remodelling and compared these effects over a standard ACE-I therapy in a rat model of myocardial cryodamage.</p> <p>Forty two adult inbread Fisher-F344 rats were randomized into three groups: untreated (UT; n = 12), pharmacological therapy (ACE-I; n = 14, receiving quinapril), and cellular therapy (BMMNCs; n = 16, receiving BMMNCs infusion). Rats underwent to a standard echocardiogram in the acute setting and 14 days after the damage, before the sacrifice. Pro-CKs analysis (interleukin (IL)1β, IL-6, tumor necrosis factor (TNF)α was performed (multiplex proteome arrays) on blood samples obtained by direct aorta puncture before the sacrifice; a control group of 6 rats was considered as reference.</p> <p>Results</p> <p>Concerning the extension of the infarcted area as well as the LV dimensions, no differences were observed among the animal groups; treated rats had lower left atrial diameters and higher indexes of LV function. Pro-Cks were increased in infarcted-UT rats if compared with controls, and significantly reduced by BMMNCs and ACE-I ; TNFα inversely correlated with LV fractional shortening.</p> <p>Conclusion</p> <p>After myocardial infarction, both BMMNCs and ACE-I reduce the pattern of pro-Ck response, probably contributing to prevent the deterioration of LV function observed in UT rats.</p

Cognitive Profile of Students Who Enter Higher Education with an Indication of Dyslexia

For languages other than English there is a lack of empirical evidence about the cognitive profile of students entering higher education with a diagnosis of dyslexia. To obtain such evidence, we compared a group of 100 Dutch-speaking students diagnosed with dyslexia with a control group of 100 students without learning disabilities. Our study showed selective deficits in reading and writing (effect sizes for accuracy between d = 1 and d = 2), arithmetic (d≈1), and phonological processing (d>0.7). Except for spelling, these deficits were larger for speed related measures than for accuracy related measures. Students with dyslexia also performed slightly inferior on the KAIT tests of crystallized intelligence, due to the retrieval of verbal information from long-term memory. No significant differences were observed in the KAIT tests of fluid intelligence. The profile we obtained agrees with a recent meta-analysis of English findings suggesting that it generalizes to all alphabetic languages. Implications for special arrangements for students with dyslexia in higher education are outlined

Delay aversion but preference for large and rare rewards in two choice tasks: implications for the measurement of self-control parameters

BACKGROUND: Impulsivity is defined as intolerance/aversion to waiting for reward. In intolerance-to-delay (ID) protocols, animals must choose between small/soon (SS) versus large/late (LL) rewards. In the probabilistic discount (PD) protocols, animals are faced with choice between small/sure (SS) versus large/luck-linked (LLL) rewards. It has been suggested that PD protocols also measure impulsivity, however, a clear dissociation has been reported between delay and probability discounting. RESULTS: Wistar adolescent rats (30- to 46-day-old) were tested using either protocol in drug-free state. In the ID protocol, animals showed a marked shift from LL to SS reward when delay increased, and this despite adverse consequences on the total amount of food obtained. In the PD protocol, animals developed a stable preference for LLL reward, and maintained it even when SS and LLL options were predicted and demonstrated to become indifferent. We demonstrate a clear dissociation between these two protocols. In the ID task, the aversion to delay was anti-economical and reflected impulsivity. In the PD task, preference for large reward was maintained despite its uncertain delivery, suggesting a strong attraction for unitary rewards of great magnitude. CONCLUSION: Uncertain delivery generated no aversion, when compared to delays producing an equivalent level of large-reward rarefaction. The PD task is suggested not to reflect impulsive behavior, and to generate patterns of choice that rather resemble the features of gambling. In summary, present data do indicate the need to interpret choice behavior in ID and PD protocols differently