Novel role of BRCA1 interacting C-terminal helicase 1 (BRIP1) in breast tumour cell invasion

Breast cancer (BC) is the most common malignancy and the leading cause of death in women worldwide. Only 5%-10% of mutations in BRCA genes are associated with familial breast tumours in Eastern countries, suggesting the contribution of other genes. Using a microarray gene expression profiling study of BC, we have recently identified BRIP1 (fivefold up-regulation) as a potential gene associated with BC progression in the Omani population. Although BRIP1 regulates DNA repair and cell proliferation, the precise role of BRIP1 in BC cell invasion/metastasis has not been explored yet; this prompted us to test the hypothesis that BRIP1 promotes BC cell proliferation and invasion. Using a combination of cellular and molecular approaches, our results revealed differential overexpression of BRIP1 in different BC cell lines. Functional assays validated further the physiological relevance of BRIP1 in tumour malignancy, and siRNA-mediated BRIP1 knockdown significantly reduced BC cell motility by targeting key motility-associated genes. Moreover, down-regulation of BRIP1 expression significantly attenuated cell proliferation via cell cycle arrest. Our study is the first to show the novel function of BRIP1 in promoting BC cell invasion by regulating expression of various downstream target genes. Furthermore, these findings provide us with a unique opportunity to identify BRIP1-induced pro-invasive genes that could serve as biomarkers and/or targets to guide the design of appropriate BC targeted therapies

Kardia Mobile applicability in clinical practice: A comparison of Kardia Mobile and standard 12-lead electrocardiogram records in 100 consecutive patients of a tertiary cardiovascular care center

Background: Mobile devices are gaining a rising number of users in all countries around the globe. Novel solutions to diagnose patients with out-of-hospital onset of arrhythmic symptoms can be easily used to record such events, but the effectiveness of these devices remain unknown.Methods: In a group of 100 consecutive patients of an academic cardiology care center (mean age 68 ± 14.2 years, males: 66%) a standard 12-lead electrocardiogram (ECG) and a Kardia Mobile (KM) record were registered. Both versions were assessed by three independant groups of physicians.Results: The analysis of comparisons for standard ECG and KM records showed that the latter is of lower quality (p < 0.001). It was non-inferior for detection of atrial fibrillation and atrial flutter, showed weaker rhythm detection in pacemaker stimulation (p = 0.008), and was superior in sinus rhythm detection (p = 0.02), though. The sensitivity of KM to detect pathological Q-wave was low compared to specificity (20.6% vs. 93.7%, respectively, p < 0.001). Basic intervals measured by the KM device, namely PQ, RR, and QT were significantly different (shorter) than those observed in the standard ECG method (160 ms vs. 180 ms [p < 0.001], 853 ms vs. 880 ms [p = 0.03] and 393 ms vs. 400 ms[p < 0.001], respectively).Conclusions: Initial and indicative value of atrial fibrillation and atrial flutter detection in KM is comparable to results achieved in standard ECG. KM was superior in detection of sinus rhythm than eye-ball evaluation of 12-lead ECG. Though, the PQ and QT intervals were shorter in KM as compared to 12-lead ECG. Clinical value needs to be verified in large studies, though

Structural valve deterioration of a mitral Carpentier-Edwards pericardial bioprosthesis in an 87-year-old woman 16 years after its implantation

The second-generation pericardial valve, the Carpentier-Edwards perimount bioprosthetic (CEP) valve, shows dramatically improved durability as compared to the first-generation pericardial valve, and excellent performance has been obtained, in both the aortic and mitral positions. Especially in elderly patients with an implanted CEP valve, reoperation due to structural valve deterioration (SVD) is rarely required. Here, we report the case of an 87-year-old woman with an explanted CEP valve in the mitral position due to SVD, 16 years after its implantation

Overshadowing by fixed- and variable-duration stimuli

Two experiments investigated the effect of the temporal distribution form of a stimulus on its ability to produce an overshadowing effect. The overshadowing stimuli were either of the same duration on every trial, or of a variable duration drawn from an exponential distribution with the same mean duration as that of the fixed stimulus. Both experiments provided evidence that a variable-duration stimulus was less effective than a fixed-duration cue at overshadowing conditioning to a target conditioned stimulus (CS); moreover, this effect was independent of whether the overshadowed CS was fixed or variable. The findings presented here are consistent with the idea that the strength of the association between CS and unconditioned stimulus (US) is, in part, determined by the temporal distribution form of the CS. These results are discussed in terms of time-accumulation and trial-based theories of conditioning and timing

Dorsal hippocampal involvement in conditioned-response timing and maintenance of temporal information in the absence of the CS

Involvement of the dorsal hippocampus (DHPC) in conditioned-response timing and maintaining temporal information across time gaps was examined in an appetitive Pavlovian conditioning task, in which rats with sham and DHPC lesions were first conditioned to a 15-s visual cue. After acquisition, the subjects received a series of non-reinforced test trials, on which the visual cue was extended (45 s) and gaps of different duration, 0.5, 2.5, and 7.5 s, interrupted the early portion of the cue. Dorsal hippocampal-lesioned subjects underestimated the target duration of 15 s and showed broader response distributions than the control subjects on the no-gap trials in the first few blocks of test, but the accuracy and precision of their timing reached the level of that of the control subjects by the last block. On the gap trials, the DHPC-lesioned subjects showed greater rightward shifts in response distributions than the control subjects. We discussed these lesion effects in terms of temporal versus non-temporal processing (response inhibition, generalisation decrement, and inhibitory conditioning)

The Influence of a Firms\u27 Business Strategy on the Downside Risk of Earnings, Accruals and Cash Flow

This study examines whether a firm\u27s business strategy is an underlying determinant of downside risk in accounting earnings and its components. Based on organizational theory we predict that firms following an innovative prospector strategy exhibit lower profitability tendencies than firms following a cost-oriented defender strategy. Further, we anticipate that these strategies are asymmetrically positioned towards environmental uncertainty, with defenders focusing their efforts to efficiency, cost control, and minimizing exposure to downside risk, whereas prospectors direct their resources to flexibility, innovation, and maximizing the growth potential through aggressive expansion to new product markets. We find that prospectors are indeed less profitable than defenders. We also demonstrate that prospectors have greater total and downside earnings risk. Finally, we decompose earnings into accruals and cash flow and show that the higher exposure of prospectors to earnings downside risk is driven by the cash flow component rather than the accrual component. Collectively, our results suggest that considering how strategy interacts with financial reporting attributes is a useful way for evaluating a firms\u27 risk profile

Synthesis of novel Fe3O4 nanostructures surrounded by Ti-MOF nanostructures as bioactive and efficient catalysts in three-component synthesis of new pyrazole derivatives

Synthesis and reporting of new nanoparticles with diverse properties is important in chemistry. A one-step, rapid and controllable synthesis of the new Fe3O4 surrounded in Ti-MOF nanostructures was carried out with microwave technology. After identifying and confirming the structure, Fe3O4 surrounded in Ti-MOF nanostructures was used as a suitable catalyst with high thermal resistance and recyclable in a three-component reaction of phenylhydrazine, malononitrile and aldehyde to synthesis novel pyrazole derivatives. Continuing investigations on Fe3O4 surrounded in Ti-MOF nanostructures, its antimicrobial properties were tested on Gram-positive bacterial species, Gram-negative bacterial species and fungi bacterial. Identification of Fe3O4 surrounded in Ti-MOF nanostructures with morphology and size distribution technique (SEM), surface area technique (BET), Infrared spectroscopy (FT-IR), Energy-Dispersive X-ray spectroscopy (EDX/EDX mapping), and Vibrating Sample Magnetometer (VSM) were performed. Synthesized pyrazole derivatives with Fe3O4 surrounded in Ti-MOF nanostructures than previously reported methods have less synthesis time and high efficiency. In antimicrobial properties high effects were observed based on MIC, MBC, and MFC values

Improvement of Cardiac Function in Mouse Myocardial Infarction after Transplantation of Epigenetically-Modified Bone Marrow Progenitor Cells

OBJECTIVE: To study usefulness of bone marrow progenitor cells (BPCs) epigenetically altered by chromatin modifying agents in mediating heart repair after myocardial infarction in mice. METHODS AND RESULTS: We tested the therapeutic efficacy of bone marrow progenitor cells treated with the clinically-used chromatin modifying agents Trichostatin A (TSA, histone deacetylase inhibitor) and 5Aza-2-deoxycytidine (Aza, DNA methylation inhibitor) in a mouse model of acute myocardial infarction (AMI). Treatment of BPCs with Aza and TSA induced expression of pluripotent genes Oct4, Nanog, Sox2, and thereafter culturing these cells in defined cardiac myocyte-conditioned medium resulted in their differentiation into cardiomyocyte progenitors and subsequently into cardiac myocytes. Their transition was deduced by expression of repertoire of markers: Nkx2.5, GATA4, cardiotroponin T, cardiotroponin I, α-sarcomeric actinin, Mef2c and MHC-α. We observed that the modified BPCs had greater AceH3K9 expression and reduced histone deacetylase1 (HDAC1) and lysine-specific demethylase1 (LSD1) expression compared to untreated BPCs, characteristic of epigenetic changes. Intra-myocardial injection of modified BPCs after AMI in mice significantly improved left ventricular function. These changes were ascribed to differentiation of the injected cells into cardiomyocytes and endothelial cells. CONCLUSION: Treatment of BPCs with Aza and TSA converts BPCs into multipotent cells, which can then be differentiated into myocyte progenitors. Transplantation of these modified progenitor cells into infarcted mouse hearts improved left ventricular function secondary to differentiation of cells in the niche into myocytes and endothelial cells