Behavioral characterization of a mouse model overexpressing DSCR1/ RCAN1

DSCR1/ RCAN1 is a chromosome 21 gene found to be overexpressed in the brains of Down syndrome (DS) and postulated as a good candidate to contribute to mental disability. However, even though Rcan1 knockout mice have pronounced spatial learning and memory deficits, the possible deleterious effects of its overexpression in DS are not well understood. We have generated a transgenic mouse model overexpressing DSCR1/RCAN1 in the brain and analyzed the effect of RCAN1 overexpression on cognitive function. TgRCAN1 mice present a marked disruption of the learning process in a visuo-spatial learning task. However, no significant differences were observed in the performance of the memory phase of the test (removal session) nor in a step-down passive avoidance task, thus suggesting that once learning has been established, the animals are able to consolidate the information in the longer term

Hyaluronan Binding Motifs of USP17 and SDS3 Exhibit Anti-Tumor Activity

BACKGROUND: We previously reported that the USP17 deubiquitinating enzyme having hyaluronan binding motifs (HABMs) interacts with human SDS3 (suppressor of defective silencing 3) and specifically deubiquitinates Lys-63 branched polyubiquitination of SDS3 resulting in negative regulation of histone deacetylase (HDAC) activity in cancer cells. Furthermore, USP17 and SDS3 mutually interact with each other to block cell proliferation in HeLa cells but the mechanism for this inhibition in cell proliferation is not known. We wished to investigate whether the HABMs of USP17 were responsible for tumor suppression activity. METHODOLOGY/PRINCIPAL FINDINGS: Similarly to USP17, we have identified that SDS3 also has three consecutive HABMs and shows direct binding with hyaluronan (HA) using cetylpyridinium chloride (CPC) assay. Additionally, HA oligosaccharides (6-18 sugar units) competitively block binding of endogenous HA polymer to HA binding proteins. Thus, administration of HA oligosaccharides antagonizes the interaction between HA and USP17 or SDS3. Interestingly, HABMs deleted USP17 showed lesser interaction with SDS3 but retain its deubiquitinating activity towards SDS3. The deletion of HABMs of USP17 could not alter its functional regulation on SDS3-associated HDAC activity. Furthermore, to explore whether HABMs in USP17 and SDS3 are responsible for the inhibition of cell proliferation, we investigated the effect of USP17 and SDS3-lacking HABMs on cell proliferation by soft agar, apoptosis, cell migration and cell proliferation assays. CONCLUSIONS: Our results have demonstrated that these HABMs in USP17 and its substrate SDS3 are mainly involved in the inhibition of anchorage-independent tumor growth

Two loop electroweak corrections to Bˉ→Xsγ\bar B\rightarrow X_s\gamma and Bs0→μ+μ−B_s^0\rightarrow \mu^+\mu^- in the B-LSSM

The rare decays $\bar B\rightarrow X_s\gamma$ and $B_s^0\rightarrow \mu^+\mu^-$ are important to research new physics beyond standard model. In this work, we investigate two loop electroweak corrections to $\bar B\rightarrow X_s\gamma$ and $B_s^0\rightarrow \mu^+\mu^-$ in the minimal supersymmetric extension of the SM with local $B-L$ gauge symmetry (B-LSSM), under a minimal flavor violating assumption for the soft breaking terms. In this framework, new particles and new definition of squarks can affect the theoretical predictions of these two processes, with respect to the MSSM. Considering the constraints from updated experimental data, the numerical results show that the B-LSSM can fit the experimental data for the branching ratios of $\bar B\rightarrow X_s\gamma$ and $B_s^0\rightarrow \mu^+\mu^-$. The results of the rare decays also further constrain the parameter space of the B-LSSM.Comment: 33 pages, 9 figures, Published in EPJ

Structured cost analysis of robotic TME resection for rectal cancer:a comparison between the da Vinci Si and Xi in a single surgeon's experience

Background: Robotic-assisted surgery by the da Vinci Si appears to benefit rectal cancer surgery in selected patients, but still has some limitations, one of which is its high costs. Preliminary studies have indicated that the use of the new da Vinci Xi provides some added advantages, but their impact on cost is unknown. The aim of the present study is to compare surgical outcomes and costs of rectal cancer resection by the two platforms, in a single surgeon’s experience. Methods: From April 2010 to April 2017, 90 robotic rectal resections were performed, with either the da Vinci Si (Si-RobTME) or the da Vinci Xi (Xi-RobTME). Based on CUSUM analysis, two comparable groups of 40 consecutive Si-RobTME and 40 consecutive Xi-RobTME were obtained from the prospectively collected database and used for the present retrospective comparative study. Data costs were analysed based on the level of experience on the proficiency–gain curve (p–g curve) by the surgeon with each platform. Results: In both groups, two homogeneous phases of the p–g curve were identified: Si1 and Xi1: cases 1–19, Si2 and Xi2: cases 20–40. A significantly higher number of full RAS operations were achieved in the Xi-RobTME group (p < 0.001). A statistically significant reduction in operating time (OT) during Si2 and Xi2 phase was observed (p < 0.001), accompanied by reduced overall variable costs (OVC), personnel costs (PC) and consumable costs (CC) (p < 0.001). All costs were lower in the Xi2 phase compared to Si2 phase: OT 265 versus 290 min (p = 0.052); OVC 7983 versus 10231.9 (p = 0.009); PC 1151.6 versus 1260.2 (p = 0.052), CC 3464.4 versus 3869.7 (p < 0.001). Conclusions: Our experience confirms a significant reduction of costs with increasing surgeon’s experience with both platforms. However, the economic gain was higher with the Xi with shorter OT, reduced PC and CC, in addition to a significantly larger number of cases performed by the fully robotic approach

Individually Modified Saliva Delivery Changes the Perceived Intensity of Saltiness and Sourness

Individuals vary largely in their salivary flow and composition, and given the importance of saliva on perception of taste, this might influence how the tastant stimuli are perceived. We therefore hypothesise that altering the individual salivary flow rates has an impact on the perceived taste intensity. In this study, we investigated the role of saliva amount on the perceived taste intensity by excluding parotid saliva and adding artificial saliva close to the parotid duct at preset flow rates. Significant decreases in perception with increasing salivary flow rates were observed for citric acid and sodium chloride. This can partially be explained by a dilution effect which is in line with previous studies on detectable concentration differences. However, since the bitterness and sweetness remained unaffected by the salivary flow conditions and the dilution effect was comparable to that of saltiness, further explanation is needed. Furthermore, we investigated whether the suppression of taste intensity in binary mixtures (taste–taste interactions) could possibly be caused by the increased salivary flow rate induced by an additional taste attribute. The results show, however, that suppression of taste intensity in binary mixtures was not affected by the rate of salivation. This was more likely to be explained by psychophysics

A three-dimensional comparison of a morphometric and conventional cephalometric midsagittal planes for craniofacial asymmetry

Morphometric methods are used in biology to study object symmetry in living organisms and to determine the true plane of symmetry. The aim of this study was to determine if there are clinical differences between three-dimensional (3D) cephalometric midsagittal planes used to describe craniofacial asymmetry and a true symmetry plane derived from a morphometric method based on visible facial features. The sample consisted of 14 dry skulls (9 symmetric and 5 asymmetric) with metallic markers which were imaged with cone-beam computed tomography. An error study and statistical analysis were performed to validate the morphometric method. The morphometric and conventional cephalometric planes were constructed and compared. The 3D cephalometric planes constructed as perpendiculars to the Frankfort horizontal plane resembled the morphometric plane the most in both the symmetric and asymmetric groups with mean differences of less than 1.00 mm for most variables. However, the standard deviations were often large and clinically significant for these variables. There were clinically relevant differences (>1.00 mm) between the different 3D cephalometric midsagittal planes and the true plane of symmetry determined by the visible facial features. The difference between 3D cephalometric midsagittal planes and the true plane of symmetry determined by the visible facial features were clinically relevant. Care has to be taken using cephalometric midsagittal planes for diagnosis and treatment planning of craniofacial asymmetry as they might differ from the true plane of symmetry as determined by morphometrics

Unintended learning in primary school practical science lessons from Polanyi’s perspective of intellectual passion

This study explored, from the perspective of intellectual passion developed by Michael Polanyi, the unintended learning that occurred in primary practical science lessons. We use the term ‘unintended’ learning to distinguish it from ‘intended’ learning that appears in teachers’ learning objectives. Data were collected using video and audio recordings of a sample of twenty-four whole class practical science lessons, taught by five teachers, in Korean primary schools with 10- to 12-year-old students. In addition, video and audio recordings were made for each small group of students working together in order to capture their activities and intra-group discourse. Pre-lesson interviews with the teachers were undertaken and audio-recorded to ascertain their intended learning objectives. Selected key vignettes, including unintended learning, were analysed from the perspective of intellectual passion developed by Polanyi. What we found in this study is that unintended learning could occur when students got interested in something in the first place and could maintain their interest. In addition, students could get conceptual knowledge when they tried to connect their experience to their related prior knowledge. It was also found that the processes of intended learning and of unintended learning were different. Intended learning was characterized by having been planned by the teacher who then sought to generate students’ interest in it. In contrast, unintended learning originated from students’ spontaneous interest and curiosity as a result of unplanned opportunities. Whilst teachers’ persuasive passion comes first in the process of intended learning, students’ heuristic passion comes first in the process of unintended learning. Based on these findings, we argue that teachers need to be more aware that unintended learning, on the part of individual students, can occur during their lesson and to be able to better use this opportunity so that this unintended learning can be shared by the whole class. Furthermore, we argue that teachers’ deliberate action and a more interactive classroom culture are necessary in order to allow students to develop, in addition to heuristic passion, persuasive passion towards their unintended learning

Cadmium resistance in tobacco plants expressing the MuSI gene

MuSI, a gene that corresponds to a domain that contains the rubber elongation factor (REF), is highly homologous to many stress-related proteins in plants. Since MuSI is up-regulated in the roots of plants treated with cadmium or copper, the involvement of MuSI in cadmium tolerance was investigated in this study. Escherichia coli cells overexpressing MuSI were more resistant to Cd than wild-type cells transfected with vector alone. MuSI transgenic plants were also more resistant to Cd. MuSI transgenic tobacco plants absorbed less Cd than wild-type plants. Cd translocation from roots to shoots was reduced in the transgenic plants, thereby avoiding Cd toxicity. The number of short trichomes in the leaves of wild-type tobacco plants was increased by Cd treatment, while this was unchanged in MuSI transgenic tobacco. These results suggest that MuSI transgenic tobacco plants have enhanced tolerance to Cd via reduced Cd uptake and/or increased Cd immobilization in the roots, resulting in less Cd translocation to the shoots

Optimal Use of Conservation and Accessibility Filters in MicroRNA Target Prediction

It is generally accepted that filtering microRNA (miRNA) target predictions by conservation or by accessibility can reduce the false discovery rate. However, these two strategies are usually not exploited in a combined and flexible manner. Here, we introduce PACCMIT, a flexible method that filters miRNA binding sites by their conservation, accessibility, or both. The improvement in performance obtained with each of these three filters is demonstrated on the prediction of targets for both i) highly and ii) weakly conserved miRNAs, i.e., in two scenarios in which the miRNA-target interactions are subjected to different evolutionary pressures. We show that in the first scenario conservation is a better filter than accessibility (as both sensitivity and precision are higher among the top predictions) and that the combined filter improves performance of PACCMIT even further. In the second scenario, on the other hand, the accessibility filter performs better than both the conservation and combined filters, suggesting that the site conservation is not equally effective in rejecting false positive predictions for all miRNAs. Regarding the quality of the ranking criterion proposed by Robins and Press and used in PACCMIT, it is shown that top ranking interactions correspond to more downregulated proteins than do the lower ranking interactions. Comparison with several other target prediction algorithms shows that the ranking of predictions provided by PACCMIT is at least as good as the ranking generated by other conservation-based methods and considerably better than the energy-based ranking used in other accessibility-based methods