N‐terminus of hMLH1 confers interaction of hMutLα and hMutLβ with hMutSα

Mismatch repair is a highly conserved system that ensures replication fidelity by repairing mispairs after DNA synthesis. In humans, the two protein heterodimers hMutSα (hMSH2‐hMSH6) and hMutLα (hMLH1‐hPMS2) constitute the centre of the repair reaction. After recognising a DNA replication error, hMutSα recruits hMutLα, which then is thought to transduce the repair signal to the excision machinery. We have expressed an ATPase mutant of hMutLα as well as its individual subunits hMLH1 and hPMS2 and fragments of hMLH1, followed by examination of their interaction properties with hMutSα using a novel interaction assay. We show that, although the interaction requires ATP, hMutLα does not need to hydrolyse this nucleotide to join hMutSα on DNA, suggesting that ATP hydrolysis by hMutLα happens downstream of complex formation. The analysis of the individual subunits of hMutLα demonstrated that the hMutSα–hMutLα interaction is predominantly conferred by hMLH1. Further experiments revealed that only the N‐terminus of hMLH1 confers this interaction. In contrast, only the C‐terminus stabilised and co‐immunoprecipitated hPMS2 when both proteins were co‐expressed in 293T cells, indicating that dimerisation and stabilisation are mediated by the C‐terminal part of hMLH1. We also examined another human homologue of bacterial MutL, hMutLβ (hMLH1–hPMS1). We show that hMutLβ interacts as efficiently with hMutSα as hMutLα, and that it predominantly binds to hMutSα via hMLH1 as well

A dynamic neural model of localization of brief successive stimuli in saltation

Somatosensory saltation is an illusion robustly generated using short tactile stimuli [1,2]. There is a perceived displacement of a first stimulus if followed by a subsequent nearby stimulus with a short stimulus onset asynchrony (SOA). Experimental reports suggest that this illusion results from spatiotemporal integration in early processing stages, but the exact neural mechanism is unknown. The neuronal mechanism involved is probably quite generic as similar phenomena occur in other modalities, audition for example [3]

SEMS vs cSEMS in duodenal and small bowel obstruction : high risk of migration in the covered stent group

Aim: To compare clinical success and complications of uncovered self-expanding metal stents (SEMS) vs covered SEMS (cSEMS) in obstruction of the small bowel. Methods: Technical success, complications and outcome of endoscopic SEMS or cSEMS placement in tumor related obstruction of the duodenum or jejunum were retrospectively assessed. The primary end points were rates of stent migration and overgrowth. Secondary end points were the effect of concomitant biliary drainage on migration rate and overall survival. The data was analyzed according to the Strengthening the Reporting of Observational Studies in Epidemiology guidelines. Results: Thirty-two SEMS were implanted in 20 patients. In all patients, endoscopic stent implantation was successful. Stent migration was observed in 9 of 16 cSEMS (56%) in comparison to 0/16 SEMS (0%) implantations (P = 0.002). Stent overgrowth did not significantly differ between the two stent types (SEMS: 3/16, 19%; cSEMS: 2/16, 13%). One cSEMS dislodged and had to be recovered from the jejunum by way of laparotomy. Time until migration between SEMS and cSEMS in patients with and without concomitant biliary stents did not significantly differ (HR = 1.530, 95%CI 0.731-6.306; P = 0.556). The mean follow-up was 57 ± 71 d (range: 1-275 d). Conclusion: SEMS and cSEMS placement is safe in small bowel tumor obstruction. However, cSEMS is accompanied with a high rate of migration in comparison to uncovered SEMS

Portal vein thrombosis and arterioportal shunts : effects on tumor response after chemoembolization of hepatocellular carcinoma

AIM: To evaluate the effect of portal vein thrombosis and arterioportal shunts on local tumor response in advanced cases of unresectable hepatocellular carcinoma treated by transarterial chemoembolization. METHODS: A retrospective study included 39 patients (mean age: 66.4 years, range: 45-79 years, SD: 7) with unresectable hepatocellular carcinoma (HCC) who were treated with repetitive transarterial chemoembolization (TACE) in the period between March 2006 and October 2009. The effect of portal vein thrombosis (PVT) (in 19 out of 39 patients), the presence of arterioportal shunt (APS) (in 7 out of 39), the underlying liver pathology, Child-Pugh score, initial tumor volume, number of tumors and tumor margin definition on imaging were correlated with the local tumor response after TACE. The initial and end therapy local tumor responses were evaluated according to the response evaluation criteria in solid tumors (RECIST) and magnetic resonance imaging volumetric measurements. RESULTS: The treatment protocols were well tolerated by all patients with no major complications. Local tumor response for all patients according to RECIST criteria were partial response in one patient (2.6%), stable disease in 34 patients (87.1%), and progressive disease in 4 patients (10.2%). The MR volumetric measurements showed that the PVT, APS, underlying liver pathology and tumor margin definition were statistically significant prognostic factors for the local tumor response (P = 0.018, P = 0.008, P = 0.034 and P = 0.001, respectively). The overall 6-, 12- and 18-mo survival rates from the initial TACE were 79.5%, 37.5% and 21%, respectively. CONCLUSION: TACE may be exploited safely for palliative tumor control in patients with advanced unresectable HCC; however, tumor response is significantly affected by the presence or absence of PVT and APS

Impact of Neoadjuvant Chemotherapy on Postoperative Morbidity after Gastrectomy for Gastric Cancer

Background/Aims: Patients with locally advanced gastric cancer benefit from neoadjuvant chemotherapy. Potential disadvantages of neoadjuvant chemotherapy include increased surgical complications, leading to increased postoperative morbidity. Methods: We retrospectively studied medical records of 135 patients with resectable cancer of the stomach who underwent gastrectomy between 2002 and 2009. The impact of neoadjuvant chemotherapy on postoperative morbidity was investigated. We compared demographic, clinical and operative data, morbidity and mortality from 105 patients who received surgical treatment immediately after diagnosis (SURG group), versus 30 patients who first received neoadjuvant chemotherapy (CHEMO group). Results: Demographic, clinical and surgical procedure parameters did not differ significantly between both groups. Postoperative morbidity was 46.7% in CHEMO- and 41.9% in SURG-patients (p = 0.680). There were eight cases of death, 2/30 (6.7%) in CHEMO and 6/105 (5.7%) in the SURG group (p = 1). The overall complications according to Clavien- classification did not differ significantly (p = 0.455). The wound infection rate (23.3 vs. 3.8%; p = 0.002) and insufficiency of the duodenal stump (13.3 vs. 1.9%; p = 0.022) were significantly higher in the CHEMO group. Conclusion: This study showed no significant impact of neoadjuvant chemotherapy on postoperative morbidity after gastrectomy using the Clavien-classification. Only an increase in wound infections in CHEMO compared with the SURG group were noted. Therefore, neoadjuvant chemotherapy can be considered safe and feasible

The rubber hand illusion induced by visual-thermal stimulation

Trojan J, Fuchs X, Speth S-L, Diers M. The rubber hand illusion induced by visual-thermal stimulation. Scientific Reports. 2018;8(1): 12417.In the rubber hand illusion (RHI), synchronous touch of a real hand and an artificial hand leads to the feeling of the artificial hand belonging to one’s own body. This study examined whether the RHI can be induced using visual–thermal instead of visual–tactile stimulus patterns and to which extent the congruency between temperature and colour of the visual stimulus influences the RHI. In a within-subject design, we presented cold vs. warm thermal stimuli to the participants’ hidden hand combined with red vs. blue visual stimuli presented synchronously vs. asynchronously at a fake hand. The RHI could be induced using visual–thermal stimuli, yielding RHI vividness ratings comparable to the visual-tactile variant. Congruent (warm–red, cold–blue) synchronous stimulus patterns led to higher RHI vividness than incongruent (warm–blue, cold–red) synchronous combinations; in the asynchronous conditions, an inverse effect was present. Temperature ratings mainly depended on the actual stimulus temperature and were higher with synchronous vs. asynchronous patterns; they were also slightly higher with red vs. blue light, but there were no interactions with temperature or synchrony. In conclusion, we demonstrated that the RHI can be induced via visual-thermal stimuli, opening new perspectives in research on multi-sensory integration and body representations

Perceptual drifts of real and artificial limbs in the rubber hand illusion

Fuchs X, Riemer M, Diers M, Flor H, Trojan J. Perceptual drifts of real and artificial limbs in the rubber hand illusion. Scientific Reports. 2016;6(1): 24362

Do Mirror Glasses Have the Same Effect on Brain Activity as a Mirror Box? Evidence from a Functional Magnetic Resonance Imaging Study with Healthy Subjects

Milde C, Rance M, Kirsch P, et al. Do Mirror Glasses Have the Same Effect on Brain Activity as a Mirror Box? Evidence from a Functional Magnetic Resonance Imaging Study with Healthy Subjects. PLOS ONE. 2015;10(5): e0127694

An augmented reality home-training system based on the mirror training and imagery approach

Trojan J, Diers M, Fuchs X, et al. An augmented reality home-training system based on the mirror training and imagery approach. Behavior Research Methods. 2013;46(3):634-640