Intrinsically disordered Meningioma-1 stabilizes the BAF complex to cause AML

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The Tick-Tock of Language: Is Language Processing Sensitive to Circadian Rhythmicity and Elevated Sleep Pressure?

The master circadian pacemaker emits signals that trigger organ-specific oscillators and, therefore, constitutes a basic biological process that enables organisms to anticipate daily environmental changes by adjusting behavior, physiology, and gene regulation. Although circadian rhythms are well characterized on a physiological level, little is known about circadian modulations of higher cognitive functions. Thus, we investigated circadian repercussions on language performance at the level of minimal syntactic processing by means of German noun phrases in ten young healthy men under the unmasking conditions of a 40 h constant-routine protocol. Language performance for both congruent and incongruent noun phrases displayed a clear diurnal rhythm with a peak performance decrement during the biological night. The nadirs, however, differed such that worst syntactic processing of incongruent noun phrases occurred 3 h earlier (07:00 h) than that of congruent noun phrases (10:00 h). Our results indicate that language performance displays an internally generated circadian rhythmicity with optimal time for parsing language between 3 to 6 h after the habitual wake time, which usually corresponds to 10:00–13:00 h. These results may have important ramifications for establishing optimal times for shiftwork changes or testing linguistically impaired people.     

Comparative characterization of novel ene‐reductases from cyanobacteria

The growing importance of biocatalysis in the syntheses of enantiopure molecules results from the benefits of enzymes regarding selectivity and specificity of the reaction and ecological issues of the process. Ene‐reductases (ERs) from the old yellow enzyme family have received much attention in the last years. These flavo‐enzymes catalyze the trans‐specific reduction of activated C?C bonds, which is an important reaction in asymmetric synthesis, because up to two stereogenic centers can be created in one reaction. However, limitations of ERs described in the literature such as their moderate catalytic activity and their strong preference for NADPH promote the search for novel ERs with improved properties. In this study, we characterized nine novel ERs from cyanobacterial strains belonging to different taxonomic orders and habitats. ERs were identified with activities towards a broad spectrum of alkenes. The reduction of maleimide was catalyzed with activities of up to 35.5 U mg^?1 using NADPH. Ketoisophorone and (R)‐carvone, which were converted to the highly valuable compounds (R)‐levodione and (2R,5R)‐dihydrocarvone, were reduced with reaction rates of up to 2.2 U mg^?1 with NADPH. In contrast to other homologous ERs from the literature, NADH was accepted at moderate to high rates as well: Enzyme activities of up to 16.7 U mg^?1 were obtained for maleimide and up to 1.3 U mg^?1 for ketoisophorone and (R)‐carvone. Additionally, excellent stereoselectivities were achieved in the reduction of (R)‐carvone (97–99% de). In particular, AnabaenaER3 from Anabaena variabilis ATCC 29413 and AcaryoER1 from Acaryochloris marina MBIC 11017 were identified as useful biocatalysts. Therefore, novel ERs from cyanobacteria with high catalytic efficiency were added to the toolbox for the asymmetric reduction of alkenes. Biotechnol. Bioeng. 2013; 110: 1293–1301. © 2012 Wiley Periodicals, Inc.     

Differential Effects of Motor Efference Copies and Proprioceptive Information on Response Evaluation Processes

It is well-kown that sensory information influences the way we execute motor responses. However, less is known about if and how sensory and motor information are integrated in the subsequent process of response evaluation. We used a modified Simon Task to investigate how these streams of information are integrated in response evaluation processes, applying an in-depth neurophysiological analysis of event-related potentials (ERPs), time-frequency decomposition and sLORETA. The results show that response evaluation processes are differentially modulated by afferent proprioceptive information and efference copies. While the influence of proprioceptive information is mediated via oscillations in different frequency bands, efference copy based information about the motor execution is specifically mediated via oscillations in the theta frequency band. Stages of visual perception and attention were not modulated by the interaction of proprioception and motor efference copies. Brain areas modulated by the interactive effects of proprioceptive and efference copy based information included the middle frontal gyrus and the supplementary motor area (SMA), suggesting that these areas integrate sensory information for the purpose of response evaluation. The results show how motor response evaluation processes are modulated by information about both the execution and the location of a response.     

Inter-Physician Variation in Follow-Up Colonoscopies after Screening Colonoscopy

Background and Aims

Surveillance is an integral part of the colorectal cancer (CRC) screening process. We aimed to investigate inter-physician variation in follow-up procedures after screening colonoscopy in an opportunistic CRC screening program.

Methods

A historical cohort study in the German statutory health insurance system was conducted. 55,301 individuals who underwent screening colonoscopy in 2006 in Bavaria, Germany, and who were not diagnosed with CRC were included. Utilization of follow-up colonoscopies performed by the same physician (328 physicians overall) within 3 years was ascertained. Mixed effects logistic regression modelling was used to assess the effect of physicians and other potential predictors (screening result, age group, and sex) on re-utilization of colonoscopy. Physicians were grouped into quintiles according to individual effects estimated in a preliminary model. Predicted probabilities of follow-up colonoscopy by screening result and physician group were calculated.

Results

The observed rate of follow-up colonoscopy was 6.2% (95% confidence interval: 5.9-6.4%), 18.6% (17.8-19.4%), and 37.0% (35.5-38.4%) after negative colonoscopy, low-risk adenoma and high-risk adenoma detection, respectively. All considered predictors were statistically significantly associated with follow-up colonoscopy. The predicted probabilities of follow-up colonoscopy ranged from 1.7% (1.4-2.0%) to 11.0% (10.2-11.7%), from 7.3% (6.2-8.5%) to 35.1% (32.6-37.7%), and from 17.9% (15.5-20.6%) to 56.9% (53.5-60.3%) in the 1^st quintile (lowest rates of follow-up) and 5^th quintile (highest rates of follow-up) of physicians after negative colonoscopy, low-risk adenoma and high-risk adenoma detection, respectively.

Conclusions

This study suggests substantial inter-physician variation in follow-up habits after screening colonoscopy. Interventions, including organizational changes in CRC screening should be considered to reduce this variation.     

Transferrin-Directed Internalization and Cycling of Transferrin Receptor 2

Transferrin receptor 2 (TfR2) is a homologue of transferrin receptor 1 (TfR1) but has distinct functions from TfR1 in iron homeostasis. In keeping with its proposed role in iron sensing, previous studies showed that TfR2 has a short half-life and that holo-Tf stabilizes TfR2 by redirecting it from a degradative pathway to a recycling pathway. In this study, we characterized how the endocytosis, recycling and degradation of TfR2 relates to its function and differs from TfR1. TfR2 endocytosis was adaptor protein-2 (AP-2) dependent. Flow cytometry analysis showed that TfR1 and TfR2 utilized the same endocytic pathway only in the presence of holo-Tf, indicating that holo-Tf alters the interaction of TfR2 with the endocytic machinery. Unlike TfR1, phosphofurin acidic cluster sorting protein 1 (PACS-1) binds to the cytoplasmic domain of TfR2 and data suggest that PACS-1 is involved in the TfR2 recycling. Depletion of TSG101 by siRNA or expression of a dominant negative Vps4 inhibited TfR2 degradation, indicating that TfR2 degradation occurs through a multivesicular body (MVB) pathway. TfR2 degradation is not mediated through ubiquitination on the single lysine (K31) in the cytoplasmic domain or on the amino terminal residue. No ubiquitination of TfR2 by HA-ubiquitin was detected, indicating a lack of direct TfR2 ubiquitination involvement in its degradation.