High Magnetic Field Microwave Conductivity of 2D Electrons in an Array of Antidots

We measure the high magnetic field ($B$) microwave conductivity, Re$\sigma_{xx}$, of a high mobility 2D electron system containing an antidot array. Re$\sigma_{xx}$ vs frequency ($f$) increases strongly in the regime of the fractional quantum Hall effect series, with Landau filling $1/3<\nu<2/3$. At microwave $f$, Re$\sigma_{xx}$ vs $B$ exhibits a broad peak centered around $\nu=1/2$. On the peak, the 10 GHz Re$\sigma_{xx}$ can exceed its dc-limit value by a factor of 5. This enhanced microwave conductivity is unobservable for temperature $T \gtrsim 0.5$ K, and grows more pronounced as $T$ is decreased. The effect may be due to excitations supported by the antidot edges, but different from the well-known edge magnetoplasmons.Comment: 4 pages, 3 figures, revtex

Assessing stimulus–stimulus (semantic) conflict in the Stroop task using saccadic two-to-one color response mapping and preresponse pupillary measures

© 2015, The Psychonomic Society, Inc. Conflict in the Stroop task is thought to come from various stages of processing, including semantics. Two-to-one response mappings, in which two response-set colors share a common response location, have been used to isolate stimulus–stimulus (semantic) from stimulus–response conflict in the Stroop task. However, the use of congruent trials as a baseline means that the measured effects could be exaggerated by facilitation, and recent research using neutral, non-color-word trials as a baseline has supported this notion. In the present study, we sought to provide evidence for stimulus–stimulus conflict using an oculomotor Stroop task and an early, preresponse pupillometric measure of effort. The results provided strong (Bayesian) evidence for no statistical difference between two-to-one response-mapping trials and neutral trials in both saccadic response latencies and preresponse pupillometric measures, supporting the notion that the difference between same-response and congruent trials indexes facilitation in congruent trials, and not stimulus–stimulus conflict, thus providing evidence against the presence of semantic conflict in the Stroop task. We also demonstrated the utility of preresponse pupillometry in measuring Stroop interference, supporting the idea that pupillary effects are not simply a residue of making a response

Neural dynamics of shooting decisions and the switch from freeze to fight

Real-life shooting decisions typically occur under acute threat and require fast switching between vigilant situational assessment and immediate fight-or-flight actions. Recent studies suggested that freezing facilitates action preparation and decision-making but the neurocognitive mechanisms remain unclear. We applied functional magnetic resonance imaging, posturographic and autonomic measurements while participants performed a shooting task under threat of shock. two independent studies, in unselected civilians (N = 22) and police recruits (N = 54), revealed that preparation for shooting decisions under threat is associated with postural freezing, bradycardia, midbrain activity (including the periaqueductal gray-PAG) and PAG-amygdala connectivity. Crucially, stronger activity in the midbrain/pAG during this preparatory stage of freezing predicted faster subsequent accurate shooting. Finally, the switch from preparation to active shooting was associated with tachycardia, perigenual anterior cingulate cortex (pgACC) activity and pgACC-amygdala connectivity. These findings suggest that threat-anticipatory midbrain activity centred around the PAG supports decision-making by facilitating action preparation and highlight the role of the pgACC when switching from preparation to action. These results translate animal models of the neural switch from freeze-to-action. In addition, they reveal a core neural circuit for shooting performance under threat and provide empirical evidence for the role of defensive reactions such as freezing in subsequent action decision-making

Biosynthetic Gene Cluster for the Cladoniamides, Bis-Indoles with a Rearranged Scaffold

The cladoniamides are bis-indole alkaloids isolated from Streptomyces uncialis, a lichen-associated actinomycete strain. The cladoniamides have an unusual, indenotryptoline structure rarely observed among bis-indole alkaloids. I report here the isolation, sequencing, and annotation of the cladoniamide biosynthetic gene cluster and compare it to the recently published gene cluster for BE-54017, a closely related indenotryptoline natural product. The cladoniamide gene cluster differs from the BE-54017 gene cluster in gene organization and in the absence of one N-methyltransferase gene but otherwise contains close homologs to all genes in the BE-54017 cluster. Both gene clusters encode enzymes needed for the construction of an indolocarbazole core, as well as flavin-dependent enzymes putatively involved in generating the indenotryptoline scaffold from an indolocarbazole. These two bis-indolic gene clusters exemplify the diversity of biosynthetic routes that begin from the oxidative dimerization of two molecules of l-tryptophan, highlight enzymes for further study, and provide new opportunities for combinatorial engineering

RAD21 Cooperates with Pluripotency Transcription Factors in the Maintenance of Embryonic Stem Cell Identity

For self-renewal, embryonic stem cells (ESCs) require the expression of specific transcription factors accompanied by a particular chromosome organization to maintain a balance between pluripotency and the capacity for rapid differentiation. However, how transcriptional regulation is linked to chromosome organization in ESCs is not well understood. Here we show that the cohesin component RAD21 exhibits a functional role in maintaining ESC identity through association with the pluripotency transcriptional network. ChIP-seq analyses of RAD21 reveal an ESC specific cohesin binding pattern that is characterized by CTCF independent co-localization of cohesin with pluripotency related transcription factors Oct4, Nanog, Sox2, Esrrb and Klf4. Upon ESC differentiation, most of these binding sites disappear and instead new CTCF independent RAD21 binding sites emerge, which are enriched for binding sites of transcription factors implicated in early differentiation. Furthermore, knock-down of RAD21 causes expression changes that are similar to expression changes after Nanog depletion, demonstrating the functional relevance of the RAD21 - pluripotency transcriptional network association. Finally, we show that Nanog physically interacts with the cohesin or cohesin interacting proteins STAG1 and WAPL further substantiating this association. Based on these findings we propose that a dynamic placement of cohesin by pluripotency transcription factors contributes to a chromosome organization supporting the ESC expression program

Dosage Effects of Cohesin Regulatory Factor PDS5 on Mammalian Development: Implications for Cohesinopathies

Cornelia de Lange syndrome (CdLS), a disorder caused by mutations in cohesion proteins, is characterized by multisystem developmental abnormalities. PDS5, a cohesion protein, is important for proper chromosome segregation in lower organisms and has two homologues in vertebrates (PDS5A and PDS5B). Pds5B mutant mice have developmental abnormalities resembling CdLS; however the role of Pds5A in mammals and the association of PDS5 proteins with CdLS are unknown. To delineate genetic interactions between Pds5A and Pds5B and explore mechanisms underlying phenotypic variability, we generated Pds5A-deficient mice. Curiously, these mice exhibit multiple abnormalities that were previously observed in Pds5B-deficient mice, including cleft palate, skeletal patterning defects, growth retardation, congenital heart defects and delayed migration of enteric neuron precursors. They also frequently display renal agenesis, an abnormality not observed in Pds5B−/− mice. While Pds5A−/− and Pds5B−/− mice die at birth, embryos harboring 3 mutant Pds5 alleles die between E11.5 and E12.5 most likely of heart failure, indicating that total Pds5 gene dosage is critical for normal development. In addition, characterization of these compound homozygous-heterozygous mice revealed a severe abnormality in lens formation that does not occur in either Pds5A−/− or Pds5B−/− mice. We further identified a functional missense mutation (R1292Q) in the PDS5B DNA-binding domain in a familial case of CdLS, in which affected individuals also develop megacolon. This study shows that PDS5A and PDS5B functions other than those involving chromosomal dynamics are important for normal development, highlights the sensitivity of key developmental processes on PDS5 signaling, and provides mechanistic insights into how PDS5 mutations may lead to CdLS

Early Weight Bearing of Calcaneal Fractures Treated by Intraoperative 3D-Fluoroscopy and Locked-Screw Plate Fixation

Operative therapy of intraarticular fractures of the calcaneus is an established surgical standard. The aim is an accurate reduction of the fracture with reconstruction of Boehler’s angle, length, axis and subtalar joint surface. Intraoperative 3D-fluoroscopy with the Siremobil Iso-C 3D® mobile C-arm system is a valuable assistant for accurate reconstruction of these anatomical structures. Remaining incongruities can be recognized and corrected intraoperatively. The achieved reduction can be fixed by the advantages of an internal fixator (locked-screw plate interface). In the period of October 2002 until April 2007 we operated 136 patients with intraarticular fractures of the calcaneus by means of anatomical reduction, and internal plate fixator under intraoperative control of 3D-fluoroscopy. All patients were supplied with an orthesis after the operation which allowed weight bearing of 10 kg for 12 weeks for the patients operated between October 2002 and October 2004 (Group A). Transient local osteoporosis was observed in all X-Rays at follow-up after an average of 8,6 months. Therefore we changed our postoperative treatment plan for the patients operated between November 2004 and April 2007 (Group B). Weight bearing started with 20 KG after 6 weeks, was increased to 40 KG after 8 weeks and full weight bearing was allowed after 10 weeks for these patients. In no case a secondary dislocation of the fracture was seen. No bone graft was used. At follow up the average American Foot and Ankle Society Score (AOFAS) were 81 for Group_A, compared to 84 for Group B, treated with earlier weight bearing. Autologous bone graft was not necessary even if weight bearing was started after a period of six weeks postoperatively. The combination of 3D-fluoroscopy with locked internal fixation showed promising results. If the rate of patients developing subtalar arthrosis will decrease by this management will have to be shown in long term follow up

A Zebrafish Model of Roberts Syndrome Reveals That Esco2 Depletion Interferes with Development by Disrupting the Cell Cycle

The human developmental diseases Cornelia de Lange Syndrome (CdLS) and Roberts Syndrome (RBS) are both caused by mutations in proteins responsible for sister chromatid cohesion. Cohesion is mediated by a multi-subunit complex called cohesin, which is loaded onto chromosomes by NIPBL. Once on chromosomes, cohesin binding is stabilized in S phase upon acetylation by ESCO2. CdLS is caused by heterozygous mutations in NIPBL or cohesin subunits SMC1A and SMC3, and RBS is caused by homozygous mutations in ESCO2. The genetic cause of both CdLS and RBS reside within the chromosome cohesion apparatus, and therefore they are collectively known as “cohesinopathies”. However, the two syndromes have distinct phenotypes, with differences not explained by their shared ontology. In this study, we have used the zebrafish model to distinguish between developmental pathways downstream of cohesin itself, or its acetylase ESCO2. Esco2 depleted zebrafish embryos exhibit features that resemble RBS, including mitotic defects, craniofacial abnormalities and limb truncations. A microarray analysis of Esco2-depleted embryos revealed that different subsets of genes are regulated downstream of Esco2 when compared with cohesin subunit Rad21. Genes downstream of Rad21 showed significant enrichment for transcriptional regulators, while Esco2-regulated genes were more likely to be involved the cell cycle or apoptosis. RNA in situ hybridization showed that runx1, which is spatiotemporally regulated by cohesin, is expressed normally in Esco2-depleted embryos. Furthermore, myca, which is downregulated in rad21 mutants, is upregulated in Esco2-depleted embryos. High levels of cell death contributed to the morphology of Esco2-depleted embryos without affecting specific developmental pathways. We propose that cell proliferation defects and apoptosis could be the primary cause of the features of RBS. Our results show that mutations in different elements of the cohesion apparatus have distinct developmental outcomes, and provide insight into why CdLS and RBS are distinct diseases

Hemiarthroplasty versus angle-stable locking compression plate osteosynthesis in the treatment of three- and four-part fractures of the proximal humerus in the elderly: design of a randomized controlled trial

ABSTRACT: BACKGROUND: The optimal surgical management of dislocated three- and four-part fractures of the proximal humerus in elderly patients remains unclear. Most used techniques are hemiarthroplasty and angle-stable locking compression plate osteosynthesis. In the current literature there is no evidence available presenting superior results between hemiarthroplasty and angle-stable locking compression plate osteosynthesis in terms of speed of recovery, pain, patient satisfaction, functional outcome, quality of life or complications. METHODS/DESIGN: A randomized controlled multicenter trial will be conducted. Patients older than 60 years of age with a dislocated three- or four-part fracture of the proximal humerus as diagnosed by X-rays and CT-scans will be included. Exclusion criteria are a fracture older than 14 days, multiple comorbidity, multitrauma, a pathological fracture, previous surgery on the injured shoulder, severely deranged function caused by a previous disease, "head-split" proximal humerus fracture and unwillingness or inability to follow instructions. Participants will be randomized between surgical treatment with hemiarthroplasty and angle-stable locking compression plate osteosynthesis. Measurements will take place preoperatively and 3 months, 6 months, 9 months, 12 months and 24 months postoperatively. Primary outcome measure is speed of recovery of functional capacity of the affected upper limb using the Disabilities of Arm, Shoulder and Hand score (DASH). Secondary outcome measures are pain, patient satisfaction, shoulder function, quality of life, radiological evaluation and complications. Data will be analyzed on an intention-to-treat basis, using univariate and multivariate analyses. DISCUSSION: Both hemiarthroplasty and angle-stable locking compression plate osteosynthesis are used in the current treatment of dislocated three-and four-part fractures of the proximal humerus. There is a lack of level-1 studies comparing these two most-used surgical treatment options. This randomized controlled multicenter trial has been designed to determine which surgical treatment option provides the fastest recovery of functional capacity of the affected upper limb, and will provide better outcomes in pain, satisfaction, shoulder function, quality of life, radiological evaluation and complications. TRIAL REGISTRATION NUMBER: The trial is registered in the Netherlands Trial Registry (NTR2461)