Genetic differences in transcript responses to low-dose ionizing radiation identify tissue functions associated with breast cancer susceptibility.

High dose ionizing radiation (IR) is a well-known risk factor for breast cancer but the health effects after low-dose (LD, <10 cGy) exposures remain highly uncertain. We explored a systems approach that compared LD-induced chromosome damage and transcriptional responses in strains of mice with genetic differences in their sensitivity to radiation-induced mammary cancer (BALB/c and C57BL/6) for the purpose of identifying mechanisms of mammary cancer susceptibility. Unirradiated mammary and blood tissues of these strains differed significantly in baseline expressions of DNA repair, tumor suppressor, and stress response genes.

Crystal structure of human CDC7 kinase in complex with its activator DBF4.

CDC7 is a serine/threonine kinase that is essential for the initiation of eukaryotic DNA replication. CDC7 activity is controlled by its activator, DBF4. Here we present crystal structures of human CDC7-DBF4 in complex with a nucleotide or ATP-competing small molecules, revealing the active and inhibited forms of the kinase, respectively.

The possible price of auditory cueing: influence on obstacle avoidance in Parkinson's disease.

Background: Under carefully controlled conditions, rhythmic auditory cueing can improve gait in patients with Parkinson's disease (PD). In complex environments, attention paid to cueing might adversely affect gait, for example when a simultaneous task-such as avoiding obstacles-has to be executed. We primarily examined whether concurrent auditory cueing interferes with an obstacle avoidance task in patients with PD.

"On" state freezing of gait in Parkinson disease: a paradoxical levodopa-induced complication.

Objective: To describe the phenotype of levodopa-induced "on" freezing of gait (FOG) in Parkinson disease (PD).

Methods: We present a diagnostic approach to separate "on" FOG (deterioration during the "on state") from other FOG forms. Four patients with PD with suspected "on" FOG were examined in the "off state" (>12 hours after last medication intake), "on state" (peak effect of usual medication), and "supra-on" state (after intake of at least twice the usual dose).

MicroRNA regulation of Cbx7 mediates a switch of Polycomb orthologs during ESC differentiation.

The Polycomb Group (PcG) of chromatin modifiers regulates pluripotency and differentiation. Mammalian genomes encode multiple homologs of the Polycomb repressive complex 1 (PRC1) components, including five orthologs of the Drosophila Polycomb protein (Cbx2, Cbx4, Cbx6, Cbx7, and Cbx8). We have identified Cbx7 as the primary Polycomb ortholog of PRC1 complexes in embryonic stem cells (ESCs).

[The role of Robben Island as a stock breeding station for the settlement at the Cape of Good Hope].

The universal notoriety of Robben Island as a penitentiary for political prisoners, notably in the 19th and 20th centuries, overshadows its previous historical significance established centuries ago. The Island, initially a source of seals and penguins to European mariners rounding the southern tip of Africa, and later for several other reasons, including its proximity to the Cape of Good Hope, played a pivotal role in the selection of this halfway station. The seals would provide blubber for train oil and the penguins, meat and eggs.

Two distinct routes to oral cancer differing in genome instability and risk for cervical node metastasis.

Purpose: Problems in management of oral cancers or precancers include identification of patients at risk for metastasis, tumor recurrence, and second primary tumors or risk for progression of precancers (dysplasia) to cancer. Thus, the objective of this study was to clarify the role of genomic aberrations in oral cancer progression and metastasis.

Experimental Design: The spectrum of copy number alterations in oral dysplasia and squamous cell carcinomas (SCC) was determined by array comparative genomic hybridization.

Freezer or non-freezer: clinical assessment of freezing of gait.

Introduction: Freezing of gait (FOG) is both common and debilitating in patients with Parkinson's disease (PD). Future pathophysiology studies will depend critically upon adequate classification of patients as being either 'freezers' or 'non-freezers'. This classification should be based ideally upon objective confirmation by an experienced observer during clinical assessment.

Bicycling breaks the ice for freezers of gait.

Patients with freezing of gait (FOG) have episodic problems with generating adequate steps. This phenomenon is both common and debilitating in patients with Parkinson's disease (PD) or atypical parkinsonism. We recently presented a video case of a patient with longstanding PD and severe FOG, who showed a remarkably preserved ability to ride a bicycle.

Structural basis for CRISPR RNA-guided DNA recognition by Cascade.

The CRISPR (clustered regularly interspaced short palindromic repeats) immune system in prokaryotes uses small guide RNAs to neutralize invading viruses and plasmids. In Escherichia coli, immunity depends on a ribonucleoprotein complex called Cascade. Here we present the composition and low-resolution structure of Cascade and show how it recognizes double-stranded DNA (dsDNA) targets in a sequence-specific manner.

Walking patterns in Parkinson's disease with and without freezing of gait.

The pathophysiology underlying freezing of gait (FOG) in Parkinson's disease remains incompletely understood. Patients with FOG ("freezers") have a higher temporal variability and asymmetry of strides compared to patients without FOG ("non-freezers"). We aimed to extend this view, by assessing spatial variability and asymmetry of steps and interlimb coordination between the upper and lower limbs during gait.

Recent advances in the assessment and treatment of falls in Parkinson's disease.

Falls are among the most incapacitating features of Parkinson's disease. Prevention of falls requires a systematic assessment of all contributing factors (with emphasis on freezing of gait and frontal executive dysfunction), and a multidisciplinary treatment approach tailored to the specific pathophysiology of falls for each individual patient.

Gait-related cerebral alterations in patients with Parkinson's disease with freezing of gait.

Freezing of gait is a common, debilitating feature of Parkinson's disease. We have studied gait planning in patients with freezing of gait, using motor imagery of walking in combination with functional magnetic resonance imaging. This approach exploits the large neural overlap that exists between planning and imagining a movement.

Maternal depressive symptoms in relation to perinatal mortality and morbidity: results from a large multiethnic cohort study.

Objective: To explore whether 1) maternal depressive symptoms during pregnancy are associated with preterm birth (PTB), small for gestational age (SGA), a low Apgar score and child loss; 2) maternal smoking mediates the associations; and 3) the associations differ by ethnic background.

Methods: Pregnant women in Amsterdam were approached during their first prenatal visit to participate in the Amsterdam Born Children and their Development study. They filled out a questionnaire covering sociodemographic data, life-style, and (psychosocial) health.

Shotgun proteome analysis utilising mixed mode (reversed phase-anion exchange chromatography) in conjunction with reversed phase liquid chromatography mass spectrometry analysis.

The 2-D peptide separations employing mixed mode reversed phase anion exchange (MM (RP-AX)) HPLC in the first dimension in conjunction with RP chromatography in the second dimension were developed and utilised for shotgun proteome analysis. Compared with strong cation exchange (SCX) typically employed for shotgun proteomic analysis, peptide separations using MM (RP-AX) revealed improved separation efficiency and increased peptide distribution across the elution gradient. In addition, improved sample handling, with no significant reduction in the orthogonality of the peptide separations was observed.

Comparative network clustering of direct repeats (DRs) and cas genes confirms the possibility of the horizontal transfer of CRISPR locus among bacteria.

CRISPRs are a diverse family of DNA repeat sequences that are widely distributed among archaea and bacteria. The CRISPR locus is usually composed of three key elements; direct repeats (DRs), spacer sequences and the cas genes. Although recent studies have suggested that spacers may be of extrachromosomal origin, the evolutionary origin of the other two elements of the CRISPR locus has remained unresolved.

Objective detection of subtle freezing of gait episodes in Parkinson's disease.

Freezing of gait (FOG) is a clinically defined phenomenon of Parkinson's disease (PD). Recent evidence suggests that subtle FOG episodes can be elicited in a gait laboratory using suddenly appearing obstacles during treadmill walking. We evaluated which quantitative gait parameters identify such subtle FOG episodes.

Arginine methylation of REF/ALY promotes efficient handover of mRNA to TAP/NXF1.

The REF/ALY mRNA export adaptor binds TAP/NXF1 via an arginine-rich region, which overlaps with its RNA-binding domain. When TAP binds a REF:RNA complex, it triggers transfer of the RNA from REF to TAP. Here, we have examined the effects of arginine methylation on the activities of the REF protein in mRNA export.

Obstacle avoidance to elicit freezing of gait during treadmill walking.

Freezing of gait (FOG) is a common and disabling feature of Parkinson's disease (PD). Detailed pathophysiological studies are hampered by the fact that FOG episodes are difficult to elicit in a gait laboratory. We evaluated whether the need to avoid sudden obstacles on a treadmill can provoke FOG.

Analysis of arginine and lysine methylation utilizing peptide separations at neutral pH and electron transfer dissociation mass spectrometry.

Arginine and lysine methylation are widespread protein post-translational modifications. Peptides containing these modifications are difficult to retain using traditional reversed-phase liquid chromatography because they are intrinsically basic/hydrophilic and often fragment poorly during collision induced fragmentation (CID). Therefore, they are difficult to analyze using standard proteomic workflows.

UIF, a New mRNA export adaptor that works together with REF/ALY, requires FACT for recruitment to mRNA.

Messenger RNA (mRNA) export adaptors play an important role in the transport of mRNA from the nucleus to the cytoplasm. They couple early mRNA processing events such as 5' capping and 3' end formation with loading of the TAP/NXF1 export receptor onto mRNA. The canonical adaptor REF/ALY/Yra1 is recruited to mRNA via UAP56 and subsequently delivers the mRNA to NXF1 [1].

Structure of the ribosome associating GTPase HflX.

The HflX-family is a widely distributed but poorly characterized family of translation factor-related guanosine triphosphatases (GTPases) that interact with the large ribosomal subunit. This study describes the crystal structure of HflX from Sulfolobus solfataricus solved to 2.0-A resolution in apo- and GDP-bound forms.