A new approach to investigative interviews with children: what can we learn from the interviewers?

Abstract available at each chapte

The Histone Deacetylase Complex (HDC) 1 protein of Arabidopsis thaliana has the capacity to interact with multiple proteins including histone 3-binding proteins and histone 1 variants

Intrinsically disordered proteins can adopt multiple conformations thereby enabling interaction with a wide variety of partners. They often serve as hubs in protein interaction networks. We have previously shown that the Histone Deacetylase Complex (HDC) 1 protein from Arabidopsis thaliana interacts with histone deacetylases and quantitatively determines histone acetylation levels, transcriptional activity and several phenotypes, including ABA-sensitivity during germination, vegetative growth rate and flowering time. HDC1-type proteins are ubiquitous in plants but they contain no known structural or functional domains. Here we explored the protein interaction spectrum of HDC1. In addition to binding histone deacetylases, HDC1 directly interacted with core histone H3-binding proteins and co-repressor associated proteins, but not with H3 or the co-repressors themselves. Surprisingly, HDC1 was also able to interact with variants of the linker histone H1. Truncation of HDC1 to the ancestral core sequence narrowed the spectrum of interactions and of phenotypic outputs but maintained binding to a H3-binding protein and to H1. The results indicate a potential link between H1 and histone modifying complexes

Deformation in the Greiner Shear Zone ̶ Pfitsch Valley, Southwestern Tauern Window

The Greiner Shear Zone is located within the Subpenninic core of the southwestern Tauern Window, Eastern Alps. It strikes SW-NE and separates the upright folded Zillertaler and Tuxer Zentralgneis Nappes from one another, whilst transecting their parautochthonous cover and allochthonous hanging-wall units. The Greiner Shear Zone is generally regarded as a transpressive shear zone, composed of multiple high strain zone splays, in which dextral, but dominantly sinistral shear sense indicators have been reported (Behrmann & Frisch 1990; Barnes et al. 2004). Deformation in the Greiner Shear Zone is pervasive and characterized by a sub-vertical foliation and west-southwest plunging lineation. However, the tectono-metamorphic history of the Greiner Shear Zone has not yet been fully clarified. To better constrain the structural architecture, kinematics, relative timing and spatial extent of the Greiner Shear Zone, geologic mapping within the Pfitsch Valley was carried out and structural data were collected. Optical and scanning electron microscopy analyses including EBSD were utilized to characterize the microstructure of deformed Furtschagl Schists incorporated within the shear zone. Deformed, inter-tectonic(ally grown) biotite porphyroblasts were characterized to ascertain the finite deformation history, as well as conduct a Schmid Factor analysis for (001)-slip of biotite grains, which is indicative of post-growth kinematics. Crystallographic dispersion axes of quartz grains were used to derive a vorticity axes distribution to better constrain the kinematics of the late Greiner Shear Zone. Furthermore, thermodynamic modelling using Theriak Domino was conducted to constrain the metamorphic evolution for shear zone samples stemming from the Furtschagl Schists, Venediger Nappe and Glockner Nappe. Geologic mapping resulted in a new geologic map of the study area, and three cross-sections constructed perpendicular to strike of the Greiner Shear Zone of the Pfitsch Valley section. Unoriented biotite grains in the Furtschagl Schist are interpreted to have grown a) over a pre-existing foliation and b) prior to the (late) Greiner Shear Zone activity, the latter resulting in a co-planar fabric with a rather minute overprint of the pre-existing deformation fabric. Schmid Factor analysis on those biotites indicates a sub-horizontal to N-plunging, N-S directed compression direction which resulted in sinistral shearing at the time deformation was ceasing. Results of the crystallographic dispersion axis analyses suggest shallow NE to E plunging axes on a shallow N- to steep NW-dipping flow plane, respectively. Based on the petrological investigations and thermodynamic modelling, a clockwise pT-path from blueschist facies to amphibolite facies conditions of approx. ~570°C and 6.8-7.5 kb could be derived for the Furtschagl Schists of the Venediger Nappe. Peak amphibolite facies conditions occur at the transition from early, syn-kinematic Greiner shearing to an inter-tectonic phase (Tauern Crystallization) as indicated by garnet and biotite growth. Therefore, post-Tauern Crystallization deformation of the Greiner Shear Zone within the Furtschagl Schists is the result of general shear dominated transpression at amphibolite facies metamorphic conditions, linked to sinistral strike-slip kinematics, which were active during N-S directed compression. The shear zone is further interpreted to exhibit a heterogenous monoclinic deformation symmetry, which is likely the result of an interconnected, anastomosing shear zone network

Patient-Reported, Not Performance Based, Outcome Measures Are Correlated With Future Falls in Community Dwelling Older Adults

Background: One-third of community-dwelling older adults fall at least once a year, yet many commonly used performance-based outcome measures for falls have ceiling effects. Additionally, psychological factors such as fear of falling and avoidance behaviors may contribute to fall risk. Purpose: To determine whether balance confidence, fear of falling avoidance behaviors, or performance on high-level mobility outcome measures can predict falls in community-dwelling older adults. Methods: Eighty-nine participants (76 ± 7 years) completed the Activities-specific Balance Confidence Scale (ABC), Fear of Falling Avoidance Behaviors Questionnaire (FFABQ), Functional Gait Assessment (FGA), and Community Balance & Mobility Scale (CB&M) and then recorded their falls for 6 months. Spearman’s rho, a Point-Biserial Correlation, and Receiver Operating Curves were used to analyze the relationship of the selected outcome measures, past falls, and future falls. Results: There were statistically significant correlations between falls and both the ABC (r2=-.235, p=.022) and the FFABQ (r2=.286, p=.019). There was a positive correlation between history of falls and future falls (r=.323, p=.002). The ABC (area under curve [AUC] =.632, p=.038) and the FFABQ (AUC=.655, p=.015) were significant predictors of future falls. The optimal cutoff scores for determining individuals who experienced falls were: ABC-96% (79% sensitivity, 66% specificity) and FFABQ-1.50 (79%, 55%). Conclusion: No single outcome measure was found to be strongly correlated with falls. The ABC, FFABQ, and history of falls were weakly correlated with future falls. A cutoff score of 96% on the ABC and 1.50 on the FFABQ had adequate sensitivity, but low specificity for predicting falls

Community Pediatrics and Growing Kids South Burlington An assessment of collaboration between area pediatricians and integrated services for families of young children in South Burlington, VT

Background: It is widely accepted for pediatric and family medicine practitioners to use developmental screening tools for effective identification of children who require additional support. A recent study in Pediatrics reported that between 2002 and 2009, the percentage of pediatricians using standardized screening tools for developmental delay increased from 23.0% to 47.7%. While improvement was found, less than half of pediatricians used these tools. In addition, it is known that early intervention for children requiring extra support is essential for preventing further delay in reaching milestones. Practitioners’ use of screening tools and their collaboration with their community resources can contribute to better delivery of these services and aid in children meeting developmental milestones.https://scholarworks.uvm.edu/comphp_gallery/1070/thumbnail.jp

Conventionalisation and discrimination as competing pressures on continuous speech-like signals

© John Benjamins Publishing Company. Arbitrary communication systems can emerge from iconic beginnings through processes of conventionalisation via interaction. Here, we explore whether this process of conventionalisation occurs with continuous, auditory signals. We conducted an artificial signalling experiment. Participants either created signals for themselves, or for a partner in a communication game. We found no evidence that the speech-like signals in our experiment became less iconic or simpler through interaction. We hypothesise that the reason for our results is that when it is difficult to be iconic initially because of the constraints of the modality, then iconicity needs to emerge to enable grounding before conventionalisation can occur. Further, pressures for discrimination, caused by the expanding meaning space in our study, may cause more complexity to emerge, again as a result of the restrictive signalling modality. Our findings have possible implications for the processes of conventionalisation possible in signed and spoken languages, as the spoken modality is more restrictive than the manual modality

Senataxin modulates resistance to cisplatin through an R-loop mediated mechanism in HPV-associated Head and Neck Squamous Cell Carcinoma

AbstractIntroductionOropharyngeal Squamous Cell Carcinoma (OPSCC) is a site defined subtype of head and neck cancer with two distinct clinical subtypes: HPV-associated (HPV+) and HPV-independent (HPV-); both of which are commonly treated with chemoradiotherapy involving cisplatin. Cisplatin creates DNA crosslinks, which lead to eventual cell death via apoptosis. Clinical outcomes in HPV-OPSCC are poor and although HPV+ has an improved response to therapy, a subset of patients suffer from distant metastases, with a poor prognosis. Therefore, there is a need to understand the molecular basis underlying treatment resistance. A common mechanism of chemotherapy resistance is upregulation of DNA repair, and a major source of endogenous DNA damage are DNA/RNA hybrids, known as R-loops. R-loops are three stranded DNA/RNA hybrids formed in the genome as a by- product of transcription and are normally transient; however, they can persist and become a source of genomic instability. The contribution of R-loops to the development of cisplatin resistance in OPSCC is unknown.MethodsHPV+ and HPV- cisplatin resistant cell lines were developed, and RNA-sequencing was used to investigate changes in gene expression. Changes in R-loop dynamics were explored using slot blots and DRIP-qPCR. The effect of depleting known R-loop regulators on cisplatin sensitivity was assessed using siRNA. R-loop burden in a cohort of HPV+ and HPV- OPSCC tumours was explored using S9.6 immunohistochemistry.ResultsDevelopment of cisplatin resistant clones led to changes in gene expression consistent with resistance, alongside alterations in the expression of known R-loop regulators. Both HPV+ and HPV- resistant cells had elevated global R-loop levels and in HPV+ resistant cells there was a corresponding upregulation of the R-loop resolving protein, senataxin, which was not observed in HPV- resistant cells. Depletion of senataxin led to increased sensitivity to cisplatin in both HPV+ and HPV- resistant cells, however, the effect was greater in HPV+ cells. Quantification of R-loop levels by S9.6 immunohistochemistry revealed that HPV+ tumours and tumours with bone metastases had a higher R-loop burden.ConclusionR-loops are involved in modulating sensitivity to cisplatin and may represent a potential therapeutic target.</jats:sec