The teneurin C-terminal domain possesses nuclease activity and is apoptogenic.

Teneurins are type 2 transmembrane proteins expressed by developing neurons during periods of synaptogenesis and apoptosis. Neurons expressing teneurin-1 synapse with other teneurin-1-expressing neurons, and neurons expressing teneurin-2 synapse with other teneurin-2-expressing neurons. Knockdowns and mutations of teneurins lead to abnormal neuronal connections, but the mechanisms underlying teneurin action remain unknown. Teneurins appear to have evolved via horizontal gene transfer from prokaryotic proteins involved in bacterial self-recognition. The bacterial teneurin-like proteins contain a cytotoxic C-terminal domain that is encapsulated in a tyrosine-aspartic acid repeat barrel. Teneurins are likely to be organized in the same way, but it is unclear if the C-terminal domains of teneurins have cytotoxic properties. Here we show that expression of teneurin C-terminal domains or the addition of purified teneurin C-terminal domains leads to an increase in apoptosis in vitro The C-terminal domains of teneurins are most similar to bacterial nucleases, and purified C-terminal domains of teneurins linearize pcDNA3 and hydrolyze mitochondrial DNA. We hypothesize that yet to be identified stimuli lead to the release of the encapsulated teneurin C-terminal domain into the intersynaptic region, resulting in programmed cell death or the disruption of mitochondrial DNA and the subsequent pruning of inappropriate contacts

Geology and structure of the Brothers Fault Zone in the central part of the Millican SE quadrangle, Deschutes County, Oregon

The thesis is a structural and petrographic study of approximately 23 square miles in the Millican SE quadrangle, Deschutes County, Oregon. The area lies along the Brothers fault zone. Bedrock in the area is of Pliocene to Recent age and consists of an older basaltic unit with an associated dacite, a younger dacite, and a younger basaltic unit. The older basaltic unit and both dacites have been severely faulted. The younger basaltic unit has filled in topographic lows and is relatively undeformed. The dominant faults in the area are en echelon high-angle normal faults trending N. 40°W. with vertical displacements up to 600 feet. Cross faults with smaller displacements trend N. 45°E. The normal faults are Reidel and conjugate Reidel shears and are interpreted as the surface expression of a deep-seated right lateral displacement. The fault zone displaces units of Miocene to Pleistocene age and is considered to have been active during that time

Teneurin-1 is expressed in interconnected regions of the developing brain and is processed in vivo

<p>Abstract</p> <p>Background</p> <p>Teneurins are a unique family of transmembrane proteins conserved from <it>C. elegans </it>and <it>D. melanogaster </it>to mammals. In vertebrates there are four paralogs (teneurin-1 to -4), all of which are expressed prominently in the developing central nervous system.</p> <p>Results</p> <p>Analysis of teneurin-1 expression in the developing chick brain by in situ hybridization and immunohistochemistry defined a unique, distinct expression pattern in interconnected regions of the brain. Moreover we found complementary patterns of teneurin-1 and-2 expression in many parts of the brain, including the retina, optic tectum, olfactory bulb, and cerebellum as well as in brain nuclei involved in processing of sensory information. Based on these expression patterns, we suspect a role for teneurins in neuronal connectivity.</p> <p>In contrast to the cell-surface staining of the antibody against the extracellular domain, an antibody recognizing the intracellular domain revealed nuclear staining in subpopulations of neurons and in undifferentiated mesenchyme. Western blot analysis of brain lysates showed the presence of N-terminal fragments of teneurin-1 containing the intracellular domain indicating that proteolytic processing occurs. Finally, the teneurin-1 intracellular domain was found to contain a nuclear localization signal, which is required for nuclear localization in transfected cells.</p> <p>Conclusion</p> <p>Teneurin-1 and -2 are expressed by distinct interconnected populations of neurons in the developing central nervous system. Our data support the hypothesis that teneurins can be proteolytically processed leading to the release of the intracellular domain and its translocation to the nucleus.</p

Decision Making At The Local Level - The Missing Link? An empirical study of the localism act and sure start 2010-2012

The tension between top-down directives and local-level decision-making is a constant theme running through implementation studies. Through the case study of Sure Start (a UK early childhood program introduced in 1997, which brings together services for children under four and their families and has a particular focus on local level decision-making), this thesis provides a deeper understanding of these relationship tensions by examining the impact of the Localism Act 2011 (UK) on decision-making at the local level. (The aim of the Localism Act, introduced in November 2011, is to facilitate the devolution of decision-making powers from central government to individuals, communities and local councils). The research involved interviews with local-level service providers and bureaucrats, county- and national-level bureaucrats, government ministers and national peak bodies involved in the implementation of Sure Start. Interviews with key actors revealed little evidence of the Localism Act positively influencing decision making at the local level. As well as identifying the reasons why the Localism Act has had so little impact on local-level decision making, the thesis combines policy implementation and complexity leadership theories to develop a new way of thinking about the complex relationships that characterise implementation of local-level programs initiated and funded by central government. This new way of thinking about complex relationship tensions is based on three discoveries. The first is the importance of adequate resources in managing complexity and change. The second is the need for a generative leadership style to nurture an enabling approach to leadership. The third is that fragmentation can have positive as well as negative impacts

Infant Neural Sensitivity to Dynamic Eye Gaze relates to quality of parent–infant interaction at 7-months in infants at risk for Autism

Links between brain function measures and quality of parent–child interactions within the early developmental period have been investigated in typical and atypical development. We examined such links in a group of 104 infants with and without a family history for autism in the first year of life. Our findings suggest robust associations between event related potential responses to eye gaze and observed parent–infant interaction measures. In both groups, infants with more positive affect exhibit stronger differentiation to gaze stimuli. This association was observed with the earlier P100 waveform component in the control group but with the later P400 component in infants at-risk. These exploratory findings are critical in paving the way for a better understanding of how infant laboratory measures may relate to overt behavior and how both can be combined in the context of predicting risk or clinical diagnosis in toddlerhood

Theology, News and Notes - Vol. 42, No. 01

Theology News & Notes was a theological journal published by Fuller Theological Seminary from 1954 through 2014.https://digitalcommons.fuller.edu/tnn/1202/thumbnail.jp

Common single nucleotide polymorphisms in genes related to immune function and risk of papillary thyroid cancer

Accumulating evidence suggests that alterations in immune function may be important in the etiology of papillary thyroid cancer (PTC). To identify genetic markers in immune-related pathways, we evaluated 3,985 tag single nucleotide polymorphisms (SNPs) in 230 candidate gene regions (adhesion-extravasation-migration, arachidonic acid metabolism/eicosanoid signaling, complement and coagulation cascade, cytokine signaling, innate pathogen detection and antimicrobials, leukocyte signaling, TNF/NF-kB pathway or other) in a case-control study of 344 PTC cases and 452 controls. We used logistic regression models to estimate odds ratios (OR) and calculate one degree of freedom P values of linear trend (P(SNP-trend)) for the association between genotype (common homozygous, heterozygous, variant homozygous) and risk of PTC. To correct for multiple comparisons, we applied the false discovery rate method (FDR). Gene region- and pathway-level associations (P(Region) and P(Pathway)) were assessed by combining individual P(SNP-trend) values using the adaptive rank truncated product method. Two SNPs (rs6115, rs6112) in the SERPINA5 gene were significantly associated with risk of PTC (P(SNP-FDR)/P(SNP-trend) = 0.02/6×10(−6) and P(SNP-FDR)/P(SNP-trend) = 0.04/2×10(−5), respectively). These associations were independent of a history of autoimmune thyroiditis (OR = 6.4; 95% confidence interval: 3.0–13.4). At the gene region level, SERPINA5 was suggestively associated with risk of PTC (P(Region-FDR)/P(Region = )0.07/0.0003). Overall, the complement and coagulation cascade pathway was the most significant pathway (P(Pathway) = 0.02) associated with PTC risk largely due to the strong effect of SERPINA5. Our results require replication but suggest that the SERPINA5 gene, which codes for the protein C inhibitor involved in many biological processes including inflammation, may be a new susceptibility locus for PTC

Virtual World16: virtual design collaboration for the intersection of academia and industry.

Over the past 13 years, the 'World16'-group has collaborated face-to-face on various challenges that architectural design faces within VR, architecture, urban design, and its delivery to the professional industries. The focus of the collaboration is to foster pathways of academic research and developments to industries and professions. In 2020, due to the restrictions of the pandemic, the group had to rethink and redevelop how to collaborate meaningfully and become resilient: the World16 collaborated akin to the Virtual Design Studios (VDS) of the Nineties for the first time exclusively virtually becoming the 'Virtual World16'. The paper presents the group's various projects that are transformative to the praxis in VR architecture, design and urban design, and critically reflects on the lessons learned from VDS-paradigm

Telomere Length and the Risk of Cutaneous Malignant Melanoma in Melanoma-Prone Families with and without CDKN2A Mutations

Introduction: Recent evidence suggests a link between constitutional telomere length (TL) and cancer risk. Previous studies have suggested that longer telomeres were associated with an increased risk of melanoma and larger size and number of nevi. The goal of this study was to examine whether TL modified the risk of melanoma in melanoma-prone families with and without CDKN2A germline mutations. Materials and Methods We measured TL in blood DNA in 119 cutaneous malignant melanoma (CMM) cases and 208 unaffected individuals. We also genotyped 13 tagging SNPs in TERT. Results: We found that longer telomeres were associated with an increased risk of CMM (adjusted OR = 2.81, 95% CI = 1.02–7.72, P = 0.04). The association of longer TL with CMM risk was seen in CDKN2A- cases but not in CDKN2A+ cases. Among CMM cases, the presence of solar injury was associated with shorter telomeres (P = 0.002). One SNP in TERT, rs2735940, was significantly associated with TL (P = 0.002) after Bonferroni correction. Discussion Our findings suggest that TL regulation could be variable by CDKN2A mutation status, sun exposure, and pigmentation phenotype. Therefore, TL measurement alone may not be a good marker for predicting CMM risk

High-Pressure Transformation of SiO2 Glass from a Tetrahedral to an Octahedral Network:A Joint Approach Using Neutron Diffraction and Molecular Dynamics

International audienceA combination of in situ high-pressure neutron diffraction at pressures up to 17.5(5) GPa and moleculardynamics simulations employing a many-body interatomic potential model is used to investigate thestructure of cold-compressed silica glass. The simulations give a good account of the neutron diffractionresults and of existing x-ray diffraction results at pressures up to ∼60 GPa. On the basis of the moleculardynamics results, an atomistic model for densification is proposed in which rings are “zipped” by a pairingof five- and/or sixfold coordinated Si sites. The model gives an accurate description for the dependence ofthe mean primitive ring size hni on the mean Si-O coordination number, thereby linking a parameter that issensitive to ordering on multiple length scales to a readily measurable parameter that describes the localcoordination environment