Regulatory Architecture of Non-Apoptotic Cell Death Program in C. Elegans

Cell death is prevalent in animal development, homeostasis, and disease. While apoptotic cell death has been extensively studied, many dying cells in development do not exhibit apoptotic morphology, and mice lacking core apoptotic regulators have mostly normal rates of developmental programmed cell death. However, little is known about how alternative death programs are set in motion. In the nematode Caenorhabditis elegans, most cells fated to die by apoptosis are eliminated as young, undifferentiated cells, for no obvious functional reasons. The male nematode’s linker cell, in contrast, dies as an older, differentiated cell, whose life and death subserve precise and important functions. The linker cell first undertakes a long migration along a characteristic path, elongating the male gonad into its proper, mature shape. Once the gonad has attained its final shape and the linker cell has completed its migration, the linker cell then dies to connect the gonad to the environment and allow male fertility. Linker cell death is genetically and morphologically non-apoptotic. Instead, this death program requires the temporal regulator LIN-29, the SARM-like protein TIR-1, the mitogen-activated protein kinase kinase (MAPKK) SEK-1, and the glutamine-rich protein PQN-41. SARM and MAPKKs have been implicated in non-apoptotic degeneration of axon distal segments following axotomy, and some developmental and pathological cell death events in vertebrates resemble the morphology of the dying linker cell. Thus, the molecular mechanism governing linker cell death may be conserved; however, neither the initiating death signals nor the target/s of linker cell death regulators are known. Using classical genetics, I have investigated the initiating mechanisms of linker cell death. I have characterized the cell-autonomous involvement of a histone 3, lysine 4 methyltransferase complex centered on the Trithorax/MLL-like catalytic subunit SET-16. I then demonstrated that two opposing spatial cues, the Wnt ligands EGL-20 and LIN-44, cooperate with LIN-29 to control linker cell death initiation. I showed that the Abdominal- B-like Hox transcription factor NOB-1 likely acts upstream of these two Wnt pathways, and that the Tailless/Tlx nuclear hormone receptor NHR-67 acts in parallel to these regulators to promote linker cell death in addition to linker cell migration. Finally, I show that the Wnt pathways and all known linker cell death mediators require the heat shock factor HSF-1 for cell death. Importantly, HSF-1 function in linker cell death is distinct from, and competes with, its role in stress responses. My studies demonstrate that HSF-1, previously thought to be primarily protective, is a key downstream regulator of a nonapoptotic cell death program. I have also developed a method to isolate large numbers of linker cells from staged worms populations, to enable a comprehensive characterization of the transcriptional program driving linker cell death

Residual strain monitoring during composite manufacturing

This work explores a new possibility in accurate measurement of multi-axial residual strains during the production of composite structures. It investigates the usability of the polarization dependent loss (PDL) of an optical fibre Bragg grating as a sensitive indicator of multi-axial residual strains. The experimental work presented is done on a cross-ply carbon fibre reinforced polymer fabricated using an autoclave cycle

GCXGC coupled to fast scanning quadrupole MS for trace analysis of POPs

peer reviewe

Group treatment for survivors of torture and severe violence: A literature review

Methods: The authors conducted a systematic review of scholarly journals and manuscripts. The search was limited to articles published in English that focused on group treatment with torture survivors. Findings: The authors identified 36 articles and chapters for review describing a variety of group interventions for survivors of torture, including: Supportive Group Therapy Empowerment Workshops Group Treatment for Sleep Disorders Den Bosch model Wraparound approach Stage-oriented model The literature examined varied in approach and format: present-day and past-focused groups; structured, time-limited groups; and flexible, ongoing support groups. The studies took place in diverse locations, including Denmark, Germany, Guinea, Namibia, the Netherlands, Palestine, Serbia, the U.S., the UK, and Zimbabwe, and, in conflict, post-conflict and/or humanitarian settings. The interventions were facilitated by licensed mental health professionals, paraprofessionals, and bilingual/bicultural staff – or a combination of the latter two.  Interpretations: Group treatment is an approach which can be administered to larger groups of survivors to address a range of treatment issues. The authors examined key clinical practice issues for group treatment including group composition and content, facilitation and measurement strategies. While the literature does provide a compelling conceptual rationale for using group treatment, the empirical literature is in fact very limited at this time and needs to be strengthened in order to build confidence in outcomes across contexts and survivor communities. Conclusions: This paper points to a growing interest in the topic of group treatment for survivors of torture and severe violence, providing a comprehensive picture of group-based interventions and highlighting the need for additional research and knowledge-building

Correcting cold wire measurements in isotropic turbulence with a DNS database

We estimate the effect of the finite spatial resolution of a cold wire for scalar measurements, using a database from direct numerical simulations (DNS). These are for homogeneous isotropic turbulence at low Taylor-microscale Reynolds number (≃ 42) and Schmidt number unity. Correction factors for the scalar variance, scalar mean dissipation rate, and mixed velocity-scalar derivative skewness are evaluated, for a sensor length of up to 15 times the Batchelor length scale. The largest attenuation effect is found on the dissipation rate, followed by the scalar variance. The mixed skewness,which is affected the least, is overestimated