Identifying common prognostic factors in genomic cancer studies: A novel index for censored outcomes

Background  

With the growing number of public repositories for high-throughput genomic data, it is of great interest to combine the results produced by independent research groups. Such a combination allows the identification of common genomic factors across multiple cancer types and provides new insights into the disease process. In the framework of the proportional hazards model, classical procedures, which consist of ranking genes according to the estimated hazard ratio or the p-value obtained from a test statistic of no association between survival and gene expression level, are not suitable for gene selection across multiple genomic datasets with different sample sizes. We propose a novel index for identifying genes with a common effect across heterogeneous genomic studies designed to remain stable whatever the sample size and which has a straightforward interpretation in terms of the percentage of separability between patients according to their survival times and gene expression measurements.     

Exon skipping in the sterol 27-hydroxylase gene leads to cerebrotendinous xanthomatosis

We report a new mutation in the sterol 27-hydroxylase (CYP 27) gene in a Dutch family with cerebrotendinous xanthomatosis: a G→A transition in the splice donor site in intron 4. This mutation leads to skipping of exon 4, resulting in a loss of 66 amino acids in the CYP 27 enzyme molecule. Received: 15 March 1997 / Accepted: 26 March 1997     

Biomedical implications from a morphoelastic continuum model for the simulation of contracture formation in skin grafts that cover excised burns

A continuum hypothesis-based model is developed for the simulation of the (long term) contraction of skin grafts that cover excised burns in order to obtain suggestions regarding the ideal length of splinting therapy and when to start with this therapy such that the therapy is effective optimally. Tissue is modeled as an isotropic, heterogeneous, morphoelastic solid. With respect to the constituents of the tissue, we selected the following constituents as primary model components: fibroblasts, myofibroblasts, collagen molecules, and a generic signaling molecule. Good agreement is demonstrated with respect to the evolution over time of the surface area of unmeshed skin grafts that cover excised burns between outcomes of computer simulations obtained in this study and scar assessment data gathered previously in a clinical study. Based on the simulation results, we suggest that the optimal point in time to start with splinting therapy is directly after placement of the skin graft on its recipient bed. Furthermore, we suggest that it is desirable to continue with splinting therapy until the concentration of the signaling molecules in the grafted area has become negligible such that the formation of contractures can be prevented. We conclude this study with a presentation of some alternative ideas on how to diminish the degree of contracture formation that are not based on a mechanical intervention, and a discussion about how the presented model can be adjusted.     

Molecular Characterization of Larval Peripheral Thermosensory Responses of the Malaria Vector Mosquito Anopheles gambiae

Thermosensation provides vital inputs for the malaria vector mosquito, Anopheles gambiae which utilizes heat-sensitivity within a broad spectrum of behaviors, most notably, the localization of human hosts for blood feeding. In this study, we examine thermosensory behaviors in larval-stage An. gambiae, which as a result of their obligate aquatic habitats and importance for vectorial capacity, represents an opportunistic target for vector control as part of the global campaign to eliminate malaria. As is the case for adults, immature mosquitoes respond differentially to a diverse array of external heat stimuli. In addition, larvae exhibit a striking phenotypic plasticity in thermal-driven behaviors that are established by temperature at which embryonic development occurs. Within this spectrum, RNAi-directed gene-silencing studies provide evidence for the essential role of the Transient Receptor Potential sub-family A1 (TRPA1) channel in mediating larval thermal-induced locomotion and thermal preference within a discrete upper range of ambient temperatures.     

The vascular plant collections of R. S. Williams from Bolivia and Peru (1901–1902): Addenda et corrigenda

Notes that augment an earlier essay on R. S. Williams’ botanical activities and the distribution of his collections from Bolivia and Peru are presented. Twelve species based on Williams’ vascular plant collections are added to a catalog that was previously published. Synonymies of an additional 22 taxa are corrected or updated. Notes also are provided concerning the typification or orthography of two species.     

The oncolytic peptide LTX-315 triggers necrotic cell death

The oncolytic peptide LTX-315 has been designed for killing human cancer cells and turned out to stimulate anti-cancer immune responses when locally injected into tumors established in immunocompetent mice. Here, we investigated the question whether LTX-315 induces apoptosis or necrosis. Transmission electron microscopy or morphometric analysis of chromatin-stained tumor cells revealed that LTX-315 failed to induce apoptotic nuclear condensation and rather induced a necrotic phenotype. Accordingly, LTX-315 failed to stimulate the activation of caspase-3, and inhibition of caspases by means of Z-VAD-fmk was unable to reduce cell killing by LTX-315. In addition, 2 prominent inhibitors of regulated necrosis (necroptosis), namely, necrostatin-1 and cycosporin A, failed to reduce LTX-315-induced cell death. In conclusion, it appears that LTX-315 triggers unregulated necrosis, which may contribute to its pro-inflammatory and pro-immune effects.