A trait‐based approach for predicting species responses to environmental change from sparse data: how well might terrestrial mammals track climate change?

Estimating population spread rates across multiple species is vital for projecting biodiversity responses to climate change. A major challenge is to parameterise spread models for many species. We introduce an approach that addresses this challenge, coupling a trait‐based analysis with spatial population modelling to project spread rates for 15 000 virtual mammals with life histories that reflect those seen in the real world. Covariances among life‐history traits are estimated from an extensive terrestrial mammal data set using Bayesian inference. We elucidate the relative roles of different life‐history traits in driving modelled spread rates, demonstrating that any one alone will be a poor predictor. We also estimate that around 30% of mammal species have potential spread rates slower than the global mean velocity of climate change. This novel trait‐space‐demographic modelling approach has broad applicability for tackling many key ecological questions for which we have the models but are hindered by data availability.     

Nitrobenzoxadiazole-based GSTP1-1 inhibitors containing the full peptidyl moiety of (pseudo)glutathione

Context: The inhibition of glutathione S-transferase P1-1 (GSTP1-1) is a sound strategy to overcome drug resistance in oncology practice.

Objective: The nitrobenzoxadiazolyl (NBD) S-conjugate of glutathione and the corresponding γ-oxa-glutamyl isostere (compounds 1 and 5, respectively) have been disclosed as GST inhibitors. The rationale of their design is discussed in juxtaposition to non-peptide NBD thioethers.

Materials and methods: Synthesis of derivatives 1 and 5 and in vitro evaluation on human GSTP1-1 and M2-2 are reported.

Results: Conjugates 1 and 5 were found to be low micromolar inhibitors of both isoforms. Furthermore, they display a threefold reduction in selectivity for GSTM2-2 over the P1-1 isozyme in comparison with the potent non-peptide inhibitor nitrobenzoxadiazolyl-thiohexanol (NBDHEX).

Discussion and conclusions: Spectroscopic data are congruent with the formation of a stable sigma-complex between GSH and the inhibitors in the protein active site. Conjugate 5 is suitable for in vivo modulation of GST activity in cancer treatment.     

The three dimensional analysis of the Sforzesco brace correction

Background

Scoliosis is a three dimensional deformity, and brace correction should be 3D too. There is a lack of knowledge of the effect of braces, particularly in the sagittal and transverse plane. The aim of this study is to analyse the Sforzesco Brace correction, through all the parameters provided by Eos 3D imaging system.

Method

Design: This is a cross sectional study from a prospective database started in March 2003.Participants: 16 AIS girls (mean age 14.01) in Sforzesco brace treatment, with EOS x-rays, at start, in brace after 1 month and out of brace after the first 4 months of treatment. Outcome measures: All the parameters and the Torsio-Index obtained from 3D Eos System, in and out of brace, in the three planes. Statistical analysis: the variability of the parameters and the mean differences were analyzed and compared using paired T test. ANOVA was used for multiple comparisons. Critical P value was set at 0.05.

Results

In the comparison of in-brace vs start of treatment, the mean Cobb angle changed significantly from 36.44 +/? 4 to 28.99?+??3.9° (p?=?0.01). Significant changes in all the sagittal parameters were found (p?=?0.02). In the axial plane, the Torsio Index changed significantly in-brace for thoracolumbar and lumbar curves (P?<?0.05). The analysis of the single vertebral tilt demonstrated that the effect of the brace is mostly concentrated at specific segments: T4-T5, T10-T12, L1 and L5 in the axial plane and T3-T6 and T10-L1 in the frontal plane.

Conclusion

The Sforzesco brace mostly modifies the middle of the spine and preserves the sagittal balance. The single vertebral orientation in each plane should be considered together with the typically used values to assess brace effect.

     

The Influence of Tissue Ischemia Time on RNA Integrity and Patient-Derived Xenografts (PDX) Engraftment Rate in a Non-Small Cell Lung Cancer (NSCLC) Biobank

Introduction

Bio-repositories are invaluable resources to implement translational cancer research and clinical programs. They represent one of the most powerful tools for biomolecular studies of clinically annotated cohorts, but high quality samples are required to generate reliable molecular readouts and functional studies. The objective of our study was to define the impact of cancer tissue ischemia time on RNA and DNA quality, and for the generation of Patient-Derived Xenografts (PDXs).

Methods

One-hundred thirty-five lung cancer specimens were selected among our Institutional BioBank samples. Associations between different warm (surgical) and cold (ex-vivo) ischemia time ranges and RNA quality or PDXs engraftment rates were assessed. RNA quality was determined by RNA integrity number (RINs) values. Fresh viable tissue fragments were implanted subcutaneously in NSG mice and serially transplanted.

Results

RNAs with a RIN>7 were detected in 51% of the sample (70/135), with values of RIN significantly lower (OR 0.08, P = 0.01) in samples preserved for more than 3 hours before cryopreservation. Higher quality DNA samples had a concomitant high RIN. Sixty-three primary tumors (41 adenocarcinoma) were implanted with an overall engraftment rate of 33%. Both prolonged warm (>2 hours) and ex-vivo ischemia time (>10 hours) were associated to a lower engraftment rate (OR 0.09 P = 0.01 and OR 0.04 P = 0.008, respectively).

Conclusion

RNA quality and PDXs engraftment rate were adversely affected by prolonged ischemia times. Proper tissue collection and processing reduce failure rate. Overall, NSCLC BioBanking represents an innovative modality, which can be successfully executed in routine clinical settings, when stringent Standard Operating Procedures are adopted.