Expansion of Cord Blood CD34+ Cells in Presence of zVADfmk and zLLYfmk Improved Their In Vitro Functionality and In Vivo Engraftment in NOD/SCID Mouse

BACKGROUND: Cord blood (CB) is a promising source for hematopoietic stem cell transplantations. The limitation of cell dose associated with this source has prompted the ex vivo expansion of hematopoietic stem and progenitor cells (HSPCs). However, the expansion procedure is known to exhaust the stem cell pool causing cellular defects that promote apoptosis and disrupt homing to the bone marrow. The role of apoptotic machinery in the regulation of stem cell compartment has been speculated in mouse hematopoietic and embryonic systems. We have consistently observed an increase in apoptosis in the cord blood derived CD34(+) cells cultured with cytokines compared to their freshly isolated counterpart. The present study was undertaken to assess whether pharmacological inhibition of apoptosis could improve the outcome of expansion. METHODOLOGY/PRINCIPAL FINDINGS: CB CD34(+) cells were expanded with cytokines in the presence or absence of cell permeable inhibitors of caspases and calpains; zVADfmk and zLLYfmk respectively. A novel role of apoptotic protease inhibitors was observed in increasing the CD34(+) cell content of the graft during ex vivo expansion. This was further reflected in improved in vitro functional aspects of the HSPCs; a higher clonogenicity and long term culture initiating potential. These cells sustained superior long term engraftment and an efficient regeneration of major lympho-myeloid lineages in the bone marrow of NOD/SCID mouse compared to the cells expanded with growth factors alone. CONCLUSION/SIGNIFICANCE: Our data show that, use of either zVADfmk or zLLYfmk in the culture medium improves expansion of CD34(+) cells. The strategy protects stem cell pool and committed progenitors, and improves their in vitro functionality and in vivo engraftment. This observation may complement the existing protocols used in the manipulation of hematopoietic cells for therapeutic purposes. These findings may have an impact in the CB transplant procedures involving a combined infusion of unmanipulated and expanded grafts

Data Descriptor: Ash leaf metabolomes reveal differences between trees tolerant and susceptible to ash dieback disease

CMS was funded by the ‘Nornex’ project jointly by UK BBSRC (BBS/E/J/000CA5323) and DEFRA and a BBSRC Tools and Resources grant (BB/N021452/1) awarded to M.G. and D.J.S

Dovetailing biology and chemistry: integrating the Gene Ontology with the ChEBI chemical ontology

Background The Gene Ontology (GO) facilitates the description of the action of gene products in a biological context. Many GO terms refer to chemical entities that participate in biological processes. To facilitate accurate and consistent systems-wide biological representation, it is necessary to integrate the chemical view of these entities with the biological view of GO functions and processes. We describe a collaborative effort between the GO and the Chemical Entities of Biological Interest (ChEBI) ontology developers to ensure that the representation of chemicals in the GO is both internally consistent and in alignment with the chemical expertise captured in ChEBI. Results We have examined and integrated the ChEBI structural hierarchy into the GO resource through computationally-assisted manual curation of both GO and ChEBI. Our work has resulted in the creation of computable definitions of GO terms that contain fully defined semantic relationships to corresponding chemical terms in ChEBI. Conclusions The set of logical definitions using both the GO and ChEBI has already been used to automate aspects of GO development and has the potential to allow the integration of data across the domains of biology and chemistry. These logical definitions are available as an extended version of the ontology from http://purl.obolibrary.org/obo/go/extensions/go-plus.ow

Clinical research without consent in adults in the emergency setting: a review of patient and public views

<p>Abstract</p> <p>Background</p> <p>In emergency research, obtaining informed consent can be problematic. Research to develop and improve treatments for patients admitted to hospital with life-threatening and debilitating conditions is much needed yet the issue of research without consent (RWC) raises concerns about unethical practices and the loss of individual autonomy. Consistent with the policy and practice turn towards greater patient and public involvement in health care decisions, in the US, Canada and EU, guidelines and legislation implemented to protect patients and facilitate acute research with adults who are unable to give consent have been developed with little involvement of the lay public. This paper reviews research examining public opinion regarding RWC for research in emergency situations, and whether the rules and regulations permitting research of this kind are in accordance with the views of those who ultimately may be the most affected.</p> <p>Methods</p> <p>Seven electronic databases were searched: Medline, Embase, CINAHL, Cochrane Database of Systematic Reviews, Philosopher's Index, Age Info, PsychInfo, Sociological Abstracts and Web of Science. Only those articles pertaining to the views of the public in the US, Canada and EU member states were included. Opinion pieces and those not published in English were excluded.</p> <p>Results</p> <p>Considering the wealth of literature on the perspectives of professionals, there was relatively little information about public attitudes. Twelve studies employing a range of research methods were identified. In five of the six questionnaire surveys around half the sample did <it>not </it>agree generally with RWC, though paradoxically, a higher percentage would <it>personally </it>take part in such a study. Unfortunately most of the studies were not designed to investigate individuals' views in any depth. There also appears to be a level of mistrust of medical research and some patients were more likely to accept an experimental treatment 'outside' of a research protocol.</p> <p>Conclusion</p> <p>There are too few data to evaluate whether the rules and regulations permitting RWC protects – or is acceptable to – the public. However, any attempts to engage the public should take place in the context of findings from further basic research to attend to the apparently paradoxical findings of some of the current surveys.</p

Network capitalism and the role of strategy, contracts and performance expectations for Asia-Pacific innovation partnerships

© Springer Nature Singapore Pte Ltd. 2018. With the growth of emerging economies in Asia-Pacific over the last three decades collaboration with the aim of innovation between firms within and with partners outside the region have developed substantially. Not always have such partnerships fulfilled their anticipated strategic objectives. The literature suggests that the nature of market arrangements and the role of government within that system play a role, but also innate contracting practices and governance of innovation partnerships are related. Yet, our understanding about the specific relationships between these factors and the emerging partnership innovation culture that facilitates joint business activities in an Asia-Pacific context remains vague. In this conceptual chapter we suggest how characteristics of so called network capitalism in conjunction with the nature of contractual agreements between partners, the alignment of their innovation objectives and the ambiguity inherent in their mutual contributions to the partnership can be interpreted as indicators of joint innovation culture. However, while innovation partnerships generally may result to be bureaucratic, market, clan, or adhocracy, we discuss how in an Asia Pacific context, innovation partnerships are limited by the extent of codification and diffusion of information and the social embeddedness of economic transactions

An ultra-sensitive delta R/R measurement system for biochemical sensors using Piezoresistive Micro-Cantilevers

Piezoresistive micro-cantilevers are interesting bio-sensing tool whose base resistance value (R) changes by a few parts per million (Delta R) in deflected conditions. Measuring such a small deviation is always being a challenge due to noise. An advanced and reliable Delta R/R measurement scheme is presented in this paper which can sense resistance changes down to 6 parts per million. The measurement scheme includes the half-bridge connected micro-cantilevers with mismatch compensation, precision op-amp based filters and amplifiers, and a lock-in amplifier based detector. The input actuating sine wave is applied from a function generator and the output dc voltage is displayed on a digital multimeter. The calibration is performed and instrument sensitivity is calculated. An experimental set-up using a probe station is discussed that demonstrates a combined performance of the measurement system and SU8-polysilicon cantilevers. The deflection sensitivity of such polymeric cantilevers is calculated. The system will be highly useful to detect bio-markers such as myoglobin and troponin that are released in blood during or after heart attacks