Protective Microbiota: From Localized to Long-Reaching Co-Immunity

Resident microbiota do not just shape host immunity, they can also contribute to host protection against pathogens and infectious diseases. Previous reviews of the protective roles of the microbiota have focused exclusively on colonization resistance localized within a microenvironment. This review shows that the protection against pathogens also involves the mitigation of pathogenic impact without eliminating the pathogens (i.e., “disease tolerance”) and the containment of microorganisms to prevent pathogenic spread. Protective microorganisms can have an impact beyond their niche, interfering with the entry, establishment, growth, and spread of pathogenic microorganisms. More fundamentally, we propose a series of conceptual clarifications in support of the idea of a “co-immunity,” where an organism is protected by both its own immune system and components of its microbiota

Effects of Endolithic Parasitism on Invasive and Indigenous Mussels in a Variable Physical Environment

Biotic stress may operate in concert with physical environmental conditions to limit or facilitate invasion processes while altering competitive interactions between invaders and native species. Here, we examine how endolithic parasitism of an invasive and an indigenous mussel species acts in synergy with abiotic conditions of the habitat. Our results show that the invasive Mytilus galloprovincialis is more infested than the native Perna perna and this difference is probably due to the greater thickness of the protective outer-layer of the shell of the indigenous species. Higher abrasion due to waves on the open coast could account for dissimilarities in degree of infestation between bays and the more wave-exposed open coast. Also micro-scale variations of light affected the level of endolithic parasitism, which was more intense at non-shaded sites. The higher levels of endolithic parasitism in Mytilus mirrored greater mortality rates attributed to parasitism in this species. Condition index, attachment strength and shell strength of both species were negatively affected by the parasites suggesting an energy trade-off between the need to repair the damaged shell and the other physiological parameters. We suggest that, because it has a lower attachment strength and a thinner shell, the invasiveness of M. galloprovincialis will be limited at sun and wave exposed locations where endolithic activity, shell scouring and risk of dislodgement are high. These results underline the crucial role of physical environment in regulating biotic stress, and how these physical-biological interactions may explain site-to-site variability of competitive balances between invasive and indigenous species

Targeting the hypoxic fraction of tumours using hypoxia activated prodrugs

The presence of a microenvironment within most tumours containing regions of low oxygen tension or hypoxia has profound biological and therapeutic implications. Tumour hypoxia is known to promote the development of an aggressive phenotype, resistance to both chemotherapy and radiotherapy and is strongly associated with poor clinical outcome. Paradoxically, it is recognised as a high priority target and one therapeutic strategies designed to eradicate hypoxic cells in tumours are a group of compounds known collectively as hypoxia activated prodrugs (HAPs) or bioreductive drugs. These drugs are inactive prodrugs that require enzymatic activation (typically by 1 or 2 electron oxidoreductases) to generate cytotoxic species with selectivity for hypoxic cells being determined by (i) the ability of oxygen to either reverse or inhibit the activation process and (ii) the presence of elevated expression of oxidoreductases in tumours. The concepts underpinning HAP development were established over 40 years ago and have been refined over the years to produce a new generation of HAPs that are under preclinical and clinical development. The purpose of this article is to describe current progress in the development of HAPs focusing on the mechanisms of action, preclinical properties and clinical progress of leading examples

EFFECTS OF BODY MASS AND CHAIR HEIGHT ON MUSCLE ACTIVATION AND BALANCE DURING SIT TO STAND

P. Mack, A. Gutierrez, G. Weiler, N. Denny, R.S. McCulloch Gonzaga University, Spokane, WA Performance of the sit to stand movement (STSm), a critical aspect of daily life, has been primarily studied in elderly populations. In addition, obesity has been shown to affect stability, but its relation to STSm has not been studied. PURPOSE: This study examined the impact of simulated weight gain on muscle activation and balance at varying chair heights in a young, healthy population. METHODS: Subjects (n=30, aged 20.9±1.25 yr), were asked to perform six STSm, at three different chair heights, under a bodyweight (BW) and added-weight (AW) condition. The chair heights were set at 80%, 100% and 120% of their knee height (lateral condyle of tibia to the floor) while the added weight (via a weight vest) was equal to 15% of their body weight. Muscle activation was evaluated for the rectus femoris (RF) and biceps femoris (BF) and normalized to their respective maximum voluntary contractions (MVCs). All trials were randomized and counter-balanced. CoP distance and velocity were compared between trials. RESULTS: RF Activation was the highest at the 80% seat height in both the AW (78.37 + 30.37%) and BW conditions (63.42 + 26.73%). Additionally, RF recruitment was significantly higher in AW vs. BW at all seat heights (p\u3c.05). BF activation was significantly higher at the 80% AW seat height (19.80 + 11.56%) when compared to the 120% AW height (18.05 + 9.90%, p=.004). There were no changes in CoP distance or velocity for either seat height or weight condition. CONCLUSION: Increasing chair height under added and body weight conditions leads to decreased activation of the RF and BF suggesting a reduced difficulty in performing this movement. The RF, under the AW condition, was most effected by seat height changes. The findings indicate that increasing seat height does not alter balance. Our study suggests that weight gain impedes the ability to perform the STSm and that increasing chair height is a successful method in easing the difficulty of performing this movement

Requirements analysis and specification for a molecular tumor board platform based on cBioPortal

Clinicians in molecular tumor boards (MTB) are confronted with a growing amount of genetic high-throughput sequencing data. Today, at German university hospitals, these data are usually handled in complex spreadsheets from which clinicians have to obtain the necessary information. The aim of this work was to gather a comprehensive list of requirements to be met by cBioPortal to support processes in MTBs according to clinical needs. Therefore, oncology experts at nine German university hospitals were surveyed in two rounds of interviews. To generate an interview guideline a scoping review was conducted. For visual support in the second round, screenshot mockups illustrating the requirements from the first round were created. Requirements that cBioPortal already meets were skipped during the second round. In the end, 24 requirements with sometimes several conceivable options were identified and 54 screenshot mockups were created. Some of the identified requirements have already been suggested to the community by other users or are currently being implemented in cBioPortal. This shows, that the results are in line with the needs expressed by various disciplines. According to our findings, cBioPortal has the potential to significantly improve the processes and analyses of an MTB after the implementation of the identified requirements

Requirements Analysis and Specification for a Molecular Tumor Board Platform Based on cBioPortal

Clinicians in molecular tumor boards (MTB) are confronted with a growing amount of genetic high-throughput sequencing data. Today, at German university hospitals, these data are usually handled in complex spreadsheets from which clinicians have to obtain the necessary information. The aim of this work was to gather a comprehensive list of requirements to be met by cBioPortal to support processes in MTBs according to clinical needs. Therefore, oncology experts at nine German university hospitals were surveyed in two rounds of interviews. To generate an interview guideline a scoping review was conducted. For visual support in the second round, screenshot mockups illustrating the requirements from the first round were created. Requirements that cBioPortal already meets were skipped during the second round. In the end, 24 requirements with sometimes several conceivable options were identified and 54 screenshot mockups were created. Some of the identified requirements have already been suggested to the community by other users or are currently being implemented in cBioPortal. This shows, that the results are in line with the needs expressed by various disciplines. According to our findings, cBioPortal has the potential to significantly improve the processes and analyses of an MTB after the implementation of the identified requirements