3D Microstructural Architecture of Muscle Attachments in Extant and Fossil Vertebrates Revealed by Synchrotron Microtomography

Background

Firm attachments binding muscles to skeleton are crucial mechanical components of the vertebrate body. These attachments (entheses) are complex three-dimensional structures, containing distinctive arrangements of cells and fibre systems embedded in the bone, which can be modified during ontogeny. Until recently it has only been possible to obtain 2D surface and thin section images of entheses, leaving their 3D histology largely unstudied except by extrapolation from 2D data. Entheses are frequently preserved in fossil bones, but sectioning is inappropriate for rare or unique fossil material.

Methodology/Principal Findings

Here we present the first non-destructive 3D investigation, by propagation phase contrast synchrotron microtomography (PPC-SRµCT), of enthesis histology in extant and fossil vertebrates. We are able to identify entheses in the humerus of the salamander Desmognathus from the organization of bone-cell lacunae and extrinsic fibres. Statistical analysis of the lacunae differentiates types of attachments, and the orientation of the fibres, reflect the approximate alignment of the muscle. Similar histological structures, including ontogenetically related pattern changes, are perfectly preserved in two 380 million year old fossil vertebrates, the placoderm Compagopiscis croucheri and the sarcopterygian fish Eusthenopteron foordi.

Conclusions/Significance

We are able to determine the position of entheses in fossil vertebrates, the approximate orientation of the attached muscles, and aspects of their ontogenetic histories, from PPC-SRµCT data. Sub-micron microtomography thus provides a powerful tool for studying the structure, development, evolution and palaeobiology of muscle attachments.     

Recent changes in endometrial cancer trends among menopausal-age US women

BackgroundChanges in endometrial cancer incidence rates after the precipitous decline in menopausal hormone therapy (MHT) use in 2002 have not been evaluated.MethodsUsing data from the Surveillance, Epidemiology, and End Results Program from 1992 to 2009 (SEER 13), we identified 63 428 incident endometrial cancer cases among women ages 20–74. We compared annual percent change (APC) in endometrial cancer incidence rates from 1992 to 2002 to rates from 2003 to 2009.ResultsIn contrast to the constant endometrial cancer rate pattern observed from 1992 to 2002 (APC 0.0%), rates increased after 2002 in women 50–74 years old (2.5%; P_{APC comparison} < 0.01). Endometrial cancer incidence increased over the entire time period among women ages 20–49 (1992–2002: 1.1%; 2003–2009: 2.1%; P_{APC comparison} = 0.21). Post-2002 increases in incidence among women ages 50–74 were specific to Type I endometrial tumors (1992–2002: ?0.6%; 2003–2009: 1.6%; P_{APC comparison} < 0.01).DiscussionThe increase in endometrial cancer incidence rates after 2002 may be related to the widespread decrease in estrogen plus progestin MHT use, which has been reported to lower endometrial cancer risk in overweight and obese women.     

Biocontrol agents promote growth of potato pathogens,depending on environmental conditions

There is a pressing need to understand and optimize biological control so as to avoid over‐reliance on the synthetic chemical pesticides that can damage environmental and human health. This study focused on interactions between a novel biocontrol‐strain, Bacillus sp. JC12GB43, and potato‐pathogenic Phytophthora and Fusarium species. In assays carried out in vitro and on the potato tuber, the bacterium was capable of near‐complete inhibition of pathogens. This Bacillus was sufficiently xerotolerant (water activity limit for growth = 0.928) to out‐perform Phytophthora infestans (~0.960) and challenge Fusarium coeruleum (~0.847) and Fusarium sambucinum (~0.860) towards the lower limits of their growth windows. Under some conditions, however, strain JC12GB43 stimulated proliferation of the pathogens: for instance, Fusarium coeruleum growth‐rate was increased under chaotropic conditions in vitro (132 mM urea) by >100% and on tubers (2‐M glycerol) by up to 570%. Culture‐based assays involving macromolecule‐stabilizing (kosmotropic) compatible solutes provided proof‐of‐principle that the Bacillus may provide kosmotropic metabolites to the plant pathogen under conditions that destabilize macromolecular systems of the fungal cell. Whilst unprecedented, this finding is consistent with earlier reports that fungi can utilize metabolites derived from bacterial cells. Unless the antimicrobial activities of candidate biocontrol strains are assayed over a full range of field‐relevant parameters, biocontrol agents may promote plant pathogen infections and thereby reduce crop yields. These findings indicate that biocontrol activity, therefore, ought to be regarded as a mode‐of‐behaviour (dependent on prevailing conditions) rather than an inherent property of a bacterial strain.     

B Cell,Th17, and Neutrophil Related Cerebrospinal Fluid Cytokine/Chemokines Are Elevated in MOG Antibody Associated Demyelination

Background

Myelin oligodendrocyte glycoprotein antibody (MOG Ab) associated demyelination represents a subgroup of autoimmune demyelination that is separate from multiple sclerosis and aquaporin 4 IgG-positive NMO, and can have a relapsing course. Unlike NMO and MS, there is a paucity of literature on immunopathology and CSF cytokine/chemokines in MOG Ab associated demyelination.

Aim

To study the differences in immunopathogenesis based on cytokine/chemokine profile in MOG Ab-positive (POS) and -negative (NEG) groups.

Methods

We measured 34 cytokines/chemokines using multiplex immunoassay in CSF collected from paediatric patients with serum MOG Ab POS [acute disseminated encephalomyelitis (ADEM = 8), transverse myelitis (TM = 2) n = 10] and serum MOG Ab NEG (ADEM = 5, TM = 4, n = 9) demyelination. We generated normative data using CSF from 20 non-inflammatory neurological controls.

Results

The CSF cytokine and chemokine levels were higher in both MOG Ab POS and MOG Ab NEG demyelination groups compared to controls. The CSF in MOG Ab POS patients showed predominant elevation of B cell related cytokines/chemokines (CXCL13, APRIL, BAFF and CCL19) as well as some of Th17 related cytokines (IL-6 AND G-CSF) compared to MOG Ab NEG group (all p<0.01). In addition, patients with elevated CSF MOG antibodies had higher CSF CXCL13, CXCL12, CCL19, IL-17A and G-CSF than patients without CSF MOG antibodies.

Conclusion

Our findings suggest that MOG Ab POS patients have a more pronounced CNS inflammatory response with elevation of predominant humoral associated cytokines/chemokines, as well as some Th 17 and neutrophil related cytokines/chemokines suggesting a differential inflammatory pathogenesis associated with MOG antibody seropositivity. This cytokine/chemokine profiling provides new insight into disease pathogenesis, and improves our ability to monitor inflammation and response to treatment. In addition, some of these molecules may represent potential immunomodulatory targets.     

An Avida-ED digital evolution curriculum for undergraduate biology

We present an inquiry-based curriculum based on the digital evolution platform Avida-ED (http://avida-ed.msu.edu). We designed an instructional sequence and lab book consisting of an introduction to Avida-ED and a set of three lessons focused on specific evolutionary concepts. These served to familiarize students with experimental evolution and Avida-ED. Students then developed independent Avida-ED research projects to test their own questions. Curriculum design and implementation occurred over the course or two semesters, with a pilot implementation in the first semester, followed by curriculum revision and full implementation in the second semester. The curriculum was implemented in an undergraduate Introductory Cell and Molecular Biology course at a major research university. Full implementation of the curriculum in semester two involved the use of Avida-ED mainly in the teaching lab in parallel with a bacterial antibiotic resistance experimental research stream, allowing students to draw connections between Avidian digital evolution and the evolution of antibiotic resistance in microbial populations. After carrying out the introductory exercises, students developed independent Avida-ED projects to test their own research questions, and presented their data to researchers in the NSF-funded BEACON Center for the Study of Evolution in Action. Preliminary results of our studies to assess the impacts of an Avida-ED curriculum indicate a positive effect on student learning of evolutionary concepts, particularly in increasing the level of complexity of student explanations about the random nature of mutation.     

Short-Term Effects of Traditional and Alternative Community Interventions to Address Food Insecurity

Background

Despite the effects of food insecurity on health are well documented, clear governmental policies to face food insecurity do not exist in western countries. In Canada, interventions to face food insecurity are developed at the community level and can be categorized into two basic strategies: those providing an immediate response to the need for food, defined “traditional” and those targeting the improvement of participants’ social cohesion, capabilities and management of their own nutrition, defined “alternative”.

Objective

The objective of this study was to evaluate the effects of food insecurity interventions on food security status and perceived health of participants.

Design

This was a longitudinal multilevel study implemented in Montreal, Quebec, Canada. Participants were recruited in a two-stage cluster sampling frame. Clustering units were community organizations working on food insecurity; units of analysis were participants in community food security interventions. A total of 450 participants were interviewed at the beginning and after 9 months of participation in traditional or alternative food security interventions. Food security and perceived health were investigated as dependent variables. Differences overtime were assessed through multilevel regression models.

Results

Participants in traditional interventions lowered their food insecurity at follow-up. Decreases among participants in alternative interventions were not statistically significant. Participants in traditional interventions also improved physical (B coefficient 3.00, CI 95% 0.42–5.59) and mental health (B coefficient 6.25, CI 95% 4.15–8.35).

Conclusions

Our results challenge the widely held view suggesting the ineffectiveness of traditional interventions in the short term. Although effects may be intervention-dependent, food banks decreased food insecurity and, in so doing, positively affected perceived health. Although study findings demonstrate that food banks offer short term reprise from the effects of food insecurity, the question as to whether food banks are the most appropriate solution to food insecurity still needs to be addressed.     

Behavioural Risk Factors in Mid-Life Associated with Successful Ageing,Disability, Dementia and Frailty in Later Life: A Rapid Systematic Review

Background

Smoking, alcohol consumption, poor diet and low levels of physical activity significantly contribute to the burden of illness in developed countries. Whilst the links between specific and multiple risk behaviours and individual chronic conditions are well documented, the impact of these behaviours in mid-life across a range of later life outcomes has yet to be comprehensively assessed. This review aimed to provide an overview of behavioural risk factors in mid-life that are associated with successful ageing and the primary prevention or delay of disability, dementia, frailty and non-communicable chronic conditions.

Methods

A literature search was conducted to identify cohort studies published in English since 2000 up to Dec 2014. Multivariate analyses and a minimum follow-up of five years were required for inclusion. Two reviewers screened titles, abstracts and papers independently. Studies were assessed for quality. Evidence was synthesised by mid-life behavioural risk for a range of late life outcomes.

Findings

This search located 10,338 individual references, of which 164 are included in this review. Follow-up data ranged from five years to 36 years. Outcomes include dementia, frailty, disability and cardiovascular disease. There is consistent evidence of beneficial associations between mid-life physical activity, healthy ageing and disease outcomes. Across all populations studied there is consistent evidence that mid-life smoking has a detrimental effect on health. Evidence specific to alcohol consumption was mixed. Limited, but supportive, evidence was available relating specifically to mid-life diet, leisure and social activities or health inequalities.

Conclusions

There is consistent evidence of associations between mid-life behaviours and a range of late life outcomes. The promotion of physical activity, healthy diet and smoking cessation in all mid-life populations should be encouraged for successful ageing and the prevention of disability and chronic disease.     

Effects of the Commercial Flame Retardant Mixture DE-71 on Cytokine Production by Human Immune Cells

IntroductionAlthough production of polybrominated diphenyl ethers (PBDEs) is now banned, release from existing products will continue for many years. The PBDEs are assumed to be neurotoxic and toxic to endocrine organs at low concentrations. Their effect on the immune system has not been investigated thoroughly. We aimed to investigate the influence of DE-71 on cytokine production by peripheral blood mononuclear cells (PBMCs) stimulated with Escherichia Coli lipopolysaccharide (LPS) or phytohaemagglutinin-L (PHA-L).ResultsAt non-cytotoxic concentrations (0.01–10 μg/mL), DE-71 significantly enhanced secretion of IL-1β, IL-6, CXCL8, IL-10, and TNF-α (p<0.001–0.019; n = 6) from LPS-stimulated PBMCs. IFN-γ, TNF-α, IL-17A, and IL-17F (p = <0.001–0.043; n = 6) secretion were enhanced from PHA-L-stimulated PBMCs as well. Secretion of IL-1β, IL-2, IL-10, IL-8 and IL-6 was not significantly affected by DE-71.ConclusionsWe demonstrate an enhancing effect of DE-71 on cytokine production by normal human PBMCs stimulated with LPS or PHA-L ex vivo.