The Way to a Man's Heart Is through His Stomach: What about Horses?

Background

How do we bond to one another? While in some species, like humans, physical contact plays a role in the process of attachment, it has been suggested that tactile contact''s value may greatly differ according to the species considered. Nevertheless, grooming is often considered as a pleasurable experience for domestic animals, even though scientific data is lacking. On another hand, food seems to be involved in the creation of most relationships in a variety of species.

Methodology/Principal Findings

In this study, we used the horse training context to test the effects of food versus grooming during repeated human-horse interactions. The results reveal that food certainly holds a key role in the attachment process, while tactile contact was here clearly insufficient for bonding to occur.

Conclusion/Significance

This study raises important questions on the way tactile contact is perceived, and shows that large inter-species differences are to be expected.     

The Q-cycle – A Personal Perspective

In this Minireview, I provide an overview of the developments over the period 1970 to 1990 that led to the current view of the Q-cycle mechanism of the cytochrome bc (1) complex. The perspective is necessarily personal, and places some emphasis on research on the complex in the photosynthetic bacteria, where the kinetics could be studied in situ and with better time resolution than in mitochondria. Peter Mitchell's original Q-cycle underwent several early revisions. The version of the Q-cycle currently accepted in most labs owed much to a perceptive critique by Peter Garland, who proposed a modified Q-cycle that allowed the complex to act independently. This was among several variants discussed by Mitchell in a seminal review from 1976. Six years later, despite significant advances in both mitochondrial and bacterial work, discrimination between the half-dozen or so variants that remained in active contention had proved elusive, and the kinetic data from both mitochondrial and photosynthetic systems was refractory. This was the basis of my own opposition to the Q-cycle. While trying to explain this opposition to an undergraduate student in the lab I was led to a re-evaluation of the kinetic data in the light of the substantial advances in our understanding of the biochemistry and thermodynamic properties of the complex. From this it became apparent that one version of the Q-cycle could account with satisfactory economy for the data from the photosynthetic bacteria, and for most results from work with mitochondrial complexes. The resulting model was highly constrained, and, since it incorporated Garland's suggestions for an independent mechanism, was called the modified Q-cycle. The modified Q-cycle has stood the test of time well, and the recent structural information has both confirmed the general mechanism, and allowed extension to a more detailed understanding of the molecular architecture, and the relation between structure and function.     

The Ecosystem: Model or Metaphor?

Industrial ecology offers an original way of looking at economic activities. The approach is based on an analogy between certain objects studied by the science of ecology (ecosystems, metabolisms, symbiosis, biocenosis, etc.) and industrial systems. However, this analogical relationship raises difficulties due to the various interpretations to which it is open. Although there is agreement regarding its heuristic function, the analogy can nevertheless be understood either as a model or as a metaphor. The present article first attempts to show how models differ from metaphors. It then sets out to justify the epistemological relevance of this distinction for industrial ecology research. The reflection should thus contribute to clarifying the debate on the (supposed or desired) role of analogy in the field of industrial ecology and heighten the interest this field of investigation represents for implementing sustainable development.     

Autophagy and Self-Preservation: A Step Ahead from Cell Plasticity?

Silencing the SPINK-related gene Kazal1 in hydra gland cells induces an excessive autophagy of both gland and digestive cells, leading to animal death. Moreover, during regeneration, autophagosomes are immediately detected in regenerating tips, where Kazal1 expression is lowered. When Kazal1 is completely silenced, hydra no longer survive the amputation stress (Chera S, de Rosa R, Miljkovic-Licina M, Dobretz K, Ghila L, Kaloulis K, and Galliot B. Silencing of the hydra serine protease inhibitor Kazal1 gene mimics the human Spink1 pancreatic phenotype. J Cell Sci 2006; 119:846-57). These results highlight the essential digestive and cytoprotective functions played by Kazal1 in hydra. In mammals, autophagy of exocrine pancreatic cells is also induced upon SPINK1/Spink3 inactivation, whereas SPINK3 is activated in injured pancreatic cells. Hence SPINKs, by preventing an excessive autophagy, appear to act as key players of the stress-induced self-preservation program. In hydra, this program is a prerequisite to the early cellular transition, whereby digestive cells of the regenerating tips transform into a head-organizer center. Enhancing the self-preservation program in injured tissues might therefore be the condition for unmasking their potential cell and/or developmental plasticity.

Addendum to:

Silencing of the Hydra Serine Protease Inhibitor Kazal1 Gene Mimics the HumanSpink1 Pancreatic Phenotype

S. Chera, R. de Rosa, M. Miljkovic-Licina, K. Dobretz, L. Ghila, K. Kaloulis and B. Galliot

J Cell Sci 2006; 119:846-57     

The Punctum Fixum-Punctum Mobile Model: A Neuromuscular Principle for Efficient Movement Generation?

According to the “punctum fixum–punctum mobile model” that was introduced in prior studies, for generation of the most effective intentional acceleration of a body part the intersegmental neuromuscular onset succession has to spread successively from the rotation axis (punctum fixum) toward the body part that shall be accelerated (punctum mobile). The aim of the present study was to investigate whether this principle is, indeed, fundamental for any kind of efficient rotational accelerations in general, independent of the kind of movements, type of rotational axis, the current body position, or movement direction. Neuromuscular onset succession was captured by surface electromyography of relevant muscles of the anterior and posterior muscle chain in 16 high-level gymnasts during intentional accelerating movement phases while performing 18 different gymnastics elements (in various body positions to forward and backward, performed on high bar, parallel bars, rings and trampoline), as well as during non-sport specific pivot movements around the longitudinal axis. The succession patterns to generate the acceleration phases during these movements were described and statistically evaluated based on the onset time difference between the muscles of the corresponding muscle chain. In all the analyzed movement phases, the results clearly support the hypothesized succession pattern from punctum fixum to punctum mobile. This principle was further underlined by the finding that the succession patterns do change their direction running through the body when the rotational axis (punctum fixum) has been changed (e.g., high bar or rings [hands] vs. floor or trampoline [feet]). The findings improve our understanding of intersegmental neuromuscular coordination patterns to generate intentional movements most efficiently. This could help to develop more specific methods to facilitate such patterns in particular contexts, thus allowing for shorter motor learning procedures of context-specific key movement sequences in different disciplines of sports, as well as during non-sport specific movements.     

7 The Molecular Biology of Tryptophan Synthase: A Model for Protein–Protein Interaction

Abstract

The use of plastic produced from non-renewable resources constitutes a major environmental problem of the modern society. Polylactide polymers (PLA) have recently gained enormous attention as one possible substitution of petroleum derived polymers. A prerequisite for high quality PLA production is the provision of optically pure lactic acid, which cannot be obtained by chemical synthesis in an economical way. Microbial fermentation is therefore the commercial option to obtain lactic acid as monomer for PLA production. However, one major economic hurdle for commercial lactic acid production as basis for PLA is the costly separation procedure, which is needed to recover and purify the product from the fermentation broth. Yeasts, such as Saccharomyces cerevisiae (bakers yeast) offer themselves as production organisms because they can tolerate low pH and grow on mineral media what eases the purification of the acid. However, naturally yeasts do not produce lactic acid. By metabolic engineering, ethanol was exchanged with lactic acid as end product of fermentation. A vast amount of effort has been invested into the development of yeasts for lactic acid production since the first paper on this topic by Dequin and process insight. If pH stress is used as basis for DNA microarray analyses, in order to improve the host, what exactly is addressed? Growth? Or productivity? They might be connected, but can be negatively correlated. A better growing strain might not be a better producer. So if the question was growth, the answer might not be what was initially intended (productivity).

A major task for the future is to learn to ask the right questions – a lot of studies intended to lead to better productivity, did lead to interesting results, but NOT to better production strains.

Taking together what we learned from lactic acid production with yeasts, we see a bright future for bulk and fine chemical production with these versatile hosts.     

An Integrative Model of Patient-Centeredness – A Systematic Review and Concept Analysis

Background

Existing models of patient-centeredness reveal a lack of conceptual clarity. This results in a heterogeneous use of the term, unclear measurement dimensions, inconsistent results regarding the effectiveness of patient-centered interventions, and finally in difficulties in implementing patient-centered care. The aim of this systematic review was to identify the different dimensions of patient-centeredness described in the literature and to propose an integrative model of patient-centeredness based on these results.

Methods

Protocol driven search in five databases, combined with a comprehensive secondary search strategy. All articles that include a definition of patient-centeredness were eligible for inclusion in the review and subject to subsequent content analysis. Two researchers independently first screened titles and abstracts, then assessed full texts for eligibility. In each article the given definition of patient-centeredness was coded independently by two researchers. We discussed codes within the research team and condensed them into an integrative model of patient-centeredness.

Results

4707 records were identified through primary and secondary search, of which 706 were retained after screening of titles and abstracts. 417 articles (59%) contained a definition of patient-centeredness and were coded. 15 dimensions of patient-centeredness were identified: essential characteristics of clinician, clinician-patient relationship, clinician-patient communication, patient as unique person, biopsychosocial perspective, patient information, patient involvement in care, involvement of family and friends, patient empowerment, physical support, emotional support, integration of medical and non-medical care, teamwork and teambuilding, access to care, coordination and continuity of care. In the resulting integrative model the dimensions were mapped onto different levels of care.

Conclusions

The proposed integrative model of patient-centeredness allows different stakeholders to speak the same language. It provides a foundation for creating better measures and interventions. It can also be used to inform the development of clinical guidance documents and health policy directives, and through this support the shift towards patient-centered health care.     

The Novel Coronavirus – A Snapshot of Current Knowledge

Another animal to human transmission of a coronavirus occurred in December 2019 on a live animal market in the Chinese city of Wuhan causing an epidemic in China, reaching now different continents. This minireview summarizes the research literature on the virological, clinical and epidemiological aspects of this epidemic published until end of February 2020.     

Epigenetics of Host–Pathogen Interactions: The Road Ahead and the Road Behind

A growing body of evidence points towards epigenetic mechanisms being responsible for a wide range of biological phenomena, from the plasticity of plant growth and development to the nutritional control of caste determination in honeybees and the etiology of human disease (e.g., cancer). With the (partial) elucidation of the molecular basis of epigenetic variation and the heritability of certain of these changes, the field of evolutionary epigenetics is flourishing. Despite this, the role of epigenetics in shaping host–pathogen interactions has received comparatively little attention. Yet there is plenty of evidence supporting the implication of epigenetic mechanisms in the modulation of the biological interaction between hosts and pathogens. The phenotypic plasticity of many key parasite life-history traits appears to be under epigenetic control. Moreover, pathogen-induced effects in host phenotype may have transgenerational consequences, and the bases of these changes and their heritability probably have an epigenetic component. The significance of epigenetic modifications may, however, go beyond providing a mechanistic basis for host and pathogen plasticity. Epigenetic epidemiology has recently emerged as a promising area for future research on infectious diseases. In addition, the incorporation of epigenetic inheritance and epigenetic plasticity mechanisms to evolutionary models and empirical studies of host–pathogen interactions will provide new insights into the evolution and coevolution of these associations. Here, we review the evidence available for the role epigenetics on host–pathogen interactions, and the utility and versatility of the epigenetic technologies available that can be cross-applied to host–pathogen studies. We conclude with recommendations and directions for future research on the burgeoning field of epigenetics as applied to host–pathogen interactions.     

MASP-1 Induced Clotting – The First Model of Prothrombin Activation by MASP-1

Mannan-binding lectin-associated serine protease-1 (MASP-1), a protein of the complement lectin pathway, resembles thrombin in terms of structural features and substrate specificity. Due to its interplay with several coagulation factors, it has the ability to induce fibrin clot formation independent of the usual coagulation activation pathways. We have recently shown that MASP-1 activates prothrombin and identified arginine (R) 155, R271, and R393 as potential cleavage sites. FXa cleaves R320 instead of R393, and thrombin cleaves R155 and R284 in prothrombin. Here we have used three arginine-to-glutamine mutants of prothrombin, R271Q, R320Q, R393Q and the serine-to-alanine active site mutant S525A to investigate in detail the mechanism of MASP-1 mediated prothrombin activation. Prothrombin wildtype and mutants were digested with MASP-1 and the cleavage products were analysed by SDS-PAGE and N-terminal sequencing. A functional clotting assay was performed by thrombelastography. We have found that MASP-1 activates prothrombin via two simultaneous pathways, either cleaving at R271 or R393 first. Both pathways result in the formation of several active alternative thrombin species. Functional studies confirmed that both R393 and R320 are required for prothrombin activation by MASP-1, whereas R155 is not considered to be an important cleavage site in this process. In conclusion, we have described for the first time a detailed model of prothrombin activation by MASP-1.     

Longer Sleep – Slimmer Kids: The ENERGY-Project

Background

Few studies have differentiated between weekday and weekend day sleep duration in their association with indicators of weight status in children. Therefore, we examined the association of week and weekend day sleep duration with indicators of body composition in 10–12 year old European school children.

Methods and Findings

Multi-level linear regression analysis was performed to examine the association between parent-reported week and weekend day sleep duration and objectively assessed child BMI and WC, adjusting for socio-demographic variables and energy balanced related behaviours EBRBs (i.e. dietary, physical and sedentary behaviour). Compared to sleeping 10 hrs/night or more, sleeping on average less than 10 hrs/night during weekdays was associated with higher BMI (for example, B = 0.86 and CI = [0.27;1.45] when sleeping ≤7 hrs) and WC (for example, B = 1.99 and CI = [0.32;3.65] when sleeping ≤7 hrs). Sleeping 9 hrs/night during weekend days, but not ≤8 hrs, was associated with higher WC (B = 0.66; CI = [0.04;1.28]) compared to sleeping more than 10 hrs/night. Average (week and weekend) sleep duration less than 10 hrs/night was associated with higher values for BMI (B = 0.98; CI = [0.24;1.73] and WC (B = 2.35; CI = [0.08;4.31]).

Conclusions

Weekday sleep duration seems more strongly associated with body composition in European school children than weekend day sleep duration. Promoting adequate sleep duration may contribute to healthy weight in children.     

Cost-Effectiveness of a Community Pharmacist-Led Sleep Apnea Screening Program – A Markov Model

Background

Despite the high prevalence and major public health ramifications, obstructive sleep apnea syndrome (OSAS) remains underdiagnosed. In many developed countries, because community pharmacists (CP) are easily accessible, they have been developing additional clinical services that integrate the services of and collaborate with other healthcare providers (general practitioners (GPs), nurses, etc.). Alternative strategies for primary care screening programs for OSAS involving the CP are discussed.

Objective

To estimate the quality of life, costs, and cost-effectiveness of three screening strategies among patients who are at risk of having moderate to severe OSAS in primary care.

Design

Markov decision model.

Data Sources

Published data.

Target Population

Hypothetical cohort of 50-year-old male patients with symptoms highly evocative of OSAS.

Time Horizon

The 5 years after initial evaluation for OSAS.

Perspective

Societal.

Interventions

Screening strategy with CP (CP-GP collaboration), screening strategy without CP (GP alone) and no screening.

Outcomes measures

Quality of life, survival and costs for each screening strategy.

Results of base-case analysis

Under almost all modeled conditions, the involvement of CPs in OSAS screening was cost effective. The maximal incremental cost for “screening strategy with CP” was about 455€ per QALY gained.

Results of sensitivity analysis

Our results were robust but primarily sensitive to the treatment costs by continuous positive airway pressure, and the costs of untreated OSAS. The probabilistic sensitivity analysis showed that the “screening strategy with CP” was dominant in 80% of cases. It was more effective and less costly in 47% of cases, and within the cost-effective range (maximum incremental cost effectiveness ratio at €6186.67/QALY) in 33% of cases.

Conclusions

CP involvement in OSAS screening is a cost-effective strategy. This proposal is consistent with the trend in Europe and the United States to extend the practices and responsibilities of the pharmacist in primary care.     

A Screen-and-Treat Strategy Targeting Visceral Leishmaniasis in HIV-Infected Individuals in Endemic East African Countries: The Way Forward?

In the wake of the HIV epidemic, visceral leishmaniasis (VL), a disseminated protozoan infection caused by the Leishmania donovani complex, has been re-emerging, particularly in North Ethiopia where up to 40% of patients with VL are co-infected with HIV. Management of VL in HIV co-infection is complicated by increased drug toxicity, and high treatment failure and relapse rates with all currently available drugs, despite initiation of antiretroviral treatment. Tackling L. donovani infection before disease onset would thus be a logical approach. A screen-and-treat approach targeting latent or the early stage of infection has successfully been implemented in other HIV-associated opportunistic infections. While conceptually attractive in the context of VL–HIV, the basic understanding and evidence underpinning such an approach is currently lacking. Prospective cohort studies will have to be conducted to quantify the risk of VL in different risk groups and across CD4 cell count levels. This will allow developing clinical prognostic tools, integrating clinical, HIV and Leishmania infection markers. Interventional studies will be needed to evaluate prophylactic or pre-emptive treatment strategies for those at risk, ideally relying on an oral (combination) regimen. Issues like tolerability, emergence of resistance and drug interactions will require due attention. The need for maintenance therapy will have to be assessed. Based on the risk–benefit data, VL risk cut-offs will have to be identified to target treatment to those most likely to benefit. Such a strategy should be complemented with early initiation of antiretroviral treatment and other strategies to prevent HIV and Leishmania infection.