Reframing conservation physiology to be more inclusive, integrative, relevant and forward-looking: reflections and a horizon scan

Applying physiological tools, knowledge and concepts to understand conservation problems (i.e. conservation physiology) has become common place and confers an ability to understand mechanistic processes, develop predictive models and identify cause-and-effect relationships. Conservation physiology is making contributions to conservation solutions; the number of 'success stories' is growing, but there remain unexplored opportunities for which conservation physiology shows immense promise and has the potential to contribute to major advances in protecting and restoring biodiversity. Here, we consider howconservation physiology has evolved with a focus on reframing the discipline to be more inclusive and integrative. Using a 'horizon scan', we further exploreways in which conservation physiology can be more relevant to pressing conservation issues of today (e.g. addressing the Sustainable Development Goals; delivering science to support the UN Decade on Ecosystem Restoration), as well as more forward-looking to inform emerging issues and policies for tomorrow. Our horizon scan provides evidence that, as the discipline of conservation physiology continues to mature, it provides a wealth of opportunities to promote integration, inclusivity and forward-thinking goals that contribute to achieving conservation gains. To advance environmenta lmanagement and ecosystem restoration, we need to ensure that the underlying science (such as that generated by conservation physiology) is relevant with accompanying messaging that is straightforward and accessible to end users

Periodontal Ehlers-Danlos Syndrome Is Caused by Mutations in C1R and C1S, which Encode Subcomponents C1r and C1s of Complement

Periodontal Ehlers-Danlos syndrome (pEDS) is an autosomal-dominant disorder characterized by early-onset periodontitis leading to premature loss of teeth, joint hypermobility, and mild skin findings. A locus was mapped to an approximately 5.8 Mb region at 12p13.1 but no candidate gene was identified. In an international consortium we recruited 19 independent families comprising 107 individuals with pEDS to identify the locus, characterize the clinical details in those with defined genetic causes, and try to understand the physiological basis of the condition. In 17 of these families, we identified heterozygous missense or in-frame insertion/deletion mutations in C1R (15 families) or C1S (2 families), contiguous genes in the mapped locus that encode subunits C1r and C1s of the first component of the classical complement pathway. These two proteins form a heterotetramer that then combines with six C1q subunits. Pathogenic variants involve the subunit interfaces or inter-domain hinges of C1r and C1s and are associated with intracellular retention and mild endoplasmic reticulum enlargement. Clinical features of affected individuals in these families include rapidly progressing periodontitis with onset in the teens or childhood, a previously unrecognized lack of attached gingiva, pretibial hyperpigmentation, skin and vascular fragility, easy bruising, and variable musculoskeletal symptoms. Our findings open a connection between the inflammatory classical complement pathway and connective tissue homeostasis

Coping with Thermal Challenges: Physiological Adaptations to Environmental Temperatures

Temperature profoundly influences physiological responses in animals, primarily due to the effects on biochemical reaction rates. Since physiological responses are often exemplified by their rate dependency (e.g., rate of blood flow, rate of metabolism, rate of heat production, and rate of ion pumping), the study of temperature adaptations has a long history in comparative and evolutionary physiology. Animals may either defend a fairly constant temperature by recruiting biochemical mechanisms of heat production and utilizing physiological responses geared toward modifying heat loss and heat gain from the environment, or utilize biochemical modifications to allow for physiological adjustments to temperature. Biochemical adaptations to temperature involve alterations in protein structure that compromise the effects of increased temperatures on improving catalytic enzyme function with the detrimental influences of higher temperature on protein stability. Temperature has acted to shape the responses of animal proteins in manners that generally preserve turnover rates at animals’ normal, or optimal, body temperatures. Physiological responses to cold and warmth differ depending on whether animals maintain elevated body temperatures (endothermic) or exhibit minimal internal heat production (ectothermic). In both cases, however, these mechanisms involve regulated neural and hormonal over heat flow to the body or heat flow within the body. Examples of biochemical responses to temperature in endotherms involve metabolic uncoupling mechanisms that decrease metabolic efficiency with the outcome of producing heat, whereas ectothermic adaptations to temperature are best exemplified by the numerous mechanisms that allow for the tolerance or avoidance of ice crystal formation at temperatures below 0°C

Degradation of collagen I by activated C1s in periodontal Ehlers-Danlos Syndrome

International audiencePeriodontal Ehlers-Danlos syndrome (pEDS) is an autosomal dominant disorder characterized by early-onset periodontitis leading to premature loss of teeth, lack of attached gingiva and thin and fragile gums leading to gingival recession. Connective tissue abnormalities of pEDS typically include easy bruising, pretibial plaques, distal joint hypermobility, hoarse voice, and less commonly manifestations such as organ or vessel rupture. pEDS is caused by heterozygous missense mutations in C1R and C1S genes of the classical complement C1 complex. Previously we showed that pEDS pathogenic variants trigger intracellular activation of C1r and/or C1s, leading to extracellular presence of activated C1s. However, the molecular link relating activated C1r and C1s proteases to the dysregulated connective tissue homeostasis in pEDS is unknown. Using cell- and molecular-biological assays, we identified activated C1s (aC1s) as an enzyme which degrades collagen I in cell culture and in in vitro assays. Matrix collagen turnover in cell culture was assessed using labelled hybridizing peptides, which revealed fast and comprehensive collagen protein remodeling in patient fibroblasts. Furthermore, collagen I was completely degraded by aC1s when assays were performed at 40°C, indicating that even moderate elevated temperature has a tremendous impact on collagen I integrity. This high turnover is expected to interfere with the formation of a stable ECM and result in tissues with loose compaction a hallmark of the EDS phenotype. Our results indicate that pathogenesis in pEDS is not solely mediated by activation of the complement cascade but by inadequate C1s-mediated degradation of matrix proteins, confirming pEDS as a primary connective tissue disorder

<i>Mycobacterium marinum</i>, a further infectious agent associated with sarcoidosis: the polyetiology hypothesis

A 39-y-old male had a diagnosis of sarcoidosis and corticosteroid therapy was started. Surprisingly, following his discharge from hospital, Mycobacterium marinum was isolated in 1 of 3 sputum samples taken 7 weeks earlier on admission. After this, Mycobacterium marinum-DNA was identified in the stored lung biopsies by the PCR-RFLP of the hsp65 gene

C1R Mutations Trigger Constitutive Complement 1 Activation in Periodontal Ehlers-Danlos Syndrome

International audienc

Italian registry of patients with alpha-1 antitrypsin deficiency: General data and quality of life evaluation

Alpha1-antitrypsin Deficiency (AATD) is a rare hereditary disorder with an estimated prevalence of about 1/5000 individuals in Italy. Deficient patients are at a higher risk of developing lung emphysema and chronic liver disease. The low estimated prevalence of AATD prompted the establishment of a registry with the aim of learning more about the natural history and the quality of care of these patients. The Italian registry for AATD was established in 1996. In this study, genetic and clinical findings of Italian AATD patients are presented. Moreover, we also evaluated the changes in health-related quality of life (HRQoL) in patients with COPD and AAT deficiency over a three-year period, in relation to augmentation therapy. In a period spanning 18 years (1996-2014) a total of 422 adult subjects with severe AATD were enrolled, namely 258 PI*ZZ, 74 PI*SZ, 4 PI*SS and 86 patients with at least one rare deficient allele. The 21.3% frequency for AATD patients with at least one deficient rare variant is the highest so far recorded in national registries of AATD. The registry data allow a detailed characterization of the natural course of the disease and the level of patient care, as well as confirm the usefulness of early AATD detection