Tendinopathy—from basic science to treatment

Chronic tendon pathology (tendinopathy), although common, is difficult to treat. Tendons possess a highly organized fibrillar matrix, consisting of type I collagen and various 'minor' collagens, proteoglycans and glycoproteins. The tendon matrix is maintained by the resident tenocytes, and there is evidence of a continuous process of matrix remodeling, although the rate of turnover varies at different sites. A change in remodeling activity is associated with the onset of tendinopathy. Major molecular changes include increased expression of type III collagen, fibronectin, tenascin C, aggrecan and biglycan. These changes are consistent with repair, but they might also be an adaptive response to changes in mechanical loading. Repeated minor strain is thought to be the major precipitating factor in tendinopathy, although further work is required to determine whether it is mechanical overstimulation or understimulation that leads to the change in tenocyte activity. Metalloproteinase enzymes have an important role in the tendon matrix, being responsible for the degradation of collagen and proteoglycan in both healthy patients and those with disease. Metalloproteinases that show increased expression in painful tendinopathy include ADAM (a disintegrin and metalloproteinase)-12 and MMP (matrix metalloproteinase)-23. The role of these enzymes in tendon pathology is unknown, and further work is required to identify novel and specific molecular targets for therapy

Restoring the orangutan in a whole- or half-earth context

Various global-scale proposals exist to reduce the loss of biological diversity. These include the Half-Earth and Whole-Earth visions that respectively seek to set aside half the planet for wildlife conservation or to diversify conservation practices fundamentally and change the economic systems that determine environmental harm. Here we assess these visions in the specific context of Bornean orangutans Pongo pygmaeus and their conservation. Using an expert-led process we explored three scenarios over a 10-year time frame: continuation of Current Conditions, a Half-Earth approach and a Whole-Earth approach. In addition, we examined a 100-year population recovery scenario assuming 0% offtake of Bornean orangutans. Current Conditions were predicted to result in a population c. 73% of its current size by 2032. Half-Earth was judged comparatively easy to achieve and predicted to result in an orangutan population of c. 87% of its current size by 2032. Whole-Earth was anticipated to lead to greater forest loss and ape killing, resulting in a prediction of c. 44% of the current orangutan population for 2032. Finally, under the recovery scenario, populations could be c. 148% of their current size by 2122. Although we acknowledge uncertainties in all of these predictions, we conclude that the Half-Earth and Whole-Earth visions operate along different timelines, with the implementation of Whole-Earth requiring too much time to benefit orangutans. None of the theorized proposals provided a complete solution, so drawing elements from each will be required. We provide recommendations for equitable outcomes

Relative position of primers used in DNA amplification and sequencing of the complete orang-utan mitochondrial DNA control region.

<p>The sizes of each region in this schematic are proportional to their sizes in the orang-utan mitochondrial genome.</p

Nucleotide diversity throughout the complete orang-utan mitochondrial DNA control region.

<p>Diversity was computed for alignments comprising, a) all 38 sequences (1022 sites), b) 13 sequences of Sumatran maternal ancestry (1018 sites), and c) 25 sequences of Bornean maternal ancestry (1002 sites). Data were computed under the sliding window method, using a window length of 100 sites and a step size of 25 sites, excluding sites with gaps.</p

Segments of the left domain of the orang-utan mitochondrial DNA control region, of varying lengths and positions, as published and analysed in prior studies.

<p>Many were cut by the original authors from longer sequences (<i>i</i>.<i>e</i>. larger PCR amplicons, containing flanking regions) prior to analysis and/or publication; only those bases derived from the control region are specified here. Nucleotide positions correspond to those of the complete Sumatran orang-utan mitochondrial DNA genome (GenBank accession code X97707; [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0168715#pone.0168715.ref050" target="_blank">50</a>]) and are estimated for unpublished sequences based on the lengths noted in each manuscript. The control region spans positions 15484–16499 of the reference genome.</p

Diversity indices computed from three alignments of 35 novel and unique complete control-region sequences generated in this study, plus three published complete control-region sequences, for all sequences and for those of Bornean or Sumatran orang-utans only.

<p>Alignments were trimmed to the lengths of various shorter segments sequenced in prior studies.</p

Flanged males have higher reproductive success in a completely wild orangutan population.

Male orangutans (Pongo spp.) exhibit bimaturism, an alternative reproductive tactic, with flanged and unflanged males displaying two distinct morphological and behavioral phenotypes. Flanged males are larger than unflanged males and display secondary sexual characteristics which unflanged males lack. The evolutionary explanation for alternative reproductive tactics in orangutans remains unclear because orangutan paternity studies to date have been from sites with ex-captive orangutans, provisioning via feeding stations and veterinary care, or that lack data on the identity of mothers. Here we demonstrate, using the first long-term paternity data from a site free of these limitations, that alternative reproductive tactics in orangutans are condition-dependent, not frequency-dependent. We found higher reproductive success by flanged males than by unflanged males, a pattern consistent with other Bornean orangutan (Pongo pygmaeus) paternity studies. Previous paternity studies disagree on the degree of male reproductive skew, but we found low reproductive skew among flanged males. We compare our findings and previous paternity studies from both Bornean and Sumatran orangutans (Pongo abelii) to understand why these differences exist, examining the possible roles of species differences, ecology, and human intervention. Additionally, we use long-term behavioral data to demonstrate that while flanged males can displace unflanged males in association with females, flanged males are unable to keep other males from associating with a female, and thus they are unable to completely mate guard females. Our results demonstrate that alternative reproductive tactics in Bornean orangutans are condition-dependent, supporting the understanding that the flanged male morph is indicative of good condition. Despite intense male-male competition and direct sexual coercion by males, female mate choice is effective in determining reproductive outcomes in this population of wild orangutans

Reproductive skew calculation and nonac’s b interpretation.

Reproductive skew calculation and nonac’s b interpretation.</p

Male displacement in male-female associations.

The proportion of (a) all male-female associations, (b) a subset of male-female associations where the female is a sexually active, and (c) a subset of male-female associations where the female is a non-sexually active in which the first male is displaced by an ‘extra-pair male’ (EPM). Male displacement is represented by darker shading. N values at the top of each column show the number of male-female associations by male morph. Dark gray represents encounters with displacement and light gray represents encounter with no displacement. Significance values from Fisher’s exact tests (* = P 0.05).</p

Paternity determination and paternity skew across study sites.

Paternity determination and paternity skew across study sites.</p