Application of pharmacogenomics and bioinformatics to exemplify the utility of human <i>ex vivo</i> organoculture models in the field of precision medicine

Here we describe a collaboration between industry, the National Health Service (NHS) and academia that sought to demonstrate how early understanding of both pharmacology and genomics can improve strategies for the development of precision medicines. Diseased tissue ethically acquired from patients suffering from chronic obstructive pulmonary disease (COPD), was used to investigate inter-patient variability in drug efficacy using ex vivo organocultures of fresh lung tissue as the test system. The reduction in inflammatory cytokines in the presence of various test drugs was used as the measure of drug efficacy and the individual patient responses were then matched against genotype and microRNA profiles in an attempt to identify unique predictors of drug responsiveness. Our findings suggest that genetic variation in CYP2E1 and SMAD3 genes may partly explain the observed variation in drug response

Primates in peril: the significance of Brazil, Madagascar, Indonesia and the Democratic Republic of the Congo for global primate conservation

Primates occur in 90 countries, but four—Brazil, Madagascar, Indonesia, and the Democratic Republic of the Congo (DRC)—harbor 65% of the world’s primate species (439) and 60% of these primates are Vulnerable, Endangered, or Critically Endangered (IUCN Red List of Threatened Species 2017-3). Considering their importance for global primate conservation, we examine the anthropogenic pressures each country is facing that place their primate populations at risk. Habitat loss and fragmentation are main threats to primates in Brazil, Madagascar and Indonesia. However, in DRC hunting for the commercial bushmeat trade is the primary threat. Encroachment on primate habitats driven by local and global market demands for food and non-food commodities hunting, illegal trade, the proliferation of invasive species, and human and domestic-animal borne infectious diseases cause habitat loss, population declines, and extirpation. Modeling agricultural expansion in the 21st century for the four countries under a worst-case-scenario, showed a primate range contraction of 78% for Brazil, 72% for Indonesia 62% for Madagascar and 32% for DRC. These pressures unfold in the context of expanding human populations with low levels of development. Weak governance across these four countries may limit effective primate conservation planning. We examine landscape and local approaches to effective primate conservation policies and assess the distribution of protected areas and primates in each country. P rimates in Brazil and Madagascar have 38% of their range inside protected areas, 17% in Indonesia and 14% in DRC, suggesting that the great majority of primate populations remain vulnerable. We list the key challenges faced by the four countries to avert primate extinctions now and in the future. In the short term, effective law enforcement to stop illegal hunting and illegal forest destruction is absolutely key. Long-term success can only be achieved by focusing local and global public awareness, actively engaging with international organizations, multinational businesses and consumer nations to reduce unsustainable demands on the environment. Finally, the four primate range states need to ensure that integrated, sustainable land-use planning for economic development includes the maintenance of biodiversity and intact, functional natural ecosystems

Age related decline in female lar gibbon great call performance suggests that call features correlate with physical condition

Background: White-handed gibbons (Hylobates lar) are small Asian apes known for living in stable territories and producing loud, elaborate vocalizations (songs), often in well-coordinated male/female duets. The female great call, the most conspicuous phrase of the repertoire, has been hypothesized to function in intra-sexual territorial defense. We therefore predicted that characteristics of the great call would correlate with a caller’s physical condition, and thus might honestly reflect resource holding potential (RHP). Because measurement of RHP is virtually impossible for wild animals, we used age as a proxy, hypothesizing that great call climaxes are difficult to produce and maintain over time, and that older adults will therefore perform lower quality great calls than young adults. To test this we analyzed the great call climaxes of 15 wild lar gibbon females at Khao Yai National Park, Thailand and 2 captive females at Leo Conservation Center, Greenwich, CT. Results: Findings show that call climaxes correlate with female age, as young animals (n = 8, mean age: 12.9 years) produced climaxes with a higher frequency range (delta F0), maximum F0 frequency and duty cycle than old animals (n = 9, mean age: 29.6 years). A permuted discriminant function analysis also correctly classified calls by age group. During long song bouts the maximum F0 frequency of great call climaxes’ also decreased. Additional data support the hypothesis that short high notes, associated with rapid inhalation as an individual catches its breath, reflect increased caller effort. Older females produced more high notes than younger females, but the difference only approached statistical significance, suggesting that calling effort may be similar across different ages. Finally, for the first time in this species, we measured peak intensity of calls in captive females. They were capable of producing climaxes in excess of 100 dB at close range (2.7 m). Conclusions: Age and within-bout differences in the lar gibbon great call climax suggest that call features correlate with physical condition and thus the call may have evolved as an honest signal in the context of intra-sexual territorial defense and possibly also in male mate choice via sexual selection, although further testing of these hypotheses is necessary. Results: Findings show that call climaxes correlate with female age, as young animals (n = 8, mean age: 12.9 years) produced climaxes with a higher frequency range (delta F0), maximum F0 frequency and duty cycle than old animals (n = 9, mean age: 29.6 years). A permuted discriminant function analysis also correctly classified calls by age group. During long song bouts the maximum F0 frequency of great call climaxes’ also decreased. Additional data support the hypothesis that short high notes, associated with rapid inhalation as an individual catches its breath, reflect increased caller effort. Older females produced more high notes than younger females, but the difference only approached statistical significance, suggesting that calling effort may be similar across different ages. Finally, for the first time in this species, we measured peak intensity of calls in captive females. They were capable of producing climaxes in excess of 100 dB at close range (2.7 m). Conclusions: Age and within-bout differences in the lar gibbon great call climax suggest that call features correlate with physical condition and thus the call may have evolved as an honest signal in the context of intra-sexual territorial defense and possibly also in male mate choice via sexual selection, although further testing of these hypotheses is necessary

Down from the treetops: Red langur (Presbytis rubicunda) terrestrial behaviour

Using direct observations and camera traps at eight sites across Indonesian Borneo we show how red langurs (Presbytis rubicunda) are more terrestrial than previously believed, regularly coming to the ground. This unusual behavior has been found at six of the eight sites surveyed. We find that red langurs come to the ground more frequently in disturbed forests, specifically ones which have been impacted by logging, fire, and hunting, though more data are needed to confirm this as a direct correlation. We also found a trend towards decreased ground use with increased elevation of the habitat. When on the ground, red langurs are predominantly engaged in feeding (50% direct observations, 61% camera traps) and traveling (29% direct observations, 13% camera traps). Red langurs are found on the ground throughout the day, at similar times to activity periods of the apex predator, the Sunda clouded leopard (Neofelis diardi). We suggest that ground use by red langurs could be an adaptation to disturbed forest to exploit additional food sources and to facilitate travel

The (Re)-emerging And ePidemic Infectious Diseases (RAPID) Stigma Scales: a cross-outbreak scale development and pyschometric validation study

Reducing stigma during infectious disease outbreaks is crucial for delivering an effective response. However, no validated stigma scales exist for use across outbreaks, and outbreak-specific scales are developed too slowly to guide timely interventions. To enable more real-time monitoring and mitigation of stigma across outbreak contexts, we developed and validated the (Re)-emerging and ePidemic Infectious Diseases (RAPID) Stigma Scales. Field testing and psychometric validation were conducted in communities affected by Ebola disease in Uganda, mpox in the UK, and Nipah virus disease in Bangladesh. Content validity was established through cognitive interviews and expert Delphi scoring. 1008 respondents were included across the three countries. The final RAPID Community Stigma Scale (12 items) captures initial social stigma, provider or authority-related stigma, structural stigma, and enduring social stigma. The RAPID Self Stigma Scale (4 items) is unidimensional. Both scales were found to have robust psychometric properties, including content validity, structural validity (factor loadings ≥0·6), and reliability (ordinal alphas 0·79–0·92). High scores on both scales predicted an increased hesitancy to report symptoms and seek care. The RAPID Stigma Scales are validated tools for real-time assessment of stigma across outbreak settings, enabling responders to design targeted interventions to improve health outcomes and promote equitable care

Robot-assisted image-guided transcranial magnetic stimulation for somatotopic mapping of the motor cortex: a clinical pilot study

Shape and exact location of motor cortical areas varies among individuals. The exact knowledge of these locations is crucial for planning of neurosurgical procedures. In this study, we have used robot-assisted image-guided transcranial magnetic stimulation (Ri-TMS) to elicit MEP response recorded for individual muscles and reconstruct functional motor maps of the primary motor cortex

Are Hylobates lar Extirpated from China?

The Nangunhe Nature Reserve in Southwest Yunnan (PRC) has long been presumed to be the last stronghold of lar (or white-handed) gibbons (Hylobates lar) in China and the likely last place of occurrence of Hylobates lar yunnanensis. We conducted a comprehensive survey to assess the status of lar gibbons at Nangunhe. We found no visual or auditory evidence of them still residing at the reserve and therefore tentatively conclude that lar gibbons have become extinct in China. It appears that large-scale destruction of primary forests in the 1960s and 1970s brought about an initial decline in their numbers, and subsequent uncontrolled hunting has resulted in their extirpation. The situation for the six Chinese ape taxa is nothing less than disastrous, with 1 taxon assumed to have become extinct during the last few years, 1 taxon not having been confirmed since the 1980s, and 2 species at the very brink of extinction with only tens of individuals remaining in China

Tropical forest and peatland conservation in Indonesia: Challenges and directions

1. Tropical forests and peatlands provide important ecological, climate and socio‐economic benefits from the local to the global scale. However, these ecosystems and their associated benefits are threatened by anthropogenic activities, including agricultural conversion, timber harvesting, peatland drainage and associated fire. Here, we identify key challenges, and provide potential solutions and future directions to meet forest and peatland conservation and restoration goals in Indonesia, with a particular focus on Kalimantan. 2.Through a round‐table, dual‐language workshop discussion and literature evaluation, we recognized 59 political, economic, legal, social, logistical and research challenges, for which five key underlying factors were identified. These challenges relate to the 3Rs adopted by the Indonesian Peatland Restoration Agency (Rewetting, Revegetation and Revitalization), plus a fourth R that we suggest is essential to incorporate into (peatland) conservation planning: Reducing Fires. 3.Our analysis suggests that (a) all challenges have potential for impact on activities under all 4Rs, and many are inter‐dependent and mutually reinforcing, implying that narrowly focused solutions are likely to carry a higher risk of failure; (b) addressing challenges relating to Rewetting and Reducing Fire is critical for achieving goals in all 4Rs, as is considering the local socio‐political situation and acquiring local government and community support; and (c) the suite of challenges faced, and thus conservation interventions required to address these, will be unique to each project, depending on its goals and prevailing local environmental, social and political conditions. 4.With this in mind, we propose an eight‐step adaptive management framework, which could support projects in both Indonesia and other tropical areas to identify and overcome their specific conservation and restoration challenges.Biotechnology and Biosciences Research Council; Borneo Nature Foundatio

A Severe Lack of Evidence Limits Effective Conservation of the World's Primates

Threats to biodiversity are well documented. However, to effectively conserve species and their habitats, we need to know which conservation interventions do (or do not) work. Evidence-based conservation evaluates interventions within a scientific framework. The Conservation Evidence project has summarized thousands of studies testing conservation interventions and compiled these as synopses for various habitats and taxa. In the present article, we analyzed the interventions assessed in the primate synopsis and compared these with other taxa. We found that despite intensive efforts to study primates and the extensive threats they face, less than 1% of primate studies evaluated conservation effectiveness. The studies often lacked quantitative data, failed to undertake postimplementation monitoring of populations or individuals, or implemented several interventions at once. Furthermore, the studies were biased toward specific taxa, geographic regions, and interventions. We describe barriers for testing primate conservation interventions and propose actions to improve the conservation evidence base to protect this endangered and globally important taxon