Less than 7000 cheetahs (Acinonyx jubatus) persist in Africa. Although human-wildlife conflict, habitat degradation, and loss of prey are major threats to cheetah populations, illegal trade in live cubs for pets may have the most significant impact on populations in the Horn of Africa. We developed a novel, stepwise decision support tool to predict probable trafficking routes by leveraging the power of distinct modeling approaches. First, we created a cheetah habitat suitability index (HSI) to determine where source cheetah populations may occur. We then created a trafficking network model linking known and predicted cheetah populations with documented destinations in the Arabian Peninsula. A significant area in Eastern Ethiopia and Northern Somalia was estimated to harbor undocumented cheetahs. When these predicted populations were used as a supply source, the trafficking network model showed multiple routes passing through Somaliland and across the Gulf of Aden to Yemen, supporting the notion that undocumented cheetahs may be supplying pet market demands. Though we demonstrate how our decision support tool can inform law enforcement, conservation strategies, and community engagement, we caution that our results are not fully validated due to limited accessibility, alternative trafficking routes, and the cryptic nature of illegal wildlife trade.

Coexistence with large carnivores poses challenges to human well-being, livelihoods, development, resource management, and policy. Even where people and carnivores have historically coexisted, traditional patterns of behavior toward large carnivores may be disrupted by wider processes of economic, social, political, and climate change. Conservation interventions have typically focused on changing behaviors of those living alongside large carnivores to promote sustainable practices. While these interventions remain important, their success is inextricably linked to broader socio-political contexts, including natural resource governance and equitable distribution of conservation-linked costs and benefits. In this context we propose a Theory of Change to identify logical pathways of action through which coexistence with large carnivores can be enhanced. We focus on Africa's dryland landscapes, known for their diverse guild of large carnivores that remain relatively widespread across the continent. We review the literature to understand coexistence and its challenges; explain our Theory of Change, including expected outcomes and pathways to impact; and discuss how our model could be implemented and operationalized. Our analysis draws on the experience of coauthors, who are scientists and practitioners, and on literature from conservation, political ecology, and anthropology to explore the challenges, local realities, and place-based conditions under which expected outcomes succeed or fail. Three pathways to impact were identified: (a) putting in place good governance harmonized across geographic scales; (b) addressing coexistence at the landscape level; and (c) reducing costs and increasing benefits of sharing a landscape with large carnivores. Coordinated conservation across the extensive, and potentially transboundary, landscapes needed by large carnivores requires harmonization of top-down approaches with bottom-up community-based conservation. We propose adaptive co-management approaches combined with processes for active community engagement and informed consent as useful dynamic mechanisms for navigating through this contested space, while enabling adaptation to climate change. Success depends on strengthening underlying enabling conditions, including governance, capacity, local empowerment, effective monitoring, and sustainable financial support. Implementing the Theory of Change requires ongoing monitoring and evaluation to inform adaptation and build confidence in the model. Overall, the model provides a flexible and practical framework that can be adapted to dynamic local socio-ecological contexts.

Research on the African cheetah (Acinonyx jubatus) exhibits strong geographical biases, with most studies taking place within a few, well-studied populations. Here, we provide the first insights into the status and distribution of a globally important cheetah population in the 50,000 km(2) Ruaha-Rungwa landscape in southern Tanzania. We employed data from four methods (systematic camera trap surveys, sign surveys, community camera trapping, and observations by photo-tourism guides) to improve knowledge of this understudied population. Our findings indicate that cheetah are widespread across the landscape, although they appear to exist at relatively low population densities, likely primarily due to biotic factors. Our surveys revealed an extension of confirmed geographical range of the species and provide some of the first evidence that miombo woodlands may be an important habitat for cheetah across its eastern African range. We employ these findings to identify research priorities for the species elsewhere in the region. Community camera trapping revealed that cheetah are using unprotected areas, although rarely. Finally, we show that collaborations with tourism operators can be employed to monitor cheetah populations, but also identify limitations of this method. Our results have implications for conservation of the species both in southern Tanzania and across its African range.

Effective conservation management is underpinned by science. Yet, there are often barriers against the incorporation of up-to-date scientific research into decision-making and policy. Here, we draw on experience from a multi-nation approach to conserve cheetah and African wild dogs across Africa, using relationships between scientists and managers established over more than a decade, to better understand scientific information needs of managers. While our analysis focuses on Africa, many of our findings are likely to be relevant to other regions. Managers view science as critical to their decision-making processes and strongly support scientific research, particularly when research directly addresses their information needs. However, managers reported problems in accessing final results and highlighted the need to access raw ecological data from research undertaken within protected areas. Fundamental to improving the management relevance of scientific research is the need for scientists to engage with managers through all steps of the research process, from project design and implementation through to scientific publication and end-of-project agreements. Effective engagement requires open and clear communication; including agreed processes for access to biodiversity data and submission of final results. In order to foster future scientific endeavours and collaborations, systems should be established to better facilitate information exchange, while also safeguarding the rights of scientists to publish their data and protect their academic freedom. Our analysis also calls for a greater awareness of the geo-political context under which science is undertaken, and for increased scientific participation through an inclusive approach that recognizes, and gives credit to, a wider diversity of scientific contributions and expertise. This article is part of the theme issue ‘Linking behaviour to dynamics of populations and communities: application of novel approaches in behavioural ecology to conservation’.

It is estimated that, between November 2005 and December 2015, over 1000 cheetahs (Acinonyx jubatus) have been removed from the wild for the illegal pet trade, or killed for their pelts and other body parts for clothing, ornaments, traditional ceremonies, and folk remedies. The main problem is the smuggling of young cheetah cubs snatched from their mothers from the Horn of Africa, through Yemen, to the wealthy countries of the Arabian Peninsula, where ownership of pet cheetahs is significant, as evidenced by thousands of images on social media. International efforts are underway to improve enforcement and education to reduce both demand and supply. Cheetahs are just one of many species poached or trafficked, but as a species with low genetic diversity and low numbers, illegal trade represents a significant threat to their survival. Consequently, it is crucial that all governments, international enforcement bodies, and non-governmental organizations join forces and resources to fight the major threat that trafficking poses to cheetah conservation.

Significance Here, we compile and present the most comprehensive data available on cheetah distribution and status. Our analysis shows dramatic declines of cheetah across its distributional range. Most cheetah occur outside protected areas, where they are exposed to multiple threats, but there is little information on population status. Simulation modeling shows that, where cheetah population growth rates are suppressed outside protected areas, extinction risk increases markedly. This result can be generalized to other “protection-reliant” species, and a decision tree is provided to improve their extinction risk estimation. Ultimately, the persistence of protection-reliant species depends on their survival outside and inside protected areas and requires a holistic approach to conservation that engages rather than alienates local communities.

Sarah M. Durant[1],[2],[3]*, Nicholas Mitchell1,2, Rosemary Groom1,2, Nathalie Pettorelli1,3, Audrey Ipavec1,2, Andrew P Jacobson1,[4], Rosie Woodroffe1,3, Monika Böhm1,3, Luke T. B. Hunter[5], Matt Becker[6],[7], Femke Broekuis[8],[9], Sultana Bashir1, Leah Andresen[10], Ortwin Aschenborn[11], Mohammed Beddiaf[12], Farid Belbachir[13], Amel Belbachir-Bazi13, Ali Berbash[14], Iracelma Brandao de Matos Machado[15], Christine Breitenmoser[16],[17], Monica Chege[18], Deon Cilliers[19], Harriet Davies-Mostert[20], Amy J Dickman8, Ezequiel Fabiano[21], Mohammad Farhadinia8, Paul Funston5, Philipp Henschel5, Jane Horgan[22], Hans de Iongh[23], Houman Jowkar[24],[25], Rebecca Klein23, Peter A. Lindsey5, Laurie Marker[26], Kelly Marnewick20, Joerg Melzheimer[27], Johnathan Merkle6, Jassiel Msoka[28], Maurus Msuha[29], Helen O'Neill1,3, Megan Parker[30], Gianetta Purchase1, Sahailou Samaila[31], Yohanna Saidu[32], Abdoulkarim Samna30, Anne Schmidt-Küentzel25, Eda Selebatso[33], Etotépé A. Sogbohossou[34], Alaaeldin Soultan[35], Emma Stone[36], Esther van der Meer[37], Rudie van Vuuren[38], Mary Wykstra[39], Kim Young-Overton5

Ferrocenylated-Au(i) carbenes were designed, synthesized, and studied for their ability to generate reactive oxygen species and target antioxidant pathways via multiple mechanisms.

Summary In dryland ecosystems, mobility is essential for both wildlife and people to access unpredictable and spatially heterogeneous resources, particularly in the face of climate change. Fences can prevent connectivity vital for this mobility. There are recent calls for large‐scale barrier fencing interventions to address human–wildlife conflict and illegal resource extraction. Fencing has costs and benefits to people and wildlife. However, the evidence available for facilitating sound decision‐making for fencing initiatives is limited, particularly for drylands. We identify six research areas that are key to informing evaluations of fencing initiatives: economics, edge permeability, reserve design, connectivity, ecosystem services and communities. Policy implications. Implementing this research agenda to evaluate fencing interventions in dryland ecosystems will enable better management and policy decisions. The United Nations Conventions on Migratory Species (CMS) and to Combat Desertification (UNCCD) are appropriate international agreements for moving this agenda forward and leading the development of policies and guidelines on fencing in drylands.

Field tests of a real-time Drilling Advisory System (DAS) have demonstrated value in several drill well surveillance applications. This system receives drilling data and transmits recommended operating parameters to the driller using existing rig systems and Wellsite Information Transfer Specification (WITS) data records. Using this industry standard, DAS can be deployed to any suitable data acquisition system on the diverse rig equipment available in the industry. The DAS computer may also be connected to a company network to enable desktop viewing of the drilling recommendations in the office. The method embodied in the software comprises both a learning mode and an application mode. In learning mode, systematic changes in parameters are recommended to explore the operating space, and calculation of an objective function determines results. Complex decisions to change operating parameters such as weight on bit, rotary speed, and flow rate can also be made with the assistance of DAS via early detection of drilling dysfunctions which change with depth and formation. The operator’s ROP (Rate of Penetration) management process is focused on MSE (Mechanical Specific Energy) surveillance, and the DAS process extends this methodology to a real-time operating system. DAS is designed to assist the driller by capturing and organizing real-time data without imposing on their judgment and control. It is intended to be a digital helper that enhances the driller’s ability to interpret current drilling conditions and make effective decisions. Remote access capabilities and customized output to the driller’s display were demonstrated in field trials, and key lessons from field trials have been implemented. The field trials included multiple hole sections in onshore and offshore wells across a wide variety of drilling conditions. In one example provided in this paper, the use of DAS provided 35% higher ROP when DAS was used to avoid drilling dysfunctions.

Packer etal. reported that fenced lion populations attain densities closer to carrying capacity than unfenced populations. However, fenced populations are often maintained above carrying capacity, and most are small. Many more lions are conserved per dollar invested in unfenced ecosystems, which avoid the ecological and economic costs of fencing.

Sonic hedgehog (Shh) signaling is essential to the patterning of the embryonic neural tube, but its presence and function in the postmitotic differentiated neurons in the brain remain largely uncharacterized. We recently showed that Shh and its signaling components, Patched and Smoothened, are expressed in postnatal and adult hippocampal neurons. We have now examined whether Shh signaling has a function in these neurons. Using cultured hippocampal neurons as a model system, we found that presynaptic terminals become significantly larger in response to the application of Shh. Ultrastructural examination confirmed the enlarged presynaptic profiles and also revealed variable increases in the size of synaptic vesicles, with a resulting loss of uniformity. Furthermore, electrophysiological analyses showed significant increases in the frequency, but not the amplitude, of spontaneous miniature excitatory postsynaptic currents (mEPSCs) in response to Shh, providing functional evidence of the selective role of Shh in presynaptic terminals. Thus, we conclude that Shh signaling regulates the structure and functional properties of presynaptic terminals of hippocampal neurons.

The extensive prevalence of Alzheimer's disease (AD) places a tremendous burden physiologically, socially and economically upon those directly suffering and those caring for sufferers themselves. Considering the steady increases in numbers of patients diagnosed with Alzheimer's, the number of effective pharmacotherapeutic strategies to tackle the disease is still relatively few. As with many other neurodegenerative mechanisms, AD, is characterized by the continued presence and accumulation of cytotoxic protein aggregates, i.e. of beta-amyloid and the microtubule associated protein, tau. Therefore, one novel therapeutic avenue for the treatment of AD may be the actual targeting of factors that control protein synthesis, packaging and degradation. One of the prime cellular targets that, if effectively modulated, could accomplish this is the endoplasmic reticulum (ER). The ER can not only control cellular protein synthesis, trafficking and degradation but it is also closely associated with cytoprotective mechanisms, including calcium ion regulation and unfolded protein responses. This review will delineate some of the most important functional physiological features of the ER that, if effectively modulated, could result in beneficial amelioration or remediation of the negative cellular aspects of AD initiation and progression. While not a classical drug target, even with minimal levels of beneficial modulation, its multifactorial efficacy may amplify small effects resulting in significant therapeutic efficacy.

Approximately 35 million people worldwide suffer from Alzheimer's disease (AD). Existing therapeutics, while moderately effective, are currently unable to stem the widespread rise in AD prevalence. AD is associated with an increase in amyloid beta (Aβ) oligomers and hyperphosphorylated tau, along with cognitive impairment and neurodegeneration. Several antidepressants have shown promise in improving cognition and alleviating oxidative stress in AD but have failed as long-term therapeutics. In this study, amitriptyline, an FDA-approved tricyclic antidepressant, was administered orally to aged and cognitively impaired transgenic AD mice (3×TgAD). After amitriptyline treatment, cognitive behavior testing demonstrated that there was a significant improvement in both long- and short-term memory retention. Amitriptyline treatment also caused a significant potentiation of non-toxic Aβ monomer with a concomitant decrease in cytotoxic dimer Aβ load, compared to vehicle-treated 3×TgAD controls. In addition, amitriptyline administration caused a significant increase in dentate gyrus neurogenesis as well as increases in expression of neurosynaptic marker proteins. Amitriptyline treatment resulted in increases in hippocampal brain-derived neurotrophic factor protein as well as increased tyrosine phosphorylation of its cognate receptor (TrkB). These results indicate that amitriptyline has significant beneficial actions in aged and damaged AD brains and that it shows promise as a tolerable novel therapeutic for the treatment of AD.

Oxidative exposure of cells occurs naturally and may be associated with cellular damage and dysfunction. Protracted low level oxidative exposure can induce accumulated cell disruption, affecting multiple cellular functions. Accumulated oxidative exposure has also been proposed as one of the potential hallmarks of the physiological/pathophysiological aging process. We investigated the multifactorial effects of long-term minimal peroxide exposure upon SH-SY5Y neural cells to understand how they respond to the continued presence of oxidative stressors. We show that minimal protracted oxidative stresses induce complex molecular and physiological alterations in cell functionality. Upon chronic exposure to minimal doses of hydrogen peroxide, SH-SY5Y cells displayed a multifactorial response to the stressor. To fully appreciate the peroxide-mediated cellular effects, we assessed these adaptive effects at the genomic, proteomic and cellular signal processing level. Combined analyses of these multiple levels of investigation revealed a complex cellular adaptive response to the protracted peroxide exposure. This adaptive response involved changes in cytoskeletal structure, energy metabolic shifts towards glycolysis and selective alterations in transmembrane receptor activity. Our analyses of the global responses to chronic stressor exposure, at multiple biological levels, revealed a viable neural phenotype in-part reminiscent of aged or damaged neural tissue. Our paradigm indicates how cellular physiology can subtly change in different contexts and potentially aid the appreciation of stress response adaptations.

Allosteric modulators and mutations that slow AMPAR desensitization have additional effects on deactivation and agonist potency. We investigated whether these are independent actions or the natural consequence of slowing desensitization. Effects of cyclothiazide (CTZ), trichlormethiazide (TCM), and CX614 were compared at wild-type GluR1 and "nondesensitizing" GluR1-L497Y mutant receptors by patch-clamp recording with ultrafast perfusion. CTZ, TCM, or L/Y mutation all essentially blocked GluR1 desensitization; however, the effects of L/Y mutation on deactivation and glutamate EC50 were three to five times greater than for modulators. CTZ and TCM further slowed desensitization of L/Y mutant receptors but paradoxically accelerated deactivation and increased agonist EC50. Results indicate that CTZ and TCM target deactivation and agonist potency independently of desensitization, most likely by modifying agonist dissociation (koff). Conversely, CX614 slowed desensitization and deactivation without affecting EC50 in both wild-type and L/Y receptors. The S750Q or combined L497Y-S750Q mutations abolished all CTZ and TCM actions without disrupting CX614 activity. Notably, the S/Q mutation also restored L/Y deactivation and EC50 to wild-type levels without restoring desensitization, further demonstrating that desensitization can be modulated independently of deactivation and EC50 by mutagenesis and possibly by allosteric modulators.