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We report the generation and statistical analysis of the CSD drug subset: a subset of the Cambridge Structural Database (CSD) consisting of every published small-molecule crystal structure containing an approved drug molecule. By making use of InChI matching, a CSD Python API workflow to link CSD entries to the online database Drugbank.ca has been produced. This has resulted in a subset of 8632 crystal structures, representing all published solid forms of 785 unique drug molecules. We hope that this new resource will lead to improvements in targeted cheminformatics and statistical model building in a pharmaceutical setting. In addition to this, as part of the Advanced Digital Design of Pharmaceutical Therapeutics collaboration between academia and industry, we have been given the unique opportunity to run comparative analysis on the internal crystal structure databases of AstraZeneca and Pfizer, alongside comparison to the CSD as a whole., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

The lions of North Africa were unique in ecological terms as well as from a human cultural perspective and were the definitive lions of Roman and Medieval Europe. Labelled "Barbary" lions, they were once numerous in North Africa but were exterminated by the mid-20th century. Despite subsequent degeneration of the Atlas Mountain ecosystem through human pressures, the feasibility of lion reintroduction has been debated since the 1970s. Research on the long-established captive lion collection traditionally kept by the sultans and kings of Morocco has enabled selective breeding coordinated across Moroccan and European zoos involving a significant number of animals. Molecular genetic research has recently provided insights into lion phylogeny which, despite previous suggestions that all lions share recent common ancestry, now indicates clear distinctions between lions in North, West, and Central Africa, the Middle East, and India versus those in Southern and Eastern Africa. A review of the evolutionary relevance of North African lions highlights the important challenges and opportunities in understanding relationships between Moroccan lions, extinct North African lions, and extant lion populations in India and West and Central Africa and the potential role for lions in ecosystem recovery in those regions.

As species become rare and approach extinction, purported sightings can be controversial, especially when scarce management resources are at stake. We consider the probability that each individual sighting of a series is valid. Obtaining these probabilities requires a strict framework to ensure that they are as accurately representative as possible. We used a process, which has proven to provide accurate estimates from a group of experts, to obtain probabilities for the validation of 32 sightings of the Barbary lion. We consider the scenario where experts are simply asked whether a sighting was valid, as well as asking them to score the sighting based on distinguishablity, observer competence, and verifiability. We find that asking experts to provide scores for these three aspects resulted in each sighting being considered more individually, meaning that this new questioning method provides very different estimated probabilities that a sighting is valid, which greatly affects the outcome from an extinction model. We consider linear opinion pooling and logarithm opinion pooling to combine the three scores, and also to combine opinions on each sighting. We find the two methods produce similar outcomes, allowing the user to focus on chosen features of each method, such as satisfying the marginalisation property or being externally Bayesian.

The current shortfall in effectiveness within conservation biology is illustrated by increasing interest in "evidence-based conservation," whose proponents have identified the need to benchmark conservation initiatives against actions that lead to proven positive effects. The effectiveness of conservation policies, approaches, and evaluation is under increasing scrutiny, and in these areas models of excellence used in business could prove valuable. Typically, conservation programs require years of effort and involve rigorous long-term implementation processes. Successful balance of long-term efforts alongside the achievement of short-term goals is often compromised by management or budgetary constraints, a situation also common in commercial businesses. "Business excellence" is an approach many companies have used over the past 20 years to ensure continued success. Various business excellence evaluations have been promoted that include concepts that could be adapted and applied in conservation programs. We describe a conservation excellence model that shows how scientific processes and results can be aligned with financial and organizational measures of success. We applied the model to two well-documented species conservation programs. In the first, the Po'ouli program, several aspects of improvement were identified, such as more authority for decision making in the field and better integration of habitat management and population recovery processes. The second example, the black-footed ferret program, could have benefited from leadership effort to reduce bureaucracy and to encourage use of best-practice species recovery approaches. The conservation excellence model enables greater clarity in goal setting, more-effective identification of job roles within programs, better links between technical approaches and measures of biological success, and more-effective use of resources. The model could improve evaluation of a conservation program's effectiveness and may be used to compare different programs, for example during reviews of project performance by sponsoring organizations., (© 2010 Society for Conservation Biology.)

Objective: Live birth rates are increased by treatment with heparin and aspirin in cases of poor pregnancy outcome such as antiphospholipid syndrome. Both drugs may attenuate miscarriage by inhibiting aberrant coagulation or by modulating trophoblast apoptosis. Here we assessed their roles in trophoblast apoptosis in vitro., Study Design: BeWo cells and placental villi were cultured in sera from women with successful or failing in vitro fertilization, with and without heparin or aspirin. Apoptosis was assessed by using DNA laddering, cytokeratin 18 neoepitope formation, Bcl-2, and caspase 7 expression., Results: In BeWo cells, sera from in vitro fertilization failure increased trophoblast apoptosis, whereas heparin and aspirin reversed these effects. In villous trophoblast, heparin increased Bcl-2 and cytokeratin 18 protein expression. Heparin and aspirin inhibited DNA laddering., Conclusion: Heparin and aspirin modulate trophoblast apoptosis suggesting a direct impact on trophoblast biology, thus providing an additional mechanism to explain the clinical benefits of heparin and aspirin on recurrent pregnancy loss.

Objective: Lupus anticoagulant poses a significant risk factor for obstetric complications, whereas heparin improves live birth rates in those pregnancies. Pathophysiology of antiphospholipid antibodies on placental function involves coagulopathies and thrombosis but also dysregulated trophoblast turnover., Study Design: With the use of placental explant cultures, we assessed the effect of lupus anticoagulant positive sera (LA + sera) on apoptosis, mitosis, and invasion of trophoblast and determined the role of unfractionated heparin in regulating these functions., Results: LA + sera were associated with increased placental apoptosis (TUNEL, M30 formation, DNA laddering). LA + sera decreased villous trophoblast proliferation and reduced extravillous trophoblast invasion through matrigel. Heparin attenuated LA + sera-induced apoptosis and facilitated trophoblast invasion., Conclusion: Lupus anticoagulant may impair placentation by increasing apoptosis, attenuating mitosis and reducing invasion of the trophoblast. The direct effects on trophoblast viability by heparin demonstrate an alternative biologic function for this anticoagulant and raise the possibility that anomalous trophoblast development may be therapeutically regulated.

Following attenuation of progesterone production corpora lutea are selectively cleared, a process associated with recruitment of macrophages. In the rabbit little is known about luteal immune cell phenotypes and expression of cytokines, which influence immune cells and resident luteal cells, during luteolysis. Consequently, we studied luteal immune cells by immunohistochemistry as well as luteal IL-10, TNFalpha, MCP-1, IFN-gamma, and IL-1beta mRNA expression by semiquantitative RT-PCR from day 8 to day 20 in pseudopregnant rabbits (d8-d20 p.hCG). Luteal function was assayed by serum progesterone levels. Functional luteolysis commenced by d14 p.hCG as indicated by attenuation of serum progesterone levels. X4(+) tissue macrophage levels increased transiently on d12 and d14 p.hCG, whereas CD5(+) T-cell levels transiently declined on these two days. CD68(+) macrophages increased progressively after d16 p.hCG. The luteal mRNA level of the anti-inflammatory cytokine IL-10 as well as the mRNA levels of the pro-inflammatory cytokines TNFalpha and MCP-1 increased after d16 p.hCG and remained elevated up to d20 p.hCG. IFN-gamma and IL-1beta mRNA expression did not vary systematically. In summary, luteolysis was associated with an initial transient increase of X4(+) macrophages and decrease of CD5(+) T-cells, and later recruitment of CD68(+) macrophages. During structural regression pro- and anti-inflammatory cytokines are upregulated possibly to control immune cell function.