Improving the cost-effectiveness of visual devices for the control of Riverine tsetse flies, the major vectors of Human African Trypanosomiasis

Control of the Riverine (Palpalis) group of tsetse flies is normally achieved with stationary artificial devices such as traps or insecticide-treated targets. The efficiency of biconical traps (the standard control device), 161 m black targets and small 25625 cm targets with flanking nets was compared using electrocuting sampling methods. The work was done on Glossina tachinoides and G. palpalis gambiensis (Burkina Faso), G. fuscipes quanzensis (Democratic Republic of Congo), G. f. martinii (Tanzania) and G. f. fuscipes (Kenya). The killing effectiveness (measured as the catch per m2 of cloth) for small targets plus flanking nets is 5.5–15X greater than for 1 m2 targets and 8.6–37.5X greater than for biconical traps. This has important implications for the costs of control of the Riverine group of tsetse vectors of sleeping sickness

A revision of Sanpasaurus yaoi Young, 1944 from the Early Jurassic of China, and its relevance to the early evolution of Sauropoda (Dinosauria)

© 2016 McPhee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited. The attached file is the published version of the article

Reward and punishment in climate change dilemmas

Mitigating climate change effects involves strategic decisions by individuals that may choose to limit their emissions at a cost. Everyone shares the ensuing benefits and thereby individuals can free ride on the effort of others, which may lead to the tragedy of the commons. For this reason, climate action can be conveniently formulated in terms of Public Goods Dilemmas often assuming that a minimum collective effort is required to ensure any benefit, and that decision-making may be contingent on the risk associated with future losses. Here we investigate the impact of reward and punishment in this type of collective endeavors - coined as collective-risk dilemmas - by means of a dynamic, evolutionary approach. We show that rewards (positive incentives) are essential to initiate cooperation, mostly when the perception of risk is low. On the other hand, we find that sanctions (negative incentives) are instrumental to maintain cooperation. Altogether, our results are gratifying, given the a-priori limitations of effectively implementing sanctions in international agreements. Finally, we show that whenever collective action is most challenging to succeed, the best results are obtained when both rewards and sanctions are synergistically combined into a single policy.This research was supported by Fundacao para a Ciencia e Tecnologia (FCT) through grants PTDC/EEISII/5081/2014 and PTDC/MAT/STA/3358/2014 and by multiannual funding of INESC-ID and CBMA (under the projects UID/CEC/50021/2019 and UID/BIA/04050/2013). F.P.S. acknowledges support from the James S. McDonnell Foundation 21st Century Science Initiative in Understanding Dynamic and Multi-scale Systems Postdoctoral Fellowship Award. All authors declare no competing financial or non-financial interests in relation to the work described

Eight common genetic variants associated with serum dheas levels suggest a key role in ageing mechanisms

Dehydroepiandrosterone sulphate (DHEAS) is the most abundant circulating steroid secreted by adrenal glands-yet its function is unknown. Its serum concentration declines significantly with increasing age, which has led to speculation that a relative DHEAS deficiency may contribute to the development of common age-related diseases or diminished longevity. We conducted a meta-analysis of genome-wide association data with 14,846 individuals and identified eight independent common SNPs associated with serum DHEAS concentrations. Genes at or near the identified loci include ZKSCAN5 (rs11761528; p = 3.15×10-36), SULT2A1 (rs2637125; p = 2.61×10-19), ARPC1A (rs740160; p = 1.56×10-16), TRIM4 (rs17277546; p = 4.50×10-11), BMF (rs7181230; p = 5.44×10-11), HHEX (rs2497306; p = 4.64×10-9), BCL2L11 (rs6738028; p = 1.72×10-8), and CYP2C9 (rs2185570; p = 2.29×10-8). These genes are associated with type 2 diabetes, lymphoma, actin filament assembly, drug and xenobiotic metabolism, and zinc finger proteins. Several SNPs were associated with changes in gene expression levels, and the related genes are connected to biological pathways linking DHEAS with ageing. This study provides much needed insight into the function of DHEAS

Harnessing Expression Data to Identify Novel Candidate Genes in Polycystic Ovary Syndrome

Novel pathways in polycystic ovary syndrome (PCOS) are being identified in gene expression studies in PCOS tissues; such pathways may contain key genes in disease etiology. Previous expression studies identified both dickkopf homolog 1 (DKK1) and DnaJ (Hsp40) homolog, subfamily B, member 1 (DNAJB1) as differentially expressed in PCOS tissue, implicating them as candidates for PCOS susceptibility. To test this, we genotyped a discovery cohort of 335 PCOS cases and 198 healthy controls for three DKK1 single nucleotide polymorphisms (SNPs) and four DNAJB1 SNPs and a replication cohort of 396 PCOS cases and 306 healthy controls for 1 DKK1 SNP and 1 DNAJB1 SNP. SNPs and haplotypes were determined and tested for association with PCOS and component phenotypes. We found that no single nucleotide polymorphisms were associated with PCOS risk; however, the major allele of rs1569198 from DKK1 was associated with increased total testosterone (discovery cohort P = 0.0035) and dehydroepiandrosterone sulfate (replication cohort P = 0.05). Minor allele carriers at rs3962158 from DNAJB1 had increased fasting insulin (discovery cohort P = 0.003), increased HOMA-IR (discovery cohort P = 0.006; replication cohort P = 0.036), and increased HOMA-%B (discovery cohort P = 0.004). Carriers of haplotype 2 at DNAJB1 also had increased fasting insulin, HOMA-IR, and HOMA-%B. These findings suggest that genetic variation in DKK1 and DNAJB1 may have a role in the hyperandrogenic and metabolic dysfunction of PCOS, respectively. Our results also demonstrate the utility of gene expression data as a source of novel candidate genes in PCOS, a complex and still incompletely defined disease, for which alternative methods of gene identification are needed

Multiplex Zymography Captures Stage-specific Activity Profiles of Cathepsins K, L, and S in Human Breast, Lung, and Cervical Cancer

<p>Abstract</p> <p>Background</p> <p>Cathepsins K, L, and S are cysteine proteases upregulated in cancer and proteolyze extracellular matrix to facilitate metastasis, but difficulty distinguishing specific cathepsin activity in complex tissue extracts confounds scientific studies and employing them for use in clinical diagnoses. Here, we have developed multiplex cathepsin zymography to profile cathepsins K, L, and S activity in 10 μg human breast, lung, and cervical tumors by exploiting unique electrophoretic mobility and renaturation properties.</p> <p>Methods</p> <p>Frozen breast, lung, and cervix cancer tissue lysates and normal organ tissue lysates from the same human patients were obtained (28 breast tissues, 23 lung tissues, and 23 cervix tissues), minced and homogenized prior to loading for cathepsin gelatin zymography to determine enzymatic activity.</p> <p>Results</p> <p>Cleared bands of cathepsin activity were identified and validated in tumor extracts and detected organ- and stage-specific differences in activity. Cathepsin K was unique compared to cathepsins L and S. It was significantly higher for all cancers even at the earliest stage tested (stage I for lung and cervix (n = 6, p < .05), and stage II for breast; n = 6, p < .0001). Interestingly, cervical and breast tumor cathepsin activity was highest at the earliest stage we tested, stages I and II, respectively, and then were significantly lower at the latest stages tested (III and IV, respectively) (n = 6, p < 0.01 and p < 0.05), but lung cathepsin activity increased from one stage to the next (n = 6, p < .05). Using cathepsin K as a diagnostic biomarker for breast cancer detected with multiplex zymography, yielded 100% sensitivity and specificity for 20 breast tissue samples tested (10 normal; 10 tumor) in part due to the consistent absence of cathepsin K in normal breast tissue across all patients.</p> <p>Conclusions</p> <p>To summarize, this sensitive assay provides quantitative outputs of cathepsins K, L, and S activities from mere micrograms of tissue and has potential use as a supplement to histological methods of clinical diagnoses of biopsied human tissue.</p

Self-Regulated Glucose-Sensitive Neoglycoenzyme-Capped Mesoporous Silica Nanoparticles for Insulin Delivery

"This is the peer reviewed version of the following article: Oroval, Mar, Paula Díez, Elena Aznar, Carmen Coll, María Dolores Marcos, Félix Sancenón, Reynaldo Villalonga, and Ramón Martínez-Máñez. 2016. Self-Regulated Glucose-Sensitive Neoglycoenzyme-Capped Mesoporous Silica Nanoparticles for Insulin Delivery. Chemistry - A European Journal 23 (6). Wiley: 1353 60. doi:10.1002/chem.201604104, which has been published in final form at https://doi.org/10.1002/chem.201604104. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."[EN] We describe herein the preparation of glucose-sensitive capped mesoporous silica nanoparticles for insulin delivery. The new material consists of an expanded-pore nanometric silica support grafted with 1-propyl-1-H-benzimidazole groups, loaded with fluorescein isothiocyanate-labeled insulin (FITC-Ins) and capped by the formation of inclusion complexes between cyclodextrin-modified glucose oxidase (CD-GOx) and the benzimidazole groups grafted on the mesoporous support. Insulin delivery from the gated material in simulated blood plasma was assessed upon addition of glucose. Glucose is transformed by GOx into gluconic acid, which promoted the dethreading of the benzimidazole-CD-GOx inclusion complexes, allowing cargo release. Small quantities of this support would be needed to release the amount of insulin necessary to decrease diabetic blood glucose concentrations to regular levels.The authors thank the Spanish Government (projects CTQ2011-24355, MAT2015-64139-C4-1-R, CTQ2014-58989-P, and AGL2015-70235-C2-2-R (MINECO/FEDER)) and the Generalitat Valenciana (project PROMETEOII/2014/047) for support. M.O. thanks the Universitat Politecnica de Valencia for her FPI grant. P.D. thanks the Ministerio de Economia y Competitividad for her FPI grant (BES-2012-054066). C.C. thanks the Generalitat Valenciana for her postdoctoral contract VALi+D.Oroval, M.; Díez, P.; Aznar, E.; Coll Merino, MC.; Marcos Martínez, MD.; Sancenón Galarza, F.; Villalonga, R.... (2017). Self-Regulated Glucose-Sensitive Neoglycoenzyme-Capped Mesoporous Silica Nanoparticles for Insulin Delivery. Chemistry - A European Journal. 23(6):1353-1360. https://doi.org/10.1002/chem.201604104S13531360236Nicole, L., Laberty-Robert, C., Rozes, L., & Sanchez, C. (2014). Hybrid materials science: a promised land for the integrative design of multifunctional materials. Nanoscale, 6(12), 6267-6292. doi:10.1039/c4nr01788aBeltrán-Osuna, Á. A., & Perilla, J. E. (2015). Colloidal and spherical mesoporous silica particles: synthesis and new technologies for delivery applications. 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Unilateral aplasia of both cruciate ligaments

Aplasia of both cruciate ligaments is a rare congenital disorder. A 28-year-old male presented with pain and the feeling of instability of his right knee after trauma. The provided MRI and previous arthroscopy reports did not indicate any abnormalities except cruciate ligament tears. He was referred to us for reconstruction of both cruciate ligaments. The patient again underwent arthroscopy which revealed a hypoplasia of the medial trochlea and an extremely narrow intercondylar notch. The tibia revealed a missing anterior cruciate ligament (ACL) footprint and a single bump with a complete coverage with articular cartilage. There was no room for an ACL graft. A posterior cruciate ligament could not be identified. The procedure was ended since a ligament reconstruction did not appear reasonable. A significant notch plasty if not a partial resection of the condyles would have been necessary to implant a ligament graft. It is most likely that this would not lead to good knee stability. If the surgeon would have retrieved the contralateral hamstrings at the beginning of the planned ligament reconstruction a significant damage would have occurred to the patient. Even in seemingly clear diagnostic findings the arthroscopic surgeon should take this rare abdnormality into consideration and be familiar with the respective radiological findings. We refer the abnormal finding of only one tibial spine to as the "dromedar-sign" as opposed to the two (medial and a lateral) tibial spines in a normal knee. This may be used as a hint for aplasia of the cruciate ligaments

Removing Algebraic Data Types from Constrained Horn Clauses Using Difference Predicates

We address the problem of proving the satisfiability of Constrained Horn Clauses (CHCs) with Algebraic Data Types (ADTs), such as lists and trees. We propose a new technique for transforming CHCs with ADTs into CHCs where predicates are defined over basic types, such as integers and booleans, only. Thus, our technique avoids the explicit use of inductive proof rules during satisfiability proofs. The main extension over previous techniques for ADT removal is a new transformation rule, called differential replacement, which allows us to introduce auxiliary predicates corresponding to the lemmas that are often needed when making inductive proofs. We present an algorithm that uses the new rule, together with the traditional folding/unfolding transformation rules, for the automatic removal of ADTs. We prove that if the set of the transformed clauses is satisfiable, then so is the set of the original clauses. By an experimental evaluation, we show that the use of the differential replacement rule significantly improves the effectiveness of ADT removal, and we show that our transformation-based approach is competitive with respect to a well-established technique that extends the CVC4 solver with induction.Comment: 10th International Joint Conference on Automated Reasoning (IJCAR 2020) - version with appendix; added DOI of the final authenticated Springer publication; minor correction

ITGAM is associated with disease susceptibility and renal nephritis of systemic lupus erythematosus in Hong Kong Chinese and Thai

ITGAM was recently found to be associated with systemic lupus erythematosus (SLE) in populations of not only European ancestry, but also in Hispanic- and African-Americans, Mexicans and Colombians. The risk alleles in the gene, however, were found to be monomorphic in two Asian populations examined: Japanese and Korean. In this study, using a collection of 910 SLE patients and 2360 controls from Chinese living in Hong Kong, analyzed by both genome-wide association and direct sequencing, we confirmed the association of the same risk alleles in ITGAM with the disease. These findings were further replicated in the Thai population with 278 patients and 383 ethnicity- and geography-matched controls. Subphenotype stratification analyses showed significantly more involvement of the gene in patients with renal nephritis and neurological disorders. Although our results support a pivotal role by rs1143679 (R77H) in disease association, our data also suggests an additional contribution from rs1143683, another non-synonymous polymorphism in this gene (A858V). Therefore, despite the low-allele frequencies of the risk alleles of the gene in our two Asian populations, ITGAM was confirmed to be a risk factor related to disease susceptibility and probably severe manifestations of SLE