Defective phagocytic corpse processing results in neurodegeneration and can be rescued by TORC1 activation

This work was supported by NIH Grants R01 GM094452 (K.M.) and F31 GM099425 (J.I.E.), BU Alzheimer's Disease Core Center NIH Grant P30 AG13846, Boston University Undergraduate Research Opportunities Program grants (J.A.T., V.S.), and NIH Grant R01 AG044113 to M.B.F. We thank the Bloomington Stock Center, TRiP at Harvard Medical School, the Kyoto Drosophila Genetic Resource Center, Estee Kurant, Eric Baehrecke, Marc Freeman, and Mary Logan for fly strains. We thank Todd Blute for assistance with electron microscopy and the Developmental Studies Hybridoma Bank for antibodies. (R01 GM094452 - NIH; F31 GM099425 - NIH; R01 AG044113 - NIH; P30 AG13846 - BU Alzheimer's Disease Core Center NIH Grant; Boston University Undergraduate Research Opportunities Program)https://www.jneurosci.org/content/36/11/3170.longPublished versionPublished versio

A theoretical study of the mechanism of rearrangement of dihydropyrimidines into pyrroles

Pyrimidines, pyrroles, cycloreversion,CO extrusion, Two possible mechanisms for the transformation of a 1,4-dihydropyrrolo[3,2-b]pyrrole derivative into a tetrasubstituted pyrrole have been studied theoretically and one of them has been found in reasonable accord with the experimental data. This mechanismis part of the very rare example of rearrangement of dihydropyrimidines into pyrroles

Unusual Complexes of P(CH)3 with FH, ClH, and ClF

© 2020 by the authors.Ab initio MP2/aug’-cc-pVTZ calculations have been performed to determine the structures and binding energies of complexes formed by phosphatetrahedrane, P(CH)3, and HF, HCl, and ClF. Four types of complexes exist on the potential energy surfaces. Isomers A form at the P atom near the end of a P-C bond, B at a C-C bond, C at the centroid of the C-C-C ring along the C3 symmetry axis, and D at the P atom along the C3 symmetry axis. Complexes A and B are stabilized by hydrogen bonds when FH and ClH are the acids, and by halogen bonds when ClF is the acid. In isomers C, the dipole moments of the two monomers are favorably aligned but in D the alignment is unfavorable. For each of the monomers, the binding energies of the complexes decrease in the order A > B > C > D. The most stabilizing Symmetry Adapted Perturbation Theory (SAPT) binding energy component for the A and B isomers is the electrostatic interaction, while the dispersion interaction is the most stabilizing term for C and D. The barriers to converting one isomer to another are significantly higher for the A isomers compared to B. Equation of motion coupled cluster singles and doubles (EOM-CCSD) intermolecular coupling constants J(X-C) are small for both B and C isomers. J(X-P) values are larger and positive in the A isomers, negative in the B isomers, and have their largest positive values in the D isomers. Intramolecular coupling constants 1J(P-C) experience little change upon complex formation, except in the halogen-bonded complex FCl:P(CH3) AThis work was carried out with financial support from the Ministerio de Ciencia, Innovación y Universidades of Spain (Project No. PGC2018–094644-B-C22) and Comunidad Autónoma de Madrid (P2018/EMT–4329 AIRTEC-CM)

Niche partitioning of feather mites within a seabird host, Calonectris borealis

According to classic niche theory, species can coexist in heterogeneous environments by reducing interspecific competition via niche partitioning, e.g. trophic or spatial partitioning. However, support for the role of competition on niche partitioning remains controversial. Here, we tested for spatial and trophic partitioning in feather mites, a diverse and abundant group of arthropods. We focused on the two dominant mite species, Microspalax brevipes and Zachvatkinia ovata, inhabiting flight feathers of the Cory's shearwater, Calonectris borealis. We performed mite counts across and within primary and tail feathers on free-living shearwaters breeding on an oceanic island (Gran Canaria, Canary Islands). We then investigated trophic relationships between the two mite species and the host using stable isotope analyses of carbon and nitrogen on mite tissues and potential host food sources. The distribution of the two mite species showed clear spatial segregation among feathers; M. brevipes showed high preference for the central wing primary feathers, whereas Z. ovata was restricted to the two outermost primaries. Morphological differences between M. brevipes and Z. ovata support an adaptive basis for the spatial segregation of the two mite species. However, the two mites overlap in some central primaries and statistical modeling showed that Z. ovata tends to outcompete M. brevipes. Isotopic analyses indicated similar isotopic values for the two mite species and a strong correlation in carbon signatures between mites inhabiting the same individual host suggesting that diet is mainly based on shared host-associated resources. Among the four candidate tissues examined (blood, feather remains, skin remains and preen gland oil), we conclude that the diet is most likely dominated by preen gland oil, while the contribution of exogenous material to mite diets is less marked. Our results indicate that ongoing competition for space and resources plays a central role in structuring feather mite communities. They also illustrate that symbiotic infracommunities are excellent model systems to study trophic ecology, and can improve our understanding of mechanisms of niche differentiation and species coexistence

Phenology of brown bear breeding season and related geographical cues

© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited[EN] Knowledge about breeding biology is often incomplete in species with complex reproductive strategies. The brown bear Ursus arctos is a polygamous seasonal breeder inhabiting a wide variety of habitats and environmental conditions. We compiled information about brown bear breeding season dates from 36 study areas across their distribution range in the Palearctic and Nearctic regions and investigated how their breeding phenology relates to geographical factors (latitude, photoperiod, altitude and region). Brown bear matings were observed for 8 months, from April to November, with a peak in May–July. We found a 59-day difference in the onset of bear breeding season among study areas, with an average 2.3 days delay for each degree of latitude northwards. The onset of the breeding season showed a strong relationship with photoperiod and latitude, but not with region (i.e. Palearctic vs Nearctic) and altitude. First observations of bear mating occurred earlier in areas at lower latitudes. Photoperiod ranged between 14 and 18 hours at the beginning of the season for most of the study areas. The duration of the breeding season ranged from 25 to 138 days among study areas. None of the investigated factors was related to the length of the breeding season. Our results support the relevance of photoperiod to the onset of breeding, as found in other ursids, but not a shorter breeding season at higher latitudes, a pattern reported in other mammals. Our findings suggest a marked seasonality of bear reproductive behaviour, but also certain level of plasticity. Systematic field observations of breeding behaviour are needed to increase our knowledge on the factors determining mating behaviour in species with complex systems and how these species may adapt to climate change.SIWe thank Marjan Artnak, Peter Bajc, Matic Brenk, Tomáš Flajs, Uroš Grželj, Robert Hlavica, Aleš Jagodnik, Peter Klančar, Anton Marinčič, Mariusz Nędzyński, Borut Semenič and Vladimir Vician for providing information about their observations of bear mating. Robert Gatzka assisted with data collection in the Biezszcady Mountains. We thank Jon Swenson and Jumpei Tomiyasu for their help in the literature search. AGR and NS were supported by the BearConnect project funded by the National Science Centre in Poland (2016/22/Z/NZ8/00121) through the 2015-2016 BiodivERsA COFUND call for research proposals, with the national funders ANR/DLR-PT/UEFISCDI/NCN/RCN. Additional funding from the Polish Ministry of Science and Higher Education (project NN304- 294037, NS, IEC, KB), the National Science Centre in Poland (project DEC-2013/08/M/NZ9/ 00469, NS), the National Centre for Research and Development (GLOBE, POL-NOR/198352/85/ 2013, NS, TZK, FZ) and Slovenian Research Agency (P4-0059, MK) is acknowledged. AGR and NS conceived the study and wrote a first draft of the paper; AGR and NS compiled the data, AGR analyzed the data; all authors provided data and comments that improved the manuscript. We thank two anonymous reviewers for useful comments on the previous versions of the manuscript

Controlling molecular tautomerism through supramolecular selectivity

We have isolated the stable as well as the metastable tautomers of 1-deazapurine in the solid state by exploiting principles of supramolecular selectivity in the context of cocrystal design

Ecology of Phlebotomine Sand Flies in the Rural Community of Mont Rolland (Thiès Region, Senegal): Area of Transmission of Canine Leishmaniasis

BACKGROUND: Different epidemiological studies previously indicated that canine leishmaniasis is present in the region of Thiès (Senegal). However, the risks to human health, the transmission cycle and particularly the implicated vectors are unknown. METHODOLOGY/PRINCIPAL FINDINGS: To improve our knowledge on the population of phlebotomine sand flies and the potential vectors of canine leishmaniasis, sand flies were collected using sticky traps, light traps and indoor spraying method using pyrethroid insecticides in 16 villages of the rural community of Mont Rolland (Thiès region) between March and July 2005. The 3788 phlebotomine sand flies we collected (2044 males, 1744 females) were distributed among 9 species of which 2 belonged to the genus Phlebotomus: P. duboscqi (vector of cutaneous leishmaniasis in Senegal) and P. rodhaini. The other species belonged to the genus Sergentomyia: S. adleri, S. clydei, S. antennata, S. buxtoni, S. dubia, S. schwetzi and S. magna. The number of individuals and the species composition differed according to the type of trap, suggesting variable, species-related degrees of endophily or exophily. The two species of the genus Phlebotomus were markedly under-represented in comparison to the species of the genus Sergentomyia. This study also shows a heterogeneous spatial distribution within the rural community that could be explained by the different ecosystems and particularly the soil characteristics of this community. Finally, the presence of the S. dubia species appeared to be significantly associated with canine leishmaniasis seroprevalence in dogs. CONCLUSIONS/SIGNIFICANCE: Our data allow us to hypothesize that the species of the genus Sergentomyia and particularly the species S. dubia and S. schwetzi might be capable of transmitting canine leishmaniasis. These results challenge the dogma that leishmaniasis is exclusively transmitted by species of the genus Phlebotomus in the Old World. This hypothesis should be more thoroughly evaluated

Serological biomarker for assessing human exposure to Aedes mosquito bites during a randomized vector control intervention trial in northeastern Thailand.

BACKGROUND: Aedes mosquitoes are vectors for several major arboviruses of public health concern including dengue viruses. The relationships between Aedes infestation and disease transmission are complex wherein the epidemiological dynamics can be difficult to discern because of a lack of robust and sensitive indicators for predicting transmission risk. This study investigates the use of anti-Aedes saliva antibodies as a serological biomarker for Aedes mosquito bites to assess small scale variations in adult Aedes density and dengue virus (DENV) transmission risk in northeastern Thailand. Individual characteristics, behaviors/occupation and socio-demographics, climatic and epidemiological risk factors associated with human-mosquito exposure are also addressed. METHODS: The study was conducted within a randomized clustered control trial in Roi Et and Khon Kaen provinces over a consecutive 19 months period. Thirty-six (36) clusters were selected, each of ten houses. Serological and entomological surveys were conducted in all houses every four months and monthly in three sentinel households per cluster between September 2017 and April 2019 for blood spot collections and recording concurrent immature and adult Aedes indices. Additionally, the human exposure to Aedes mosquito bites (i.e., Mosquito Exposure Index or MEI) was estimated by ELISA measuring levels of human antibody response to the specific Nterm-34 kDa salivary antigen. The relationships between the MEI, vector infestation indices (adult and immature stages) and vector DENV infection were evaluated using a two-level (house and individual levels) mixed model analysis with one-month lag autoregressive correlation. RESULTS: There was a strong positive relationship between the MEI and adult Aedes (indoor and outdoor) density. Individuals from households with a medium mosquito density (mean difference: 0.091, p<0.001) and households with a high mosquito density (mean difference: 0.131, p<0.001) had higher MEI's compared to individuals from households without Aedes. On a similar trend, individuals from households with a low, medium or high indoor Aedes densities (mean difference: 0.021, p<0.007, 0.053, p<0.0001 and 0.037, p<0.0001 for low, medium and high levels of infestation, respectively) had higher MEI than individuals from houses without indoor Aedes. The MEI was driven by individual characteristics, such as gender, age and occupation/behaviors, and varied according to climatic, seasonal factors and vector control intervention (p<0.05). Nevertheless, the study did not demonstrate a clear correlation between MEI and the presence of DENV-infected Aedes. CONCLUSION: This study represents an important step toward the validation of the specific IgG response to the Aedes salivary peptide Nterm-34kDa as a proxy measure for Aedes infestation levels and human-mosquito exposure risk in a dengue endemic setting. The use of the IgG response to the Nterm-34 kDa peptide as a viable diagnostic tool for estimating dengue transmission requires further investigations and validation in other geographical and transmission settings

Let’s not forget tautomers

A compound exhibits tautomerism if it can be represented by two structures that are related by an intramolecular movement of hydrogen from one atom to another. The different tautomers of a molecule usually have different molecular fingerprints, hydrophobicities and pKa’s as well as different 3D shape and electrostatic properties; additionally, proteins frequently preferentially bind a tautomer that is present in low abundance in water. As a result, the proper treatment of molecules that can tautomerize, ~25% of a database, is a challenge for every aspect of computer-aided molecular design. Library design that focuses on molecular similarity or diversity might inadvertently include similar molecules that happen to be encoded as different tautomers. Physical property measurements might not establish the properties of individual tautomers with the result that algorithms based on these measurements may be less accurate for molecules that can tautomerize—this problem influences the accuracy of filtering for library design and also traditional QSAR. Any 2D or 3D QSAR analysis must involve the decision of if or how to adjust the observed Ki or IC50 for the tautomerization equilibria. QSARs and recursive partitioning methods also involve the decision as to which tautomer(s) to use to calculate the molecular descriptors. Docking virtual screening must involve the decision as to which tautomers to include in the docking and how to account for tautomerization in the scoring. All of these decisions are more difficult because there is no extensive database of measured tautomeric ratios in both water and non-aqueous solvents and there is no consensus as to the best computational method to calculate tautomeric ratios in different environments