bluuebunny/crossref_metadata_2025 huggingface dataset:
Conventional and natural compounds for the treatment of dermatophytosis
Authors: Lopes Ana I , Tavaria Freni K , Pintado Manuela E
Published: October 2019

Dermatophytes are a group of pathogenic fungi that exclusively infect the stratum corneum of the skin, nails, and hair, causing dermatophytosis. Superficial skin infections caused by dermatophytes have increased in the last decades. There are conventional antifungals that treat these infections, such as terbinafine, fluconazole, and others. However, the limitations of these treatments (resistance, side effects and toxicity) along with the increasing over-prescription, the misuse of these antifungals and the high treatment costs led to the search for new, alternative, natural-based antifungal drugs. These have multiple mechanisms of action, which works to their advantage, making it difficult for a fungus to create resistance mechanisms against all of them at the same time. The main objective of this work is to provide a state-of-the-art review on dermatophytes, dermatophytosis, and the existing treatments, both conventional and natural, such as chitosan and essential oils.
The K2 Galactic Caps Project – going beyond the Kepler field and ageing the Galactic disc
Authors: Rendle B M , Miglio A , Chiappini C , Valentini M , Davies G R , Mosser B , Elsworth Y , García R A , Mathur S , Jofré P , Worley C C , Casagrande L , Girardi L , Lund M N , Feuillet D K , Gavel A , Magrini L , Khan S , Rodrigues T S , Johnson J A , Cunha K , Lane R L , Nitschelm C , Chaplin W J
Published: October 2019

Analyses of data from spectroscopic and astrometric surveys have led to conflicting results concerning the vertical characteristics of the Milky Way. Ages are often used to provide clarity, but typical uncertainties of >40 per cent from photometry restrict the validity of the inferences made. Using the Kepler APOKASC sample for context, we explore the global population trends of two K2 campaign fields (3 and 6), which extend further vertically out of the Galactic plane than APOKASC. We analyse the properties of red giant stars utilizing three asteroseismic data analysis methods to cross-check and validate detections. The Bayesian inference tool PARAM is used to determine the stellar masses, radii, and ages. Evidence of a pronounced red giant branch bump and an [α/Fe] dependence on the position of the red clump is observed from the K2 fields radius distribution. Two peaks in the age distribution centred at ∼5 and ∼12 Gyr are found using a sample with σage < 35 per cent. In comparison with Kepler, we find the older peak to be more prominent for K2. This age bimodality is also observed based on a chemical selection of low-[α/Fe] (≤0.1) and high-[α/Fe] (>0.1) stars. As a function of vertical distance from the Galactic mid-plane (|Z|), the age distribution shows a transition from a young to old stellar population with increasing |Z| for the K2 fields. Further coverage of campaign targets with high-resolution spectroscopy is required to increase the yield of precise ages achievable with asteroseismology.
Isolated dark matter deprived galaxies in hydrodynamical simulations: real objects or artefacts?
Authors: Saulder Christoph , Snaith Owain , Park Changbom , Laigle Clotilde
Published: October 2019

We searched for isolated dark matter deprived galaxies within several state-of-the-art hydrodynamical simulations: Illustris, IllustrisTNG, EAGLE, and Horizon-AGN and found a handful of promising objects in all except Horizon-AGN. While our initial goal was to study their properties and evolution, we quickly noticed that all of them were located at the edge of their respective simulation boxes. After carefully investigating these objects using the full particle data, we concluded that they are not merely caused by a problem with the algorithm identifying bound structures. We provide strong evidence that these oddballs were created from regular galaxies that get torn apart due to unphysical processes when crossing the edge of the simulation box. We show that these objects are smoking guns indicating an issue with the implementation of the periodic boundary conditions of the particle data in Illustris, IllustrisTNG, and EAGLE, which was eventually traced down to be a minor bug occurring for a very rare set of conditions.
Determining Quasar Orientation
Authors: Yong Suk Yee , Webster Rachel L , King Anthea L , Bate Nicholas F , Labrie Kathleen , O’Dowd Matthew J
Published: October 2019

Since the discovery of active galactic nuclei (AGN) and their subclasses, a unification scheme of AGN has been long sought. Orientation-based unified models predict that some of the diversity within AGN subclasses can be explained by the different viewing angles of the observer. Several orientation categorisations have been suggested, but a widely applicable measure has yet to be found. Using the properties of the ultraviolet and optical broad emission lines of quasars, in particular the velocity offsets and line widths of high-ionisation C iv and low-ionisation Mg ii lines, a correlation has been measured. It is postulated that this correlation is due to the viewing angle of the observer. Comparison with other orientation tracers shows consistency with this interpretation. Using a simulation of a wide angle disk-wind model for the broad emission line region, we successfully replicate the observed correlation with inclination. Future more detailed modelling will not only enable improved accuracy in the determination of the viewing angle to individual AGN, but will also substantially increase our understanding of the emitting regions of AGN.
MetaboLights: a resource evolving in response to the needs of its scientific community
Authors: Haug Kenneth , Cochrane Keeva , Nainala Venkata Chandrasekhar , Williams Mark , Chang Jiakang , Jayaseelan Kalai Vanii , O’Donovan Claire
Published: October 2019

MetaboLights is a database for metabolomics studies, their raw experimental data and associated metadata. The database is cross-species and cross-technique and it covers metabolite structures and their reference spectra as well as their biological roles and locations. MetaboLights is the recommended metabolomics repository for a number of leading journals and ELIXIR, the European infrastructure for life science information. In this article, we describe the significant updates that we have made over the last two years to the resource to respond to the increasing amount and diversity of data being submitted by the metabolomics community. We refreshed the website and most importantly, our submission process was completely overhauled to enable us to deliver a far more user-friendly submission process and to facilitate the growing demand for reproducibility and integration with other ‘omics. Metabolomics resources and data are available under the EMBL-EBI’s Terms of Use via the web at https://www.ebi.ac.uk/metabolights and under Apache 2.0 at Github (https://github.com/EBI-Metabolights/).
A 35-year-old female Central Africa Republican refugee with an uneventful medical and family past histories presented to a hospital with a 3-year history of a progressive painful outgrowth of the five nails of the left hand
Authors: Noula Aimé Mbonda , Tochie Joel Noutakdie
Published: October 2019

Onychogryphosis is a dermatological disease characterized by hypertrophy, opaque or yellow-brown thickening, gross hyperkeratosis, elongation, and excessive curving of the nail plate, especially that of the big toe of the foot. The resultant nail deformity is often termed “ram’s horn nail” or “claw-hand” deformity. Affected patients suffer mainly from pain, and cosmetic concerns. This disorder can be acquired or congenital. Herein, we present the case of an usual form of acquired onychogryphosis affecting all the five nail plates of the left hand in a bit to raise awareness of demaytologist and podiatricians on the occurrence of this a typical form for a timely diagnosis and treament, especially in resource-limited settings where this disease is rare or perhatrps under-diagnosed. We also briefly discuss its diagbosis and management.
Comparative cardiovascular risk in users versus non-users of xanthine oxidase inhibitors and febuxostat versus allopurinol users
Authors: Ju Chengsheng , Lai Rachel Wing Chuen , Li Ka Hou Christien , Hung Joshua Kai Fung , Lai Jenny C L , Ho Jeffery , Liu Yingzhi , Tsoi Man Fung , Liu Tong , Cheung Bernard Man Yung , Wong Ian Chi Kei , Tam Lai Shan , Tse Gary
Published: October 2019

Objectives

The aim of this study is to determine major adverse cardiovascular events (MACE) and all-cause mortality comparing between xanthine oxidase inhibitors (XOIs) and non-XOI users, and between allopurinol and febuxostat.

Methods

This is a retrospective cohort study of gout patients prescribed anti-hyperuricemic medications between 2013 and 2017 using a territory-wide administrative database. XOI users were matched 1:1 to XOI non-users using propensity scores. Febuxostat users were matched 1:3 to allopurinol users. Subgroup analyses were conducted based on colchicine use.

Results

Of the 13 997 eligible participants, 3607 (25.8%) were XOI users and 10 390 (74.2%) were XOI non-users. After propensity score matching, compared with non-users (n = 3607), XOI users (n = 3607) showed similar incidence of MACE (hazard ratio [HR]: 0.997, 95% CI, 0.879, 1.131; P>0.05) and all-cause mortality (HR = 0.972, 95% CI 0.886, 1.065, P=0.539). Febuxostat (n = 276) users showed a similar risk of MACE compared with allopurinol users (n = 828; HR: 0.672, 95% CI, 0.416, 1.085; P=0.104) with a tendency towards a lower risk of heart failure-related hospitalizations (HR = 0.529, 95% CI 0.272, 1.029; P=0.061). Concurrent colchicine use reduced the risk for all-cause mortality amongst XOI users (HR = 0.671, 95% 0.586, 0.768; P<0.001).

Conclusion

In gout patients, XOI users showed similar risk of MACE and all-cause mortality compared with non-users. Compared with allopurinol users, febuxostat users showed similar MACE and all-cause mortality risks but lower heart failure-related hospitalizations.
Treatment decision-making in diffuse cutaneous systemic sclerosis: a patient’s perspective
Authors: Spierings Julia , van Rhijn-Brouwer Femke C C , de Bresser Carolijn J M , Mosterman Petra T M , Pieterse Arwen H , Vonk Madelon C , Voskuyl Alexandre E , de Vries-Bouwstra Jeska K , Kars Marijke C , van Laar Jacob M
Published: October 2019

Objectives

To examine the treatment decision-making process of patients with dcSSc in the context of haematopoietic stem cell transplantation (HSCT).

Methods

A qualitative semi-structured interview study was done in patients before or after HSCT, or patients who chose another treatment than HSCT. Thematic analysis was used. Shared decision-making (SDM) was assessed with the 9-item Shared Decision Making Questionnaire (SDM-Q-9).

Results

Twenty-five patients [16 male/nine female, median age 47 (range 27–68) years] were interviewed: five pre-HSCT, 16 post-HSCT and four following other treatment. Whereas the SDM-Q-9 showed the decision-making process was perceived as shared [median score 81/100 (range 49–100)], we learned from the interviews that the decision was predominantly made by the rheumatologist, and patients were often steered towards a treatment option. Strong guidance of the rheumatologist was appreciated because of a lack of accessible, reliable and SSc-specific information, due to the approach of the decision-making process of the rheumatologist, the large consequence of the decision and the trust in their doctor. Expectations of outcomes and risks also differed between patients. Furthermore, more than half of patients felt they had no choice but to go for HSCT, due to rapid deterioration of health and the perception of HSCT as ‘the holy grail’.

Conclusion

This is the first study that provides insight into the decision-making process in dcSSc. This process is negatively impacted by a lack of disease-specific education about treatment options. Additionally, we recommend exploring patients’ preferences and understanding of the illness to optimally guide decision-making and to provide tailor-made information.
ATP synthase inhibitory factor 1 (IF1), a novel myokine, regulates glucose metabolism by AMPK and Akt dual pathways
Authors: Lee Hye Jeong , Moon Jiyoung , Chung InHyeok , Chung Ji Hyung , Park Chan , Lee Jung Ok , Han Jeong Ah , Kang Min Ju , Yoo Eun Hye , Kwak So‐Young , Jo Garam , Park Wonil , Park Jonghoon , Kim Kyoung Min , Lim Soo , Ngoei Kevin R. W. , Ling Naomi X. Y. , Oakhill Jonathan S. , Galic Sandra , Murray‐Segal Lisa , Kemp Bruce E. , Mantzoros Christos S. , Krauss Ronald M. , Shin Min‐Jeong , Kim Hyeon Soo
Published: October 2019

ATPase inhibitory factor 1 (IF1) is an ATP synthase‐interacting protein that suppresses the hydrolysis activity of ATP synthase. In this study, we observed that the expression of IF1 was up‐regulated in response to electrical pulse stimulation of skeletal muscle cells and in exercized mice and healthy men. IF1 stimulates glucose uptake via AMPK in skeletal muscle cells and primary cultured myoblasts. Reactive oxygen species and Rac family small GTPase 1 (Rac1) function in the upstream and downstream of AMPK, respectively, in IF1‐mediated glucose uptake. In diabetic animal models, the administration of recombinant IF1 improved glucose tolerance and down‐regulated blood glucose level. In addition, IF1 inhibits ATP hydrolysis by β‐F1‐ATPase in plasma membrane, thereby increasing extracellular ATP and activating the protein kinase B (Akt) pathway, ultimately leading to glucose uptake. Thus, we suggest that IF1 is a novel myokine and propose a mechanism by which AMPK and Akt contribute independently to IF1‐mediated improvement of glucose tolerance impairment. These results demonstrate the importance of IF1 as a potential antidiabetic agent.—Lee, H. J., Moon, J., Chung, I., Chung, J. H., Park, C., Lee, J. O., Han, J. A., Kang, M. J., Yoo, E. H., Kwak, S.‐Y., Jo, G., Park, W., Park, J., Kim, K. M., Lim, S., Ngoei, K. R. W., Ling, N. X. Y., Oakhill, J. S., Galic, S., Murray‐Segal, L., Kemp, B. E., Mantzoros, C. S., Krauss, R. M., Shin, M.‐J., Kim, H. S. ATP synthase inhibitory factor 1 (IF1), a novel myokine, regulates glucose metabolism by AMPK and Akt dual pathways. FASEB J. 33, 14825‐14840 (2019). www.fasebj.org
Autologous bone marrow mononuclear cells modulate joint homeostasis in an equinein vivomodel of synovitis
Authors: Menarim Bruno C. , Gillis Kiersten H. , Oliver Andrea , Mason Caitlin , Ngo Ying , Werre Stephen R. , Barrett Sarah H. , Luo Xin , Byron Christopher R. , Dahlgren Linda A.
Published: October 2019

Osteoarthritis (OA) is characterized by macrophage‐driven synovitis. Macrophages promote synovial health but become inflammatory when their regulatory functions are overwhelmed. Bone marrow mononuclear cells (BMNCs) are a rich source of macrophage progenitors used for treating chronic inflammation and produce essential molecules for cartilage metabolism. This study investigated the response to autologous BMNC injection in normal and inflamed joints. Synovitis was induced in both radiocarpal joints of 6 horses. After 8 h, 1 inflamed radiocarpal and 1 normal tarsocrural joint received BMNC injection. Contralateral joints were injected with saline. Synovial fluid was collected at 24, 96, and 144 h for cytology, cytokine quantification, and flow cytometry. At 144 h, horses were euthanatized, joints were evaluated, and synovium was harvested for histology and immunohistochemistry. Four days after BMNC treatment, inflamed joints had 24% higher macrophage counts with 10% more IL‐10+cells than saline‐treated controls. BMNC‐treated joints showed gross and analytical improvements in synovial fluid and synovial membrane, with increasing regulatory macrophages and synovial fluid IL‐10 concentrations compared with saline‐treated controls. BMNC‐treated joints were comparable to healthy joints histologically, which remained abnormal in saline‐treated controls. Autologous BMNCs are readily available, regulate synovitis through macrophage‐associated effects, and can benefit thousands of patients with OA.—Menarim, B. C., Gillis, K.H., Oliver, A., Mason, C., Ngo, Y., Werre, S.R., Barrett, S.H., Luo, X., Byron, C.R., Dahlgren, L. A. Autologous bone marrow mononuclear cells modulate joint homeostasis in an equinein vivomodel of synovitis. FASEB J. 33, 14337‐14353 (2019).www.fasebj.org
Post‐transcriptional regulation of Nrf2‐mRNA by the mRNA‐binding proteins HuR and AUF1
Authors: Poganik Jesse R. , Long Marcus J. C. , Disare Michael T. , Liu Xuyu , Chang Sung‐Hee , Hla Timothy , Aye Yimon
Published: October 2019

The nuclear factor erythroid 2‐related factor 2 (Nrf2) signaling axis is a target of covalent drugs and bioactive native electrophiles. However, much of our understanding of Nrf2 regulation has been focused at the protein level. Here we report a post‐transcriptional modality to directly regulate Nrf2‐mRNA. Our initial studies focused on the effects of the key mRNA‐binding protein (mRBP) HuR on global transcriptomic changes incurred upon oxidant or electrophile stimulation. These RNA‐sequencing data and subsequent mechanistic analyses led us to discover a novel role of HuR in regulating Nrf2 activity, and in the process, we further identified the related mRBP AUF1 as an additional novel Nrf2 regulator. Both mRBPs regulate Nrf2 activity by direct interaction with the Nrf2 transcript. Our data showed that HuR enhances Nrf2‐mRNA maturation and promotes its nuclear export, whereas AUF1 stabilizes Nrf2‐mRNA. Both mRBPs target the 3'‐UTR of Nrf2‐mRNA. Using a Nrf2 activity‐reporter zebrafish strain, we document that this post‐transcriptional control of Nrf2 activity is conserved at the whole‐vertebrate level.—Poganik, J. R., Long, M. J. C., Disare, M. T., Liu, X., Chang, S.‐H., Hla, T., Aye, Y. Post‐transcriptional regulation of Nrf2‐mRNA by the mRNA‐binding proteins HuR and AUF1. FASEB J. 33, 14636‐14652 (2019). www.fasebj.org
Antiviral activity of betacyanins from red pitahaya (Hylocereus polyrhizus) and red spinach (Amaranthus dubius) against dengue virus type 2 (GenBank accession no. MH488959)
Authors: Chang Ying Jun , Pong Lian Yih , Hassan Sharifah S. , Choo Wee Sim
Published: October 2019

This study investigated the antiviral activity of betacyanins from red pitahaya (Hylocereus polyrhizus) and red spinach (Amaranthus dubius) against dengue virus type 2 (DENV-2). The pulp of red pitahaya and the leaves of red spinach were extracted using methanol followed by sub-fractionation and Amberlite XAD16N column chromatography to obtain betacyanin fractions. The half maximum cytotoxicity concentration for betacyanin fractions from red pitahaya and red spinach on Vero cells were 4.346 and 2.287 mg ml−1, respectively. The half-maximal inhibitory concentration (IC50) of betacyanin fraction from red pitahaya was 125.8 μg ml−1 with selectivity index (SI) of 5.8. For betacyanin fraction from red spinach, the IC50 value was 14.62 µg ml−1 with SI of 28.51. Using the maximum non-toxic betacyanin concentration, direct virucidal effect against DENV-2 was obtained from betacyanin fraction from red pitahaya (IC50 of 126.70 μg ml−1; 95.0 % virus inhibition) and red spinach (IC50 value of 106.80 μg ml−1; 65.9 % of virus inhibition). Betacyanin fractions from red pitahaya and red spinach inhibited DENV-2 in vitro.
Nuclear pore protein Nup98 is involved in replication of Rift Valley fever virus and nuclear import of virulence factor NSs
Authors: Lau Simone , Weber Friedemann
Published: October 2019

The non-structural protein NSs is the main virulence factor of Rift Valley fever virus, a major zoonotic pathogen in Africa. NSs forms large aggregates in the nucleus and impairs induction of the antiviral type I IFN system by several mechanisms, including degradation of subunit p62 of the general RNA polymerase II transcription factor TFIIH. Here, we show that depletion of the nuclear pore protein Nup98 affects the nuclear import of NSs. Nonetheless, NSs was still able to degrade TFIIH-p62 under these conditions. Depletion of Nup98, however, had a negative effect on Rift Valley fever virus multiplication. Our data thus indicate that NSs utilizes Nup98 for import into the nucleus, but also plays a general role in the viral replication cycle.
Using the Tea Bag Index to determine how two human pharmaceuticals affect litter decomposition by aquatic microorganisms
Authors: Hunter William Ross , Williamson Ashley , Sarneel Judith Maria
Published: October 2019

This study demonstrates that independent additive effects of two human pharmaceuticals, the antibiotic trimethoprim and the artificial estrogen 17a-Ethinylestradiol (EE2), inhibit plant litter decomposition by aquatic microorganisms. The constant release of pharmaceuticals, such as these, has the potential to affect aquatic microbial metabolism and alter biogeochemical cycling of carbon and nutrients. Here we advance the Tea Bag Index (TBI) for decomposition by using it in a series of contaminant exposure experiments testing how interactions between trimethoprim and EE2 affect aquatic microbial activity. The TBI is a citizen science tool used to test microbial activity by measuring the differential degradation of green and rooibos tea as proxies for respectively labile and recalcitrant litter decomposition. Exposure to either trimethoprim or EE2 decreased decomposition of green tea, suggesting additive effects upon microbial activity. Exposure to EE2 alone decreased rooibos tea decomposition. Consequently, trimethoprim and EE2 stabilized labile organic matter against microbial degradation and restricted decomposition. We propose that the method outlined could provide a powerful tool for testing the impacts of multiple interacting pollutants upon microbial activity, at a range of scales, across aquatic systems and over ecologically relevant time scales.
Comparative Evaluation of Micronaut-AM and CLSI broth micro-dilution method for antifungal susceptibility testing of Aspergillus species against four commonly used antifungals
Authors: Nuh Ali , Ramadan Newara , Schelenz Silke , Armstrong-James Darius
Published: October 2019

The aim of this study was to evaluate a colorimetric method, Micronaut-AM, for determining susceptibility testing of anidulafungin, amphotericin, voriconazole and itraconazole by comparing the Minimum Inhibitory (Effective) Concentrations (MICs/MECs) obtained by this method to those generated by the reference Clinical Laboratory Standard Investigation (CLSI) method. 78 clinical isolates of Aspergillus species, nine of them azole-resistant, were tested against above antifungals. A fumigatus ATCC 204305 was used as a reference strain and test was performed in accordance with slightly modified yeast susceptibility testing instruction of the manufacture; conidia suspension inoculum and alamarBlue concentration were optimised. These same isolates were referred to Bristol Mycology reference laboratory and tested by CLSI method. The MICs and MECs generated by the two methods were compared using concordance analysis.

Micronaut-AM (MN) showed significant concordance (P< 0.0001) with CLSI method and overall agreement was high (≥ 90%). In addition, Micronaut-AM produced echinocandin MECs results within 18-24h incubation time and reliably detected azole resistant isolates. Essential agreement (within 2 log2 dilution of median) between MN and CLSI reference laboratory method was 99 % for anidulafungin, 100 % for amphotericin; 90% for voriconazole and 87 % for itraconazole. Categorical agreement for anidulafungin, amphotericin B, voriconazole and itraconazole were 100%, 96%, 97% and 99% respectively.

Micronaut-AM showed very good agreement with the reference broth micro-dilution method results for all antifungal agents tested and was able to detect azole resistance. This colorimetric method is very promising and appears to be a suitable alternative susceptibility testing method to labour intensive broth microdilution method for Aspergillus species.
Knowledge and interactions of the local community with the herpetofauna in the forest reserve of Quininí (Tibacuy, Cundinamarca)
Authors: Ríos-Orjuela Juan Camilo , Falcón-Espitia Nelson , Arias-Escobar Alejandra , Espejo-Uribe María José , Chamorro-Vargas Carol Tatiana
Published: October 2019

Background

The study of human-nature relationship has made possible to understand the life dynamics of the communities and the biodiversity with which cohabits. Although ethnobiological studies have been rise over the last decade, little is known about human interaction with herpetofauna in South America and in Colombia. In this work, we analyzed the knowledge, perception, and interaction of a local community located in the forest reserve of Quininí (RFPCQ) in Cundinamarca (Colombia), with respect to the herpetofauna that inhabits the area.

Methods

We performed semi-structured surveys containing 30 questions categorized into three groups: academic knowledge (1), use and cultural beliefs (2) and interaction and perception (3) related to the herpetofauna that occurs in the region. For the obtained data in question groups 1 and 2, an analysis and classification of the answers in percentages were made. For the question group 3, we assigned the answers with a hostility value according to the possible reaction of each individual interviewed in a hypothetical encounter with the herpetofauna, and performed a Multivariate Ordinal Logistic Regression test (MOLR), in order to know if the positive or negative reactions could be predicted by demographic variables.

Results

The community recognized the presence of amphibians and reptiles that cohabit their space, as well as their potential habitats. In addition, the role of herpetofauna was recognized in the magical/religious traditions for some inhabitants of the region, mainly associated with the fate and cure of chronic diseases. In general, the perception of amphibians and reptiles varied according to the origin and gender of the people, tend to have a more positive perception about reptiles than amphibians in most cases.

Conclusions

Although there was a general lack of knowledge on the part of the inhabitants of the RFPCQ about the biological and ecological aspects of herpetofauna, the population recognized the basic information about the habitats of these animals within the area of the reserve. There is a wide variety of uses of amphibians and reptiles in traditional medicine. Greater efforts should be made in the transmission and dissemination of knowledge about the ecological functions of herpetofauna.
Attentional reorientation along the meridians of the visual field: are there different neural mechanisms at play?
Authors: Steinkamp Simon R. , Vossel Simone , Fink Gereon R. , Weidner Ralph
Published: October 2019

Hemispatial neglect, after unilateral lesions to parietal brain areas, is characterized by an inability to respond to unexpected stimuli in contralesional space. As the visual field’s horizontal meridian is most severely affected, the brain networks controlling visuospatial processes might be tuned explicitly to this axis. We investigated such a potential directional tuning in the dorsal and ventral frontoparietal attention networks, with a particular focus on attentional reorientation. We used an orientation-discrimination task where a spatial pre-cue indicated the target position with 80% validity. Healthy participants (n = 29) performed this task in two runs and were required to (re-)orient attention either only along the horizontal or the vertical meridian, while fMRI and behavioral measures were recorded. By using a General Linear Model for behavioral and fMRI data, Dynamic Causal Modeling for effective connectivity, and other predictive approaches, we found strong statistical evidence for a reorientation effect for horizontal and vertical runs. However, neither neural nor behavioral measures differed between vertical and horizontal reorienting. Moreover, models from one run successfully predicted the cueing condition in the respective other run. Our results suggest that activations in the dorsal and ventral attention networks represent higher-order cognitive processes related to spatial attentional (re-)orientating that are independent of directional tuning.
Charrs of the genus Salvelinus (Salmonidae): hybridization, phylogeny and evolution
Authors: Osinov Alexander G. , Volkov Alexander A. , Mugue Nikolai S.
Published: October 2019

Evolutionary history, systematics and taxonomy of charrs of the genus Salvelinus and especially of the representatives of the S. alpinus – S. malma species complex remain confused that is connected with a substantial ecological and morphological flexibility of this group and with supposed ancient hybridization between some taxa. For the analysis of phylogenetic relationships and introgressive hybridization between the species of the genus Salvelinus including three endemic species from Lake El’gygytgyn and all main representatives of the S. alpinus – S. malma species complex, nucleotide sequences of mtDNA control region (960 bp) and two nuclear genes (ITS1 (581 bp) and RAG1 (899 bp)) were analyzed. The differences in the topologies of individual gene trees, among others reasons, were connected with incomplete lineage sorting and historical introgressive hybridization between certain taxa. Several cases of mtDNA capture by different taxa and phylogenetic groups were proposed. In particular, the following taxa participated in introgressive hybridization: northern Dolly Varden S. m. malma, representatives of the S. alpinus complex (including mainly Taranets charr S. a. taranetzi), southern Dolly Varden S. m. lordi from North America and bull trout S. confluentus. Main phylogenetic groups of the S. alpinus – S. malma species complex were revised. The origin and phylogenetic relationships of southern Dolly Varden from North America were not unambiguously defined. We proposed that introgressive hybridization had an important role in the evolutionary history of charrs, in particular, in the appearance of a high level of morphological, ecological and taxonomical diversity.
Incorporating genetic selection into individual-based models (IBMs) of malaria and other infectious diseases
Authors: Hastings Ian M. , Sharma Raman
Published: October 2019

Optimal control strategies for human infections are often investigated by computational approaches using individual-based models (IBMs). These typically track humans and evaluate the impact of control interventions in terms of human deaths, clinical cases averted, interruption of transmission etc. Genetic selection can be incorporated into these IBMs and used to track the spread of mutations whose origin and spread are often driven by the intervention, and which subsequently undermine the control strategy; for example, mutations which encode antimicrobial drug resistance or diagnosis- or vaccine-escape phenotypes. Basic population genetic descriptions of selection are based on infinite population sizes (so that chance fluctuations in allele frequency are absent) but IBMs track finite population sizes. We describe how the finite sizes of IBMs affect simulating the dynamics of genetic selection and how best to incorporate genetic selection into these models. We use the OpenMalaria IBM of malaria as an example, but the same principles apply to IBMs of other diseases. We identify four strategies to incorporate selection into IBMs and make the following four recommendations. Firstly, calculate and report the selection coefficients, s, of the advantageous allele as the key genetic parameter. Secondly, use these values of ‘s’ to calculate the wait-time until a mutation successful establishes itself in the population. The wait time for the mutation can be added to speed of selection, s, to calculate when the mutation will reach significant, operationally important levels. Thirdly, quantify the ability of the IBM to robustly estimate small selection coefficients. Fourthly, optimise computational efficacy: when ‘s’ is small it is plausible that fewer replicates of larger IBMs will be more efficient than a larger number of replicates of smaller size.
The Arabidopsis R-SNARE VAMP714 is essential for polarization of PIN proteins in the establishment and maintenance of auxin gradients
Authors: Gu Xiaoyan , Fonseka Kumari , Casson Stuart A. , Smertenko Andrei , Guo Guangqin , Topping Jennifer F. , Hussey Patrick J. , Lindsey Keith
Published: October 2019

The plant hormone auxin and its directional intercellular transport plays a major role in diverse aspects of plant growth and development. The establishment of auxin gradients in plants requires asymmetric distribution of members of the auxin efflux carrier PIN-FORMED (PIN) protein family to the plasma membrane. An endocytic pathway regulates the recycling of PIN proteins between the plasma membrane and endosomes, providing a mechanism for dynamic localization.

N-ethylmaleimide-sensitive factor adaptor protein receptors (SNAP receptors, SNAREs) mediate fusion between vesicles and target membranes and are classed as Q- or R-SNAREs based on their sequence. We analysed gain- and loss-of-function mutants, dominant negative transgenics and protein localization of the Arabidopsis R-SNARE VAMP714 to understand its function.

We demonstrate that VAMP714 is essential for the insertion of PINs into the plasmamembrane, for polar auxin transport, and for root gravitropism and morphogenesis.VAMP714gene expression is upregulated by auxin, and the VAMP714 protein co-localizes with ER and Golgi vesicles and with PIN proteins at the plasma membrane.

It is proposed that VAMP714 mediates the delivery of PIN-carrying vesicles to the plasma membrane, and that this forms part of a positive regulatory loop in which auxin activates a VAMP714-dependent PIN/auxin transport system to control development.
A Recurrent Neural Network Based Method for Genotype Imputation on Phased Genotype Data
Authors: Kojima Kaname , Tadaka Shu , Katsuoka Fumiki , Tamiya Gen , Yamamoto Masayuki , Kinoshita Kengo
Published: October 2019

Genotype imputation estimates genotypes of unobserved variants from genotype data of other observed variants, and such estimation is enabled using haplotype data of a large number of other individuals. Although existing imputation methods explicitly use haplotype data, the accessibility of haplotype data is often limited because the agreement is necessary from donors of genome data. We propose a new imputation method that uses bidirectional recurrent neural network, and haplotype data of a large number of individuals are encoded as its model parameters through the training step, which can be shared publicly due to the difficulty in restoring genotype data at the individual-level. In the performance evaluation using the phased genotype data in the 1000 Genomes Project, the imputation accuracy of the proposed method inR2is comparative with existing methods for variants with MAF ≥ 0.05 and is slightly worse than those of the existing methods for variants with MAF < 0.05. In a scenario of limited availability of haplotype data to the existing methods, the accuracy of the proposed method is higher than those of the existing methods at least for variants with MAF ≥ 0.005. Python code of our implementation for imputation is available athttps://github.com/kanamekojima/rnnimp/.
Pre-adaptation to climate change through topography-driven evolution of traits and their plasticity
Authors: De Kort H. , Panis B. , Janssens S.B. , Helsen K. , Honnay O.
Published: October 2019

Climate change is expected to increase the level of drought stress experienced by many plant populations, yet the spatial distribution of changes in dryness remains highly uncertain. Species can, to some extent, adapt to climate uncertainty through evolving increased trait plasticity. Biodiversity conservation could capitalize on such natural variation in the ability of populations to cope with climate variability. Yet, disentangling evolution of trait means vs. trait plasticity is challenging, as it requires a sampling design with genetic replicates grown under distinct environmental conditions. Here, we applied different soil moisture treatments to clones of Fragaria vesca plants that were raised from seeds that were sampled in distinct mountainous topographical settings, to study adaptive trait and plasticity divergence in response to drought. We demonstrate that various fitness traits evolved along topographical gradients, including increased specific leaf area (SLA) with increasing slope, and increased growth plasticity with increasing altitude. Our results indicate that traits and their plasticity can evolve independently in response to distinct topographical stressors. We further show that trait heritability varies considerably among traits and topographical settings. Heritability of phenotypic plasticity tended to increase with altitude for all traits, with populations from high altitudes harboring more than twice the heritability for growth and SLA plasticity compared to populations from low altitudes. We conclude that (i) low altitudinal populations, which are expected to be least vulnerable to climate change, may only withstand limited increases in drought stress, while (ii) populations that evolved to thrive under more heterogeneous mountain conditions are pre-adapted to climate change through high plasticity and heritability. Highly heterogeneous landscapes may thus represent invaluable sources of quantitative genetic variation that could support conservation under climate change across the globe.
Heterogeneity in heat shock response dynamics caused by translation fidelity decline and proteostasis collapse
Authors: Vertti-Quintero Nadia , Berger Simon , Casadevall i Solvas Xavier , Statzer Cyril , Annis Jillian , Ruppen Peter , Stavrakis Stavros , Ewald Collin Y. , Gunawan Rudiyanto , deMello Andrew
Published: October 2019

Genetics, environment, and stochasticity influence the rate of ageing in living organisms. Individual Caenorhabditis elegans that are genetically identical and cultured in the same environment have different lifespans, suggesting a significant role of stochasticity in ageing. We have developed a novel microfluidic methodology to measure heat-shock response as a surrogate marker for heterogeneity associated with lifespan and have quantified the heat-shock response of C. elegans at the population, single individual, and tissue levels. We have further mathematically modelled our data to identify the major drivers determining such heterogeneity. This approach demonstrates that protein translation and degradation rate constants explain the individuality of the heat-shock time-course dynamic. We observed a decline of protein turnover capacity in early adulthood, co-incidentally occurring as the predicted proteostasis collapse. We identified a decline of intestinal response as the tissue that underlies the individual heterogeneity. Additionally, we verified that individuals with enhanced translation fidelity in early adulthood live longer. Altogether, our results reveal that the stochastic onset of proteostasis collapse of somatic tissues during early adulthood reflects individual protein translation capacity underlying heterogenic ageing of isogenic C. elegans.
The inactivation of enzymes belonging to the central carbon metabolism, a novel mechanism of developing antibiotic resistance
Authors: Gil-Gil Teresa , Corona Fernando , Martínez José Luis , Bernardini Alejandra
Published: October 2019

Fosfomycin is a bactericidal antibiotic, analogous to phosphoenolpyruvate (PEP) that exerts its activity by inhibiting the activity of MurA. This enzyme catalyzes the first step of peptidoglycan biosynthesis, the transfer of enolpyruvate from PEP to uridine-diphosphate-N-acetylglucosamine. Fosfomycin is increasingly used in the last years, mainly for treating infections caused by Gram-negative multidrug resistant bacteria asStenotrophomonas maltophilia, an opportunistic pathogen characterized by its low susceptibility to antibiotics of common use. The mechanisms of mutational resistance to fosfomycin inS. maltophiliawere studied in the current work. None of the mechanisms so far described for other organisms, which include the production of fosfomycin inactivating enzymes, target modification, induction of alternative peptidoglycan biosynthesis pathway and the impaired entrance of the antibiotic, are involved in the acquisition of such resistance by this bacterial species. Rather the unique cause of resistance in the studied mutants is the mutational inactivation of different enzymes belonging to the Embden-Meyerhof-Parnas central metabolism pathway. The amount of intracellular fosfomycin accumulation did not change in any of these mutants showing that neither the inactivation nor the transport of the antibiotic were involved. Transcriptomic analysis also showed that the mutants did not present changes in the expression level of putative alternative peptidoglycan biosynthesis pathway genes neither any related enzyme. Finally, the mutants did not present an increased PEP concentration that might compete with fosfomycin for its binding to MurA. Based on these results, we describe a completely novel mechanism of antibiotic resistance based on the remodeling ofS. maltophiliametabolism.

Significance

Antibiotic resistance (AR) has been largely considered as a specific bacterial response to an antibiotic challenge. Indeed, its study has been mainly concentrated in mechanisms that affect the antibiotics (mutations in transporters, the activity of efflux pumps and antibiotic modifying enzymes) or their targets (i.e.: target mutations, protection or bypass). Usually, AR-associated metabolic changes were considered to be a consequence (fitness costs) and not a cause of AR. Herein, we show that strong alterations in the bacterial metabolism can also be the cause of AR. In the study here presented,Stenotrophomonas maltophiliaacquires fosfomycin resistance through the inactivation of glycolytic enzymes belonging to the Embden-Meyerhof-Parnas. Besides resistance to fosfomycin, this inactivation also impairs the bacterial gluconeogenic pathway. Together with previous work showing that AR can be under metabolic control, our results provide evidence that AR is intertwined with the bacterial metabolism.
Using Unmanned Aerial Vehicles (UAV) for free-roaming dog population size estimation
Authors: Warembourg Charlotte , Berger-González Monica , Alvarez Danilo , Sousa Filipe Maximiano , Hernández Alexis López , Roquel Pablo , Eyermann Joe , Benner Merlin , Dürr Salome
Published: October 2019

Population size estimation is performed for several reasons including disease surveillance and control, for example to design adequate control strategies such as vaccination programs or to estimate a vaccination campaign coverage. In this study, we aimed at assessing the benefits and challenges of using Unmanned Aerial Vehicles (UAV) to estimate the size of free-roaming domestic dog (FRDD) populations and compare the results with two regularly used methods for population estimations: a Bayesian statistical model based on capture-recapture data and the human:dog ratio estimation. Three studies sites of one square kilometer were selected in Petén department, Guatemala. UAV flight were conducted twice during two consecutive days per study site. The UAV’s camera was set to regularly take pictures and cover the entire surface of the selected areas. A door-to-door survey was conducted in the same areas, all available dogs were marked with a collar and owner were interviewed. Simultaneously to the UAV’s flight, transect walks were performed and the number of collared and non-collared dogs were recorded. Data collected during the interviews and the number of dogs counted during the transect walks informed a Bayesian statistical model. The number of dogs counted on the UAV’s pictures and the estimates given by the Bayesian statistical model, as well as the estimates derived from using a 5:1 human:dog ratio were compared to dog census data. FRDD could be detected using the UAV’s method. However, the method lacked of sensitivity, which could be overcome by choosing the flight timing and the study area wisely, or using infrared camera or automatic detection of the dogs. We also suggest to combine UAV and capture-recapture methods to obtain reliable FRDD population size estimated. This publication may provide helpful directions to design dog population size estimation methods using UAV.
The intrinsic neonatal hippocampal network: rsfMRI findings
Authors: Howell Athena L. , Osher David E. , Li Jin , Saygin Zeynep M.
Published: October 2019

Many adults cannot voluntarily recall memories before the ages of 3-5, a phenomenon referred to as “infantile amnesia” The development of the hippocampal network likely plays a significant part in the emergence of the ability to form long-lasting memories. In adults, the hippocampus has specialized and privileged connections with certain cortical networks, which presumably facilitate its involvement in memory encoding, consolidation, and retrieval. Is the hippocampus already specialized in these cortical connections at birth? And are the topographical principles of connectivity (e.g. long-axis specialization) present at birth? We analyzed resting-state hippocampal connectivity in neonates scanned within one week of birth (Developmental Human Connectome Project) and compared them to adults (Human Connectome Project). We explored the connections of the whole hippocampus and its long-axis specialization to seven canonical cortical networks. We found that the neonatal hippocampal networks show clear immaturity at birth: adults showed hippocampal connectivity that was unique for each cortical network, whereas neonates showed no differentiation in hippocampal connectivity across these networks. Further, neonates lacked long-axis specialization (i.e., along anterior-posterior axis) of the hippocampus in its differential connectivity patterns to the cortical networks. This immaturity in connectivity may contribute to immaturity in memory formation in the first years of life.

“New and Noteworthy”

While animal data, and anatomical and behavioral human data from young children suggest that the hippocampus is immature at birth, to date, there are no direct assessments of human hippocampal functional connectivity (FC) very early in life. Our study explores the FC of the hippocampus to the cortex at birth, allowing insight into the development of human memory systems.