bluuebunny/crossref_metadata_2025 huggingface dataset:
Timing of and factors associated with HIV disclosure among perinatally infected children in rural Zambia
Authors: Sutcliffe Catherine G. , Drogt Carolyn S. , van Dijk Janneke H. , Hamangaba Francis , Muleka Mathias , Munsanje Bornface , Munsanje Jeridy , Thuma Philip E. , Moss William J.
Published: October 2019

Objective:

This study was conducted to understand the process of disclosure among HIV-infected children receiving care in rural Zambia.

Design:

Cross-sectional and longitudinal analyses were conducted within an ongoing clinical cohort study of HIV-infected children receiving care in Macha, Zambia from 2007 to 2016.

Methods:

Children receiving HIV care were enrolled into the cohort study and assessed every 3 months. At each study visit, disclosure status was ascertained through questionnaire. Disclosure was categorized as none (child did not know they were chronically ill), partial (child knew they were chronically ill but not of their HIV infection status), or full (child knew they had HIV infection). Barriers to disclosure, and the timing of and factors associated with disclosure, were evaluated among children 5–15 years of age.

Results:

At study entry, the prevalence of full disclosure increased with age, from 2.1 to 76.2% among children 5–6 and 13–15 years of age, respectively. Reasons provided by caregivers for not disclosing the child's status included they felt the child was too young, they were afraid to, or they did not know how to tell the child. During follow-up, the median age at full disclosure was 9.0 years. Among children with full disclosure, 89.5% first had partial disclosure at a median age of 7.4 years. Factors associated with disclosure included being female, sharing responsibility for taking their own medication, and low weight-for-age z-score.

Conclusion:

Given the complexity of the disclosure process and potential for health benefits, interventions and protocols are needed to support caregivers through the disclosure process.
The matrix reasoning item bank (MaRs-IB): novel, open-access abstract reasoning items for adolescents and adults
Authors: Chierchia Gabriele , Fuhrmann Delia , Knoll Lisa J. , Pi-Sunyer Blanca Piera , Sakhardande Ashok L. , Blakemore Sarah-Jayne
Published: October 2019

Existing non-verbal ability tests are typically protected by copyright, preventing them from being freely adapted or computerized. Working towards an open science framework, we provide 80 novel, open-access abstract reasoning items, an online implementation and item-level data from 659 participants aged between 11 and 33 years: the matrix reasoning item bank (MaRs-IB). Each MaRs-IB item consists of an incomplete matrix containing abstract shapes. Participants complete the matrices by identifying relationships between the shapes. Our data demonstrate age differences in non-verbal reasoning accuracy, which increased during adolescence and stabilized in early adulthood. There was a slight linear increase in response times with age, resulting in a peak in efficiency (i.e. a measure combining speed and accuracy) in late adolescence. Overall, the data suggest that the MaRs-IB is sensitive to developmental differences in reasoning accuracy. Further psychometric validation is recommended.
Enhancement of thermoelectric properties of La-doped SrTiO
3
bulk by introducing nanoscale porosity
Authors: Ahmed Al Jumlat , Nazrul Islam Sheik Md. Kazi , Hossain Ridwone , Kim Jeonghun , Kim Minjun , Billah Motasim , Hossain Md. Shahriar A. , Yamauchi Yusuke , Wang Xiaolin
Published: October 2019

Electron-doped SrTiO
3
is a well-known
n
-type thermoelectric material, although the figure of merit of SrTiO
3
is still inferior compared with
p
-type metal oxide-based thermoelectric materials due to its high lattice thermal conductivity. In this study, we have used a different amount of the non-ionic surfactant F127 during sample preparation to introduce nanoscale porosities into bulk samples of La-doped SrTiO
3
. It has been observed that the porosities introduced into the bulk sample significantly improve the Seebeck coefficient and reduce the thermal conductivity by the charge carrier and phonon scattering respectively. Therefore, there is an overall enhancement in the power factor (PF) followed by a dimensionless figure of merit (
zT
) over a wide scale of temperature. The sample 20 at% La-doped SrTiO
3
with 600 mg of F127 surfactant (SLTO 600F127) shows the maximum PF of 1.14 mW m
−1
K
−2
at 647 K which is 35% higher than the sample without porosity (SLTO 0F127), and the same sample (SLTO 600F127) shows the maximum value of z
T
is 0.32 at 968 K with an average enhancement of 62% in
zT
in comparison with the sample without porosity (SLTO 0F127).
Optimization and characterization of poly(lactic-co-glycolic acid) nanoparticles loaded with astaxanthin and evaluation of anti-photodamage effect
in vitro
Authors: Hu Fangbin , Liu Weikang , Yan Liuliu , Kong Fanhui , Wei Kun
Published: October 2019

Astaxanthin is a xanthophyll carotenoid with high beneficial biological activities, such as antioxidant function and scavenging oxygen free radicals, but its application is limited because of poor water solubility and low bioavailability. Here, we prepared and optimized poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with astaxanthin using the emulsion solvent evaporation technique and investigated the anti-photodamage effect in HaCaT cells. The four-factor three-stage Box–Behnken design was used to optimize the nanoparticle formulation. The experimental determination of the optimal nanoparticle size was 154.4 ± 0.35 nm, the zeta potential was 22.07 ± 0.93 mV, encapsulation efficiency was 96.42 ± 0.73% and drug loading capacity was 7.19 ± 0.12%. The physico-chemical properties of the optimized nanoparticles were characterized by dynamic light scattering, scanning electron microscopy, transmission electron microscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, differential scanning calorimetry and thermo-gravimetric analyser.
In vitro
study exhibited the excellent cell viability and cellular uptake of optimized nanoparticles on HaCaT cells. The anti-photodamage studies (cytotoxicity assay, reactive oxygen species content and JC-1 assessment) demonstrated that the optimized nanoparticles were more effective and safer than pure astaxanthin in HaCaT cells. These results suggest that our PLGA-coated astaxanthin nanoparticles synthesis method was highly feasible and can be used in cosmetics or the treatment of skin diseases.
Shear-sensitive adhesion enables size-independent adhesive performance in stick insects
Authors: Labonte David , Struecker Marie-Yon , Birn-Jeffery Aleksandra V. , Federle Walter
Published: October 2019

The ability to climb with adhesive pads conveys significant advantages and is widespread in the animal kingdom. The physics of adhesion predict that attachment is more challenging for large animals, whereas detachment is harder for small animals, due to the difference in surface-to-volume ratios. Here, we use stick insects to show that this problem is solved at both ends of the scale by linking adhesion to the applied shear force. Adhesive forces of individual insect pads, measured with perpendicular pull-offs, increased approximately in proportion to a linear pad dimension across instars. In sharp contrast, whole-body force measurements suggested area scaling of adhesion. This discrepancy is explained by the presence of shear forces during whole-body measurements, as confirmed in experiments with pads sheared prior to detachment. When we applied shear forces proportional to either pad area or body weight, pad adhesion also scaled approximately with area or mass, respectively, providing a mechanism that can compensate for the size-related loss of adhesive performance predicted by isometry. We demonstrate that the adhesion-enhancing effect of shear forces is linked to pad sliding, which increased the maximum adhesive force per area sustainable by the pads. As shear forces in natural conditions are expected to scale with mass, sliding is more frequent and extensive in large animals, thus ensuring that large animals can attach safely, while small animals can still detach their pads effortlessly. Our results therefore help to explain how nature’s climbers maintain a dynamic attachment performance across seven orders of magnitude in body weight.
Synchrotron X-ray absorption spectroscopy of melanosomes in vertebrates and cephalopods: implications for the affinity of
Tullimonstrum
Authors: Rogers Christopher S. , Astrop Timothy I. , Webb Samuel M. , Ito Shosuke , Wakamatsu Kazumasa , McNamara Maria E.
Published: October 2019

Screening pigments are essential for vision in animals. Vertebrates use melanins bound in melanosomes as screening pigments, whereas cephalopods are assumed to use ommochromes. Preserved eye melanosomes in the controversial fossil
Tullimonstrum
(Mazon Creek, IL, USA) are partitioned by size and/or shape into distinct layers. These layers resemble tissue-specific melanosome populations considered unique to the vertebrate eye. Here, we show that extant cephalopod eyes also show tissue-specific size- and/or shape-specific partitioning of melanosomes; these differ from vertebrate melanosomes in the relative abundance of trace metals and in the binding environment of copper. Chemical signatures of melanosomes in the eyes of
Tullimonstrum
more closely resemble those of modern cephalopods than those of vertebrates, suggesting that an invertebrate affinity for
Tullimonstrum
is plausible. Melanosome chemistry may thus provide insights into the phylogenetic affinities of enigmatic fossils where melanosome size and/or shape are equivocal.
It's what's on the inside that counts: stress physiology and the bacterial microbiome of a wild urban mammal
Authors: Stothart Mason R. , Palme Rupert , Newman Amy E. M.
Published: October 2019

The microbiome's capacity to shape the host phenotype and its mutability underlie theorization that the microbiome might facilitate host acclimation to rapid environmental change. However, when environmental change occurs, it is unclear whether resultant microbiome restructuring is proximately driven by this changing external environment or by the host's physiological response to this change. We leveraged urbanization to compare the ability of host environment (urban or forest) versus multi-scale biological measures of host hypothalamic–pituitary–adrenal (HPA) axis physiology (neutrophil : lymphocyte ratio, faecal glucocorticoid metabolites, hair cortisol) to explain variation in the eastern grey squirrel (Sciurus carolinensis) faecal microbiome. Urban and forest squirrels differed across all three of the interpretations of HPA axis activity we measured. Direct consideration of these physiological measures better explained greater phylogenetic turnover between squirrels than environment. This pattern was strongly driven by trade-offs between bacteria which specialize on metabolizing digesta versus host-derived nutrient sources. Drawing on ecological theory to explain patterns in intestinal bacterial communities, we conclude that although environmental change can affect the microbiome, it might primarily do so indirectly by altering host physiology. We demonstrate that the inclusion and careful consideration of dynamic, rather than fixed (e.g. sex), dimensions of host physiology are essential for the study of host–microbe symbioses at the micro-evolutionary scale.
In-Depth Characterization and Validation in BRG1-Mutant Lung Cancers Define Novel Catalytic Inhibitors of SWI/SNF Chromatin Remodeling
Authors: Jagani Zainab , Chenail Gregg , Xiang Kay , Bushold Geoffrey , Bhang Hyo-Eun C. , Li Ailing , Elliott GiNell , Zhu Jiang , Vattay Anthony , Gilbert Tamara , Bric Anka , Kikkawa Rie , Dubost Valérie , Terranova Rémi , Cantwell John , Luu Catherine , Silver Serena , Shirley Matt , Huet Francois , Maher Rob , Reece-Hoyes John , Ruddy David , Rakiec Daniel , Korn Joshua , Russ Carsten , Ruda Vera , Dooley Julia , Costa Emily , Park Isabel , Moebitz Henrik , Nakajima Katsumasa , Adair Christopher D. , Mathieu Simon , Ntaganda Rukundo , Smith Troy , Farley David , King Daniel , Xie Xiaoling , Kulathila Raviraj , Hu Tiancen , Pan Xuewen , Ma Qicheng , Vulic Katarina , Rago Florencia , Clarkson Scott , Ge Robin , Sigoillot Frederic , Pardee Gwynn , Bagdasarian Linda , McLaughlin Margaret , Haas Kristy , Weiler Jan , Kovats Steve , Jaskelioff Mariela , Apolline-Gerard Marie , Beil Johanna , Naumann Ulrike , Fortin Pascal , Stegmeier Frank P. , Acker Michael G. , Williams Juliet , Meyer Matthew , Bradner James E. , Keen Nicholas , Sellers William R. , Hofmann Francesco , Engelman Jeffrey A. , Stuart Darrin , Papillon Julien P.N.
Published: October 2019

Members of the ATP-dependent SWI/SNF chromatin remodeling complexes are among the most frequently mutated genes in cancer, suggesting their dysregulation plays a critical role. The synthetic lethality between SWI/SNF catalytic subunits BRM/SMARCA2 and BRG1/SMARCA4 has instigated great interest in targeting BRM. Here we have performed a critical and in-depth investigation of novel dual inhibitors (BRM011 and BRM014) of BRM and BRG1 in order to validate their utility as chemical probes of SWI/SNF catalytic function, while obtaining insights into the therapeutic potential of SWI/SNF inhibition. In corroboration of on-target activity, we discovered compound resistant mutations through pooled screening of BRM variants in BRG1-mut cancer cells. Strikingly, genome-wide transcriptional and chromatin profiling (ATAC-Seq) provided further evidence of pharmacological perturbation of SWI/SNF chromatin remodeling as BRM011 treatment induced specific changes in chromatin accessibility and gene expression similar to genetic depletion of BRM. Finally, these compounds have the capacity to inhibit the growth of tumor-xenografts, yielding important insights into the feasibility of developing BRM/BRG1 ATPase inhibitors for the treatment of BRG1-mut lung cancers. Overall, our studies not only establish the feasibility of inhibiting SWI/SNF catalytic function, providing a framework for SWI/SNF therapeutic targeting, but have also yielded successful elucidation of small-molecule inhibitors that will be of importance in probing SWI/SNF function in various disease contexts.
Transcriptomic Profiling of Skeletal Muscle Adaptations to Exercise and Inactivity
Authors: Pillon Nicolas J. , Gabriel Brendan M. , Dollet Lucile , Smith Jonathon A. , Sardón Puig Laura , Botella Javier , Bishop David J. , Krook Anna , Zierath Juleen R.
Published: October 2019

The molecular mechanisms underlying the response to exercise and inactivity are not fully understood. We propose an innovative approach to profile the skeletal muscle transcriptome to exercise and inactivity using 66 published datasets. Data collected from human studies of aerobic and resistance exercise, including acute and chronic exercise training, were integrated using meta-analysis methods (www.metamex.eu). Gene ontology and pathway analyses reveal selective pathways activated by inactivity, aerobic versus resistance and acute versus chronic exercise training. We identified NR4A3 as one of the most exercise- and inactivity-responsive genes, and established a role for this nuclear receptor in mediating the metabolic responses to exercise-like stimuli in vitro. The meta-analysis (MetaMEx) also highlights the differential response to exercise in individuals with metabolic impairments. MetaMEx provides the most extensive dataset of skeletal muscle transcriptional responses to different modes of exercise and an online interface to readily interrogate the database.
Using genetics to differentiate patients with similar symptoms: application to inflammatory arthritis in the rheumatology outpatient clinic
Authors: Knevel Rachel , Cessie Saskia le , Terao Chikashi C. , Slowikowski Kamil , Cui Jing , Huizinga Tom W.J. , Costenbader Karen H. , Liao Katherine P. , Karlson Elizabeth W. , Raychaudhuri Soumya
Published: October 2019

Slow developing complex diseases are a clinical diagnostic challenge. Since genetic information is increasingly available prior to a patient’s first visit to a clinic, it might improve diagnostic accuracy. We aimed to devise a method to convert genetic information into simple probabilities discriminating between multiple diagnoses in patients presenting with inflammatory arthritis.

We developed G-Prob, which calculates for each patient the genetic probability for each of multiple possible diseases. We tested this for inflammatory arthritis-causing diseases (rheumatoid arthritis, systemic lupus erythematosus, spondyloarthropathy, psoriatic arthritis and gout). After validating in simulated data, we tested G-Prob in biobank cohorts in which genetic data were linked to electronic medical records:

-

1,200 patients identified by ICD-codes within the eMERGE database (n= 52,623);

-

245 patients identified through ICD codes and review of medical records within the Partners Biobank (n=12,604);

-

243 patients selected prospectively with final diagnoses by medical record review within the Partners Biobank (n=12,604).

The calibration of G-Prob with the disease status was high (with regression coefficients ranging from 0.90-1.08 (ideal would be 1.00) in all cohorts. G-Prob’s discriminative ability was high in all cohorts with pooled Area Under the Curve (AUC)=0.69 [95%CI 0.67-0.71], 0.81 [95%CI 0.76-0.84] and 0.84 [95%CI 0.81-0.86]. For all patients, at least one disease could be ruled out, and in 45% of patients a most likely diagnosis could be identified with an overall 64% positive predictive value. In 35% of instances the clinician’s initial diagnosis was incorrect. Initial clinical diagnosis explained 39% of the variance in final disease prediction which improved to 51% (P<0.0001) by adding G-Prob genetic data.

In conclusion, by converting genotypes into an interpretable probability value for five different inflammatory arthritides, we can better discriminate and diagnose rheumatic diseases. Genotypes available prior to a clinical visit could be considered part of patients’ medical history and potentially used to improve precision and diagnostic efficiency in clinical practice.
miRViz: a novel webserver application to visualize and interpret microRNA datasets
Authors: Giroux Pierre , Bhajun Ricky , Segard Stéphane , Picquenot Claire , Charavay Céline , Desquilles Lise , Pinna Guillaume , Ginestier Christophe , Denis Josiane , Cherradi Nadia , Guyon Laurent
Published: October 2019

MicroRNAs (miRNAs) are small non-coding RNAs that are involved in the regulation of major pathways in eukaryotic cells through repression of their target genes at the post-transcriptional level1. While high-throughput approaches are broadly used to decipher the biological relevance of miRNAs, extraction of significant information from large miRNA datasets remains challenging. For example, sequencing technologies can quantify the relative expression of up to thousands of mature miRNAs under various experimental conditions. However, in such datasets, small subsets of miRNAs can often show significant differential expression, and deciding which one(s) should be further analyzed can prove difficult. Thus, the current challenge resides in objective analysis, interpretation and visualization of these large datasets, for which specifically suited methods are lacking.
Maximally efficient prediction in the early fly visual system may support evasive flight maneuvers
Authors: Wang Siwei , Segev Idan , Borst Alexander , Palmer Stephanie
Published: October 2019

The visual system must make predictions to compensate for inherent delays in its processing. Yet little is known, mechanistically, about how prediction aids natural behaviors. Here, we show that despite a 20-30ms intrinsic processing delay, the vertical motion sensitive (VS) network of the blowfly achieves maximally efficient prediction. This prediction enables the fly to fine-tune its complex, yet brief, evasive flight maneuvers according to its initial ego-rotation at the time of detection of the visual threat. Combining a rich database of behavioral recordings with detailed compartmental modeling of the VS network, we further show that the VS network has axonal gap junctions that are critical for optimal prediction. During evasive maneuvers, a VS subpopulation that directly innervates the neck motor center can convey predictive information about the fly’s future ego-rotation, potentially crucial for ongoing flight control. These results suggest a novel sensory-motor pathway that links sensory prediction to behavior.

Author summary

Survival-critical behaviors shape neural circuits to translate sensory information into strikingly fast predictions, e.g. in escaping from a predator faster than the system’s processing delay. We show that the fly visual system implements fast and accurate prediction of its visual experience. This provides crucial information for directing fast evasive maneuvers that unfold over just 40ms. Our work shows how this fast prediction is implemented, mechanistically, and suggests the existence of a novel sensory-motor pathway from the fly visual system to a wing steering motor neuron. Echoing and amplifying previous work in the retina, our work hypothesizes that the efficient encoding of predictive information is a universal design principle supporting fast, natural behaviors.
A multifaceted approach to analyzing taxonomic, functional and phylogenetic β-diversity
Authors: Nakamura Gabriel , Vicentin Wagner , Súarez Yzel Rondon , Duarte Leandro
Published: October 2019

Ecological literature offers a myriad of methods for quantifying β-diversity. One such methods is determining BDtotal (BD), which, unlike other methods, can be decomposed into meaningful components that indicate how unique a community is regarding its composition (local contribution) and how unique a species is regarding its occurrence in the metacommunity (species contribution). Despite this advantage, the original formulation of the BD metric only assesses taxonomic variation and neglects other important dimensions of biodiversity. We expanded the original formulation of BD to capture variation in the functional and phylogenetic dimensions of a metacommunity by computing two new metrics — BDFun and BDPhy — as well as their respective components that represent the local and species contribution. We tested the statistical performance of these new metrics for capturing variation in functional and phylogenetic composition through simulated metacommunities and illustrated the potential use of these new metrics by analyzing β-diversity of stream fish communities. Our results demonstrated that BDPhy and BDFun have acceptable type I error and great power to detect the effect of deep evolutionary relationships and attributes mediating patterns of β-diversity. The empirical example illustrates how BDPhy and BDFun reveal complementary aspects of β-diversity relative to the original BD metric. These new metrics can be used to identify local communities that are of conservation importance because they represent unique functional, phylogenetic and taxonomic compositions. We conclude that BDPhy and BDFun are important tools for providing complementary information in the investigation of the structure of metacommunities.
Emergence of opposite neurons in a firing-rate model of multisensory integration
Authors: Chau Ho Yin , Zhang Wen-Hao , Lee Tai Sing
Published: October 2019

Opposite neurons, found in macaque dorsal medial superior temporal (MSTd) and ventral intraparietal (VIP) areas, combine visual and vestibular cues of self-motion in opposite ways. A neural circuit recently proposed utilizes opposite neurons to perform causal inference and decide whether the visual and vestibular cues in MSTd and VIP should be integrated or segregated. However, it is unclear how these opposite connections can be formed with biologically realistic learning rules. We propose a network model capable of learning these opposite neurons, using Hebbian and Anti-Hebbian learning rules. The learned neurons are topographically organized and have von Mises-shaped feedforward connections, with tuning properties characteristic of opposite neurons. Our purpose is two-fold: on the one hand, we provide a circuit-level mechanism that explains the properties and formation of opposite neurons; on the other hand, we present a way to extend current theories of multisensory integration to account for appropriate segregation of sensory cues.
Reciprocal regulation of pancreatic ductal adenocarcinoma growth and molecular subtype by HNF4α and SIX1/4
Authors: Camolotto Soledad A. , Belova Veronika K. , Torre-Healy Luke , Vahrenkamp Jeffery M. , Berrett Kristofer C. , Conway Hannah , Stubben Chris , Moffitt Richard , Gertz Jason , Snyder Eric L.
Published: October 2019

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a five-year survival of less than 5%. Transcriptomic analysis has identified two clinically relevant molecular subtypes of PDAC: Classical and Basal-like. The Classical subtype is characterized by a more favorable prognosis and better response to chemotherapy than the Basal-like subtype. The Classical subtype also expresses higher levels of lineage specifiers that regulate endodermal differentiation, including the nuclear receptor HNF4α. Using in vitro and in vivo PDAC models, we show that HNF4α restrains tumor growth and drives tumor cells toward an epithelial identity. Gene expression analysis from murine models and human tumors shows that HNF4α activates expression of genes associated with the Classical subtype. Although HNF4α loss is not sufficient for complete conversion to the Basal-like subtype gene expression profile, HNF4α directly represses SIX4 and SIX1, mesodermal lineage specifiers expressed in the Basal-like subtype. Finally, HNF4α-negative PDAC cells rely on expression of SIX4 and SIX1 for proliferation in vitro and in vivo. Overall, our data show that HNF4α regulates the growth and molecular subtype of PDAC by multiple mechanisms, including activation of the Classical gene expression program and repression of SIX4 and SIX1, which may represent novel dependencies of the Basal-like subtype.
Small-scale spatial structure influences large-scale invasion rates
Authors: Plank Michael J. , Simpson Matthew J. , Binny Rachelle N.
Published: October 2019

Local interactions among individual members of a population can generate intricate small-scale spatial structure, which can strongly influence population dynamics. The two-way interplay between local interactions and population dynamics is well understood in the relatively simple case where the population occupies a fixed domain with a uniform average density. However, the situation where the average population density is spatially varying is less well understood. This situation includes ecologically important scenarios such as species invasions, range shifts, and moving population fronts. Here, we investigate the dynamics of the spatial stochastic logistic model in a scenario where an initially confined population subsequently invades new, previously unoccupied territory. This simple model combines density-independent proliferation with dispersal, and density-dependent mortality via competition with other members of the population. We show that, depending on the spatial scales of dispersal and competition, either a clustered or a regular spatial structure develops over time within the invading population. In the short-range dispersal case, the invasion speed is significantly lower than standard predictions of the mean-field model. We conclude that mean-field models, even when they account for non-local processes such as dispersal and competition, can give misleading predictions for the speed of a moving invasion front.
In vitro activity of beauvericin against all developmental stages of Sarcoptes scabiei
Authors: Khoury Charbel Al , Nemer Nabil , Nemer Georges , Kurban Mazen , Bernigaud Charlotte , Fischer Katja , Guillot Jacques
Published: October 2019

Background

Scabies is a frequent cutaneous infection caused by the mite Sarcoptes scabiei in a large number of mammals including humans. As the resistance of S. scabiei against several chemical acaricides has been previously documented, the establishment of alternative and effective control molecules is required.

Objectives

In this study, the potential acaricidal activity of beauvericin was assessed against different life stages of S. scabiei var. suis and, in comparison with dimpylate and ivermectin, two commercially available molecules used for the treatment of S. scabiei infection in animals and/or humans.

Methods

In our in vitro model, developmental stages of S. scabiei have been placed in Petri dishes filled with Columbia agar supplemented with pig serum and different concentrations of the drugs. Moreover, the toxicity of beauvericin against cultured human fibroblast skin cells was evaluated using an MTT proliferation assay

Results

Beauvericin showed higher activity against adults and eggs of S. scabiei when compared to dimpylate and ivermectin. In addition, cell sensitivity assays demonstrated low toxicity of beauvericin against primary human fibroblast skin cells.

Conclusion

These results revealed that the use of beauvericin is promising and might be considered for the treatment of S. scabiei infection.
Topoisomerase IIα Prevents, But Does Not Resolve, Ultrafine Anaphase Bridges By Two Mechanisms
Authors: Gemble Simon , Buhagiar-Labarchède Géraldine , Onclercq-Delic Rosine , Lambert Sarah , Amor-Guéret Mounira
Published: October 2019

Topoisomerase IIα (Topo IIα), a well-conserved double-stranded DNA (dsDNA)-specific decatenase, processes dsDNA catenanes resulting from DNA replication during mitosis. Topo IIα defects lead to an accumulation of ultrafine anaphase bridges (UFBs), a type of chromosome non-disjunction. Topo IIα has been reported to resolve DNA anaphase threads, possibly accounting for the increase in UFB frequency upon Topo IIα inhibition. We hypothesized that the excess UFBs might also result, at least in part, from an impairment of the prevention of UFB formation by Topo IIα. We found that Topo IIα inhibition promotes UFB formation without affecting UFB resolution during anaphase. Moreover, we showed that Topo IIα inhibition promotes the formation of two types of UFBs depending on cell-cycle phase. Topo IIα inhibition during S-phase compromises complete DNA replication, leading to the formation of UFB-containing unreplicated DNA, whereas Topo IIα inhibition during mitosis impedes DNA decatenation at metaphase-anaphase transition, leading to the formation of UFB-containing DNA catenanes. Thus, Topo IIα activity is essential to prevent UFB formation in a cell-cycle dependent manner, but dispensable for UFB resolution during anaphase.
A new method of teaching medical statistics at medical universities in Guangdong
Authors: Chen Qing-shan , Ma Xin-yue , Cheng Xin , Yang Xuesong
Published: October 2019

Although statistics play a significant role in the medical profession, studying medical statistics is challenging because this topic is more difficult to comprehend than other subjects included in medical curricula. Therefore, improving the teaching of medical statistics to meet the requirements of modern medical students/physicians is an essential task. In this study, based on responses about studying medical statistics completed by medical students, we developed a novel approach to teaching medical statistics named “purpose, database, types of variable, and relationship between variables (PDTR)”, which emphasizes how to simply master statistical applications and reduces class hours for students. Also, pilot course was implemented. We discovered that the participants using PDTR performed better on examinations of medical statistics than did graduates of institutions using traditional teaching methods (86.39±3.72 vs 73.72±6.58, P < 0.001). In addition, positive feedback was received by participants (>80%). Altogether, as a completely novel pedagogical method of teaching medical statistics, PDTR overcomes the negative attitudes of students towards medical statistics, enhances enthusiasm for learning statistics, and remarkably simplifies the process of studying statistical applications. These advantages are undoubtedly conductive to improving the effective use of medical statistics in physicians’ professional work.
The influence of relationship closeness on default-mode network connectivity during social interactions
Authors: Fareri Dominic S. , Smith David V. , Delgado Mauricio R.
Published: October 2019

Reciprocated trust plays a critical role in forming and maintaining relationships, and has consistently been shown to implicate neural circuits involved in reward-related processing and social cognition. Less is known about neural network connectivity during social interactions involving trust, however, particularly as a function of closeness between an investor and a trustee. We examined network reactivity and connectivity in participants who played an economic trust game with close friends, strangers and a computer. Network reactivity analyses showed enhanced activation of the DMN to social relative to non-social outcomes. A novel network psychophysiological interaction analysis (nPPI) revealed enhanced connectivity between the DMN and the superior frontal gyrus and superior parietal lobule when experiencing reciprocated vs. violated trust from friends relative to strangers. Such connectivity tracked with differences in self-reported social closeness with these partners. Interestingly, reactivity of the executive control network (ECN), involved in decision processes, demonstrated no social vs. non-social preference, and ECN-ventral striatum (VS) connectivity did not track social closeness. Taken together, these novel findings suggest that DMN interacts with components of attention and control networks to signal the relative importance of positive experiences with close others vs. strangers.
An exact, unifying framework for region-based association testing in family-based designs, including higher criticism approaches, SKATs, multivariate and burden tests
Authors: Hecker Julian , Townes F. William , Kachroo Priyadarshini , Lasky-Su Jessica , Ziniti John , Cho Michael H. , Weiss Scott T. , Laird Nan M. , Lange Christoph
Published: October 2019

Analysis of rare variants in family-based studies remains a challenge. To perform a region/set-based association analysis of rare variants in family-based studies, we propose a general methodological framework that integrates higher criticism, maximum, SKATs, and burden approaches into the family-based association testing (FBAT) framework. Using the haplotype algorithm for FBATs to compute the conditional genotype distribution under the null hypothesis of Mendelian transmissions, virtually any association test statistics can be implemented in our approach and simulation-based or exact p-values can be computed without the need for asymptotic settings. Using simulations, we compare the features of the proposed test statistics in our framework with the existing region-based methodology for family-based studies under various scenarios. The tests of our framework outperform the existing approaches. We provide general guidelines for which scenarios, e.g., sparseness of the signals or local LD structure, which test statistic will have distinct power advantages over the others. We also illustrate our approach in an application to a whole-genome sequencing dataset with 897 asthmatic trios.
A method to estimate the frequency of chromosomal rearrangements induced by CRISPR/Cas9 multiplexing in Drosophila
Authors: Ng William A. , Reed Bruce H.
Published: October 2019

Using CRISPR/Cas9 to simultaneously induce mutations in two or more target genes, commonly referred to as multiplexing, may result in chromosomal rearrangements such as inversions or translocations. While this may be undesirable in some contexts, the ability to recover chromosomal rearrangements targeted to specific sites in the genome is potentially a powerful tool. Before developing such tools, however, it is first important to measure the frequency with which chromosome rearrangements are induced by CRISPR/Cas9 multiplexing. To do this, we have developed a self-selecting screening system using a Drosophila line that carries an autosomal pericentric inversion in what is known as the autosynaptic form. All progeny of normal females crossed to males of this autosynaptic stock are lethal due to excessive aneuploidy. If an inversion is induced within the female germline, and if it is analogous to the inversion in the male autosynaptic line, then it is possible to recover progeny in which aneuploidy is reduced and viability is restored. Using this self-selection method, we screened 130 females and recovered one new autosynaptic element. Salivary gland polytene chromosome analysis, PCR, and sequencing confirmed the recovery of a breakpoint induced precisely between the two sgRNA target sites. Overall, we demonstrate that CRISPR/Cas9 multiplexing can induce chromosomal rearrangements in Drosophila. Also, in using this particular system, the recovery of chromosomal rearrangements was not a high frequency event.
Distinct DNA metabolism and anti-proliferative effects of goat urine metabolites: An explanation for xeno-tumor heterogeneity
Authors: Kumar Ajay , Swami Swati , Sharma Nilesh Kumar
Published: October 2019

Background

The tumor microenvironment, including microbiome populations in the local niche of several types of solid tumors like mammary and colorectal cancer are distinct. The occurrence of one type of cancer over another varies from animals to human individuals. Further, clinical data suggest that specific cancer types such as mammary and colorectal cancer are rare in ruminant like goat.

Methods

Fresh urine samples were collected from healthy ruminates including cow, goat, buffalo, ox, horse, jenny and human and subjected to fractionation using drying, vortexing, centrifugation and sterile filtration in DMSO solvent. Collected urine DMSO fraction (UDF) samples from all sources were subjected DNA metabolizing assay with plasmid DNA pBR322 and genomic DNA of MCF-7 cells. Further, based on the discernible DNA metabolizing effects, goat UDF was tested for anti-proliferative effects upon HCT-116 and MCF-7 cells using Trypan blue due exclusion assay.

Results

This paper reports that goat UDF possesses very clear DNA metabolizing effects (up to 95%) upon plasmid and genomic DNA compared to other ruminants and human UDF samples. Interestingly autoclaving of goat UDF and other sample results in the significant loss of DNA metabolizing effects. In this way, data potentially indicate that the goat UDF sample contains metabolite or similar organic compounds. Further, in vitro treatment of the goat UDF sample shows discernible anti-proliferative effects upon HCT-116 (up to 75%) and MCF-7 (up to 40%).

Conclusion

This study signifies the clear differences in DNA metabolizing effects of goat UDF and well correlated with anti-proliferative effects upon HCT-116 and MCF-7 cells. This study is of first report to show the comparison of urine metabolites and an indirect link to support the possible reasons behind xeno-tumor heterogeneity as rare occurrences of colorectal and mammary cancer in goat over other ruminants and human.
Dysbiosis in a canine model of human fistulizing Crohn’s disease
Authors: Maldonado-Contreras Ana , Ferrer Lluís , Cawley Caitlin , Crain Sarah , Toscano Juan , Ward Doyle V. , Hoffman Andrew
Published: October 2019

Background

Crohn’s disease (CD) is a chronic immune-mediated inflammatory condition caused by the loss of mucosal tolerance towards the commensal microbiota. Approximately 70% of CD patients experience perianal complications. Perianal fistulizing is a predictor of poor long-term outcomes. Animal models of gut inflammation have failed to fully recapitulate the human manifestations of fistulizing CD. Here, we evaluated dogs with spontaneous canine anal furunculosis (CAF), a disease with clinical similarities to fistulizing CD, as a surrogate model for human fistulizing CD.

Results

By comparing the gut microbiomes between dogs suffering from CAF (CAF dogs) and healthy dogs, we show that similar to microbiome population trends in CD humans, CAF dogs microbiomes are either very dissimilar (dysbiotic) or similar, yet unique, to healthy dog’s microbiomes. Compared to healthy or healthy-like CAF microbiomes, dysbiotic CAF microbiomes showed an increased abundance ofBacteroides vulgatusandEscherichia coliand a decreased abundance ofMegamonasspecies andPrevotella copri. These same determinant bacteria are associated with human CD.

Conclusions

Our results highlight the similarities in microbiome community patterns between CAF dogs and CD humans, including overlapping determinant bacterial taxa, and support the use of CAF dogs as a surrogate model to study human fistulizing CD.
Heritability and family-based GWAS analyses of the N-acyl ethanolamine and ceramide plasma lipidome
Authors: McGurk Kathryn A. , Williams Simon G. , Guo Hui , Watkins Hugh , Farrall Martin , Cordell Heather J. , Nicolaou Anna , Keavney Bernard D.
Published: October 2019

Signalling lipids of the N-acyl ethanolamine (NAE) and ceramide (CER) classes are emerging as novel cardiovascular disease biomarkers. We sought to establish the heritability of plasma NAEs (including the endocannabinoid anandamide) and CERs, and identify common DNA variants influencing the circulating concentrations of the heritable lipid species. Nine NAE and sixteen CER species were analysed in plasma samples from 999 members of 196 British Caucasian families, using targeted mass spectrometry (UPLC-MS/MS). Heritability was estimated and GWAS analyses were undertaken; all target lipids were significantly heritable (h2 = 36%-62%). A missense variant (rs324420) in the gene encoding the enzyme fatty acid amide hydrolase (FAAH), which degrades NAEs, associated at GWAS significance (P<2.15×10−8) with four NAEs (DHEA, PEA, LEA, VEA). The A allele of this SNP was associated with a 0.23 SD per-allele increase in plasma NAE species. Additionally, we found association between rs680379 in the SPTLC3 gene, which encodes a subunit of the rate limiting enzyme in CER biosynthesis, and a range of CER species (e.g. CER[N(24)S(19)]; P =4.82×10−27). We also observed three novel associations (CD83, SGPP1, FBXO28-DEGS1) influencing plasma CER traits, two of which (SGPP1 and DEGS1) implicate CER species in haematological phenotypes. NAE and CER are substantially heritable bioactive lipids, influenced by SNPs in key metabolic enzymes.
Novel PDGFRB rearrangement in multifocal infantile myofibromatosis is tumorigenic and sensitive to imatinib
Authors: Hassan Mohammed , Butler Erin , Wilson Raphael , Roy Angshumoy , Zheng Yanbin , Liem Priscilla , Rakheja Dinesh , Pavlick Dean , Young Lauren L. , Rosenzweig Mark , Erlich Rachel , Ali Siraj M. , Leavey Patrick J. , Parsons D. Williams , Skapek Stephen X. , Laetsch Theodore W.
Published: October 2019

Infantile myofibromatosis (IM) is an aggressive neoplasm composed of myofibroblast-like cells in children. Although typically localized, it can also present as multifocal disease, which represents a challenge for effective treatment. IM has previously been linked to activating somatic and germline point mutations in the PDGFRβ tyrosine kinase encoded by the PDGFRB gene. Clinical panel-based targeted tumor sequencing of a tumor from a newborn with multifocal IM revealed a novel PDGFRB rearrangement, which was reported as being of unclear significance. Additional sequencing of cDNA from tumor and germline DNA confirmed a complex somatic/mosaic PDGFRB rearrangement with an apparent partial tandem duplication disrupting the juxtamembrane domain. Ectopic expression of cDNA encoding the mutant form of PDGFRB markedly enhanced cell proliferation of mouse embryo fibroblasts (MEFs) compared to wild-type PDGFRB and conferred tumor-forming capacity on nontumorigenic 10T1/2 fibroblasts. The mutated protein enhanced MAPK activation and retained sensitivity to the PDGFRβ inhibitor imatinib. Our findings reveal a new mechanism by which PDGFRB can be activated in IM, suggest that therapy with tyrosine kinase inhibitors including imatinib may be beneficial, and raise the possibility that this receptor tyrosine kinase might be altered in a similar fashion in additional cases that would similarly present annotation challenges in clinical DNA sequencing analysis pipelines.
The persistent effect of socioeconomic status on education and labor market outcomes
Authors: Correa Juan A. , Gutiérrez Pablo , Lorca Miguel , Morales Raúl , Parro Francisco
Published: October 2019

Purpose

This paper aims to study the effect of family socioeconomic status (SES) on academic and labor market outcomes.

Design/methodology/approach

The authors used a rich data set of administrative records for test scores, individual background and adult earnings of a cohort of agents, covering a period spanning the agents' upper-secondary education and their early years in the labor market.

Findings

The authors find that students with the highest SES obtained a 1.5 standard deviations higher score in the college admission test than students who had the same academic outcomes in the eighth grade test but belong to the lowest SES. Similarly, among students that obtained the same scores in the college admission test, those with the highest SES earned monthly wages 0.7 standard deviations higher than those with the lowest SES.

Originality/value

The findings highlight that family socioeconomic background continues to influence outcomes during individuals’ upper secondary education and early years in the labor market.
Geospatial data in the UK
Authors: Jozefowicz Suzanne , Stone Merlin , Aravopoulou Eleni
Published: October 2019

Purpose

The purpose of this paper is to explain the rise of geospatial data, its importance for business and some of the problems associated with its development and use.

Design/methodology/approach

The paper reviews a certain amount of previously published literature but is based mainly on analysis of the very large number of responses to a consultation paper on geospatial data published by the UK Government.

Findings

The findings are that while there is strong appreciation of the potential benefits of using geospatial data, there are many barriers to the development, sharing and use of geospatial data, ranging from problems of incompatibility in data definitions and systems to regulatory issues. The implication for governments and for providers and users of geospatial data relates to the need to take a long-term approach to planning in resolving the issues identified.

Research limitations/implications

The research findings are limited to the UK, but similar findings would be likely in any other large Western country.

Practical implications

This paper confirms the need for a strong and coherent approach to the planning of geospatial data and systems for the establishment of a clear basis for the different parties to work together and the need to clearly separate the roles of the government in establishing frameworks and standards and the role of the private sector in developing applications and solutions.

Social implications

Society is increasingly dependent on the use of geospatial data, in improving living standards and dealing with social problems. The recommendations identified in this paper, if followed, will facilitate these improvements.

Originality/value

The value of this paper is the tight synthesis that it provides of a wide ranging and complex range of responses to the UK Government consultation and placing these responses in the wider context of the development of geospatial data.