bluuebunny/crossref_metadata_2025 huggingface dataset:
Transdiagnostic validity of the MATRICS Consensus Cognitive Battery across the autism-schizophrenia spectrum
Authors: Kuo Susan S. , Wojtalik Jessica A. , Mesholam-Gately Raquelle I. , Keshavan Matcheri S. , Eack Shaun M.
Published: July 2019

Background

Autism Spectrum Disorder (ASD) and schizophrenia are neurodevelopmental disorders which share substantial overlap in cognitive deficits during adulthood. However, treatment evaluation in ASD and treatment comparisons across ASD and schizophrenia are limited by a dearth of empirical work establishing the validity of a standard cognitive battery across ASD and schizophrenia. Promisingly, the MATRICS Consensus Cognitive Battery (MCCB) has been validated in schizophrenia and encompasses cognitive domains that are impacted in ASD. Thus, this study aimed to establish MCCB's generalizability from schizophrenia to ASD.

Methods

Community-residing adults with schizophrenia (N = 100) and ASD (N = 113) underwent MCCB assessment. Using multigroup confirmatory factor analysis, MCCB's transdiagnostic validity was evaluated by examining whether schizophrenia and ASD demonstrate the same configuration, magnitude, and directionality of relationships within and among measures and their underlying cognitive domains.

Results

Across schizophrenia and ASD, the same subsets of MCCB measures inform three cognitive domains: processing speed, attention/working memory, and learning. Except for group means in category fluency, continuous performance, and spatial span, both groups show vastly comparable factor structures and characteristics.

Conclusions

To our knowledge, this study is the first to establish the validity of a standard cognitive battery in adults with ASD and furthermore the first to establish a cognitive battery's comparability across ASD and schizophrenia. Cognitive domain scores can be compared across new samples using weighted sums of MCCB scores resulting from this study. These findings highlight MCCB's applicability to ASD and support its utility for standardizing treatment evaluation of cognitive outcomes across the autism-schizophrenia spectrum.
Who will benefit from computerized cognitive remediation therapy? Evidence from a multisite randomized controlled study in schizophrenia
Authors: Tan Shuping , Zhu Xiaolin , Fan Hongzhen , Tan Yunlong , Yang Fude , Wang Zhiren , Zhao Yanli , Fan Fengmei , Guo Junhua , Li Zhanjiang , Quan Wenxiang , Wang Xiangqun , Reeder Clare , Zhou Dongfeng , Zou Yizhuang , Wykes Til
Published: July 2019

Background

Computerized cognitive remediation therapy (CCRT) is generally effective for the cognitive deficits of schizophrenia. However, there is much uncertainty about what factors mediate or moderate effectiveness and are therefore important to personalize treatment and boost its effects.

Method

In total, 311 Chinese inpatients with Diagnostic and Statistical Manual of Mental Disorders-IV schizophrenia were randomized to receive CCRT or Active control for 12 weeks with four to five sessions per week. All participants were assessed at baseline, post-treatment and 3-month follow-up. The outcomes were cognition, clinical symptoms and functional outcomes.

Results

There was a significant benefit in the MATRICS Consensus Cognitive Battery (MCCB) total score for CCRT (F1,258 = 5.62; p = 0.02; effect size was 0.27, 95% confidence interval 0.04–0.49). There were no specific moderators of CCRT improvements. However, across both groups, Wisconsin Card Sort Test improvement mediated a positive effect on functional capacity and Digit Span benefit mediated decreases in positive symptoms. In exploratory analyses younger and older participants showed cognitive improvements but on different tests (younger on Symbol Coding Test, while older on the Spatial Span Test). Only the older age group showed MSCEIT benefits at post-treatment. In addition, cognition at baseline negatively correlated with cognitive improvement and those whose MCCB baseline total score was around 31 seem to derive the most benefit.

Conclusions

CCRT can improve the cognitive function of patients with schizophrenia. Changes in cognitive outcomes also contributed to improvements in functional outcomes either directly or solely in the context of CCRT. Age and the basic cognitive level of the participants seem to affect the cognitive benefits from CCRT.
Minimum Base Disturbance Control of Free-Floating Space Robot during Visual Servoing Pre-capturing Process
Authors: Zhao Xiaoyu , Xie Zongwu , Yang Haitao , Liu Jiarui
Published: July 2019

During visual servoing space activities, the attitude of free-floating space robot may be disturbed due to dynamics coupling between the satellite base and the manipulator. And the disturbance may cause communication interruption between space robot and control center on earth. However, it often happens that the redundancy of manipulator is not enough to fully eliminate this disturbance. In this paper, a method named off-line optimizing visual servoing algorithm is innovatively proposed to minimize the base disturbance during the visual servoing process where the degrees-of-freedom of the manipulator is not enough for a zero-reaction control. Based on the characteristic of visual servoing process and the robot system modeling, the optimal control method is applied to achieve the optimization, and a pose planning method is presented to achieve a second-order continuity of quaternion getting rid of the interruption caused by ambiguity. Then simulations are carried out to verify the method, and the results show that the robot is controlled with optimized results during visual servoing process and the joint trajectories are smooth.
Learning music theory en passant: a study in an internationally recognised South African University student choir
Authors: Barrett Michael , Page-Shipp Roy , van Niekerk Caroline , Ferreira Johan
Published: July 2019

While mastery of aspects of music theory is relevant to rapid learning and understanding of a new choral part, many choirs comprise members with no formal education in music theory. Also, the language of music theory is not intuitive, with many terms having meanings different from those in common use, which can present obstacles for mature learners. The authors hypothesised that students joining an internationally recognised university choir might master aspects of music theory as a by-product of rehearsals. This was tested by having new admissions to such a choir complete a music theory test at the commencement and at the end of a year. The test evaluated the ability to name and write intervals and name notes and the duration of notes. Overall results did not reject the hypothesis. Subjects with no formal music training also showed most, and statistically significant, improvement in the questions related to intervals, which are arguably the most useful skills for choristers who do not sight-read. This appears to be a new finding: the literature shows occasional references to music theory skills, but their acquisition in a learning-by-doing style is not reported. Some insights into ways of enhancing choral performance are a by-product of the principal focus of the study.
Explaining diversity patterns in dark waters – a study of aquatic caves in Yucatán, Mexico
Authors: Hendus Barbara , Medina-González Róger , Sélem-Salas Celia , Vanschoenwinkel Bram
Published: July 2019

In the tropics, limestone caves in karstic areas are known for their unique biodiversity. However, many caves remain unstudied and little is known about underlying gradients that determine diversity and biomass in aquatic microhabitats. Here, we sampled zooplankton and benthos in a set of 12 aquatic caves, locally called closed cenotes in Yucatán, Mexico. Our aim was to explain diversity patterns and differences in biomass with particular attention for correlations between bat colony characteristics and other biota. Compared with caves that support photosynthesis, diversity was low with an average of four planktonic and two benthic species in these dark caves. Undetectable phosphorus concentrations in the water suggest this nutrient is limiting. Several associations hint at a potential link between bat abundance and functional guild composition, water quality and aquatic biota. As such, more bats were linked to higher nitrate concentrations. Yet this was not translated to higher invertebrate biomass, probably since phosphorus is limiting. Overall, the trends found in this survey suggest that bats could be important as fertilizers of the caves although mechanistic links that mediate the flux of nutrients need to be confirmed experimentally.
Method and Dialogue in History and Originalism
Authors: Sawyer Logan Everett
Published: July 2019

There is a sharp separation between the scholarly literature of originalists and professional historians. Originalists cite one another, but regularly ignore recent work by historians. Historians are generally happy to return the favor. Engagement between the two communities is too often limited to methodological disputes and amicus briefs. As a result, historical inquiry offers less to constitutional law than it might, and constitutional lawyers offer less to history than they could. Some of this separation is due to unavoidable methodological tension, but those tensions have not always frustrated productive dialogue. Originalism, in fact, emerged as an important theory of constitutional interpretation because of developments in professional historiography. Post-Revisionist approaches to the historiography of Reconstruction inspired and legitimated the book that set originalism on its current trajectory: Raoul Berger's Government by Judiciary. The revolution in the historiography of the founding embodied in Gordon Wood's Creation of the American Republic offered originalists other opportunities. It was not methodological disagreements but technological, institutional, and disciplinary developments since the 1980s that separated history and originalism. Those trends have mostly accelerated in the twenty-first century, but the role historians played in creating originalism suggests opportunities for productive dialogue still exist and should be pursued.
Syndemic effects of HIV risk behaviours: results from the NHANES study
Authors: Smith L. , Cao C. , Zong X. , McDermott D. T. , Stefanac S. , Haider S. , Jackson S. E. , Veronese N. , López-Sánchez G. F. , Koyanagi A. , Yang L. , Grabovac I.
Published: July 2019

The aim of the present study is to use the syndemic framework to investigate the risk of contracting HIV in the US population. Cross-sectional analyses are from The National Health and Nutrition Examination Survey. We extracted and aggregated data on HIV antibody test, socio-demographic characteristics, alcohol use, drug use, depression, sexual behaviours and sexually transmitted diseases from cycle 2009–2010 to 2015–2016. We carried out weighted regression among young adults (20–39 years) and adults (40–59 years) separately. In total, 5230 men and 5794 women aged 20–59 years were included in the present analyses. In total, 0.8% men and 0.2% women were tested HIV-positive. Each increasing HIV risk behaviour was associated with elevated odds of being tested HIV-positive (1.15, 95% CI 1.15–1.15) among young adults and adults (1.61, 95% CI 1.61–1.61). Multi-faceted, community-based interventions are urgently required to reduce the incidence of HIV in the USA.
Precision QALYs, Precisely Unjust
Authors: FLECK LEONARD M.
Published: July 2019

Warwick Heale has recently defended the notion of individualized and personalized Quality-Adjusted Life Years (QALYs) in connection with health care resource allocation decisions. Ordinarily, QALYs are used to make allocation decisions at the population level. If a health care intervention costs £100,000 and generally yields only two years of survival, the cost per QALY gained will be £50,000, far in excess of the £30,000 limit per QALY judged an acceptable use of resources within the National Health Service in the United Kingdom. However, if we know with medical certainty that a patient will gain four extra years of life from that intervention, the cost per QALY will be £25,000. Heale argues fairness and social utility require such a patient to receive that treatment, even though all others in the cohort of that patient might be denied that treatment (and lose two years of potential life). Likewise, Heale argues that personal commitments of an individual (religious or otherwise), that determine how they value a life-year with some medical intervention, ought to be used to determine the value of a QALY for them. I argue that if Heale’s proposals were put into practice, the result would often be greater injustice. In brief, requirements for the just allocation of health care resources are more complex than pure cost-effectiveness analysis would allow.
Urban Bioethics: A Call for the Prestige
Authors: JOHNSON NIA , WAHLERT LANCE
Published: July 2019

Many teaching hospitals in the United States were founded on philanthropic principles and aimed to aid the urban poor and underserved. However, as times have changed, there has been a divide created between the urban poor and teaching hospitals. There is a plethora of reasons why this is the case. This paper will specifically focus on the histories of ten hospitals and medical schools and the effect that white flight, segregation, elitism, and marginalization had on healthcare institutions all over the United States. It will call for a reexamination of the values of Ivy League and Ivy Plus teaching hospitals and medical schools and for them to take an intentional look into their communities.
A single centre experience with an evolving approach for the repair of coarctation of the aorta
Authors: Costopoulos Kelly , Philip Joseph , Lopez-Colon Dalia , Kaliki Giridhar , Chandran Arun , Bleiweis Mark
Published: July 2019

Background:

Isolated coarctation of the aorta can be repaired by either lateral thoracotomy or sternotomy approach with end-to-end anastomosis. Most commonly, neonates with coarctation of the aorta also have hypoplasia of the arch, requiring median sternotomy and extended end-to-side anastomosis with arch augmentation. The aim of this study was to describe our experience as the institution adopted the median sternotomy approach for repair, by reviewing complications, mortality, and reintervention.

Methods:

Retrospective chart review of 66 patients aged 0–1 year who had arch repair performed by a single surgeon over an 8-year period was performed. Median age at surgery was 22 days (4–232) and median weight was 3.08 kg (1.25–8.0). Forty-one (62%) patients underwent median sternotomy.

Results:

There was 1 death from a noncardiac cause. Eighteen per cent of our patients were ≤2.5 kg. Vocal cord paresis occurred in 16% of patients under 2.5 kg and 9.5% of patients 2.5 kg or above at the time of surgery. Hypertension at 6-month follow-up was greater in patients under 2.5 kg (44%) than patients 2.5 kg or above (15%). Total surgical reintervention rate was 6%. For patients above 2.5 kg, the surgical reintervention rate was 5.4% and for patients below 2.5 kg, the surgical reintervention rate was 8.3%.

Conclusion:

We concluded that for neonates with coarctation of the aorta and hypoplastic arch, median sternotomy is a safe surgical approach with low morbidity and mortality with the possible advantage of reduced surgical re-intervention and mortality in the population below 2.5 kg.
Comparative Review on the Cost-Effectiveness Analysis of Relief Teams’ Deployment to Sudden-Onset Disasters
Authors: Bartolucci Andrea , Walter Darren , Redmond Tony
Published: July 2019

When a disaster exceeds the capacity of the affected country to cope with its own resources, the provision of external rescue and health services is required, and the deployment of relief units requested. Recently, the cost of international relief and the belief that such deployment is cost-effective has been questioned by the international community; unfortunately, there is still little informed debate and few detailed data are available. This paper presents the results of a comparative review on the cost-effectiveness analysis (CEA) of search and rescue (SAR) and Emergency Medical Team (EMT) deployment. The aim of this work is to provide an overview of the topic, highlight the criteria used to assess the effectiveness, and identify gaps in existing literature. The results show that both deployments are highly expensive, and their success is strongly related to the time they need to be operational; SAR deployments are characterized by limited outcomes in terms of lives saved, and EMTs by insufficient data and lack of detailed assessment. This research highlights that the criteria used to assess the effectiveness need to be explored further, considering different purposes, lengths of stay, and different activities performed, especially for any comparison. This study concludes that data reporting should be mandatory for humanitarian response agencies.
A graphical model approach to simulating economic variables over long horizons
Authors: Oberoi Jaideep S. , Pittea Aniketh , Tapadar Pradip
Published: July 2019

We present an application of statistical graphical models to simulate economic variables for the purpose of risk calculations over long time horizons. We show that this approach is relatively easy to implement, and argue that it is appealing because of the transparent yet flexible means of achieving dimension reduction when many variables must be modelled. Using the United Kingdom data as an example, we demonstrate the development of an economic scenario generator that can be used by life insurance companies and pension funds.We compare different algorithms to select a graphical model, based on p-values, AIC, BIC and deviance. We find the economic scenario generator to yield reasonable results and relatively stable structures in our example, suggesting that it would be beneficial for actuaries to include graphical models in their toolkit.
EFFECTIVE INSEPARABILITY, LATTICES, AND PREORDERING RELATIONS
Authors: ANDREWS URI , SORBI ANDREA
Published: July 2019

We study effectively inseparable (abbreviated as e.i.) prelattices (i.e., structures of the form$L = \langle \omega , \wedge , \vee ,0,1,{ \le _L}\rangle$whereωdenotes the set of natural numbers and the following four conditions hold: (1)$\wedge , \vee$are binary computable operations; (2)${ \le _L}$is a computably enumerable preordering relation, with$0{ \le _L}x{ \le _L}1$for everyx; (3) the equivalence relation${ \equiv _L}$originated by${ \le _L}$is a congruence onLsuch that the corresponding quotient structure is a nontrivial bounded lattice; (4) the${ \equiv _L}$-equivalence classes of 0 and 1 form an effectively inseparable pair of sets). Solving a problem in (Montagna & Sorbi, 1985) we show (Theorem 4.2), that ifLis an e.i. prelattice then${ \le _L}$is universal with respect to all c.e. preordering relations, i.e., for every c.e. preordering relationRthere exists a computable functionfreducingRto${ \le _L}$, i.e.,$xRy$if and only if$f\left( x \right){ \le _L}f\left( y \right)$, for all$x,y$. In fact (Corollary 5.3)${ \le _L}$is locally universal, i.e., for every pair$a{ < _L}b$and every c.e. preordering relationRone can find a reducing functionffromRto${ \le _L}$such that the range offis contained in the interval$\left\{ {x:a{ \le _L}x{ \le _L}b} \right\}$. Also (Theorem 5.7)${ \le _L}$is uniformly dense, i.e., there exists a computable functionfsuch that for every$a,b$if$a{ < _L}b$then$a{ < _L}f\left( {a,b} \right){ < _L}b$, and if$a{ \equiv _L}a\prime$and$b{ \equiv _L}b\prime$then$f\left( {a,b} \right){ \equiv _L}f\left( {a\prime ,b\prime } \right)$. Some consequences and applications of these results are discussed: in particular (Corollary 7.2) for$n \ge 1$the c.e. preordering relation on${{\rm{\Sigma }}_n}$sentences yielded by the relation of provable implication of any c.e. consistent extension of Robinson’s systemRorQis locally universal and uniformly dense; and (Corollary 7.3) the c.e. preordering relation yielded by provable implication of any c.e. consistent extension of Heyting Arithmetic is locally universal and uniformly dense.
DYNAMIC GRADED EPISTEMIC LOGIC
Authors: MA MINGHUI , VAN DITMARSCH HANS
Published: July 2019

Graded epistemic logic is a logic for reasoning about uncertainties. Graded epistemic logic is interpreted on graded models. These models are generalizations of Kripke models. We obtain completeness of some graded epistemic logics. We further develop dynamic extensions of graded epistemic logics, along the framework of dynamic epistemic logic. We give an extension with public announcements, i.e., public events, and an extension with graded event models, a generalization also including nonpublic events. We present complete axiomatizations for both logics.
Evaluation of auxin tolerance in selected tomato germplasm under greenhouse and field conditions
Authors: Zangoueinejad Rouzbeh , Alebrahim Mohammad Taghi , Tseng Te Ming
Published: July 2019

Tomato is injured by low doses of 2,4-D, dicamba, quinclorac, and glyphosate. New crop varieties resistant to 2,4-D and dicamba are likely to increase use of these herbicides and may increase drift problems. There is a diverse germplasm of tomato available that includes wild relatives known to be tolerant to numerous biotic and abiotic stresses. A greenhouse and field study was conducted to investigate auxin tolerance in three wild tomato accessions (TOM199, TOM198, and TOM300) and compare them with two commercial tomato cultivars (‘Money Maker’ and ‘Better Boy’). Auxin herbicides, which included 2,4-D, dicamba, and quinclorac, were applied at doses of 11, 3, and 39 g ae ha−1, respectively. Visible injury ratings of each accession for each herbicide treatment were recorded at 7, 14, 21, and 28 d after treatment (DAT) on a 0% to 100% scale. Results indicate that all three wild tomato accessions exhibited less than 15% injury compared with 100% injury for two commercial cultivars after application of dicamba. The three wild accessions (TOM199, TOM198, and TOM300) did not show any significant reduction in plant height compared with nontreated plants. At 28 DAT, plant heights of TOM199, TOM198, and TOM300 were 25, 25, and 28 cm when treated with dicamba and 31, 30, and 31 cm nontreated, respectively. Based on these results, the identified lines can serve as a genetic resource for developing herbicide-tolerant tomato, thus minimizing or eliminating the negative impacts of drift from nonlabeled herbicides tested in this project.
Protoporphyrinogen oxidase (PPO) inhibitor–resistant waterhemp (Amaranthus tuberculatus) from Nebraska is multiple herbicide resistant: confirmation, mechanism of resistance, and management
Authors: Sarangi Debalin , Stephens Trey , Barker Abigail L. , Patterson Eric L. , Gaines Todd A. , Jhala Amit J.
Published: July 2019

A waterhemp [Amaranthus tuberculatus(Moq.) J. D. Sauer] biotype (designated as “NER”) collected from a soybean [Glycine max(L.) Merr.] production field in eastern Nebraska survived the POST application of fomesafen at the labeled rate. The objectives of this study were to (1) quantify the level of resistance to protoporphyrinogen oxidase (PPO) inhibitors (acifluorfen, fomesafen, and lactofen) applied POST, (2) determine the mechanism of PPO-inhibitor resistance in the NER biotype, (3) determine whether NER possessed multiple resistance to acetolactate synthase (ALS)-, 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS)-, and photosystem II (PSII)-inhibiting herbicides, and (4) control NER with POST soybean herbicides. A whole-plant dose–response bioassay revealed that the NER biotype was 4- to 6-fold resistant to PPO-inhibiting herbicides depending on the known susceptible biotype (S1 or S2) used for comparison. A Kompetitive Allele Specific PCR (KASP™) assay was developed and performed for rapid and robust detection of the ΔG210 mutation (deletion of a codon) in thePPX2Lgene. All samples of the NER biotype tested positive for the ΔG210 mutation. Dose–response bioassays confirmed that the NER biotype was resistant to three additional herbicide sites of action. Chlorimuron and imazethapyr, both ALS inhibitors, applied at 32X the labeled rate resulted in <80% reduction in the aboveground biomass of the NER biotype. The same biotype was 3- and 7-fold resistant to glyphosate (EPSPS inhibitor) and atrazine (PSII inhibitor), respectively. Glufosinate, 2,4-D choline plus glyphosate, and dicamba were the only soybean POST herbicides that controlled NER effectively (≥92% aboveground biomass reduction).Amaranthus tuberculatusis the first confirmed weed species in Nebraska to evolve resistance to four distinct herbicide sites of action, leaving no POST herbicide choice for effective control in glyphosate-resistant and conventional (non-transgenic) soybean.
Allometric Models to Estimate Leaf Area for Tropical African Broadleaved Forests
Authors: Sirri N. F. , Libalah M. B. , Momo Takoudjou S. , Ploton P. , Medjibe V. , Kamdem N. G. , Mofack G. , Sonké B. , Barbier N.
Published: July 2019

Direct and semidirect estimations of leaf area (LA) and leaf area index (LAI) are scarce in dense tropical forests despite their importance in calibrating remote sensing products, forest dynamics, and biogeochemical models. We destructively sampled 61 trees belonging to 13 most abundant species in a semideciduous forest in southeastern Cameroon. For each tree, all leaves were weighed, and for a subsample of branches, leaves were counted and the LA measured. Allometric models were calibrated to allow semidirect estimation of LAI at tree and stand levels based on forest inventory data (R2 = 0.7, bias = 21.2%, error = 39.5%) and on predictors that could be extracted from very high resolution remote sensing data (R2 = 0.63, bias = 35.1%, error = 58.73). Using twenty‐one 1‐ha forest plots, stand level estimations of LAI ranged from 4.42–13.99. These values are higher than previous estimates generally obtained using indirect methods. These results may have important consequences on ecosystem exchanges and the role of tropical forest in global cycles.
An Approximate Model for Predicting the Specific Yield Under Periodic Water Table Oscillations
Authors: Pozdniakov Sergey P. , Wang Ping , Lekhov Vladimir A.
Published: July 2019

Predicting specific yield for a given aquifer remains a great challenge due to its dynamic characteristics, especially under periodic (e.g., seasonal and diurnal) groundwater level fluctuations. In this study, a dimensionless period of groundwater level fluctuations, which depends on the saturated hydraulic conductivity, the length of the groundwater level fluctuation period, and the soil water retention properties, is first introduced. Then, the relationship between the predicted specific yield and the dimensionless period of groundwater level fluctuations is defined based on the theory of variably saturated flow. The proposed approximate formula is tested by series of simulations of variably saturated flow within homogeneous and isotropic porous media with the Hydrus‐1D program. The results of numerical experiments demonstrate an invariant relationship between the predicted specific yield and the dimensionless period for a wide range of changes in the dimensionless period of groundwater level oscillations. Furthermore, the sensitivity analysis of the dependence of the predicted specific yield on the van Genuchten parameters indicates the applicability of estimating the specific yield via van Genuchten parameters, which can be predicted by the soil texture classes for a given length of the oscillation period and a known saturated hydraulic conductivity in the zone of groundwater level fluctuations. The proposed model can be used for predicting the dynamics of the specific yield under seasonal or diurnal groundwater level fluctuations.
Plant–microbe specificity varies as a function of elevation
Authors: Cobian Gerald M , Egan Cameron P , Amend Anthony S
Published: July 2019

Specialized associations between interacting species fundamentally determine the diversity and distribution of both partners. How the specialization of guilds of organisms varies along environmental gradients underpins popular theories of biogeography and macroecology, whereas the degree of specialization of a species is typically considered fixed. However, the extent to which environmental context impacts specialization dynamics is seldom examined empirically. In this study, we examine how specialization within a bipartite network consisting of three co-occurring plant species and their foliar fungal endophyte symbionts changes along a 1000-meter elevation gradient where host species were held constant. The gradient, along the slope of Mauna Loa shield volcano, represents almost the entire elevational range of two of the three plants. Network and plant specialization values displayed a parabolic relationship with elevation, and were highest at middle elevations, whereas bipartite associations were least specific at low and high elevations. Shannon’s diversity of fungal endophytes correlated negatively with specificity, and was highest at the ends of the transects. Although plant host was a strong determinant of fungal community composition within sites, fungal species turnover was high among sites. There was no evidence of spatial or elevational patterning in fungal community compositon. Our work demonstrates that specificity can be a plastic trait, which is influenced by the environment and centrality of the host within its natural range.
Direct visualization of a molecular handshake that governs kin recognition and tissue formation in myxobacteria
Authors: Cao Pengbo , Wall Daniel
Published: July 2019

Many organisms regulate their social life through kin recognition, but the underlying mechanisms are poorly understood. Here, we use a social bacterium, Myxococcus xanthus, to investigate kin recognition at the molecular level. By direct visualization of a cell surface receptor, TraA, we show how these myxobacteria identify kin and transition towards multicellularity. TraA is fluid on the cell surface, and homotypic interactions between TraA from juxtaposed cells trigger the receptors to coalesce, representing a ‘molecular handshake’. Polymorphisms within TraA govern social recognition such that receptors cluster only between individuals bearing compatible alleles. TraA clusters, which resemble eukaryotic gap junctions, direct the robust exchange of cellular goods that allows heterogeneous populations to transition towards homeostasis. This work provides a conceptual framework for how microbes use a fluid outer membrane receptor to recognize and assemble kin cells into a cooperative multicellular community that resembles a tissue.
Human gut microbiome changes during a 10 week Randomised Control Trial for micronutrient supplementation in children with attention deficit hyperactivity disorder
Authors: Stevens Aaron J. , Purcell Rachel V. , Darling Kathryn A. , Eggleston Matthew J. F. , Kennedy Martin A. , Rucklidge Julia J.
Published: July 2019

It has been widely hypothesized that both diet and the microbiome play a role in the regulation of attention-deficit/hyperactivity disorder (ADHD) behaviour. However, there has been very limited scientific investigation into the potential biological connection. We performed a 10-week pilot study investigating the effects of a broad spectrum micronutrient administration on faecal microbiome content, using 16S rRNA gene sequencing. The study consisted of 17 children (seven in the placebo and ten in the treatment group) between the ages of seven and 12 years, who were diagnosed with ADHD. We found that micronutrient treatment did not drive large-scale changes in composition or structure of the microbiome. However, observed OTUs significantly increased in the treatment group, and showed no mean change in the placebo group. The differential abundance and relative frequency of Actinobacteria significantly decreased post- micronutrient treatment, and this was largely attributed to species from the genus Bifidobacterium. This was compensated by an increase in the relative frequency of species from the genus Collinsella. Further research is required to establish the role that Bifidobacterium contribute towards neuropsychiatric disorders; however, these findings suggest that micronutrient administration could be used as a safe, therapeutic method to modulate Bifidobacterium abundance, which could have potential implications for modulating and regulating ADHD behaviour. Our pilot study provides an initial observation into this area of research, and highlights an interesting avenue for further investigation in a larger cohort. Furthermore, these novel results provide a basis for future research on the biological connection between ADHD, diet and the microbiome.
Regulation of the expression of nine antimicrobial peptide genes by TmIMD confers resistance against Gram-negative bacteria
Authors: Jo Yong Hun , Patnaik Bharat Bhusan , Hwang Jihun , Park Ki Beom , Ko Hye Jin , Kim Chang Eun , Bae Young Min , Jung Woo Jin , Lee Yong Seok , Han Yeon Soo
Published: July 2019

Immune deficiency (IMD) is a death domain-containing protein that is essential for the IMD/NF-κB humoral and epithelial immune responses to Gram-negative bacteria and viruses in insects. In the immune signaling cascade, IMD is recruited together with FADD and the caspase DREDD after the mobilization of PGRP receptors. Activated IMD regulates the expression of effector antimicrobial peptides (AMP) that protect against invading microorganisms. To date, most studies of the IMD pathway, and the IMD gene in particular, have been restricted to Drosophila; few similar studies have been conducted in other model insects. Herein, we cloned and functionally characterized an IMD homolog from the mealworm beetle Tenebrio molitor (TmIMD) and studied its role in host survival in the context of pathogenic infections. Phylogenetic analysis revealed the conserved caspase cleavage site and inhibitor of apoptosis (IAP)-binding motif (IBM). TmIMD expression was high in the hemocytes and Malpighian tubules of Tenebrio late-instar larvae and adults. At 3 and 6 hours’ post-infection with Escherichia coli, Staphylococcus aureus, or Candida albicans, TmIMD expression significantly increased compared with mock-infected controls. Knockdown of the TmIMD transcript by RNAi significantly reduced host resistance to the Gram-negative bacterium E. coli and fungus C. albicans in a survival assay. Strikingly, the expression of nine T. molitor AMPs (TmTenecin1, TmTenecin2, TmTenecin4, TmDefensin2, TmColeoptericin1, TmColeoptericin2, TmAttacin1a, TmAttacin1b, and TmAttacin2) showed significant downregulation in TmIMD knockdown larvae challenged with E. coli. These results suggest that TmIMD is required to confer humoral immunity against the Gram-negative bacteria, E. coli by inducing the expression of critical transcripts that encode AMPs.
Impact of coxsackievirus-B4E2 combined with a single low dose of streptozotocin on pancreas of outbred mice: investigation of viral load, pathology and inflammation
Authors: Benkahla Mehdi A. , Sane Famara , Bertin Antoine , Vreulx Anais-Camille , Elmastour Firas , Jaidane Hela , Desailloud Rachel , Hober Didier
Published: July 2019

Coxsackieviruses B (CV-B) belong to the EV-B species. CV-B and particularly CV-B4 are thought to be involved in the development of chronic diseases like type 1 diabetes (T1D). The mechanisms of the enteroviral pathogenesis of T1D are not well known, yet. The in vitro studies are rich with information but in vivo infection models are needed to investigate the impact of viruses onto organs. Our objective was to study the impact of CV-B4E2 combined with a single sub-diabetogenic dose of streptozotocin (STZ) on the pancreas of mice. The infection with CV-B4E2 of CD1 outbred mice treated with a sub-diabetogenic dose of STZ induced hyperglycemia and hypoinsulinemia. Along with the chemokine IP-10, viral RNA and infectious particles were detected in the pancreas. The pancreas of these animals was also marked with insulitis and other histological alterations. The model combining STZ and CV-B4E2 opens the door to new perspectives to better understand the interactions between virus and host, and the role of environmental factors capable, like STZ, to predispose the host to the diabetogenic effects of enteroviruses.
Late Eocene onset of the Proto-Antarctic Circumpolar Current
Authors: Sarkar Sudipta , Basak Chandranath , Frank Martin , Berndt Christian , Huuse Mads , Badhani Shray , Bialas Joerg
Published: July 2019

The formation of the Antarctic Circumpolar Current (ACC) is critical for the evolution of the global climate, but the timing of its onset is not well constrained. Here, we present new seismic evidence of widespread Late Eocene to Oligocene marine diagenetic chert in sedimentary drift deposits east of New Zealand indicating prolonged periods of blooms of siliceous microorganisms starting ~36 million years ago (Ma). These major blooms reflect the initiation of the arrival and upwelling of northern-sourced, nutrient-rich deep equatorial Pacific waters at the high latitudes of the South Pacific. We show that this change in circulation was linked to the initiation of a proto-ACC, which occurred ~6 Ma earlier than the currently estimated onset of the ACC at 30 Ma. We propose that the associated increased primary productivity and carbon burial facilitated atmospheric carbon dioxide reduction contributing to the expansion of Antarctic Ice Sheet at the Eocene-Oligocene Transition.
Evaluation of in silico designed inhibitors targeting MelF (Rv1936) against Mycobacterium marinum within macrophages
Authors: Dharra Renu , Radhakrishnan V. S. , Prasad Tulika , Thakur Zoozeal , Cirillo Jeffrey D. , Sheoran Abhishek , Pandey Amit K. , Kulharia Mahesh , Mehta Promod K.
Published: July 2019

We recently identified inhibitors targeting Mycobacterium marinum MelF (Rv1936) by in silico analysis, which exhibited bacteriostatic/bactericidal activity against M. marinum and M. tuberculosis in vitro. Herein, we evaluated the effect of best four inhibitors (# 5175552, # 6513745, # 5255829, # 9125618) obtained from the ChemBridge compound libraries, on intracellular replication and persistence of bacteria within IFN-γ activated murine RAW264.7 and human THP-1 macrophages infected with M. marinum. Inhibitors # 5175552 and # 6513745 significantly reduced (p < 0.05) the intracellular replication of bacilli during day 7 post-infection (p.i.) within RAW264.7 and THP-1 macrophages infected at multiplicity of infection (MOI) of ~1.0. These observations were substantiated by electron microscopy, which revealed the protective effect of # 5175552 in clearing the bacilli inside murine macrophages. Strikingly, # 6513745 displayed synergism with isoniazid against M. marinum in murine macrophages, whereas # 5175552 significantly suppressed (p < 0.05) the persistent bacilli during day 10–14 p.i. in infected RAW264.7 and THP-1 macrophages (MOI of ~ 0.1). Moreover, # 5175552 and # 6513745 were non-cytotoxic to host macrophages at both 1X and 5X MIC. Further validation of these inhibitors against M. tuberculosis-infected macrophages and animal models has potential for development as novel anti-tubercular agents.
Generating kinetic environments to study dynamic cellular processes in single cells
Authors: Thiemicke Alexander , Jashnsaz Hossein , Li Guoliang , Neuert Gregor
Published: July 2019

Cells of any organism are consistently exposed to changes over time in their environment. The kinetics by which these changes occur are critical for the cellular response and fate decision. It is therefore important to control the temporal changes of extracellular stimuli precisely to understand biological mechanisms in a quantitative manner. Most current cell culture and biochemical studies focus on instant changes in the environment and therefore neglect the importance of kinetic environments. To address these shortcomings, we developed two experimental methodologies to precisely control the environment of single cells. These methodologies are compatible with standard biochemistry, molecular, cell and quantitative biology assays. We demonstrate applicability by obtaining time series and time point measurements in both live and fixed cells. We demonstrate the feasibility of the methodology in yeast and mammalian cell culture in combination with widely used assays such as flow cytometry, time-lapse microscopy and single-molecule RNA Fluorescentin-situHybridization (smFISH). Our experimental methodologies are easy to implement in most laboratory settings and allows the study of kinetic environments in a wide range of assays and different cell culture conditions.
The association between childbirth, breastfeeding, and uterine fibroids: an observational study
Authors: Delli Carpini Giovanni , Morini Stefano , Papiccio Maria , Serri Matteo , Damiani Valentina , Grelloni Camilla , Clemente Nicolò , Ciavattini Andrea
Published: July 2019

The aim of this study was to investigate the effect of childbirth and breastfeeding on uterine fibroids and to identify the factors associated with size variations. This was a monocenter observational study carried on women with a sonographic diagnosis of uterine fibroids from January 2007 to December 2016, with no indication for immediate treatment, and who became pregnant within one year from diagnosis. All patients were re-evaluated six months after delivery. Fibroid diameters were compared between pre-pregnancy period, first, second, third trimester and post-delivery. The rate of “regressed” (growth of diameter <−40%), “unchanged” (growth of diameter between −40% and +40%) or “increased” (growth of diameter >+40%) fibroids at the post-delivery evaluation with respect to the pre-pregnancy state was calculated. One-hundred fifty-seven women were included in the final analysis. At the post-delivery ultrasound, a significant reduction of the fibroid diameter with respect to all previous examinations was observed, and there was no evidence of 67 (37.2%) fibroids. Ongoing breastfeeding was positively associated with an “unchanged” or “regressed” fibroid diameter (adOR 3.23, 95%CI: 1.35–7.70, p < 0.01). Smaller pre-gravidic fibroids were more likely to return to pre-pregnancy dimensions or to regress, with a cut-off of 32 mm for lactating women and of 26 mm for non-lactating women. In conclusion, fibroids seem to return to pre-pregnancy dimensions or to regress in the post-partum period. This process may be sustained by uterine involution and hormonal variations, with an additional role of breastfeeding.
Circulating CXCR3+ Tfh cells positively correlate with neutralizing antibody responses in HCV-infected patients
Authors: Zhang Jian , Liu Wenpei , Wen Bo , Xie Ting , Tang Ping , Hu Yabin , Huang Liyan , Jin Kun , Zhang Ping , Liu Ziyan , Niu Ling , Qu Xiaowang
Published: July 2019

Circulating T follicular helper (cTfh) cells have been identified as counterparts of germinal center Tfh (GC Tfh) cells in humans and can support T-dependent B cell maturation and antibody production in vitro. However, the role of cTfh cells in neutralizing antibody (nAb) responses in HCV infection remains unclear. Here, we characterized the phenotype and function of cTfh cells and demonstrated the associations of cTfh cells and their subsets with nAb responses in HCV infection. A total of 38 HCV-infected individuals and 28 healthy controls were enrolled from a pool of injection drug users. The frequency and function of blood Tfh cells were analyzed by flow cytometry. The titers and breadths of serum nAbs were measured using HCV pseudo-particle neutralization assays. Herein, we report several key observations. First, HCV infection skewed cTfh toward CXCR3+ cTfh cell differentiation. Second, the frequency of CXCR3+ cTfh cells positively correlated with HCV nAb titers and breadths. Third, CXCR3+ cTfh cells showed higher expression of Tfh-associated molecules (PD-1, ICOS, IL-21, Bcl-6) compared with CXCR3− cTfh cells from individuals with HCV infection. Coculture of cTfh cells and autologous memory B cells in vitro indicated that CXCR3+ cTfh cells show a superior ability to support HCV E2-specific B cell expansion compared with CXCR3− cTfh cells from individuals with HCV infection. HCV infection skews cTfh cells toward CXCR3-biased Tfh cell differentiation, which positively correlates with the magnitude and breadth of the HCV nAb response. It is our hope that these findings will provide insights for the rational design of a nAb-based HCV vaccine.
Intra-articularly injected mesenchymal stem cells promote cartilage regeneration, but do not permanently engraft in distant organs
Authors: Satué María , Schüler Christiane , Ginner Nikole , Erben Reinhold G.
Published: July 2019

Intra-articular (IA) injection of mesenchymal stem cells (MSCs) promotes articular cartilage repair. However, cell fate and action after transplantation remain unclear. This study aimed at evaluating the biodistribution and efficacy of MSCs after IA injection. We used an immunocompetent, dual transgenic rat model, which is based on donor rats ubiquitously expressing heat stable human placental alkaline phosphatase (ALPP), and recipient rats expressing a heat sensitive ALPP form. A focal cartilage defect was created in the patellofemoral groove of recipient rats. Bone marrow-derived MSCs isolated from donor rats were injected into the synovial cavity of recipients, and cell tracking was performed in distant organs and knees over 6 months post-injection. A few donor MSCs were observed in the lung of one of the recipients, 1 day post-injection. We failed to detect donor MSCs in any of the studied tissues at all later time points. IA-injected MSCs remained in the synovial cavity, engrafted within the cartilage lesion, and were detectable up to 1 month post-injection. Although the number of MSCs decreased over time, MSCs injection promoted cartilage regeneration as evidenced by histology and immunofluorescent collagen staining. Our study supports the safety and efficacy of using MSCs for cartilage repair via IA delivery.
In vivo two-photon microscopy of the human eye
Authors: Ávila Francisco J. , Gambín Adrián , Artal Pablo , Bueno Juan M.
Published: July 2019

Two-photon (2P) microscopy is a powerful tool for imaging and exploring label-free biological tissues at high resolution. Although this type of microscopy has been demonstrated in ex vivo ocular tissues of both humans and animal models, imaging the human eye in vivo has always been challenging. This work presents a novel compact 2P microscope for non-contact imaging of the anterior part of the living human eye. The performance of the instrument was tested and the maximum permissible exposure to protect ocular tissues established. To the best of our knowledge, 2P images of the in vivo human cornea, the sclera and the trabecular meshwork are shown for the very first time. Acquired images are of enough quality to visualize collagen arrangement and morphological features of clinical interest. Future implementations of this technique may constitute a potential tool for early diagnosis of ocular diseases at submicron scale.