bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel Use of Cryopreserved Ultra-thick Human Amniotic Membrane for Management of Anophthalmic Socket Contracture
Authors: Slentz Dane H. , Nelson Christine C.
Published: November 2018

Purpose:

To describe the use of cryopreserved ultra-thick human amniotic membrane for management of anophthalmic socket contracture.

Methods:

A chart review was performed to identify patients undergoing fornix reconstruction with cryopreserved ultra-thick human amniotic membrane for management of anophthalmic socket contracture. Patient demographics, disease etiology, and data regarding postoperative prosthesis fit and complications were collected.

Results:

The technique is described in 3 female patients with anophthalmic socket contracture who underwent fornix reconstruction using cryopreserved ultra-thick human amniotic membrane. All patients had excellent prosthesis fit at final follow up (range, 10–14 months). There were no clinically significant complications and no reoperations were performed. One pyogenic granuloma developed and was excised without affecting ocular prosthesis fit.

Conclusions:

Cryopreserved ultra-thick human amniotic membrane is easy to use, well tolerated, and produces good outcomes for management of anophthalmic socket contracture.
Medial Orbital Wall Reconstruction to Facilitate Endoscopic Sinus Surgery for Erosive Polypoidal Sinus Disease
Authors: Silas Megan R. , Jeffers Johnathan V. , Farooq Asim V. , Corey Jacquelynne P. , Shah Hassan A.
Published: November 2018

The authors report the use of a 0.35-mm-thickness nylon implant for medial orbital wall reconstruction to facilitate functional endoscopic sinus surgery (FESS) for severe erosive polypoidal sinus disease while minimizing iatrogenic injuries to the orbital contents. A retrospective chart review identified 4 patients with extensive polypoidal sinus disease who underwent medial orbital wall reconstruction in the setting of FESS. All patients underwent successful reconstruction of bilateral eroded medial orbital walls using a 0.35-mm Supramid Foil Nylon Implant immediately followed by FESS. There were no permanent complications or iatrogenic injuries to the orbital contents due to FESS. All patients experienced improvement in sinus symptoms. Medial orbital wall reconstruction in the setting of erosive polypoidal sinus disease is a useful tool to help facilitate FESS. It allows the sinus surgeon to clear sinus disease aggressively with the orbits being protected from iatrogenic injury.
Assessing Clinical Utility of Cerebral Oximetry Monitoring During Pediatric Scoliosis Surgery
Authors: Mukuno Kaela , Vacchiano Charles , Funk Emily , Morgan Brett
Published: November 2018

Introduction

High-quality evidence indicates that active cerebral oximetry monitoring during surgery improves patient outcomes in populations at risk for hemodynamic instability. This project piloted the use of a near-infrared spectroscopy (NIRS) monitor in a pediatric surgical population with similar risk factors. Controlled hypotension is an anesthetic technique used to minimize blood loss during pediatric spinal surgery for scoliosis correction. Consensus for safe blood pressure thresholds does not exist, and cerebral oxygenation may be impeded during this anesthetic technique.

Methods

Fifteen pediatric patients scheduled for posterior spinal fusion and scoliosis correction received intraoperative NIRS monitoring. Regional cerebral oxygen saturation (rSO2) and blood pressure data were collected. Possible relationships between mean arterial pressure and rSO2 were also explored. Anesthesia provider feedback regarding device use was obtained via a voluntary survey.

Results

Twenty-four cerebral desaturation events (CDEs) were recorded among four patients (27%) involved in the project. The median CDE duration, nadir rSO2, and percent change from baseline was 3.38 minutes, 69%, and 22.5%, respectively (Interquartile ranges = 8.69, 22, and 22.99). There was no relationship between mean cerebral rSO2 and mean arterial pressure (rs
(25) = −0.194, p = .353).

Discussion

The results support the continued use of NIRS monitoring during pediatric scoliosis surgery. Analysis of individual CDEs reveals that some patients may incur more prolonged and significant CDEs. In addition, cerebral desaturations are difficult to predict using solely blood pressure parameters. Device ease of use, availability, and a high perception of clinical utility among anesthesia providers support adoption of the monitor in this setting.
Shared Decision Making About Starting Anti‐TNFs
Authors: Michel Hilary K. , Noll Robert B. , Siripong Nalyn , Kim Sandra C. , Lipstein Ellen A.
Published: November 2018

Shared decision making (SDM) is central to patient‐centered medicine and has the potential to improve outcomes for pediatric patients with inflammatory bowel diseases. We surveyed specialists about their use of SDM in the decision to start a tumor necrosis factor‐α inhibitor in pediatric patients. Results were compared between those who reported using SDM and those who did not. Of 209 respondents, 157 (75%) reported using SDM. Physician/practice characteristics were similar between users and nonusers. There were no statistically significant differences between groups in the components deemed important to the decision‐making process nor the number of barriers or facilitators to SDM. Exploratory analyses suggested that physicians using SDM were more accepting of adolescent involvement in the decision‐making process. Our results question the effectiveness of using reported barriers and facilitators to guide interventions to improve use of SDM, and suggest further work is needed to understand the adolescent role in decision making.
Interest of Youth Living With HIV in Long-Acting Antiretrovirals
Authors: Weld Ethel D. , Rana Md Sohel , Dallas Ronald H. , Camacho-Gonzalez Andres F. , Ryscavage Patrick , Gaur Aditya H. , Chakraborty Rana , Swindells Susan , Flexner Charles , Agwu Allison L.
Published: November 2018

Objectives:

This study's primary objective was to characterize attitudes to long-acting antiretrovirals (LAARV), among youth aged 13–24 years living with perinatally acquired HIV and nonperinatally acquired HIV. Secondary objectives included: assessing whether those with detectable HIV RNA PCR viral load had higher enthusiasm for LAARV compared to those with suppressed viral load, and examining characteristics associated with LAARV enthusiasm.

Methods:

A cross-sectional survey of 303 youth living with HIV (YHIV) followed at 4 pediatric/adolescent HIV clinics in the United States was performed to determine interest in LAARV, using a modified survey instrument previously used in adults. Interest in LAARV across groups was compared. Poisson regression with robust variance was used to determine the impact of various characteristics on interest in LAARV.

Findings:

Overall, 88% of YHIV reported probable or definite willingness to use LAARV. The enthusiasm level was similar between youth with perinatally acquired HIV and nonperinatally acquired HIV (P = 0.93). Youth with HIV viral load >1000 copies per milliliter had significantly higher interest than youth with suppressed viral load [prevalence ratio 1.12 (95% confidence interval: 1.03 to 1.20); P = 0.005]. Female youth participants who had had past experience with implantable contraceptive methods had a significantly higher interest in LAARV (100% vs. 85.5%; P = 0.002). Proportion of respondents endorsing definite willingness to use was significantly higher with decreased injection frequency compared with increased injection frequency.

Interpretation:

YHIV at 4 urban US pediatric/adolescent HIV clinics had high levels of enthusiasm for LAARV. LAARV should be given high priority as a potentially viable treatment option to improve clinical outcomes in YHIV.
Comparison of Unilateral With Bilateral Metal Stenting for Malignant Hilar Biliary Obstruction
Authors: Teng Fei , Xian Yu-Tao , Lin Jia , Li Yu , Wu An-Le
Published: November 2018

Purpose:

The main purpose of this study was to compare the clinical effectiveness between unilateral and bilateral metal stenting for malignant hilar biliary obstruction (MHBO).

Methods:

From January 2012 to October 2017, consecutive patients with MHBO underwent unilateral or bilateral stent insertion at our center. Technical and clinical success, stent patency, and survival were compared between these 2 groups.

Results:

A total of 110 patients with MHBO were included in this study. Technical successful rates of unilateral and bilateral stenting were 93.1% (54/58) and 90.4% (47/52), respectively (P=0.864). Clinical successful rates of unilateral and bilateral stenting were 96.4% (53/55) and 97.9% (46/47), respectively (P=1.000). There was no significant difference in stent patency period (unilateral, 182 d; bilateral, 198 d; P=0.999) and survival (unilateral, 189 d; bilateral, 199 d; P=0.867) between 2 groups.

Conclusions:

Unilateral and bilateral metal stenting had similar clinical effectiveness and long-term outcomes in patients with MHBO.
Genetic predisposition to hypouricemia on whole-exome sequencing analysis and its utilities in primary screening purposes
Authors: Cha Do Hyeon , Gee Heon Yung , Cachau Raul , Choi Jong Mun , Park Daeui , Jee Sun Ha , Ryu Seungho , Kim Kyeong Kyu , Winkler Cheryl A. , Cho Sung Kweon
Published: November 2018

Differentiating between inherited renal hypouricemia and transient hypouricemia is challenging. Here, we aimed to describe the genetic predisposition of hypouricemia patients using whole-exome sequencing (WES) and assess the feasibility for genetic diagnosis in primary screening. WES was performed for the discovery of diagnostic markers in discovery cohorts (N=31). Two known genetic markers SLC22A12 c.774G>A (p.Trp258*) and SLC22A12 c.269G>A (p.Arg90His) were identified, We genotyped for the 2 SLC22A12 SNPs among screened 50 hypouricemia subjects for the replication cohorts; 47 carried known SLC22A12 markers; three unexplained hypouricemic cases were analyzed by using WES. We used 46 healthy internal controls for the variant discovery. Four novel variants of SLC22A12, c.408C>A (p.Asn136Lys), c.674C>A (p.Thr225Lys), c.851G>A (p.Arg284Gln), and c.1285G>A (p.Glu429Lys), and one novel variant of SLC2A9, c. 376A>G (p.Met155Val), were identified. After filtering out known genes (SLC22A12 and SLC2A9), the p.Arg78His variant in ASB12 was overlapped in two unexplained conditions. This is the first attempt to investigate the effectiveness of integrating exome sequencing and genotype into the clinical care for hypouricemia and determine the value of genetic diagnostic screening for hypouricemia in the clinical setting. Screening of just two SNPs (p.Trp258* and p.Arg90His) identified 87.7% (71/81) of patients with hypouricemia. Early identification and intervention of hypouricemia is feasible using genetic screening to prevent acute kidney injury, especially for soldiers and athletics.
Vec2SPARQL: integrating SPARQL queries and knowledge graph embeddings
Authors: Kulmanov Maxat , Kafkas Senay , Karwath Andreas , Malic Alexander , Gkoutos Georgios V , Dumontier Michel , Hoehndorf Robert
Published: November 2018

Recent developments in machine learning have lead to a rise of large number of methods for extracting features from structured data. The features are represented as a vectors and may encode for some semantic aspects of data. They can be used in a machine learning models for different tasks or to compute similarities between the entities of the data. SPARQL is a query language for structured data originally developed for querying Resource Description Framework (RDF) data. It has been in use for over a decade as a standardized NoSQL query language. Many different tools have been developed to enable data sharing with SPARQL. For example, SPARQL endpoints make your data interoperable and available to the world. SPARQL queries can be executed across multiple endpoints. We have developed a Vec2SPARQL, which is a general framework for integrating structured data and their vector space representations. Vec2SPARQL allows jointly querying vector functions such as computing similarities (cosine, correlations) or classifications with machine learning models within a single SPARQL query. We demonstrate applications of our approach for biomedical and clinical use cases. Our source code is freely available athttps://github.com/bio-ontology-research-group/vec2sparqland we make a Vec2SPARQL endpoint available athttp://sparql.bio2vec.net/.
Capturing Multicellular System Designs Using the Synthetic Biology Open Language (SBOL)
Authors: Brown Bradley , Atallah Christian , McLaughlin James Alastair , Misirli Göksel , Goñi-Moreno Ángel , Roehner Nicholas , Skelton David James , Bartley Bryan , Beal Jacob , Poh Chueh Loo , Ofiteru Irina Dana , Wipat Anil
Published: November 2018

Synthetic biology aims to improve the development of biological systems and in-crease their reproducibility through the use of engineering principles, such as stan-dardisation and modularisation. It is important that these systems can be represented and shared in a standard way to ensure they are easily understood, reproduced, and utilised by other researchers. The Synthetic Biology Open Language (SBOL) is a data standard for sharing biological designs and information about their implementation and characterisation. Thus far, this standard has been used to represent designs in homogeneous systems, where the same design is implemented in every cell. In recent years there has been increasing interest in multicellular systems, where biological designs are split across multiple cells to optimise the system behaviour and function. Here we show how the SBOL standard can be used to represent such multicellular systems, and hence how researchers can better share designs with the community.
LeafCutter vs. MAJIQ and comparing software in the fast moving field of genomics
Authors: Vaquero-Garcia Jorge , Norton Scott , Barash Yoseph
Published: November 2018

In a recent publication, Li et al. introduced LeafCutter, a new method for detecting and quantifying differential splicing of RNA from RNASeq data. In this work, Li et al. first compared LeafCutter to existing methods, then used it for a study of splicing variations and sQTL analysis from a large set of GTEx samples. While the study was elaborate and comprehensive, we want to highlight several issues with the comparative analysis performed by Li et al. We argue these issues created an inaccurate and misleading representation of other tools, namely MAJIQ and rMATS. More broadly, we believe the points we raise regarding the comparative analysis by Li et al. are representative of general issues we all, as authors, editors, and reviewers, are faced with and must address in the current times of fast paced genomics and computational research.
Rationalizing Translation Elongation by Reinforcement Learning
Authors: Hu Hailin , Liu Xianggen , Xiao An , Song Sen , Zeng Jianyang
Published: November 2018

Translation elongation plays a crucial role in multiple aspects of protein biogenesis. In this study, we develop a novel deep reinforcement learning based framework, named RiboRL, to model the distributions of ribosomes on transcripts. In particular, RiboRL employs a policy network (PolicyNet) to perform a context-dependent feature selection to facilitate the prediction of ribosome density. Extensive tests demonstrate that RiboRL can outperform other state-of-the-art methods in predicting ribosome densities. We also show that the reinforcement learning based strategy can generate more informative features for the prediction task when compared to other commonly used attribution methods in deep learning. Moreover, the in-depth analyses and a case study also indicate the potential applications of the RiboRL framework in generating meaningful biological insights regarding translation elongation dynamics. These results have established RiboRL as a useful computational tool to facilitate the studies of the underlying mechanisms of translational regulation.
An Efficient, Scalable and Exact Representation of High-Dimensional Color Information Enabled via de Bruijn Graph Search
Authors: Almodaresi Fatemeh , Pandey Prashant , Ferdman Michael , Johnson Rob , Patro Rob
Published: November 2018

The colored de Bruijn graph (cdbg) and its variants have become an important combinatorial structure used in numerous areas in genomics, such as population-level variation detection in metagenomic samples, large scale sequence search, and cdbg-based reference sequence indices. As samples or genomes are added to the cdbg, the color information comes to dominate the space required to represent this data structure.

In this paper, we show how to represent the color information efficiently by adopting a hierarchical encoding that exploits correlations among color classes — patterns of color occurrence — present in the de Bruijn graph (dbg). A major challenge in deriving an efficient encoding of the color information that takes advantage of such correlations is determining which color classes are close to each other in the high-dimensional space of possible color patterns. We demonstrate that the dbg itself can be used as an efficient mechanism to search for approximate nearest neighbors in this space. While our approach reduces the encoding size of the color information even for relatively small cdbgs (hundreds of experiments), the gains are particularly consequential as the number of potential colors (i.e. samples or references) grows to thousands of experiments.

We apply this encoding in the context of two different applications; the implicit cdbg used for a large-scale sequence search index, Mantis, as well as the encoding of color information used in population-level variation detection by tools such as Vari and Rainbowfish. Our results show significant improvements in the overall size and scalability of representation of the color information. In our experiment on 10,000 samples, we achieved more than 11× better compression compared to RRR.
Performance Limitations in Sensorimotor Control: Tradeoffs between Neural Computation and Accuracy in Tracking Fast Movements
Authors: Saxena Shreya , Sarma Sridevi V. , Dahleh Munther
Published: November 2018

The ability to move fast and accurately track moving objects is fundamentally constrained by the biophysics of neurons and dynamics of the muscles involved. Yet, the corresponding tradeoffs between these factors and tracking motor commands have not been rigorously quantified. We use feedback control principles to quantify performance limitations of the sensorimotor control system (SCS) to track fast periodic movements. We show that (i) linear models of the SCS fail to predict known undesirable phenomena, including skipped cycles, overshoot and undershoot, produced when tracking signals in the “fast regime”, while non-linear pulsatile control models can predict such undesirable phenomena, and (ii) tools from nonlinear control theory allow us to characterize fundamental limitations in this fast regime. Using a validated and tractable nonlinear model of the SCS, we derive an analytical upper bound on frequencies that the SCS model can reliably track before producing such undesirable phenomena as a function of the neurons’ biophysical constraints and muscle dynamics. The performance limitations derived here have important implications in sensorimotor control. For example, if primary motor cortex is compromised due to disease or damage, the theory suggests ways to manipulate muscle dynamics by adding the necessary compensatory forces using an assistive neuroprosthetic device to restore motor performance, and more importantly fast and agile movements. Justhowone should compensate can be informed by our SCS model and the theory developed here.
Effects of BMP-2 on neovascularization during large bone defect regeneration
Authors: Pearson HB , Mason DE , Kegelman CD , Zhao L , Dawahare JH , Kacena MA , Boerckel JD
Published: November 2018

Insufficient blood vessel supply is a primary limiting factor for regenerative approaches to large bone defect repair. Recombinant BMP-2 delivery induces robust bone formation and has been observed to enhance neovascularization, but whether the angiogenic effects of BMP-2 are due to direct endothelial cell stimulation or to indirect paracrine signaling remains unclear. Here, we evaluated the effects of BMP-2 delivery on vascularized bone regeneration and tested whether BMP-2 induces neovascularization directly or indirectly. We found that delivery of BMP-2 (5 μg) enhanced both bone formation and neovascularization in critically sized (8 mm) rat femoral bone defects; however, BMP-2 did not directly stimulate angiogenesisin vitro. In contrast, conditioned medium from both mesenchymal progenitor cells and osteoblasts induced angiogenesisin vitro, suggesting a paracrine mechanism of BMP-2 action. Consistent with this inference, co-delivery of BMP-2 with endothelial colony forming cells (ECFCs) to a heterotopic site, distant from the bone marrow niche, induced ossification but had no effect on neovascularization. Taken together, these data suggest that BMP-2 induces neovascularization during bone regeneration primarily through paracrine activation of osteoprogenitor cells.
Gene regulation inference from single-cell RNA-seq data with linear differential equations and velocity inference
Authors: Aubin-Frankowski Pierre-Cyril , Vert Jean-Philippe
Published: November 2018

Single-cell RNA sequencing (scRNA-seq) offers new possibilities to infer gene regulation networks (GRN) for biological processes involving a notion of time, such as cell differentiation or cell cycles. It also raises many challenges due to the destructive measurements inherent to the technology. In this work we propose a new method named GRISLI for de novo GRN inference from scRNA-seq data. GRISLI infers a velocity vector field in the space of scRNA-seq data from profiles of individual data, and models the dynamics of cell trajectories with a linear ordinary differential equation to reconstruct the underlying GRN with a sparse regression procedure. We show on real data that GRISLI outperforms a recently proposed state-of-the-art method for GRN reconstruction from scRNA-seq data.
Ultrasound functional neuroimaging reveals propagation of task-related brain activity in behaving primates
Authors: Dizeux Alexandre , Gesnik Marc , Ahnine Harry , Blaize Kevin , Arcizet Fabrice , Picaud Serge , Sahel José-Alain , Deffieux Thomas , Pouget Pierre , Tanter Mickael
Published: November 2018

In recent decades, neuroimaging has played an invaluable role in improving the fundamental understanding of the brain. At the macro scale, neuroimaging modalities such as MRI, EEG, and MEG, exploit a wide field of view to explore the brain as a global network of interacting regions. However, this comes at the price of either limited spatiotemporal resolution or limited sensitivity. At the micro scale, electrophysiology is used to explore the dynamic aspects of neuronal activity with a very high temporal resolution. However, this modality requires a statistical averaging of several tens of single task responses. A large-scale neuroimaging modality of sufficient spatial and temporal resolution and sensitivity to study brain region activation dynamically would open new territories of possibility in neuroscience

We show that neurofunctional ultrasound imaging (fUS) is both able to assess brain activation during single cognitive tasks within superficial and deeper areas of the frontal cortex areas, and image the directional propagation of information within and between these regions. Equipped with an fUS device, two macaque rhesus monkeys were instructed before a stimulus appeared to rest (fixation) or to look towards (saccade) or away (antisaccade) from a stimulus. Our results identified an abrupt transient change in activity for all acquisitions in the supplementary eye field (SEF) when the animals were required to change a rule regarding the task cued by a stimulus. Simultaneous imaging in the anterior cingulate cortex and SEF revealed a time delay in the directional functional connectivity of 0.27 ± 0.07 s and 0.9 ± 0.2 s for animals S and Y, respectively. These results provide initial evidence that recording cerebral hemodynamics over large brain areas at a high spatiotemporal resolution and sensitivity with neurofunctional ultrasound can reveal instantaneous monitoring of endogenous brain signals and behavior.
Data-Independent Acquisition Mass Spectrometry to Localize Phosphosites
Authors: Li Qing-Run , Wang Shi-Sheng , Zhu Hong-Wen , Xia Fang-Ying , Roepstorff Peter , Wu Jia-Rui , Zeng Rong
Published: November 2018

In conventional data-dependent acquisition (DDA) mode used for phosphoproteome analysis by mass spectrometry, a considerable number of phosphosites are localized ambiguously. We found that data-independent acquisition (DIA) method could localize phosphosite accurately and confidently due to its acquisition nature of repeated and unbiased mode. Here, we present a robust and promising DIA workflow for modification sites determination. Through dedicated collection and analyses of site-determining ions following their chromatographic profilings, phosphosites could be assigned or rectified unambiguously.
Axonal localization of the Fragile X family of RNA binding proteins is conserved across mammals
Authors: Shepard Katherine A. , Korsak Lulu I T. , Akins Michael R.
Published: November 2018

Spatial segregation of proteins to neuronal axons arises in part from local translation of select mRNAs that are first transported into axons in ribonucleoprotein particles (RNPs), complexes containing mRNAs and RNA binding proteins. Understanding the importance of local translation for a particular circuit requires not only identifying axonal RNPs and their mRNA cargoes, but also whether these RNPs are broadly conserved or restricted to only a few species. Fragile X granules (FXGs) are axonal RNPs containing the Fragile X related family of RNA binding proteins along with ribosomes and specific mRNAs. FXGs were previously identified in mouse, rat, and human brains in a conserved subset of neuronal circuits but with species-dependent developmental profiles. Here we asked whether FXGs are a broadly conserved feature of the mammalian brain and sought to better understand the species-dependent developmental expression pattern. We found FXGs in a conserved subset of neurons and circuits in the brains of every examined species that together include mammalian taxa separated by up to 160 million years of divergent evolution. A developmental analysis of rodents revealed that FXG expression in frontal cortex and olfactory bulb followed consistent patterns in all species examined. In contrast, FXGs in hippocampal mossy fibers showed an increase in abundance across development for most species except for guinea pigs and members of the Mus genus, animals that navigate particularly small home ranges in the wild. The widespread conservation of FXGs suggests that axonal translation is an ancient, conserved mechanism for regulating the proteome of mammalian axons.
A forest model intercomparison framework and application at two temperate forests along the East Coast of the United States
Authors: Erickson Adam , Strigul Nikolay
Published: November 2018

Forest models often reflect the dominant management paradigm of their time. Until the late 1970s, this meant sustaining yields. Following landmark work in forest ecology, physiology, and biogeochemistry, the current generation of models is further intended to inform ecological and climatic forest management in alignment with national biodiversity and climate mitigation targets. This has greatly increased the complexity of models used to inform management, making them difficult to diagnose and understand. State-of-the-art forest models are often complex, analytically intractable, and computationally-expensive, due to the explicit representation of detailed biogeochemical and ecological processes. Different models often produce distinct results while predictions from the same model vary with parameter values. In this project, we developed a rigorous quantitative approach for conducting model intercomparisons and assessing model performance. We have applied our original methodology to compare two forest biogeochemistry models, the Perfect Plasticity Approximation with Simple Biogeochemistry (PPA-SiBGC) and Landscape Disturbance and Succession with Net Ecosystem Carbon and Nitrogen (LANDIS-II NECN). We simulated past-decade conditions at flux tower sites located within Harvard Forest, MA, USA (HF-EMS) and Jones Ecological Research Center, GA, USA (JERC-RD). We mined field data available for both sites to perform model parameterization, validation, and intercomparison. We assessed model performance using the following time-series metrics: net ecosystem exchange, aboveground net primary production, aboveground biomass, C, and N, belowground biomass, C, and N, soil respiration, and, species total biomass and relative abundance. We also assessed static observations of soil organic C and N, and concluded with an assessment of general model usability, performance, and transferability. Despite substantial differences in design, both models achieved good accuracy across the range of pool metrics. While LANDIS-II NECN showed better fidelity to interannual NEE fluxes, PPA-SiBGC indicated better overall performance for both sites across the 11 temporal and 2 static metrics tested (HF-EMS = 0.73, +0.07, = 4.84, −10.02; JERC-RD = 0.76, +0.04, = 2.69, −1.86). To facilitate further testing of forest models at the two sites, we provide pre-processed datasets and original software written in the R language of statistical computing. In addition to model intercomparisons, our approach may be employed to test modifications to forest models and their sensitivity to different parameterizations.
Neuroimaging Supports the Representational Nature of the Earliest Human Engravings
Authors: Mellet E , Salagnon M , Majki A , Cremona S , Joliot M , Jobard G , Mazoyer B , Tzourio Mazoyer N , d’Errico F
Published: November 2018

The earliest human graphic productions dating to the Lower and Middle Palaeolithic are associated with anatomically modern and archaic hominins. These productions, which consist of abstract patterns engraved on a variety of media, may have been used as symbols, and their emergence is thought to be associated with the evolution of the properties of the visual cortex. To test this hypothesis, we used functional magnetic resonance imaging to compare brain activations triggered by the perception of engraved patterns dating between 540,000 and 30,000 years before the present with those elicited by the perception of scenes, objects, symbol-like characters, and written words. The perception of the engravings bilaterally activated regions in the ventral route in a pattern similar to that produced by the perception of objects, suggesting that these graphic productions are processed as organized visual representations in the brain. Moreover, the perception of the engravings led to a leftward activation of the visual word form area. These results support the hypothesis that in contrast to random doodles, the earliest abstract graphic productions had a representational purpose for modern and archaic hominins.
Anterior insular cortex plays a critical role in interoceptive attention
Authors: Wang Xingchao , Wu Qiong , Egan Laura , Gu Xiaosi , Liu Pinan , Gu Hong , Yang Yihong , Luo Jing , Wu Yanhong , Gao Zhixian , Fan Jin
Published: November 2018

Although accumulating evidence indicates that the anterior insular cortex (AIC) mediates interoceptive attention, which refers the attention towards physiological signals arising from the body, the necessity of the AIC in this process has not been demonstrated. Using a novel task that directs attention toward breathing rhythm, we assessed the involvement of the AIC in interoceptive attention in healthy participants using functional magnetic resonance imaging and examined the necessity of the AIC in interoceptive attention in patients with AIC lesions. We found that interoceptive attention was associated with greater AIC activation, as well as enhanced coupling between the AIC and somatosensory area along with reduced coupling between AIC and visual sensory areas. AIC activation and connectivity were predictive of individual differences in interoceptive accuracy. Importantly, AIC lesion patients showed disrupted interoceptive discrimination accuracy and sensitivity. Together, these results provide compelling evidence that AIC plays a critical role in interoceptive attention.
Ownership, Coverage, Utilisation and Maintenance of Long-lasting insecticidal nets in Three Health Districts in Cameroon: A Cross-Sectional Study
Authors: Cho Frederick Nchang , Fru Paulette Ngum , Cho Blessing Menyi , Munguh Solange Fri , Jokwi Patrick Kofon , Ngah Yayah Emerencia , Fru Celestina Neh , Tassang Andrew N , Ekobo Albert Same
Published: November 2018

The Bamenda, Santa and Tiko Health Districts are in the highest malaria transmission strata of Cameroon. The purpose of this study was to explore the indicators of ownership and utilisation as well as maintenance of long-lasting insecticidal nets (LLINs) in three health districts in Cameroon. A cross-sectional household survey involving 1,251 households was conducted in the Bamenda, Santa and Tiko Health Districts in Cameroon. A structured questionnaire was used to collect data on LLINs ownership, utilisation, and maintenance as well as demographic characteristics. The average number of LLINs per household was higher in the Bamenda Health District (BHD) compared to the Tiko Health District (THD) (2.5±1.4 vs 2.4±1.6) as well as the household ownership of at least one LLIN (93.3% vs. 88.9%). The proportion of the de facto population with universal utilisation was higher in BHD compared to THD (13.1% vs 0.2%). In multinomial regression analysis, households in the Santa Health District (SHD) (OR = 0.4, 95% = C.I; 0.2 – 0.8, p = 6.10×10−3), were less likely to own at least one LLIN, while those in the BHD (OR = 1.3, 95% = C.I; 0.8 – 2.1, p = 0.33) were more likely to maintain LLINs compared to those in THD. Ownership of LLINs was low in SHD and THD in comparison to the goal of one LLIN for every two household members. Overall, LLINs coverage and accessibility was still low after the free Mass Distribution Campaigns, making it difficult for all household members to effectively use LLINs.
Strategies for Efficient Genome Editing Using CRISPR-Cas9
Authors: Farboud Behnom , Severson Aaron F. , Meyer Barbara J.
Published: November 2018

The targetable DNA endonuclease CRISPR-Cas9 has transformed analysis of biological processes by enabling robust genome editing in model and non-model organisms. Although rules directing Cas9 to its target DNA via a guide RNA are straightforward, wide variation occurs in editing efficiency and repair outcomes, both imprecise error-prone repair and precise templated repair. We found that imprecise and precise DNA repair from double-stranded breaks (DSBs) is asymmetric, favoring repair in one direction. Using this knowledge, we designed RNA guides and repair templates that increased the frequency of imprecise insertions and deletions and greatly enhanced precise insertion of point mutations in Caenorhabditis elegans. We devised strategies to insert long (10 kb) exogenous sequences or incorporate multiple nucleotide substitutions at considerable distance from DSBs. We expanded the repertoire of co-conversion markers appropriate for diverse nematode species. These selectable markers enable rapid identification of Cas9-edited animals also likely to carry edits in desired targets. Lastly, we explored the timing, location, frequency, sex-dependence, and categories of DSB repair events by developing loci with allele-specific Cas9 targets that can be contributed during mating from either male or hermaphrodite germ cells. Our studies revealed a striking difference in editing efficiency between maternally and paternally contributed genomes. Furthermore, imprecise repair and precise repair from exogenous repair templates occur with high frequency before and after fertilization. Our strategies enhance Cas9 targeting efficiency, lend insight into the timing and mechanisms of DSB repair, and establish guidelines for achieving predictable precise and imprecise repair outcomes with high frequency.
Roles for stress response and cell wall biosynthesis pathways in caspofungin tolerance inCryptococcus neoformans
Authors: Pianalto Kaila M. , Billmyre R. Blake , Telzrow Calla L. , Alspaugh J. Andrew
Published: November 2018

Limited antifungal diversity and availability are growing problems for the treatment of fungal infections in the face of increasing drug resistance. The echinocandins, one of the newest classes of antifungal drugs, inhibit production of a crucial cell wall component. However, these compounds do not effectively inhibit the growth of the opportunistic fungal pathogenCryptococcus neoformans, despite potent inhibition of the target enzyme. We therefore performed a forward genetic screen to identify cellular processes that mediate the relative tolerance of this organism to the echinocandin drug, caspofungin. Through these studies, we identified 14 genetic mutants that enhance caspofungin antifungal activity. Rather than directly affecting caspofungin antifungal activity, these mutations seem to prevent the activation of various stress-induced compensatory cellular processes. For example, thepfa4Δ mutant has defects in the palmitoylation and localization of many of its target proteins, including the Ras GTPase and the Chs3 chitin synthase which are both required for caspofungin tolerance. Similarly, we have confirmed the link between caspofungin treatment and calcineurin signaling in this organism, but we suggest a deeper mechanism in which caspofungin tolerance is mediated by multiple pathways downstream of calcineurin function. Additionally, a partial loss-of-function mutant of a COP9 signalosome component results in a highly caspofungin-susceptible strain ofC. neoformans. In summary, we describe here several pathways inC. neoformansthat contribute to the complex caspofungin tolerance phenotype in this organism.
PARIS, an optogenetic method for functionally mapping gap junctions
Authors: Wu Ling , Dong Ao , Dong Liting , Wang Shi-Qiang , Li Yulong
Published: November 2018

Cell-cell communication via gap junctions regulates a wide range of physiological processes by enabling the direct intercellular electrical and chemical coupling. However, the in vivo distribution and function of gap junctions remain poorly understood, partly due to the lack of non-invasive tools with both cell-type specificity and high spatiotemporal resolution. Here we developed PARIS (pairing actuators and receivers to optically isolate gap junctions), a new fully genetically encoded tool for measuring the cell-specific gap junctional coupling (GJC). PARIS successfully enabled monitoring of GJC in several cultured cell lines under physiologically relevant conditions and in distinct genetically defined neurons in Drosophila brain, with ~10-sec temporal resolution and sub-cellular spatial resolution. These results demonstrate that PARIS is a robust, highly sensitive tool for mapping functional gap junctions and study their regulation in both health and disease.
The Human Hippocampus Contributes to Egocentric Coding of Distance to a Local Landmark
Authors: Chen Xiaoli , Vieweg Paula , Wolbers Thomas
Published: November 2018

Spatial navigation can depend on path integration or environmental cues (e.g., landmarks), which are thought to be integrated in hippocampal and entorhinal circuits. This study investigates the anatomical basis of path integration and navigation based on a single local landmark using an individual differences approach, since people vary substantially in their ability to navigate with path integration cues and landmarks. In two experiments, we dissociated the use of path integration and a local landmark in the same navigation task, and investigated whether morphological variability in the hippocampus and entorhinal cortex could explain behavioral variability in young healthy humans. In Experiment 1, participants navigated in a fully immersive virtual reality environment, with body-based cues available for path integration. The participants first walked through a series of posts before attempting to walk back to the remembered location of the first post. We found that gray matter volume of the hippocampus positively predicted behavioral accuracy of retrieving the target’s distance in relation to the local landmark. Hippocampus also positively predicted path integration performance in terms of walking-distance to the target location. Experiment 2 was conducted in a desktop virtual environment, with no body-based cues available. Optic flow served as path integration cues, and participants were tested on their memory of a learned target location along a linear track. Consistent with Experiment 1, the results showed that hippocampal volume positively predicted performance on the target’s distance in relation to the local landmark. In contrast to Experiment 1, there was no correlation between hippocampal volume and path integration performance. Together, our two experiments provide novel and converging evidence that the hippocampus plays an important role in encoding egocentric distance to a single local landmark during navigation, and they suggest a stronger hippocampal involvement when path integration is based on body-based compared to optic flow cues.
Network remodeling induced by transcranial brain stimulation: A computational model of tDCS-triggered cell assembly formation
Authors: Lu Han , Gallinaro Júlia V. , Rotter Stefan
Published: November 2018

Transcranial direct current stimulation (tDCS) is a variant of non-invasive neuromodulation, which promises treatment for brain diseases like major depressive disorder. In experiments, long-lasting aftereffects were observed, suggesting that persistent plastic changes are induced. The mechanism underlying the emergence of lasting aftereffects, however, remains elusive. Here we propose a model, which assumes that tDCS triggers a homeostatic response of the network involving growth and decay of synapses. The cortical tissue exposed to tDCS is conceived as a recurrent network of excitatory and inhibitory neurons, with synapses subject to homeostatically regulated structural plasticity. We systematically tested various aspects of stimulation, including electrode size and montage, as well as stimulation intensity and duration. Our results suggest that transcranial stimulation perturbs the homeostatic equilibrium and leads to a pronounced growth response of the network. The stimulated population eventually eliminates excitatory synapses with the unstimulated population, and new synapses among stimulated neurons are grown to form a cell assembly. Strong focal stimulation tends to enhance the connectivity within new cell assemblies, and repetitive stimulation with well-chosen duty cycles can increase the impact of stimulation even further. One long-term goal of our work is to help optimizing the use of tDCS in clinical applications.
Conserved type VI secretion regulation in diverseVibriospecies by the regulatory proteins TfoX and TfoY
Authors: Metzger Lisa C. , Matthey Noémie , Stoudmann Candice , Collas Esther J. , Blokesch Melanie
Published: November 2018

Bacteria of the genusVibrioare common members of aquatic environments where they compete with other prokaryotes and defend themselves against grazing predators. A macromolecular protein complex called the type VI secretion system (T6SS) is used for both purposes. Previous research showed that the sole T6SS of the human pathogenV. choleraeis induced by extracellular (chitin) or intracellular (low c-di-GMP levels) cues and that these cues lead to distinctive signalling pathways for which the proteins TfoX and TfoY serve as master regulators. In this study, we tested whether the TfoX- and TfoY-mediated regulation of T6SS was conserved in non-cholera species, and if so, how these regulators affected the production of individual T6SSs in double-armed vibrios. We show that, alongside representative competence genes, TfoX regulates at least one T6SS in all testedVibriospecies. TfoY, on the other hand, fostered motility in all vibrios but had a more versatile T6SS response in that it did not foster T6SS-mediated killing inV. fischeriwhile it induced both systems inV. alginolyticus. Collectively, our data provide evidence that the TfoX- and TfoY-mediated signalling pathways are mostly conserved in diverseVibriospecies and important for signal-specific T6SS induction.

Originality-Significance Statement

This work provides new insight into the regulatory circuits involved in type VI secretion in diverseVibriospecies. Specifically, it is the first study to compare the effects of the two regulatory proteins TfoX and TfoY on the primary or secondary type VI secretion systems of non-cholera vibrios. Importantly, this work also shows that decreased c-di-GMP levels inV. parahaemolyticuslead to TfoY production without changingtfoYtranscript levels, thereby indirectly linking TfoY production to surface sensing.
Communication relational outcomes in the insurance industry
Authors: Marcos Anabela Maria Bello de Figueiredo , Coelho Arnaldo Fernandes de Matos
Published: November 2018

Purpose

The purpose of this paper is to understand the role that communication plays in the insurance industry, as well as its relational outcomes.

Design/methodology/approach

This investigation proposes a theoretical model tested using structural equation modelling. A questionnaire survey was developed to explore the relationships among communication, reputation, trust, commitment, loyalty and word-of-mouth (WOM). For this study, 744 valid questionnaires were collected from a sample of Portuguese car insurance holders.

Findings

The results show that communication directly influences reputation, trust and commitment. Communication also indirectly influences loyalty through reputation, trust, and commitment and communication indirectly influences WOM via trust and commitment. In turn, reputation influences trust and trust impact on relational commitment. Finally, loyalty influences WOM.

Originality/value

This investigation examines the mediating role of reputation, trust and relational commitment in the relationship among communication and loyalty and WOM, in a relational perspective. It fills a gap in the literature by exploring the importance of communication in the insurance industry. Thus, this study will be useful to decision makers in the insurance industry seeking to improve their insurance holders–insurance companies relationships.