bluuebunny/crossref_metadata_2025 huggingface dataset:
Orbit in a Box: A Simplified Technique for Patient-Specific Virtually Planned Orbital Floor Reconstruction
Authors: Menzel Christoph Lothar , Hammacher Andreas , Lommen Julian , Schorn Lara Katharina Franziska , Handschel Jörg , Holtmann Henrik
Published: January 2020

Purpose:

Possibilities for the reconstruction of orbital floor fractures have been extensive for years with regard to materials, methods and differential indications and are inconsistent worldwide. With the spread of CAD/CAM techniques, new and mostly time-consuming possibilities for orbital floor reconstructions have been added.

Methods:

The simple and time-efficient CT-to-patient-specific implant workflow presented here shows that a “form-box” can be created from a patient's computer tomography data set using planning software and a 3D printer. The box is then used to form a patient-specific implant for orbital floor reconstruction: here polydioxanone foil was used, for which stable thermoplastic deformability has been demonstrated for 3D reconstructions.

Results:

Patient-specific thermoplastic shaping of polydioxanone is feasible in a theoretical clinical setting, though its thermoplastic shaping is not yet certified for clinical use. However, a flexible adaptation of the “form-box” design to other materials is possible by setting a single planning parameter.

Conclusions:

The simple structure of the box and its straightforward planning/fabrication process with widely available low-cost materials offer the possibility that a surgeon without a 3D specialist can produce a “form-box” for next day surgery if needed.
Pediatric-Specific Midfacial Fracture Patterns and Management: Pediatric Versus Adult Patients
Authors: Fujisawa Kou , Suzuki Ayumi , Yamakawa Tomomi , Onishi Fumio , Minabe Toshiharu
Published: January 2020

Purpose:

The purpose of this study was to compare the midfacial fracture patterns and management approaches between pediatric and adult patients.

Methods:

We retrospectively analyzed 164 pediatric patients (<16 years old) and 564 nongeriatric adult patients (16 to 65 years old) with midfacial fractures at a single institution between 2011 and 2016. The location of the fractures, along with the etiology and management of the midfacial fractures, were compared.

Results:

Significantly greater proportions of pediatric versus adult patients had sports-related injuries (P < 0.001) and sustained nasal fractures (P < 0.001). On the other hand, significantly greater proportions of adult versus pediatric patients were injured in falls, traffic accidents, or assaults (P = 0.004, P < 0.001, and P = 0.002) and sustained maxillary or zygomatic fractures (P = 0.039 and P < 0.001). Bivariate logistic regression analyses revealed that the risks of nasal, maxillary, and zygomatic fractures were significantly related to age status after adjusting for etiology (P < 0.001, P = 0.045, and P < 0.001). In contrast, the risks of hospitalization and surgical treatment were significantly associated with etiology, but not with age status (P = 0.290 and P = 0.847).

Conclusion:

These data suggest that the age-related structure and composition of the facial skeleton affect the pediatric-specific fracture patterns independent of the etiology. The comparisons in this study may serve as a guide for the management of pediatric midfacial fractures.
Treatment of the Patient With Crouzon Syndrome With Orthognathic Surgery
Authors: Sancar Bahadir , Tanisik Burakhan Hakan
Published: January 2020

Crouzon syndrome is a genetic disease that is transferred by autosomal dominant inheritance. Patients with this syndrome have craniosynostosis, hypertelorism, orbital proptosis, mid-face hypoplasia, mandibular prognathism, and concave facial profile. A number of surgical treatments are used to improve facial contours, and to correct dental and maxillary relationships. Orthognathic surgery is routinely used in the treatment of these patients. We present a female patient with Crouzon syndrome treated with Le Fort I and bilateral sagittal split osteotomy. Previously, surgically assisted rapid maxillary expansion (SARME) surgery was performed to the patient by separating the pterygomaxillary junction under general anesthesia. Down fracture was performed during the Le Fort I osteotomy without the need to separate the pterygomaxillary junction again. The facial appearance was improved with bilateral sagittal split osteotomy, and skeletal malocclusion between the jaws was treated.
Surgical Protocol for a Safe Lateral Nasal Wall Osteotomy
Authors: Suzen Muazzez , Temiz Mustafa , Demirel Oguzhan , Uckan Sina
Published: January 2020

Purpose:

The purpose of this study was to define the anatomy and anatomic variations of the lateral nasal wall area to identify safe access points, determine the optimum osteotomy line for Le Fort I osteotomies, and define a surgical protocol.

Materials and Methods:

The angulations and widths of 160 lateral nasal walls and the distances of the greater palatine canal were measured on axial images from coronal sections 5 mm over the deepest point of the nasal base.

Results:

The average angle between the anterior lateral nasal wall and the medial maxillary sinus wall was 160 degrees in females and 165.67 degrees in males for the right and 155.90 degrees in females and 163.22 degrees in males for the left side. Statistically significant differences were found in the lengths, angulations, and widths of the lateral nasal walls between females and males.

Conclusion:

This study described the mean angulations and linear distances between anatomic structures of the lateral nasal wall and it defines the “Medipol protocol” for a safe osteotomy.
Adolescent Polypharmacy and Serotonin Syndrome
Authors: Davis Chemar R. , Hernandez Michael , Stock Saundra
Published: January 2020

Objectives

The objective of this study was to present a case and review serotonin syndrome and the risk of occurrence in children and adolescents on multiple psychotropic medications.

Methods

The clinical history of a patient in the University of South Florida's child and adolescent psychiatry clinic is presented. Literature review on serotonin syndrome, attention-deficit/hyperactivity disorder (ADHD), and psychostimulants was conducted through PubMed.

Results/Discussion

We have presented a case of possible serotonin-related abnormal movements in an adolescent girl prescribed stimulants and multiple serotonergic medications. Serotonin syndrome may be precipitated through drug interactions that increase serum levels of psychotropic medications. Patients with ADHD often have comorbid psychiatric illness requiring treatment with medication. Amphetamine salts are an often-overlooked agent that potentiates serotonin through monoamine oxidase inhibitor (MAO) inhibition and neurotransmitter release. Children and adolescents on multiple psychotropic medications should be closely monitored for the triad of altered mental status, neuromuscular abnormalities, and autonomic hyperactivity.

Conclusions

Patients with ADHD often have comorbid psychiatric illness and are treated with multiple psychotropic medications. Given the effects of drug-drug interactions and the serotonergic effects of psychostimulants, clinicians should remain vigilant for the triad of altered mental status, neuromuscular abnormalities, and autonomic hyperactivity seen in serotonin syndrome.
Coma Reversal After Intravenous Lipid Emulsion Therapy in a Trazodone-Poisoned Patient
Authors: Warnant Alexandra , Gerard Ludovic , Haufroid Vincent , Hantson Philippe
Published: January 2020

A 77-year-old woman developed a deep coma (Glasgow Coma Scale score at 3/15) after a trazodone overdose (maximal ingested dose, 4500 mg), and orotracheal intubation was required for mechanical ventilation. In addition, she presented sinus bradycardia (<40/min) with QTc prolongation, whereas arterial blood pressure was preserved. The administration of intravenous lipid emulsion (1.5 mL/kg as a bolus followed by a continuous infusion of 0.5 mL/kg per minute for 30 minutes) resulted in a rapid improvement of her neurological condition, with a Glasgow Coma Scale score rising from 3 to 10/15 at the end of intravenous lipid emulsion infusion. A significant increase in heart rate (from 39 to 54/min) was also observed. The treatment was well tolerated, and the patient did not experience ventricular dysrhythmias. In addition, the patient was found to have a reduced metabolic activity related to cytochrome P450 2D6 polymorphism.
Conservation of the name Aeromonas eucrenophila over the name Aeromonas punctata for the organism based on type stain NCMB 74T and universally defined as ‘Aeromonas DNA hybridization group 6’
Authors: Farmer J. Jim , Holmes Barry
Published: January 2020

In a companion paper, we requested the Judicial Commission to correct the type strain of

Aeromonas punctata

from ATCC 15468T to NCMB 74T (=ATCC 23309T). Correction of this error on the 1980 Approved Lists by an Opinion of the Judicial Commission will remove the status of the name

Aeromonas caviae

as a junior objective synonym of

A. punctata

. This is important because the scientific community continues to use the name

A. caviae

almost exclusively instead of

A. punctata

. However, the corrective action of this Opinion will cause a new problem.

A. punctata

and

A. eucrenophila

will then become objective synonyms because both species will have the same type strain NCMB 74T, and

A. punctata

would have priority because it was published first (1890 vs. 1987). Thus,

A. punctata

rather than

A. eucrenophila

would become the correct name for DNA hybridization group 6.

A. punctata

has had a very confusing history since it was first described as Bacillus punctatus by Zimmermann in 1890. It was without a type strain for over 50 years, and unfortunately, has had an incorrect type strain for some 40 years. The name

A. punctata

as a bacterial species has been used incorrectly in the literature very frequently, either based on the wrong type strain or with the wrong definition or circumscription. The name

A. punctata

is not accepted or used by most specialists who study and publish scientific papers and reviews on

Aeromonas

. Under the heading ‘Rejection of Names’ Rule 56a of the Bacterial Code states reasons why the Judicial Commission can reject a name, the first is: ‘(1) An ambiguous name (nomen ambiguum), i.e., a name which has been used with different meanings and thus has become a source of error’. Rule 56a gives the Judicial Commission authority to place names on the list of rejected names. Our analysis of its history leads us to state unequivocally that

A. punctata

currently is, and has been throughout the vast majority of its history, an ambiguous name. After considering all the possible alternatives and their consequences we request the Judicial Commission to go against the rules of priority; to invoke case (1) of Rule 56a, and issue an Opinion conserving

A. eucrenophila

over

A. punctata

; and to place the name

A. punctata

on the list of rejected names. We argue that these actions will give instant stability to a complex and confusing situation by making

A. eucrenophila

rather than

A. punctata

the correct name for ‘

Aeromonas

DNA hybridization group 6’, an association that is almost universally accepted by the scientific community as reflected in the literature.
Antibiofilm activity in the culture supernatant of a marine Pseudomonas sp. bacterium
Authors: Doghri Ibtissem , Brian-Jaisson Florence , Graber Marianne , Bazire Alexis , Dufour Alain , Bellon-Fontaine Marie-Noëlle , Herry Jean-Marie , Ferro Ana Caroline , Sopena Valérie , Lanneluc Isabelle , Sablé Sophie
Published: January 2020

In the marine environment, most solid surfaces are covered by microbial biofilms, mainly composed of bacteria and diatoms. The negative effects of biofilms on materials and equipment are numerous and pose a major problem for industry and human activities. Since marine micro-organisms are an important source of bioactive metabolites, it is possible that they synthesize natural ecofriendly molecules that inhibit the adhesion of organisms. In this work, the antibiofilm potential of marine bacteria was investigated using

Flavobacterium

sp. II2003 as a target. This strain is potentially a pioneer strain of bacteria that was previously selected from marine biofilms for its strong biofilm-forming ability. The culture supernatants of 86 marine heterotrophic bacteria were tested for their ability to inhibit

Flavobacterium

sp. II2003 biofilm formation and the

Pseudomonas

sp. IV2006 strain was identified as producing a strong antibiofilm activity. The

Pseudomonas

sp. IV2006 culture supernatant (SNIV2006) inhibited

Flavobacterium

sp. II2003 adhesion without killing the bacteria or inhibiting its growth. Moreover, SNIV2006 had no effect on the

Flavobacterium

sp. II2003 cell surface hydrophilic/hydrophobic and general Lewis acid–base characteristics, but modified the surface properties of glass, making it on the whole more hydrophilic and more alkaline and significantly reducing bacterial cell adhesion. The glass-coating molecules produced by

Pseudomonas

sp. IV2006 were found to probably be polysaccharides, whereas the antibiofilm molecules contained in SNIV2006 and acting during the 2 h adhesion step on glass and polystyrene surfaces would be proteinaceous. Finally, SNIV2006 exhibited a broad spectrum of antibiofilm activity on other marine bacteria such as

Flavobacterium

species that are pathogenic for fish, and human pathogens in both the medical environment, such as

Staphylococcus aureus

and

Pseudomonas aeruginosa

, and in the food industry, such as

Yersinia enterocolitica

. Thus, a wide range of applications could be envisaged for the SNIV2006 compounds, both in aquaculture and human health.
Defining the requirements for the conjugative transfer of Rhizobium leguminosarum plasmid pRleVF39b
Authors: Wathugala N. Dulmini , Hemananda Kasuni M. , Yip Cynthia B. , Hynes Michael F.
Published: January 2020

Rhizobium leguminosarum

strain VF39 contains a plasmid, pRleVF39b, which encodes a distinctive type of conjugation system (rhizobial type IVa) that is relatively widespread among rhizobial genomes. The cluster of genes encoding the transfer functions lacks orthologs to genes such as traCD, traF and traB, but contains 15 conserved genes of unknown function. We determined the importance of these genes in conjugation by constructing marked and unmarked mutations in each gene, and established that six genes, now designated trcA-F, played a significant role in plasmid transfer. Like the relaxase gene, traA, and the genes encoding the MPF system (trb genes), five of these genes, located in two divergently transcribed operons, are regulated by the Xre family repressor TrbR. The other gene, trcF encodes a protein with similarity to histidinol phosphatases, and its role in conjugation is unclear, but mutations in trcF are severely impaired for conjugation. TrcF does not play a role in regulation of other conjugation genes.
Ares-GT: design of guide RNAs targeting multiple genes for CRISPR-Cas experiments
Authors: Minguet Eugenio G.
Published: January 2020

Motivation

There is a lack of tools to design guide RNA for CRISPR genome editing of gene families and usually good candidate sgRNAs are tagged with low scores precisely because they match several locations in the genome, thus time-consuming manual evaluation of targets is required. Moreover, online tools are limited to a restricted list of reference genome and lack the flexibility to incorporate unpublished genomes or contemplate genomes of populations with allelic variants.

Results

To address these issues, I have developed the ARES-GT, a local command line tool in Python software. ARES-GT allows the selection of candidate sgRNAs that match multiple input query sequences, in addition of candidate sgRNAs that specifically match each query sequence. It also contemplates the use of unmapped contigs apart from complete genomes thus allowing the use of any genome provided by user and being able to handle intraspecies allelic variability and individual polymorphisms.

Availability

ARES-GT is available at GitHub (https://github.com/eugomin/ARES-GT.git).
In-depth secretome analysis ofPuccinia striiformisf. sp.triticiin infected wheat uncovers effector functions
Authors: Ozketen Ahmet Caglar , Andac-Ozketen Ayse , Dagvadorj Bayantes , Demiralay Burak , Akkaya Mahinur S.
Published: January 2020

The importance of wheat yellow rust disease, caused byPuccinia striiformisf. sp.tritici(Pst), has increased substantially due to the emergence of aggressive newPstraces in the last couple of decades. In an era of escalating human populations and climate change, it is vital to understand the infection mechanism ofPstin order to develop better strategies to combat wheat yellow disease. This study focuses on the identification of small secreted proteins (SSPs) and candidate-secreted effector proteins (CSEPs) that are used by the pathogen to support infection and control disease development. We generatedde novoassembled transcriptomes ofPstcollected from wheat fields in central Anatolia. We inoculated both susceptible and resistant seedlings withPstand analyzed haustoria formation. At 10 days post-inoculation (dpi), we analyzed the transcriptomes and identified 10,550 Differentially Expressed Unigenes (DEGs), of which 6,220 werePst-related. Among thosePst-related genes, 230 were predicted as PstSSPs.In silicocharacterization was performed using an approach combining the transcriptomic data and data mining results to provide a reliable list to narrow down the ever-expanding repertoire of predicted effectorome. The comprehensive analysis detected 14 Differentially Expressed Small-Secreted Proteins (DESSPs) that overlapped with the genes in available literature data to serve as the best CSEPs for experimental validation. One of the CSEPs was cloned and studied to test the reliability of the presented data. Biological assays show that the randomly selected CSEP, Unigene17495 (PSTG_10917), localizes in the chloroplast and is able to suppress cell death induced by INF1 in aNicotiana benthamianaheterologous expression system.
Complex genetic network underlying the convergent of Rett Syndrome like (RTT-L) phenotype in neurodevelopmental disorders
Authors: Frankel Eric , Dodson Julius , Sharifi Megan , Pillai Roshan , Ramsey Keri , Gupta Raj , Brzezinski Molly , Venugopal Pooja , Llaci Lorida , Gerald Brittany , Mills Gabrielle , Belnap Newell , Sanchez-Castillo Meredith , Balak Chris D. , Claasen Ana M. , Szelinger Szabolcs , Jepsen Wayne M. , Siniard Ashley L. , Richholt Ryan , De Both Matt , Naymik Marcus , Schrauwen Isabelle , Piras Ignazio S. , Craig David W. , Huentelman Matthew J. , Narayanan Vinodh , Rangasamy Sampathkumar
Published: January 2020

Mutations of the X-linked gene encoding methyl-CpG-binding protein 2 (MECP2) cause classical forms of Rett syndrome (RTT) in girls. Patients with features of classical Rett syndrome, but do not fulfill all the diagnostic criteria (e.g. absence of aMECP2mutation), are defined as atypical Rett syndrome. Genes encoding for cyclin-dependent kinase-like 5 (CDKL5) and forkhead box G1 (FOXG1) are more commonly found in patients with atypical Rett syndrome. Nevertheless, a subset of patients who are recognized to have an overlapping phenotype with RTT but are lacking a mutation in a gene that causes typical or atypical RTT are described as having Rett syndrome like phenotype (RTT-L). Whole Exome Sequencing (WES) of 8 RTT-L patients from our cohort revealed mutations in the genesGABRG2, GRIN1, ATP1A2, KCNQ2, KCNB1, TCF4, SEMA6B, andGRIN2A, which are seemingly unrelated to Rett syndrome genes. We hypothesized that the phenotypic overlap in RTT and RTT-L is caused by mutations in genes that affect common cellular pathways critical for normal brain development and function. We annotated the list of genes identified causing RTT-L from peer-reviewed articles and performed a protein-protein interaction (PPI) network analysis. We also investigated their interaction with RTT (typical or atypical) genes such asMECP2, CDKL5, NTNG1, andFOXG1. We found that the RTT-L-causing genes were enriched in the biological pathways such as circadian entrainment, the CREB pathway, and RET signaling, and neuronal processes like ion transport, synaptic transmission, and transcription. We conclude that genes that significantly interact with the PPI network established by RTT genes cause RTT-L, explaining the considerable feature overlap between genes that are indicated for RTT-L and RTT.
Morphological facilitators for vocal learning explored through the syrinx anatomy of a basal hummingbird
Authors: Monte Amanda , Cerwenka Alexander F. , Ruthensteiner Bernhard , Gahr Manfred , Düring Daniel N.
Published: January 2020

Vocal learning is a rare evolutionary trait that evolved independently in three avian clades: songbirds, parrots, and hummingbirds. Although the anatomy and mechanisms of sound production in songbirds are well understood, little is known about the hummingbird’s vocal anatomy. We use high-resolution micro-computed tomography (μCT) and microdissection to reveal the three-dimensional structure of the syrinx, the vocal organ of the black jacobin (Florisuga fusca), a phylogenetically basal hummingbird species. We identify three unique features of the black jacobin’s syrinx: (i) a shift in the position of the syrinx to the outside of the thoracic cavity and the related loss of the sterno-tracheal muscle, (ii) complex intrinsic musculature, oriented dorso-ventrally, and (iii) ossicles embedded in the medial vibratory membranes. Their syrinx morphology allows vibratory decoupling, precise control of complex acoustic parameters, and a large redundant acoustic space that may be key biomechanical factors facilitating the occurrence of vocal production learning.
Exploring the potential genetic heterogeneity in the incidence of hoof and leg disorders in Austrian Fleckvieh and Braunvieh cattle
Authors: Kosinska-Selbi Barbara , Suchocki Tomasz , Egger-Danner Christa , Schwarzenbacher Hermann , Fraszczak Magdalena , Szyda Joanna
Published: January 2020

Background

Genetic heterogeneity denotes the situation when different genetic architectures underlying diverse populations result in the same phenotype. In this study, we explore the nature of differences in the incidence of the number of hoof and leg disorders between Braunvieh and Fleckvieh cattle in the context of genetic heterogeneity between the breeds.

Results

Despite potentially higher power of testing due to twice as large sample size, none of the SNPs was significantly associated with the number of hoof and leg disorders in Fleckvieh, while 16 SNPs were significant in Braunvieh. The most promising candidate genes in Braunvieh are: CBLB on BTA01, which causes arthritis in rats; CAV2 on BTA04, which in effects mouse skeletal muscles; PTHLH on BTA05, which causes disease phenotypes related to the skeleton in humans, mice and zebrafish; SORCS2 on BTA06, which causes decreased susceptibility to injury in the mouse. Some of the significant SNPs (BTA01, BTA04, BTA05, BTA13, BTA16) reveal allelic heterogeneity – i.e. differences due to different allele frequencies between Fleckvieh and Braunvieh. Some of the significant regions (BTA01, BTA05, BTA13, BTA16) correlate to inter-breed differences in LD structure and may thus represent false-positive heterogeneity. However, positions on BTA06 (SORCS2), BTA14 and BTA24 mark Braunvieh-specific regions.

Conclusions

We hypothesise that the observed genetic heterogeneity of hoof and leg disorders is a by-product of multigenerational differential selection of the breeds – towards dairy production in the case of Braunvieh and towards beef production in the case of Fleckvieh. Based on the current data set it is no possibly to unequivocally confirm/exclude the hypothesis of genetic heterogeneity in the susceptibility to leg disorders between Fleckvieh and Braunvieh because only explore it through associations and not the causal mutations. Rationales against genetic heterogeneity comprise a limited power of detection of true associations as well as differences in the length of LD blocks and in linkage phase between breeds. On the other hand, multigenerational differential selection of the breeds and no systematic differences in LD structure between the breeds favour the heterogeneity hypothesis at some of the significant sites.
Retrospective Ensemble Docking of Allosteric Modulators in an Adenosine G-Protein-Coupled Receptor
Authors: Bhattarai Apurba , Wang Jinan , Miao Yinglong
Published: January 2020

Background

Ensemble docking has proven useful in drug discovery and development. It increases the hit rate by incorporating receptor flexibility into molecular docking as demonstrated on important drug targets including G-protein-coupled receptors (GPCRs). Adenosine A1receptor (A1AR) is a key GPCR that has been targeted for treating cardiac ischemia-reperfusion injuries, neuropathic pain and renal diseases. Development of allosteric modulators, compounds binding to distinct and less conserved GPCR target sites compared with agonists and antagonists, has attracted increasing interest for designing selective drugs of the A1AR. Despite significant advances, more effective approaches are needed to discover potent and selective allosteric modulators of the A1AR.

Methods

Ensemble docking that integrates Gaussian accelerated molecular dynamic (GaMD) simulations and molecular docking usingAutodockhas been implemented for retrospective docking of known positive allosteric modulators (PAMs) in the A1AR.

Results

Ensemble docking outperforms docking of the receptor cryo-EM structure. The calculated docking enrichment factors (EFs) and the area under the receiver operating characteristic curves (AUC) are significantly increased.

Conclusions

Receptor ensembles generated from GaMD simulations are able to increase the success rate of discovering PAMs of A1AR. It is important to account for receptor flexibility through GaMD simulations and flexible docking.

General Significance

Ensemble docking is a promising approach for drug discovery targeting flexible receptors.
A population-level statistic for assessing Mendelian behavior of genotyping-by-sequencing data from highly duplicated genomes
Authors: Clark Lindsay V. , Mays Wittney , Lipka Alexander E. , Sacks Erik J.
Published: January 2020

Background

Given the economic and environmental importance of allopolyploids and other species with highly duplicated genomes, there is a need for methods to distinguish paralogs, i.e. duplicate sequences within a genome, from Mendelian loci, i.e. single copy sequences that pair at meiosis. The ratio of observed to expected heterozygosity is an effective tool for filtering loci but requires genotyping to be performed first at a high computational cost, whereas counting the number of sequence tags detected per genotype is computationally quick but very ineffective in inbred or polyploid populations. Therefore, new methods are needed for filtering paralogs.

Results

We introduce a novel statistic,Hind/HE, that uses the probability that two reads sampled from a genotype will belong to different alleles, instead of observed heterozygosity. The expected value ofHind/HEis the same across all loci in a dataset, regardless of read depth or allele frequency. In contrast to methods based on observed heterozygosity, it can be estimated and used for filtering loci prior to genotype calling. In addition to filtering paralogs, it can be used to filter loci with null alleles or high overdispersion, and identify individuals with unexpected ploidy and hybrid status. We demonstrate that the statistic is useful at read depths as low as five to 10, well below the depth needed for accurate genotype calling in polyploid and outcrossing species.

Conclusions

Our methodology for estimatingHind/HEacross loci and individuals, as well as determining reasonable thresholds for filtering loci, is implemented in polyRAD v1.6, available athttps://github.com/lvclark/polyRAD. In large sequencing datasets, we anticipate that the ability to filter markers and identify problematic individuals prior to genotype calling will save researchers considerable computational time.
SnpReady for Rice (SR4R) Database
Authors: Yan Jun , Zou Dong , Li Chen , Zhang Zhang , Song Shuhui , Wang Xiangfeng
Published: January 2020

The information commons for rice (IC4R) database is a collection of ∼18 million SNPs (single nucleotide polymorphisms) identified by the resequencing of 5,152 rice accessions. Although IC4R offers ultra-high density rice variation map, these raw SNPs are not readily usable for the public. To satisfy different research utilizations of SNPs for population genetics, evolutionary analysis, association studies and genomic breeding in rice, the raw genotypic data of the 18 million SNPs were processed by unified bioinformatics pipelines. The outcomes were used to develop a daughter database of IC4R – SnpReady for Rice (SR4R). The SR4R presents four reference SNP panels, including 2,097,405 hapmapSNPs after data filtration and genotype imputation, 156,502 tagSNPs selected from linkage disequilibrium (LD)-based redundancy removal, 1,180 fixedSNPs selected from genes exhibiting selective sweep signatures, and 38 barcodeSNPs selected from DNA fingerprinting simulation. SR4R thus offers a highly efficient rice variation map that combines reduced SNP redundancy with extensive data describing the genetic diversity of rice populations. In addition, SR4R provides rice researchers with a web-interface that enables them to browse all four SNP panels, use online toolkits, and retrieve the original data and scripts for a variety of population genetics analyses on local computers. The SR4R is freely available to academic users athttp://sr4r.ic4r.org/.
Voluntary actions modulate perception and neural representation of action-consequences in a hand-dependent manner
Authors: B. Buaron , D. Reznik , R. Gilron , R. Mukamel
Published: January 2020

Evoked neural activity in sensory regions, and perception of sensory stimuli, are modulated when the stimuli are the consequence of voluntary movement as opposed to an external source. It has been suggested that such modulations are due to efference copies of the motor command that are sent to relevant sensory regions during voluntary movement. Given the anatomical-functional laterality bias of the motor system, it is plausible that the pattern of such behavioral and neural sensory modulations will exhibit a similar bias, depending on the effector that was used to trigger the stimulus (e.g. right / left hand). Here we examined this issue in the visual domain using behavioral and neural measures (fMRI). Healthy participants judged the relative brightness of identical visual stimuli that were either self-triggered (using right or left hand button presses), or triggered by the computer. By presenting stimuli to either the right or left visual field, we biased visual-evoked responses to left / right visual cortex. We found stronger perceptual modulations when the triggering hand was ipsi (rather than contra) lateral to the stimulated visual field. At the neural level, we found that despite identical physical properties of the visual consequence, evoked fMRI responses in right and left visual cortices differentiate the identity of the triggering hand (left / right). Our findings support a model in which voluntary actions induce sensory modulations that follow the anatomical-functional bias of the motor system.
Activation of Src-family kinases orchestrate secretion of flaviviruses by targeting mature progeny virions to secretory autophagosomes
Authors: Li Ming Yuan , Naik Trupti Shivaprasad , Siu Lewis Yu Lam , Acuto Oreste , Spooner Eric , Wang Peigang , Yang Xiaohan , Lin Yongping , Bruzzone Roberto , Ashour Joseph , Sanyal Sumana
Published: January 2020

Among the various host cellular processes that are hijacked by flaviviruses, very few mechanisms have been described with regard to viral secretion. Here we investigated how flaviviruses exploit the Src family kinases (SFKs) for exit from infected cells. We isolated three members of the SFK family – Src, Fyn and Lyn – that were specifically activated during secretion of Dengue and Zika or their corresponding virus like particles (VLPs). Pharmacological inhibition or genetic depletion of the SFKs blocked virus secretion, most significantly upon Lyn-deficiency. Lyn-/-cells were severely impaired in virus release, and were rescued when reconstituted with wild-type Lyn, but not a kinase- or palmitoylation-deficient Lyn mutant. We further established that Lyn, via its palmitoylation-dependent membrane association, triggered post-Golgi virus transport in specialised Rab11 and Transferrin receptor positive organelles resembling secretory autophagosomes, and distinct from conventional exocytic vesicles. In the absence of Lyn activity or its aberrant membrane association, virions were sorted into the lysosomal pathway for degradation. This mode of export was specifically triggered by processed, and mature, but not by furin-resistant virus particles, and occurred with significantly faster kinetics than the conventional secretory pathway. Our study therefore charts a previously undiscovered Lyn-dependent exit strategy, triggered by flaviviruses in secretory autophagosomes that might enable them to evade circulating antibodies and dictate tissue tropism.
Embodied Spatial Knowledge Acquisition in Immersive Virtual Reality: Comparison to Map Exploration
Authors: König Sabine U. , Keshava Ashima , Clay Viviane , Rittershofer Kirsten , Kuske Nicolas , König Peter
Published: January 2020

Investigating spatial learning in virtual environments allows studying different sources of information under controlled conditions. We built a virtual environment in the style of a European village and investigated spatial knowledge acquisition by experience in the virtual environment and by the use of an interactive map. We tested knowledge of cardinal directions, building-to-building orientation, and judgment of direction between buildings. We find that judgment of directions was more accurate after virtual reality exploration than after map exploration, and the opposite results were observed for knowledge of cardinal directions and relative orientation between buildings. Further, the alignment effect was confined to the map exploration condition. Taken together, our results suggest that the source of spatial exploration differentially influenced spatial knowledge acquisition.
Increased resolution of African Swine Fever Virus genome patterns based on profile HMM protein domains
Authors: Masembe Charles , Phan My V.T. , Robertson David L. , Cotten Matthew
Published: January 2020

African Swine Fever Virus (ASFV) was originally described in Africa almost 100 years ago and is now spreading uncontrolled across Europe and Asia and threatening to destroy the domestic pork industry. Neither effective antiviral drugs nor a protective vaccine are currently available. Efforts to understand the basis for viral pathogenicity and the development of attenuated potential vaccine strains are complicated by the large and complex ASFV genome. We report here a novel method of documenting viral diversity based on profile Hidden Markov Model domains on a genome scale. The method can be used to infer genomic relationships independent of genome alignments and also reveal ASFV genome sequence differences that alter the presence of functional protein domains in the virus. We show that the method can quickly identify differences and shared patterns between virulent and attenuated ASFV strains and will be a useful tool for developing much-needed vaccines and antiviral agents to help control this virus. The tool is rapid to run and easy to implement, readily available as a simple Docker image.
SCAPP: An algorithm for improved plasmid assembly in metagenomes
Authors: Pellow David , Zorea Alvah , Probst Maraike , Furman Ori , Segal Arik , Mizrahi Itzik , Shamir Ron
Published: January 2020

Background: Metagenomic sequencing has led to the identification and assembly of many new bacterial genome sequences. These bacteria often contain plasmids: usually small, circular double-stranded DNA molecules that may transfer across bacterial species and confer antibiotic resistance. These plasmids are generally less studied and understood than their bacterial hosts. Part of the reason for this is insufficient computational tools enabling the analysis of plasmids in metagenomic samples.

Results: We developed SCAPP (Sequence Contents-Aware Plasmid Peeler) - an algorithm and tool to assemble plasmid sequences from metagenomic sequencing. SCAPP builds on some key ideas from the Recycler algorithm while improving plasmid assemblies by integrating biological knowledge about plasmids. We compared the performance of SCAPP to Recycler and metaplasmidSPAdes on simulated metagenomes, real human gut microbiome samples, and a human gut plasmidome dataset that we generated. We also created plasmidome and metagenome data from the same cow rumen sample and used the parallel sequencing data to create a novel assessment procedure. Overall, SCAPP outperformed Recycler and metaplasmidSPAdes across this wide range of datasets.

Conclusions: SCAPP is an easy to use Python package that enables the assembly of full plasmid sequences from metagenomic samples. It outperformed existing metagenomic plasmid assemblers in most cases, and assembled novel and
clinically relevant plasmids in samples we generated such as a human gut plasmidome. SCAPP is open-source software available from: https://github.com/Shamir-Lab/SCAPP.
Avid binding by B cells to thePlasmodiumcircumsporozoite protein repeat suppresses responses to protective subdominant epitopes
Authors: Lewis Fiona J. , Chatterjee Deepyan , Kaczmarski Joe , Gao Xin , Cai Yeping , McNamara Hayley A. , Sutton Henry J. , Jackson Colin J. , Cockburn Ian A.
Published: January 2020

Antibodies targeting the NANP/NVDP repeat domain of thePlasmodium falciparumcircumsporozoite protein (CSPRepeat) can confer protection against malaria. However, it has also been suggested that this repeat domain exists as a decoy that distracts the immune system from mounting protective responses targeting other domains of CSP. Here we show that B cell responses to the repeat domain are indeed ∼10 fold higher than responses to the N- and C-terminal regions of CSP after sporozoite immunization. We investigated the role of the number of CSPRepeat-specific naïve precursor B cells and high avidity binding by B cells in driving the immunodominance of the CSPRepeat. Using adoptive transfer of germline precursors specific for the CSPRepeat, we found that increasing precursor number did indeed increase the responses to the repeat region, but not to the detriment of responses to other epitopes. To investigate the role of avid binding by B cells to the CSPRepeatin driving immunodominance we generated CSP9: a truncated CSP molecule with just 9 NANP repeats. Compared to near full length CSP molecules, CSP9 induced lower BCR signalling in CSPRepeat-specific cells and induced stronger responses to non-repeat epitopes. Finally, we found mice immunized with CSP9 molecules were strongly protected against mosquito bite challenge. Collectively these data demonstrate that the CSPRepeatdoes function as an immunodominant decoy and that truncated CSP molecules may be a promising avenue for future malaria vaccines.

Significance Statement

Malaria kills approximately 420,000 individuals each year(1). Our best vaccine, RTS,S/AS01 is based on the circumsporozoite protein that coasts the surface of the parasite. However, this vaccine is only partially protective. Here we show that responses to a repeat region in the circumsporozoite dominate the immune response. However, immunizing with a circumsporozoite protein with a shortened repeat region induces a more diverse immune response, which could be an avenue to make better malaria vaccines.
Evaluating crystallographic likelihood functions using numerical quadratures
Authors: Zwart Petrus H. , Perryman Elliott D.
Published: January 2020

Intensity-based likelihood functions in crystallographic applications have the potential to enhance the quality of structures derived from marginal diffraction data. Their usage however is complicated by the ability to efficiently compute these targets functions. Here a numerical quadrature is developed that allows for the rapid evaluation of intensity-based likelihood functions in crystallographic applications. By using a sequence of change of variable transformations, including a non-linear domain compression operation, an accurate, robust, and efficient quadrature is constructed. The approach is flexible and can incorporate different noise models with relative ease.
Shotgun Proteomics of non-depleted and depleted hemolymph of humanSchistosomiasis snail vector; Biomphalaria glabrata, revealed vital immune related proteins
Authors: Otarigho Benson , Falade Mofolusho , William Castro-Borges
Published: January 2020

Background

Biomphalaria glabratais an important host in the transmission of human schistosomiasis in the Caribbean and South America. There are serious setbacks in the current control measures, hence need to explore alternatives.

Objective

To unveilBiomphalaria glabratahemolymph proteome for possible detailed knowledge of its immunity in host-pathogen relationship.

Methods

In this study we performed a shotgun proteomic and bioinformatic analyses of the non-depleted and depleted [0.5 and 0.75% Trifluoroacetic acid (TFA) depletion] hemolymph ofB. glabrata(LE strain).

Results

Our analysis was able to mine a total of 148 proteins from the hemolymph. The highest number of protein (148) was obtained from the 0.5% TFA-depleted sample, followed by 62 proteins from the 0.75% TFA-depleted sample and only 59 from non-depleted hemolymph.

Conclusion

Most of these proteins are novel and some of them may perform an important role in the immunity of this snail against invading pathogens.
DIP/Dpr interactions and the evolutionary design of specificity in protein families
Authors: Sergeeva Alina P. , Katsamba Phinikoula S. , Cosmanescu Filip , Brewer Joshua J. , Ahlsen Goran , Mannepalli Seetha , Shapiro Lawrence , Honig Barry
Published: January 2020

Differential binding affinities among closely related protein family members underlie many biological phenomena, including cell-cell recognition.DrosophilaDIP and Dpr proteins mediate neuronal targeting in the fly through highly specific protein-protein interactions. We show here that DIPs/Dprs segregate into seven specificity subgroups defined by binding preferences between their DIP and Dpr members. We then describe a novel sequence-, structure- and energy-based computational approach, combined with experimental binding affinity measurements, to reveal how specificity is coded on the canonical DIP/Dpr interface. We show that binding specificity of DIP/Dpr subgroups is controlled by “negative constraints”, which interfere with binding. To achieve specificity, each subgroup utilizes a different combination of negative constraints, which are broadly distributed and cover the majority of the protein-protein interface. We discuss the structural origins of negative constraints, and potential general implications for the evolutionary origins of binding specificity in multi-protein families.
USP9X deubiquitinase couples the pluripotency network and cell metabolism to regulate ESC differentiation potential
Authors: de Dieuleveult Maud , Leduc Marjorie , Salataj Eralda , Ransy Céline , Dairou Julien , Homma Kengo , Le Gall Morgane , Bossard Pascale , Lombès Anne , Bouillaud Frédéric , Ferry Laure , Defossez Pierre-Antoine , Cadoret Jean-Charles , Ichijo Hidenori , Wood Stephen A. , Guillonneau François , Dressel Ralf , Miotto Benoit
Published: January 2020

Embryonic stem cells (ESC) have the unique ability to differentiate into all three germ cell layers. ESC transition through different states of pluripotency in response to growth factor signals and environmental cues before becoming terminally differentiated. Here, we demonstrated, by a multi-omic strategy, that the deubiquitinase USP9X regulates the developmental potential of ESC, and their transition from a naive to a more developmentally advance, or primed, state of pluripotency. We show that USP9X facilitates developmental gene expression and induces modifications of the mitochondrial bioenergetics, including decreased routing of pyruvate towards its oxidation and reduced respiration. In addition, USP9X binds to the pluripotency factor ESRRB, regulates its abundance and the transcriptional levels of a subset of its target genes. Finally, under permissive culture conditions, depletion of Usp9X accelerates cell differentiation in all cell lineages. We thus identified a new regulator of naive pluripotency and show that USP9X couples ESRRB pluripotency transcriptional network and cellular metabolism, both of which are important for ESC fate and pluripotency.
New mathematical modelling tools for co-culture experiments: when do we need to explicitly account for signalling molecules?
Authors: Jin Wang , Wang Haolu , Liang Xiaowen , Roberts Michael S , Simpson Matthew J
Published: January 2020

Mathematical models are often applied to describe cell migration regulated by diffusible signalling molecules. A typical feature of these models is that the spatial and temporal distribution of the signalling molecule density is reported by solving a reaction–diffusion equation. However, the spatial and temporal distributions of such signalling molecules are not often reported or observed experimentally. This leads to a mismatch between the amount of experimental data available and the complexity of the mathematical model used to simulate the experiment. To address this mismatch, we develop a discrete model of cell migration that can be used to describe a new suite of co–culture cell migration assays involving two interacting subpopulations of cells. In this model, the migration of cells from one subpopulation is regulated by the presence of signalling molecules that are secreted by the other subpopulation of cells. The spatial and temporal distribution of the signalling molecules is governed by a discrete conservation statement that is related to a reaction–diffusion equation. We simplify the model by invoking a steady state assumption for the diffusible molecules, leading to a reduced discrete model allowing us to describe how one subpopulation of cells stimulates the migration of the other subpopulation of cells without explicitly dealing with the diffusible molecules. We provide additional mathematical insight into these two stochastic models by deriving continuum limit partial differential equation descriptions of both models. To understand the conditions under which the reduced model is a good approximation of the full model, we apply both models to mimic a set of novel co–culture assays and we systematically explore how well the reduced model approximates the full model as a function of the model parameters.