bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term, patient-centered outcomes of lower-extremity vascular trauma
Authors: Perkins Zane B. , Yet Barbaros , Glasgow Simon , Marsh D. William R. , Tai Nigel R.M. , Rasmussen Todd E.
Published: May 2018

OBJECTIVE

To describe the long-term outcomes of military lower-extremity vascular injuries, and the decision making of surgeons treating these injuries.

BACKGROUND

Lower-extremity vascular trauma is an important cause of preventable death and severe disability, and decisions on amputation or limb salvage can be difficult. Additionally, the complexity of the condition is not amenable to controlled study, and there is limited data to guide clinical decision making and establish sensible treatment expectations during rehabilitation.

METHODS

A cohort study of 554 US service members who sustained lower-extremity vascular injury in Iraq or Afghanistan (March 2003 to February 2012) was performed using the military's trauma registry, its electronic health record, patient interviews, and quality-of-life surveys. Long-term surgical and functional outcomes, and the timing and rationale of surgical decisions, were analyzed.

RESULTS

Of 579 injured extremities, 49 (8.5%) underwent primary amputation and 530 (91.5%) an initial attempt at salvage. Ninety extremities underwent secondary amputation, occurring in the early (n = 60; <30 days) or late (n = 30; >30 days) phases after injury. For salvage attempts, freedom from amputation 10 years after injury was 82.7% (79.1%–85.7%). Long-term physical and mental health outcomes were similar between service members who underwent reconstruction and those who underwent amputation.

CONCLUSION

This military experience provides data that will inform an array of military and civilian providers who care for patients with severe lower-extremity injury. While the majority salvage attempts endure, success is hindered by ischemia and necrosis during the acute stage and pain, dysfunction and infection in the later phases of recovery.

LEVEL OF EVIDENCE

Therapeutic/prognostic, level III.
Interrupted versus continuous fascial closure in patients undergoing emergent laparotomy: A randomized controlled trial
Authors: Peponis Thomas , Bohnen Jordan D. , Muse Sandra , Fuentes Eva , van der Wilden Gwendolyn M. , Mejaddam Ali , Alam Hasan , Kaafarani Haytham M.A. , Fagenholz Peter J. , King David R. , Yeh D. Dante , Velmahos George C. , de Moya Marc A.
Published: May 2018

BACKGROUND

The optimal method of fascial closure, interrupted fascial closure (IFC) versus continuous fascial closure (CFC) has never been studied exclusively in the setting of emergency surgery. We hypothesized that IFC decreases postoperative incisional hernia development following emergent laparotomies.

METHODS

Between August 2008 and September 2015, patients undergoing emergent laparotomies were consented and randomly assigned to either IFC or CFC. Patients were followed up postoperatively for at least 3 months and assessed for incisional hernia, dehiscence, or wound infection. We excluded those with trauma, elective surgery, mesh in place, primary ventral hernia, previous abdominal surgery within 30 days, or those not expected to survive for more than 48 hours. Our primary endpoint was the incidence of postoperative incisional hernias.

RESULTS

One hundred thirty-six patients were randomly assigned to IFC (n = 67) or CFC (n = 69). Baseline characteristics were similar between the groups. No difference was noted in the length of the abdominal incision, or the peak inspiratory pressure after the closure. The median time needed for closure was significantly longer in the IFC group (22 minutes vs. 13 minutes, p < 0.001). Thirty-seven (55.2%) IFC and 41 (59.4%) CFC patients completed their follow-up visits. There was no statistically significant difference in baseline and intraoperative characteristics between those who completed follow-ups and those who did not. The median time from the day of surgery to the day of the last follow-up was similar between IFC and CFC (233 days vs. 216 days, p = 0.67), as were the rates of incisional hernia (13.5% versus 22.0%, p = 0.25), dehiscence (2.7% vs. 2.4%, p = 1.0), and surgical site infection (16.2% vs. 12.2%, p = 0.75).

CONCLUSION

There was no statistically detectable difference in postoperative hernia development between those undergoing IFC versus CFC after emergent laparotomies. However, this may be due to the relatively low sample size.

LEVEL OF EVIDENCE

Therapeutic/Care Management Study, level III.
High-volume hospitals are associated with lower mortality among high-risk emergency general surgery patients
Authors: Ogola Gerald O. , Crandall Marie L. , Richter Kathleen M. , Shafi Shahid
Published: May 2018

INTRODUCTION

We have previously demonstrated that Emergency General Surgery (EGS) patients treated at high-volume hospitals experience lower mortality rates than those treated at low-volume hospitals. However, EGS comprises a wide spectrum of diseases. Our goal was to determine which EGS diseases had better outcomes at high-volume hospitals.

METHODS

We undertook a retrospective analysis of the National Inpatient Sample database for 2013 (a nationwide representative sample). Patients with EGS diseases were identified using American Association for the Surgery of Trauma definitions. A hierarchical logistic regression model was used to measure risk-adjusted probability of death, adjusting for age, sex, race, ethnicity, insurance type, and comorbidities. Patients were then grouped into 16 risk groups based upon their predicted probability of death. We then compared observed mortality rates at high- versus low-volume hospitals within each risk group.

RESULTS

Nationwide, 3,006,615 patients with EGS diseases were treated at 4,083 hospitals in 2013. Patients with predicted risk of death of 4% or higher (275,615 patients, 9.2%) had lower observed mortality rates at high-volume hospitals than at low-volume hospitals (7.7% vs. 10.2%, p < 0.001). We estimated that 1,002 deaths were potentially preventable if high-risk patients who were treated at low-volume hospitals were instead transferred to high-volume hospitals.

CONCLUSION

EGS patients with predicted risk of death of 4% or higher experience lower mortality rates at high-volume hospitals than at low-volume hospitals. A regional system of EGS care that enables rapid transfer of high-risk patients to high-volume hospitals may prevent several deaths.

LEVEL OF EVIDENCE

Prognostic and epidemiological, level III; Therapeutic/Case Management, level IV.
Living Organ Video Educated Donors Program for Kidney Transplant-eligible African Americans to Approach Potential Donors: A Proof of Concept
Authors: Sieverdes John C. , Treiber Frank A. , Mueller Martina , Nemeth Lynne S. , Brunner-Jackson Brenda , Anderson Ashley , Baliga Prabhakar K.
Published: May 2018

Background

The purpose of the Living Organ Video Educated Donors (LOVED) program is to address living donor kidney transplantation (LDKT) disparities in African Americans who experience half the rates of LDKTs compared with whites in the United States.

Methods

LOVED is an iterative-designed, distance-based, navigator-led, mobile health educational program, developed via guidance from patients, Self-determination Theory and Social Cognitive Theory. The purpose of this study was to assess the feasibility of LOVED using a proof-of-concept design to increase African Americans’ knowledge about the living donor process to improve their willingness to approach others about being a potential kidney donor. The 8-week LOVED program consisted of (1) a computer tablet-delivered education program, (2) group video chat sessions with an African American LDKT recipient navigator, and (3) additional communication between group members and the navigator.

Results

Twenty-five participants completed the LOVED study. Poststudy focus groups were analyzed using inductive and deductive qualitative descriptive techniques and analysts found 6 themes reporting LOVED being highly acceptable with the program being overall empowering and helpful. The study had 0% attrition, 90.9% adherence to the education videos and 88% adherence to the video chat sessions. Surveys showed statistically significant improvements in LDKT knowledge, higher willingness to communicate to others about their need, lower donor concerns, and higher self-efficacy about LDKT.

Conclusions

Findings indicate that participation in LOVED can lead to improvements in predictors to increase the number of evaluations and LDKTs in African Americans; however, these findings need to be confirmed in adequately powered, randomized controlled trials. Using LOVED may reduce barriers to broadly address LDKT disparities. Findings from this study will inform the design of a future statewide randomized controlled trials.
Recanalization of Chronic Occlusion of the Middle Cerebral Artery With Tissue Plasminogen Activator Treatment: A Case Report
Authors: Lee Seung Jae , Cheong Jin Sung , Ryu Han Uk , Kang Hyun Goo
Published: May 2018

Objectives

Patients with chronic proximal middle cerebral artery (MCA) occlusion do not present with severe symptoms, but early recanalization of acute occlusion is associated with high morbidity and mortality. Tissue plasminogen activator (tPA) is a recombinant thrombolytic agent approved for treating ischemic stroke, although only a few cases of tPA administration in chronic MCA occlusion have yielded positive results.

Methods

A 71-year-old patient had a history of right MCA territorial infarction with the occlusion occurring 12 years ago (November 2005). Although the patient was treated with antiplatelet agents, MCA recanalization was not achieved. The patient was referred to our hospital again (January 2017) for newly discovered symptoms. We immediately administered tPA because the patient presented 2 hours after onset of symptoms.

Results

Neurological symptoms resolved within 24 hours of treatment, and magnetic resonance angiography confirmed recanalization of the right MCA territorial lesion. No neurological abnormalities were observed during the 12-week follow-up.

Conclusions

At present, tPA is the only approved treatment for acute ischemic stroke, although it presents a limited time frame to avoid severe medication-related adverse effects. Our report suggests nonatherosclerotic chronic MCA occlusion as an alternative application of tPA therapy.
Remote manipulation of magnetic nanoparticles using magnetic field gradient to promote cancer cell death
Authors: Subramanian Mahendran , Miaskowski Arkadiusz , Jenkins Stuart Iain , Lim Jenson , Dobson Jon
Published: May 2018

The manipulation of magnetic nanoparticles (MNPs) using an external magnetic field, has been demonstrated to be useful in various biomedical applications. Some techniques have evolved utilizing this non-invasive external stimulus but the scientific community widely adopts few, and there is an excellent potential for more novel methods. The primary focus of this study is on understanding the manipulation of MNPs by a time-varying static magnetic field and how this can be used, at different frequencies and displacement, to manipulate cellular function. Here we explore, using numerical modeling, the physical mechanism which underlies this kind of manipulation, and we discuss potential improvements which would enhance such manipulation with its use in biomedical applications, i.e., increasing the MNP response by improving the field parameters. From our observations and other related studies, we infer that such manipulation depends mostly on the magnetic field gradient, the magnetic susceptibility and size of the MNPs, the magnet array oscillating frequency, the viscosity of the medium surrounding MNPs, and the distance between the magnetic field source and the MNPs. Additionally, we demonstrate cytotoxicity in neuroblastoma (SH-SY5Y) and hepatocellular carcinoma (HepG2) cells in vitro. This was induced by incubation with MNPs, followed by exposure to a magnetic field gradient, physically oscillating at various frequencies and displacement amplitudes. Even though this technique reliably produces MNP endocytosis and/or cytotoxicity, a better biophysical understanding is required to develop the mechanism used for this precision manipulation of MNPs, in vitro.
Augmented Reality Powers a Cognitive Prosthesis for the Blind
Authors: Liu Yang , Stiles Noelle R. B. , Meister Markus
Published: May 2018

To restore vision for the blind several prosthetic approaches have been explored that convey raw images to the brain. So far these schemes all suffer from a lack of bandwidth and the extensive training required to interpret unusual stimuli. Here we present an alternate approach that restores vision at the cognitive level, bypassing the need to convey sensory data. A wearable computer captures video and other data, extracts the important scene knowledge, and conveys that through auditory augmented reality. This system supports many aspects of visual cognition: from obstacle avoidance to formation and recall of spatial memories, to long-range navigation. Neither training nor modification of the physical environment are required: Blind subjects can navigate an unfamiliar multi-story building on their first attempt. The combination of unprecedented computing power in wearable devices with augmented reality technology promises a new era of non-invasive prostheses that are limited only by software.

Impact Statement

A non-invasive prosthesis for blind people endows objects in the environment with voices, allowing a user to explore the scene, localize objects, and navigate through a building with minimal training.
A Neural Microcircuit Model for a Scalable Scale-invariant Representation of Time
Authors: Liu Yue , Tiganj Zoran , Hasselmo Michael E. , Howard Marc W.
Published: May 2018

Scale-invariant timing has been observed in a wide range of behavioral experiments. The firing properties of recently described time cells provide a possible neural substrate for scale-invariant behavior. Earlier neural circuit models do not produce scale-invariant neural sequences. In this paper we present a biologically detailed network model based on an earlier mathematical algorithm. The simulations incorporate exponentially decaying persistent firing maintained by the calcium-activated nonspecific (CAN) cationic current and a network structure given by the inverse Laplace transform to generate time cells with scale-invariant firing rates. This model provides the first biologically detailed neural circuit for generating scale-invariant time cells. The circuit that implements the inverse Laplace transform merely consists of off-center/on-surround receptive fields. Critically, rescaling temporal sequences can be accomplished simply via cortical gain control (changing the slope of the f-I curve).
Transcriptomic analysis reveals similarities in genetic activation of detoxification mechanisms resulting from imidacloprid and chlorothalonil exposure
Authors: Clements Justin , Sanchez-Sedillo Benjamin , Bradfield Christopher , Groves Russell L.
Published: May 2018

The Colorado potato beetle, Leptinotarsa decemlineata (Say), is an agricultural pest of commercial potatoes in parts of North America, Europe, and Asia. Plant protection strategies within this geographic range employ a variety of pesticides to combat not only the insect, but also plant pathogens. Previous research has shown that field populations of Leptinotarsa decemlineata have a chronological history of resistance development to a suite of insecticides, including the Group 4A neonicotinoids. The aim of this study is to contextualize the transcriptomic response of Leptinotarsa decemlineata when exposed to the neonicotinoid insecticide imidacloprid, or the fungicides boscalid or chlorothalonil, in order to determine whether these compounds induce similar detoxification mechanisms. We found that chlorothalonil and imidacloprid induced similar patterns of transcript expression, including the up-regulation of a cytochrome p450 and a UDP-glucuronosyltransferase transcript, which are often associated with xenobiotic metabolism. Further, transcriptomic responses varied among individuals within the same treatment group, suggesting individual insects’ responses vary within a population and may cope with chemical stressors in a variety of manners. These results further our understanding of the mechanisms involved in insecticide resistance in Leptinotarsa decemlineata.

Author Contribution Statement

Conceived and designed the experiments: JC, CB, RLG. Performed the experiments: JC, BSS. Analyzed the data: JC, BSS. Wrote the paper: JC, BSS, RLG.
A chromosome-scale assembly of the sorghum genome using nanopore sequencing and optical mapping
Authors: Deschamps Stáphane , Zhang Yun , Llaca Victor , Ye Liang , May Gregory , Lin Haining
Published: May 2018

The advent of long-read sequencing technologies has greatly facilitated assemblies of large eukaryotic genomes. In this paper, Oxford Nanopore sequences generated on a MinION sequencer were combined with BioNano Genomics Direct Label and Stain (DLS) optical maps to generate a chromosome-scale de novo assembly of the repeat-rich Sorghum bicolor Tx430 genome. The final hybrid assembly consists of 29 scaffolds, encompassing in most cases entire chromosome arms. It has a scaffold N50 value of 33.28Mbps and covers >90% of Sorghum bicolor expected genome length. A sequence accuracy of 99.67% was obtained in unique regions after aligning contigs against Illumina Tx430 data. Alignments showed that 99.4% of the 34,211 public gene models are present in the assembly, including 94.2% mapping end-to-end. Comparisons of the DLS optical maps against the public Sorghum Bicolor v3.0.1 BTx623 genome assembly suggest the presence of substantial genomic rearrangements whose origin remains to be determined.
Human IgE producing B cells have a unique transcriptional program and generate high affinity, allergen-specific antibodies
Authors: Croote Derek , Darmanis Spyros , Nadeau Kari C. , Quake Stephen R.
Published: May 2018

IgE antibodies provide defense against helminth infections, but can also cause life-threatening allergic reactions. Despite their importance to human health, these antibodies and the cells that produce them remain enigmatic due to their scarcity in humans; much of our knowledge of their properties is derived from model organisms. Here we describe the isolation of IgE producing B cells from the blood of individuals with food allergies, followed by a detailed study of their properties by single cell RNA sequencing (scRNA-seq). We discovered that IgE B cells are deficient in membrane immunoglobulin expression and that the IgE plasmablast state is more immature than that of other antibody producing cells. Through recombinant expression of monoclonal antibodies derived from single cells, we identified IgE antibodies which had unexpected cross-reactive specificity for major peanut allergens Ara h 2 and Ara h 3; not only are these among the highest affinity native human antibodies discovered to date, they represent a surprising example of convergent evolution in unrelated individuals who independently evolved nearly identical antibodies. Finally, we discovered that splicing within B cells of all isotypes reveals polarized germline transcription of the IgE, but not IgG4, isotype as well as several examples of biallelic expression of germline transcripts. Our results offer insights into IgE B cell transcriptomics, clonality and regulation, provide a striking example of adaptive immune convergence, and offer an approach for accelerating mechanistic disease understanding by characterizing a rare B cell population underlying IgE-mediated disease at single cell resolution.
Computational Screening of Potential Inhibitors ofDesulfobacter postgateifor Pyrite Scale Prevention in Oil and Gas Wells
Authors: Onawole Abdulmujeeb T. , Husseinl Ibnelwaleed A. , Saad Mohammed A. , Ahmed Musa E.M. , Nimir Hassan I.
Published: May 2018

Sulfate-reducing bacteria (SRB) such asDesulfobacter postgateiare often found in oil and gas wells. However, they lead to the release of hydrogen sulfide which in turn leads to the formation of iron sulfide scale such as pyrite. ATP sulfurylase is an enzyme present in SRB, which catalyzes the formation of adenylyl sulfate (APS) and inorganic pyrophosphatase (PPi) from ATP and sulfate which is one of the first steps in hydrogen sulfide production byD. postgatei. Virtual screening using molecular docking and machine learning tools was used to identify three potential inhibitors of ATP sulfurylase from a database of about 40 million compounds. These selected hits ((S,E)-1-(4-methoxyphenyl)-3-(9-((m-tolylimino)methyl)-9,10-dihydroanthracen-9-yl)pyrrolidine-2,5-dione;,methyl 2-[[(1S)-5-cyano-2-imino-1-(4-phenylthiazol-2-yl)-3-azaspiro[5.5]undec-4-en-4-yl]sulfanyl]acetate and (4S)-4-(3-chloro-4-hydroxy-phenyl)-1-(6-hydroxypyridazin-3-yl)-3-methyl-4,5-dihydropyrazolo[3,4-b]pyridin-6-ol), which are known as A, B and C respectively) all had good binding affinities with ATP sulfurylase and were further analyzed for their toxicological properties. The molecular docking results showed that all the compounds have negative binding energy with compound A having the highest docking score. However, based on the physicochemical and toxicological properties, compound C is the best choice as it does not violate any of the recommended properties that relate to absorption and distribution. Only compound C was predicted to be both safe and effective as a potential inhibitor of ATP sulfurylase. The binding mode of compound C revealed favorable interactions with the amino residues LEU 213, ASP 308, ARG 307, TRP 347, LEU 224, GLN 212, MET211 and HIS 309.

Importance

Scale formation formed by hydrogen sulfide, which is produced by sulfate reducing bacteria such asDesulfobacter postgateihas been a persistent problem in the oil and gas industry leading to loss of money, time and even lives. The three selected hits from the virtual screenings of about 40 million compounds would possibly inhibit the enzyme, ATP sulfurylase, which is involved in the first reaction in hydrogen sulfide formation inDesulfobacter postgatei. The selected inhibitors are expected to significantly reduce the formation of hydrogen sulfide and consequently prevent the development of pyrite scale in oil and gas wells.
Tributyltin induces a transcriptional response without a brite adipocyte signature in adipocyte models
Authors: Kim Stephanie , Li Amy , Monti Stefano , Schlezinger Jennifer J.
Published: May 2018

Tributyltin (TBT), a peroxisome proliferator-activated receptor γ (PPARγ)/retinoid X receptor (RXR) ligand and founding member of the environmental obesogen chemical class, induces adipocyte differentiation and suppresses bone formation. A growing number of environmental PPARγ ligands are being identified. However, the potential for environmental PPARγ ligands to induce adverse metabolic effects has been questioned because PPARγ is a therapeutic target in treatment of type II diabetes. We evaluated the molecular consequences of TBT exposure during bone marrow multipotent mesenchymal stromal cell (BM-MSC) differentiation in comparison to rosiglitazone, a therapeutic PPARγ ligand, and LG100268, a synthetic RXR ligand. Mouse primary BM-MSCs (female, C57BL/6J) undergoing bone differentiation were exposed to maximally efficacious and human relevant concentrations of rosiglitazone (100 nM), LG100268 (100 nM) or TBT (80 nM) for 4 days. Gene expression was assessed using microarrays, and in silico functional annotation was performed using pathway enrichment analysis approaches. Pathways related to osteogenesis were downregulated by all three ligands, while pathways related to adipogenesis were upregulated by rosiglitazone and TBT. However, pathways related to mitochondrial biogenesis and brown-in-white (brite) adipocyte differentiation were more significantly upregulated in rosiglitazone-treated than TBT-treated cells. The lack of induction of genes involved in adipocyte energy dissipation by TBT was confirmed by an independent gene expression analysis in BM-MSCs undergoing adipocyte differentiation and by analysis of a publically available 3T3 L1 data set. Furthermore, rosiglitazone, but not TBT, induced mitochondrial biogenesis. This study is the first to show that an environmental PPARγ ligand has a limited capacity to induce health promoting activities of PPARγ.
“Haplopappus platylepis(Asteraceae) resin: an adhesive trap for pest control of crawling arthropods, with antimicrobial potential”
Authors: Villagra Cristian A. , Macias-Marabolí Verónica , Schapheer Constanza , Bórquez Jorge , Simirgiotis Mario J. , Echeverría Javier , González-Teuber Marcia , Urzúa Alejandro
Published: May 2018

The use of plant secondary metabolites has been incorporated as key part of integrated pest management and as an alternative to the use of pesticides. This may even be more relevant regarding domiciliary pest insects, capable of vectoring pathogens to humans. In these environments control its more difficult due to its possible effect on non-target organisms and human health. Here we evaluated the use of the resinous exudate of Chile’s endemic bushHaplopappus platylepis(Asteraceae) as a sticky trap for crawling pest insects. We usedBlatta orientalisLinneus (oriental cockroach), a cosmopolitan synanthropic pest, as test organism. We compared effectiveness on cockroach-trapping ofH. platylepis’ resin versus a commercially available sticky trap, and analyzed these two sticky substances using UHPLC-DAD-MS and GC-MS. We found thatH. platylepisresin was as effective as the commercial adhesive on trappingB. orientalis. Plant resinous exudate was composed by a mixture of flavonoids, labdane diterpenoids and unsatured fatty acids oxylipins, which are known for their antimicrobial and antioxidant properties. In contrast, the commercial sticky trap was rich in 1-bromohexadecane and 2-clorociclohexanol, which have been described as allergens and as potentially toxic to humans. Considering these findings, we suggest the use of the resinous extract ofH. platylepisas an effective adhesive trapping method against pest cockroaches and possibly other crawling synanthropic arthropods cohabiting with humans. We highlight the importance of novel, non-toxic and eco-friendly products as strategies to be applied in the management of insect pests.
Transition from a meiotic to a somatic-like DNA damage response during the pachytene stage in mouse meiosis
Authors: Enguita-Marruedo Andrea , Martín-Ruiz Marta , García Eva , Gil-Fernández Ana , Parra M. Teresa , Viera Alberto , Rufas Julio S. , Page Jesus
Published: May 2018

Homologous recombination (HR) is the principal mechanism of DNA repair acting during meiosis and is fundamental for the segregation of chromosomes and the increase of genetic diversity. Nevertheless, non-homologous end joining (NHEJ) mechanisms also act during meiosis, mainly in response to exogenously-induced DNA damage in late stages of first meiotic prophase. In order to better understand the relationship between these two repair pathways, we studied the response to DNA damage during male mouse meiosis after gamma radiation. We clearly discerned two types of responses immediately after treatment. From leptotene to early pachytene, exogenous damage triggered the massive presence of γH2AX throughout the nucleus, which was associated with DNA repair mediated by HR components (DMC1 and RAD51). This early pathway finished with the sequential removal of DMC1 and RAD51 and was no longer inducible at mid pachytene. However, from mid pachytene to diplotene, γH2AX appeared as large discrete foci. This late repair pattern was mediated first by NHEJ, involving Ku70/80 and XRCC4, which were constitutively present, and 53BP1, which appeared at sites of damage soon after irradiation. Nevertheless, 24 hours after irradiation, a HR pathway involving RAD51 but not DMC1 mostly replaced NHEJ. Additionally, we observed the occurrence of synaptonemal complex bridges between bivalents, most likely representing chromosome translocation events that may involve DMC1, RAD51 or 53BP1. Our results reinforce the idea that the early “meiotic” repair pathway that acts by default at the beginning of meiosis is replaced from mid pachytene onwards by a “somatic-like” repair pattern. This shift might be important to resolve DNA damage (either endogenous or exogenous) that could not be repaired by the early meiotic mechanisms, for instance those in the sex chromosomes, which lack a homologous chromosome to repair with. This transition represents another layer of functional changes that occur in meiotic cells during mid pachytene, in addition to epigenetic reprograming, reactivation of transcription, expression of a new gene profile and acquisition of competence to proceed to metaphase.
Biophysically Realistic Neuron Models for Simulation of Cortical Stimulation
Authors: Aberra Aman S. , Peterchev Angel V. , Grill Warren M.
Published: May 2018

1.

Objective

We implemented computational models of human and rat cortical neurons for simulating the neural response to cortical stimulation with electromagnetic fields.

Approach

We adapted model neurons from the library of Blue Brain models to reflect biophysical and geometric properties of both adult rat and human cortical neurons and coupled the model neurons to exogenous electric fields (E-fields). The models included 3D reconstructed axonal and dendritic arbors, experimentally-validated electrophysiological behaviors, and multiple, morphological variants within cell types. Using these models, we characterized the single-cell responses to intracortical microstimulation (ICMS) and uniform E-field with dc as well as pulsed currents.

Main results

The strength-duration and current-distance characteristics of the model neurons to ICMS agreed with published experimental results, as did the subthreshold polarization of cell bodies and axon terminals by uniform dc E-fields. For all forms of stimulation, the lowest threshold elements were terminals of the axon collaterals, and the dependence of threshold and polarization on spatial and temporal stimulation parameters was strongly affected by morphological features of the axonal arbor, including myelination, diameter, and branching.

Significance

These results provide key insights into the mechanisms of cortical stimulation. The presented models can be used to study various cortical stimulation modalities while incorporating detailed spatial and temporal features of the applied E-field.
Boundary-Driven Emergent Spatiotemporal Order in Growing Microbial Colonies
Authors: Karamched Bhargav R. , Ott William , Timofeyev Ilya , Alnahhas Razan N. , Bennett Matthew R. , Josić Krešimir
Published: May 2018

We introduce a tractable stochastic spatial Moran model to explain experimentally-observed patterns of rod-shaped bacteria growing in rectangular microfluidic traps. Our model shows that spatial patterns can arise as a result of a tug-of-war between boundary effects and modulations of growth rate due to cell-cell interactions. Cells alignparallelto the long side of the trap when boundary effects dominate. However, when the magnitude of cell-cell interactions exceeds a critical value, cells align orthogonally to the trap’s long side. Our model is analytically tractable, and completely solvable under a mean-field approximation. This allows us to elucidate the mechanisms that govern the formation of population-level patterns. The model can be easily extended to examine various types of interactions that can shape the collective behavior in bacterial populations.
Rapid alignment-free phylogenetic identification of metagenomic sequences
Authors: Linard Benjamin , Swenson Krister , Pardi Fabio
Published: May 2018

Motivation

Taxonomic classification is at the core of environmental DNA analysis. When a phylogenetic tree can be built as a prior hypothesis to such classification, phylogenetic placement (PP) provides the most informative type of classification because each query sequence is assigned to its putative origin in the tree. This is useful whenever precision is sought (e.g. in diagnostics). However,likelihood-based PP algorithms struggle to scale with the ever-increasing throughput of DNA sequencing.

Results

We have developed RAPPAS (Rapid Alignment-free Phylogenetic Placement via Ancestral Sequences) which uses an alignment-free approach, removing the hurdle of query sequence alignment as a preliminary step to PP. Our approach relies on the precomputation of a database of k-mers that may be present with non-negligible probability in relatives of the reference sequences. The placement is performed by inspecting the stored phylogenetic origins of the k-mers in the query, and their probabilities. The database can be reused for the analysis of several different metagenomes. Experiments show that the first implementation of RAPPAS is already faster than competing likelihood-based PP algorithms, while keeping similar accuracy for short reads. RAPPAS scales PP for the era of routine metagenomic diagnostics.

Availability

Program and sources freely available for download at gite.lirmm.fr/linard/RAPPAS.

Contact

benjamin.linard@lirmm.fr
Genetic diversity in twoPlasmodium vivaxprotein ligands for reticulocyte invasion
Authors: Roesch Camille , Popovici Jean , Bin Sophalai , Run Vorleak , Kim Saorin , Ramboarina Stéphanie , Rakotomalala Emma , Rakotoarison Rado Lalaina , Rasoloharimanana Tsikiniaina , Andriamanantena Zo , Kumar Anuj , Guillotte-Blisnick Micheline , Huon Christèle , Serre David , Chitnis Chetan E. , Vigan-Womas Inès , Menard Didier
Published: May 2018

The interaction betweenPlasmodium vivaxDuffy binding protein (PvDBP) and Duffy antigen receptor for chemokines (DARC) has been described as critical for the invasion of human reticulocytes, although increasing reports ofP. vivaxinfections in Duffy-negative individuals questions its unique role. To investigate the genetic diversity of the two main protein ligands for reticulocyte invasion, PvDBP andP. vivaxErythrocyte Binding Protein (PvEBP), we analyzed 458 isolates collected in Cambodia and Madagascar. First, we observed a high proportion of isolates with multiple copies PvEBP from Madagascar (56%) where Duffy negative and positive individuals coexist compared to Cambodia (19%) where Duffy-negative population is virtually absent. Whether the gene amplification observed is responsible for alternate invasion pathways remains to be tested. Second, we found that thePvEBPgene was less diverse thanPvDBPgene (12vs.33 alleles) but provided evidence for an excess of nonsynonymous mutations with the complete absence of synonymous mutations. This finding reveals that PvEBP is under strong diversifying selection, and confirms the importance of this protein ligand in the invasion process of the human reticulocytes and as a target of acquired immunity. These observations highlight how genomic changes in parasite ligands improve the fitness ofP. vivaxisolates in the face of immune pressure and receptor polymorphisms.
Molecular determinants of WNT9b responsiveness in nephron progenitor cells
Authors: Dickinson Kyle K. , Hammond Leah C. , Karner Courtney M. , Hastie Nicholas D. , Carroll Thomas J. , Goodyer Paul R.
Published: May 2018

Primed nephron progenitor cells (NPCs) appear in metanephric mesenchyme by Ell.5 and differentiate in response to the inductive WNT9b signal from the ureteric bud. However, the NPC WNT-receptor complex is unknown. We obtained M15 cells from E10.5 mesonephric mesenchyme and systematically analyzed components required for canonical WNT9b-responsiveness. When M15 cells were transfected with a (β-catenin luciferase reporter plasmid, exposure to recombinant WNT9b resulted in minimal luciferase activity. We then analyzed mRNA-expression of WNT-pathway components and identifiedFzdl-6andLrp6transcripts but notRSPO1.When M15 cells were treated with recombinant RSPO1 the response to transfected WNT9b was augmented 4.8-fold. Co-transfection of M15 cells withFzd5(but no otherFzdfamily member) further increased the WNT9b signal to 16.8-fold and siRNA knockdown ofFzd5reduced the signal by 52%. Knockdown ofLrp6resulted in 60% WNT9b signal reduction. We confirmedFzd5, Lrp6andRSPO1rrtRNA expression in CITED1(+) NPCs from E15.5 embryonic mouse kidney. Thus, while many WNT signaling-pathway components are present by E10.5, optimum responsiveness of Ell.5 cap mesenchyme requires that NPCs acquire RSPO1, FZD5 and LRP6.

Summary Statement

Responsiveness to the inductive WMT9b signal from ureteric bud is crucial for nephrogenesis. Here we analyze the molecules needed to prime nephron progenitor cells in embryonic mouse kidney.
A concise synthesis of a highly substituted 6-(1H-benzimidazol-1-yl)-5-nitrosopyrimidin-2-amine: synthetic sequence and the molecular and supramolecular structures of one product and two intermediates
Authors: Cobo Justo , Vicentes Daniel E. , Rodríguez Ricaurte , Marchal Antonio , Glidewell Christopher
Published: May 2018

A concise and efficient synthesis of 6-benzimidazolyl-5-nitrosopyrimidines has been developed using Schiff base-type intermediates derived from N
4-(2-aminophenyl)-6-methoxy-5-nitrosopyrimidine-2,4-diamine. 6-Methoxy-N
4-{2-[(4-methylbenzylidene)amino]phenyl}-5-nitrosopyrimidine-2,4-diamine, (I), and N
4-{2-[(ethoxymethylidene)amino]phenyl}-6-methoxy-5-nitrosopyrimidine-2,4-diamine, (III), both crystallize from dimethyl sulfoxide solution as the 1:1 solvates C19H18N6O2·C2H6OS, (Ia), and C14H16N6O3·C2H6OS, (IIIa), respectively. The interatomic distances in these intermediates indicate significant electronic polarization within the substituted pyrimidine system. In each of (Ia) and (IIIa), intermolecular N—H...O hydrogen bonds generate centrosymmetric four-molecule aggregates. Oxidative ring closure of intermediate (I), effected using ammonium hexanitratocerate(IV), produced 4-methoxy-6-[2-(4-methylphenyl-1H-benzimidazol-1-yl]-5-nitrosopyrimidin-2-amine, C19H16N6O2, (II) [Cobo et al. (2018). Private communication (CCDC 1830889). CCDC, Cambridge, England], where the extent of electronic polarization is much less than in (Ia) and (IIIa). A combination of N—H...N and C—H...O hydrogen bonds links the molecules of (II) into complex sheets.
4,5-Diferrocenyl-1,2-dithiol-3-one
Authors: Sánchez García Jessica J. , Flores-Alamo Marcos , Klimova Elena I.
Published: May 2018

The title compound, [Fe2(C5H5)2(C13H8OS2)], crystallizes with two molecules in the asymmetric unit. Each molecule comprises a pair of ferrocenyl units bridged by a dithiol-3-one moiety. The dihedral angles between the dithiol-3-one ring and the substituted cyclopentadienyl rings are in the range 32.4 (3)–39.3 (3)°. One of the dithiol-3-one rings was refined as being disordered over two sets of sites while the same kind of disorder in the other molecule was negligible. The molecular packing is dominated by C—H...O hydrogen bonds and C—H...π interactions.
Tris(1,10-phenanthroline-κ2N,N′)nickel(II) bis(hexafluoridophosphate)
Authors: El Hamdani Hicham , El Amane Mohammed , Duhayon Carine
Published: May 2018

The asymmetric unit of the title compound, [Ni(C36H24N6)3](PF6)2, contains one and a half nickel(II) complex dications and three hexafluoridophosphate anions, one of the dications having crystallographic twofold rotational symmetry. Each NiIIatom displays a distorted octahedral coordination geometry provided by the six N atoms of three bidentate 1,10-phenanthroline ligands with bite angles of 79.68 (11)–80.76 (12)°. In the crystal, C—H...F hydrogen bonds link the anions and dications into a three-dimensional supramolecular framework. Within the framework complex dications with twofold rotational symmetry are linked by weak π–π stacking interactions [centroid-to-centroid distances = 3.712 (2) Å].
Measuring behavioural biases affecting real estate investment decisions in India: using IRT
Authors: Pandey Richa , Jessica V. Mary
Published: May 2018

Purpose

This study aims to investigate the behavioural biases influencing the real estate market investing decisions of normal non-professional investors in India.

Design/methodology/approach

As the study involves the behavioural data with polytomous response format, psychometric test- graded response model (IRT approach) was used for the study with the help of STATA 14. Multi-stage stratified sampling was used to collect a sample of 560 respondents. The study used a 14-item scale representing behavioural biases derived from two broad behavioural theories, i.e. heuristics and prospect theories. Sample characteristics were checked using SPSS 20. Pre-required assumptions for IRT (i.e. local independence and unidimensionality) were tested by CFA using AMOS 20.

Findings

Five items, four of which belong to heuristics (anchoring – 2, representativeness – 1 and availability bias – 1) and one belong to prospect theory (regret aversion) are sufficient to measure the behavioural attitude of real estate investors in the Indian scenario. Item discrimination ai ranged from 0.95 to 1.52 (average value 1.29), showing moderate discrimination power of the items. The items have done a pretty good job of assessing the lower level of agreement. For the higher level of agreement, the scale came out to be less precise, with less information and higher standard error of measurement.

Research limitations/implications

As the behavioural biases are often false, the study suggests the investors not to repeat these nasty biases to improve investment strategies. As they are shared and not easily changeable, understanding these biases may also help them in beating the market by acting as “noise traders”.

Practical implications

The traditional price index is incomplete in some essential respects. The inclusion of these behavioural biases into the construction of price index will greatly improve the traditional price index, policymakers should seriously think about it.

Social implications

Shelter is one of the basic needs; a dwelling unit is needed for one to stay in, develop and contribute to economy and society. If investors try to minimise these biases and policymakers keep a track of these while making strategies, mispricing in this sector can be controlled to some extent, which will ultimately help in the well-being of society.

Originality/value

This study contributes to the limited research by investigating the behavioural biases influencing the real estate market investment decisions of normal non-professional investors. It contributes to the lacking academe on real estate market in India. The study has used a psychometric test, i.e. the item response theory, for evaluating the quality of the items.
What doesn’t kill you makes you stronger: The burdens and benefits of toxin sequestration in a milkweed aphid
Authors: Züst Tobias , Mou Sophie , Agrawal Anurag A.
Published: May 2018

Specialized insect herbivores commonly co‐opt plant defences for protection against predators, but the costs, benefits and mechanisms of sequestration are poorly understood.

We quantified sequestration of toxic cardenolides by the specialist aphid Aphis nerii when reared on four closely related milkweed (Asclepias) species with >20‐fold variation in cardenolide content, and in the presence or absence of generalist ladybug predators.

Increasing concentrations of apolar plant cardenolides increased sequestered amounts in aphids. High concentrations in plants impaired aphid population growth, but also reduced the top‐down effects of predators. An in vitro enzymatic assay of total cardenolides in aphid bodies using the cardenolides’ target (animal Na+/K+‐ATPase) revealed that the subset of sequestered cardenolides is disproportionally more toxic than cardenolides in leaves.

All aphids accumulated two cardenolides not present in their host plant, even on plants with very low foliar cardenolide concentrations. Sequestration of potent cardenolides by A. nerii thus involves passive, concentration‐dependent uptake from the host plant, as well as a presumably more active mechanism of modification and up‐concentration of plant cardenolides.

The concentration of toxins in the host plant thus not only determines the negative impacts on growth and performance of an aphid, but also the ease and efficiency by which toxins are sequestered for the aphid’s defence, making the costs and benefits of plant toxins highly context‐dependent for both the plant and the herbivore. Therefore, variation in plant toxins is of central importance for co‐evolutionary plant–insect interactions, particularly in environments with variable predator pressure.

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In vivo profiling of four centrally administered opioids for antinociception, constipation and respiratory depression: Between‐colony differences in Sprague Dawley rats
Authors: Kuo Andy , Smith Maree T
Published: May 2018

Outbred rodent stocks including Sprague Dawley rats, are known for their genetic diversity and so they are often used to develop animal models of human disease. Although between‐colony differences in pharmaco‐behavioural studies have been published previously, a direct head‐to‐head comparison study, whereby all research was performed in the same laboratory by the same experimenter utilising the supraspinal route of drug administration in the same strain of rat, is lacking. Herein, we report our head‐to‐head comparison study, involving assessment of antinociception, constipation and respiratory depression evoked by single bolus intracerebroventricular (ICV) doses of morphine, buprenorphine, DPDPE and U69,593 using male Sprague Dawley rats sourced from a different breeding colony (BC2) from that (BC1) used by us previously. Our data show that there are marked differences in the potency rank order for morphine and buprenorphine between rats sourced from BC2 and BC1. Although ICV morphine evoked a bell‐shaped dose‐response curve in the constipation test for rats from both colonies, this occurred at higher doses for rats from BC2. In conclusion, our head‐to‐head comparison shows considerable between‐colony differences for the same rat strain, in the potency rank order of two clinically important strong opioid analgesics given by the ICV route.
Bangladeshi children with acute diarrhoea show faecal microbiomes with increased Streptococcus abundance, irrespective of diarrhoea aetiology
Authors: Kieser Silas , Sarker Shafiqul A. , Sakwinska Olga , Foata Francis , Sultana Shamima , Khan Zeenat , Islam Shoheb , Porta Nadine , Combremont Séverine , Betrisey Bertrand , Fournier Coralie , Charpagne Aline , Descombes Patrick , Mercenier Annick , Berger Bernard , Brüssow Harald
Published: May 2018

We report streptococcal dysbiosis in acute diarrhoea irrespective of aetiology. Compared with 20 healthy local controls, 71 Bangladeshi children hospitalized with acute diarrhoea (AD) of viral, mixed viral/bacterial, bacterial and unknown aetiology showed a significantly decreased bacterial diversity with loss of pathways characteristic for the healthy distal colon microbiome (mannan degradation, methylerythritol phosphate and thiamin biosynthesis), an increased proportion of faecal streptococci belonging to the Streptococcus bovis and Streptococcus salivarius species complexes, and an increased level of E. coli‐associated virulence genes. No enteropathogens could be attributed to a subgroup of patients. Elevated lytic coliphage DNA was detected in 2 out of 5 investigated enteroaggregative E. coli (EAEC)‐infected patients. Streptococcal outgrowth in AD is discussed as a potential nutrient‐driven consequence of glucose provided with oral rehydration solution.