bluuebunny/crossref_metadata_2025 huggingface dataset:
Benefits of Maxillary Expansion for a Patient With Spinal Muscular Atrophy Type 2
Authors: Abeleira María Teresa , Limeres Jacobo , Outumuro Mercedes , Vidal Paula Sofía , Diniz-Freitas Marcio , Ruíz-Piñón Manuel , Diz Dios Pedro
Published: August 2018

This case report involves a 10-yr-old boy diagnosed with spinal muscular atrophy type 2 who underwent nighttime mechanical ventilation with bilevel positive airway pressure. The oral examination revealed restricted mouth opening, lip interposition, dental crowding, and maxillary compression. After maxillary expansion, the upper airway volume increased 18.6%; 13 episodes of airway infections (20 days of hospitalization) were recorded in the 2 yrs before the maxillary expansion and only 4 episodes (no hospital admissions) in the 2 subsequent years. In conclusion, maxillary expansion in children with systemic disease that involves respiratory impairment may, in some cases, provide functional and clinical improvements, increase upper airway airflows, and possibly decrease the number of respiratory infections
Chemical Components Separation: Concepts, Evidence, and Outcomes
Authors: Motz Benjamin M. , Schlosser Kathryn A. , Heniford B. Todd
Published: August 2018

Ventral hernias with loss of domain pose a significant challenge to the hernia surgeon. Techniques such as advancement flaps, component separation, progressive pneumoperitoneum, and preoperative injection of botulinum toxin A (BTA) aim to alter the abdominal wall length or form to achieve tension-free primary fascial repair in abdominal wall reconstruction (AWR). Here, we review the current literature on BTA injection as an adjunct to AWR. A literature review identified 22 articles discussing the use of BTA associated with ventral hernia repair. Six primary studies reported preoperative use of BTA. Treatment regimens are not standardized, varying from 300 to 500 u injection on 3–5 sites per laterality, from 4 weeks before the day of surgery. After injection, computed tomography scans demonstrate elongated and thinned abdominal wall muscles with decreased mean defect size and hernia size. Primary fascial closure is usually achieved. Postoperative pain control may be improved with perioperative administration of BTA, and no adverse events associated with BTA injection were reported. Preoperative BTA injection is a promising adjunct to AWR, creating abdominal wall laxity and enabling primary fascial repair. Further investigation will be needed to determine the ideal dosage, timing, and patient population.
Mesh Selection in Abdominal Wall Reconstruction
Authors: Lak Kathleen L. , Goldblatt Matthew I.
Published: August 2018

Selection of mesh for ventral hernia repair and abdominal wall reconstruction can be challenging. Since the adoption of a tension-free mesh repair, the recurrence rates and outcomes after ventral hernia repair have substantially improved. The market for medical prostheses is constantly changing, with new technology in development attempting to create the ideal mesh for each clinical scenario. Permanent mesh is typically used for clean wounds. The various mesh materials, density, and pore sizes are discussed. In addition, the materials commonly used for contaminated wounds (absorbable synthetic and biologic meshes) are described. The latest literature regarding the use of various mesh materials is reviewed and organized to help make an informed decision regarding the appropriate use of reinforcing material.
The Perfect Plane: A Systematic Review of Mesh Location and Outcomes, Update 2018
Authors: Sosin Michael , Nahabedian Maurice Y. , Bhanot Parag
Published: August 2018

Background:

The principal approach to abdominal wall reconstruction requires implantation of mesh to decrease ventral hernia recurrence. This study compared current surgical outcomes and complications by location of anatomic mesh placement following ventral hernia repair with onlay, interposition, retromuscular, or underlay mesh reconstruction.

Methods:

A systematic search of the PubMed database published from 2013 to 2018 was performed to identify patients who underwent abdominal wall reconstruction using either biologic or prosthetic mesh for ventral hernia repair. Demographic information and outcomes were obtained from each study.

Results:

Fifty-one articles met inclusion criteria, resulting in 6,227 patients who underwent mesh repair of a ventral hernia. Mesh position included onlay in 7.6% of patients, interposition in 13.2%, retromuscular in 35.9%, and underlay placement in 43.4%. Prosthetic mesh was used in 68.5% of repairs and biological mesh in 31.5%. The mean patient age was 53.1 years (range, 18–95 years), and mean BMI was 29.1 kg/m2 (range, 15–70.9 kg/m2). The mean follow-up was 37.5 ± 2.3 months. The overall mean recurrence rate was 8.3%, with retromuscular (5.8%) and underlay (10.9%) mesh placement trending toward less recurrence than onlay (12.9%) and interposition (21.6%) mesh placement (P = 0.023). Inferior recurrence rates were identified in the onlay and interposition placement of biologic mesh (28.6% and 29.1%, respectively), and analysis of open approaches yielded significant differences with onlay and interposition repairs having the highest hernia recurrence rates (10.9% and 25.4%, respectively). Laparoscopic interposition mesh location showed highest recurrence (10%) as compared with retromuscular (0.1%) and underlay (4.2%) (P = 0.041).

Conclusions:

Mesh reinforcement of a ventral hernia repair continues to be safe and efficacious, and the anatomic location of mesh implantation appears to influence outcomes. Retromuscular or underlay mesh repair is associated with a lower recurrence rate.
Prevention and Treatment Strategies for Mesh Infection in Abdominal Wall Reconstruction
Authors: Kao Angela M. , Arnold Michael R. , Augenstein Vedra A. , Heniford B. Todd
Published: August 2018

Background:

Mesh infection remains the most feared complication after abdominal wall reconstruction, requiring prolonged hospitalizations and often, mesh removal. Understanding of current prevention and treatment strategies is necessary in the management of a common surgical problem.

Methods:

A comprehensive review of the current surgical literature was performed to determine risk factors of mesh infection after abdominal wall reconstruction and best practices in their prevention and surgical management.

Results:

Patient-related risk factors for mesh infections include smoking, obesity, diabetes mellitus, and COPD. Surgical risk factors such as prolonged operative time and prior enterotomy should also be considered. Prevention strategies emphasize reduction of modifiable risk factors, including obesity and diabetes among other comorbidities. Biologic or biosynthetic mesh is recommended in contaminated fields and use of delayed wound closure or vacuum-assisted closure therapy should be considered in high-risk patients. Conservative treatment with antibiotics, percutaneous or surgical drainage, and negative-pressure vacuum-based therapies have demonstrated limited success in mesh salvage. Mesh infection often requires mesh explantation followed by abdominal wall reconstruction. Staged repairs can be performed; however, definitive hernia repair with biologic mesh has shown promising results.

Conclusions:

Management of mesh infections is a complex, yet commonly faced problem. Strategies used in the prevention and surgical treatment of infected mesh should continue to be supported by high-quality evidence from prospective studies.
The Value Proposition for Complex Abdominal Wall Reconstruction: How to Make It Work
Authors: Ramshaw Bruce , Forman Brandie , Barker Elizabeth , Grimsley Lauren
Published: August 2018

Background:

The challenge for health care in the 21st century is to understand how to measure and improve value in the context of each patient care process for the entire cycle of care. For patients who undergo an abdominal wall reconstruction, there is a great opportunity to improve value because of the high cost and variability in outcomes for this complex operation.

Methods:

For almost a decade, our hernia team has been applying the principles of systems and data science to actual patient care. Tools from systems and data science applied to patient care include clinical quality improvement and nonlinear analytical methods such as factor analysis. The most important outcome to measure and improve is the value of care provided for the entire cycle of care.

Results:

Many measurement and improvement ideas have been applied to the abdominal wall reconstruction process in our hernia program, including the use of a less costly long-term resorbable mesh, multimodal pain management and enhanced recovery process improvement ideas, and surgical technique improvements that have led to decreased wound complications and the elimination of abdominal wall drains. More recently, the data analysis has shown an opportunity to improve outcomes through a robust prehabilitation program, including cognitive therapy to induce neural rewiring before surgery.

Conclusions:

Improving value for patients who undergo abdominal wall reconstruction and for all patients in our global health care system should be a unifying goal. Understanding and applying systems and data science tools appropriately are necessary to achieve this goal.
The Role and Impact of Registries on Abdominal Wall Reconstruction
Authors: Poulose Benjamin K. , Rosen Michael J.
Published: August 2018

Implicit to any surgeon’s abdominal wall reconstruction (AWR) practice should be the review of results after operations have been performed. This allows surgeons to ensure they are delivering high-quality care to patients. In addition, systematic collection of data centered around AWR greatly facilitates research and postmarket surveillance of medical devices and techniques. Unfortunately, systematic data collection across hospitals is a very challenging endeavor, often made difficult by health care systems focused on maximizing volume rather than delivering appropriate, high-quality care in the long term. Nonetheless, it is imperative that all stakeholders involved in AWR help clinicians collect data during routine health care delivery to help patients’ quality of life.
Brief Report: Intimate Partner Violence and Antiretroviral Therapy Initiation Among Female Sex Workers Newly Diagnosed With HIV in Zambia: A Prospective Study
Authors: Oldenburg Catherine E. , Ortblad Katrina F. , Chanda Michael M. , Mwale Magdalene , Chongo Steven , Kanchele Catherine , Kamungoma Nyambe , Fullem Andrew , Bärnighausen Till
Published: August 2018

Background:

Intimate partner violence (IPV) is common among female sex workers (FSW) globally. Here, we prospectively assessed the relationship between IPV and engagement in HIV care in a cohort of FSW who had been newly diagnosed with HIV.

Methods:

Data arose from the Zambian Peer Educators for HIV Self-Testing study, a randomized controlled trial of HIV self-test distribution among FSW in 3 transit towns in Zambia. Participants were self-reported to be HIV-uninfected or unaware of their status at baseline. IPV in the previous 12 months was assessed at baseline. At 4 months, participants were asked the results of their last HIV test and those who reported testing positive were asked whether they had engaged in HIV-related care and started antiretroviral therapy (ART).

Results:

Of 964 participants, 234 (24.3%) reported that they were living with HIV at 4 months. Of these 234 participants, 142 (60.7%) reported a history of IPV (past 12 months) at baseline and at 4 months, 152 (65.0%) reported that they were in HIV-related care, and 132 (56.7%) reported that they had initiated ART. Participants who reported IPV had significantly reduced odds of engagement in care (adjusted odds ratio = 0.48, 95% confidence interval: 0.26 to 0.91) and ART initiation (adjusted odds ratio = 0.40, 95% confidence interval: 0.22 to 0.72).

Conclusions:

FSW living with HIV in Zambia reported very high rates of IPV. Structural and individual interventions for violence prevention are urgently needed to better protect this population. Given the strong negative relationship between IPV and engagement in HIV-related care, such interventions could also substantially improve HIV-related health outcomes.
Angiostrongylus cantonensis in travelers: clinical manifestations, diagnosis, and treatment
Authors: Ansdell Vernon , Wattanagoon Yupaporn
Published: August 2018

Purpose of review

Angiostrongylus cantonensis eosinophilic meningitis is a neglected, yet important emerging disease, which has been increasingly recognized in travelers. In this review, we describe the occurrence of the disease in travelers, sources of infection, clinical manifestations, diagnosis, and currently recommended treatment.

Recent findings

Various intermediate hosts and/or paratenic hosts can be the source of infection in humans. Serological tests for antibody may be negative early in the course of the disease but PCR for antigen detection in the CSF has recently been developed and may help to make the diagnosis at an earlier stage. High-dose corticosteroids (e.g. prednisolone 60 mg per day for at least 1–2 weeks) are currently the recommended treatment. Efficacy and safety of antihelminthic drugs for treatment remains controversial because of theoretical concerns that they may worsen the inflammatory response to dead and dying worms. Previous clinical trials were conducted with small numbers of participants and were underpowered. Further well designed clinical trials are urgently needed.

Awareness about increasing numbers of A. cantonensis eosinophilic meningitis in travelers is very important. Travelers should be advised about possible sources of infection. Diagnosis should be confirmed by antigen or antibody detection in blood or CSF. High-dose corticosteroids are the recommended treatment. The efficacy of various antihelminthic drugs is unproven. A large-scale, double-blind, randomized, controlled trial of antihelminthic drug involving antihelminthic drugs such as albendazole is necessary to prove the efficacy before formally advocating their use on a regular basis
The relationship between muscle mass and function in cancer cachexia: smoke and mirrors?
Authors: Ramage Michael I. , Skipworth Richard J.E.
Published: August 2018

Purpose of review

Randomized clinical trials of cancer cachexia interventions are based on the premise that an increase in the muscle mass of patients is associated with consequent improvements in muscle function, and ultimately, quality of life. However, recent trials that have succeeded in demonstrating increases in lean body mass have been unable to show associated increases in patient physical function. In this review, we examine the potential causes for this lack of association between muscle mass and function in cancer cachexia, paying particular attention to those factors that may be at play when using body composition analysis techniques involving cross-sectional imaging. Moreover, we propose a new population-specific model for the relationship between muscle mass and physical function in patients with cancer cachexia.

Recent findings

The ROMANA 1 and 2 trials of anamorelin (a novel ghrelin agonist) and the POWER 1 and 2 trials of enobosarm (a selective androgen receptor modulator) were able to demonstrate improvements in patient lean body mass, but not the functional co-primary endpoints of handgrip strength and stair climb power, respectively. We report similar confirmatory findings in other studies, and describe potential reasons for these observations.

The relationship between muscle mass and muscle function is complex and unlikely to be linear. Furthermore, the relationship is influenced by the techniques used to assess nutritional endpoints [e.g. computed tomography (CT)]; the nature of the chosen physical function outcome measures; and the sex and severity of the recruited cachectic patients. Such factors need to be considered when designing intervention trials for cancer cachexia with functional endpoints.
Impact of Deceased Donor Cardiac Arrest Time on Postpancreas Transplant Graft Function and Survival
Authors: Schroering Joel R. , Mangus Richard S. , Powelson John A. , Fridell Jonathan A.
Published: August 2018

Introduction

Transplantation of pancreas allografts from donors that have experienced preprocurement cardiopulmonary arrest (PPCA) is not common, though use of PPCA grafts is routine in liver and kidney transplantation. This article reviews a large number of PPCA pancreas grafts at a single center and reports posttransplant outcomes including early graft dysfunction, length of hospital stay, rejection, and early and late graft survival.

Methods

Preprocurement cardiopulmonary arrest, arrest time, and donor and recipient pancreatic enzyme levels were collected from electronic and written medical records. The PPCA donors were stratified into 4 groups: none, less than 20 minutes, 20-39 minutes, and 40 minutes or greater. Graft survival was assessed at 7 and 90 days and at 1 year. Long-term graft survival was assessed by Cox regression analysis.

Results

The records of 606 pancreas transplants were reviewed, including 328 (54%) simultaneous pancreas and kidney transplants. Preprocurement cardiopulmonary arrest occurred in 176 donors (29%; median time, 20 minutes). Median peak donor lipase was higher in PPCA donors (40 μ/L vs 29 μ/L, P = 0.02). Posttransplant, peak recipient amylase, and lipase levels were similar (P = 0.63). Prolonged arrest time (>40 minutes) was associated with higher donor peak lipase and lower recipient peak amylase (P = 0.05 for both). Stratified by donor arrest time, there was no difference in 7-day, 90-day, or 1-year graft survival. Cox regression comparing the 4 groups demonstrated no statistical difference in 10-year survival.

Conclusions

These results support transplantation of pancreas allografts from PPCA donors. Prolonged asystole was associated with higher peak donor serum lipase but lower peak recipient serum amylase. There were no differences in allograft survival.
Development of an environmental DNA method for monitoring fish communities: ground truthing in diverse lakes with characterised fish faunas
Authors: Li Jianlong , Hatton-Ellis Tristan W. , Lawson Handley Lori-Jayne , Kimbell Helen S. , Benucci Marco , Peirson Graeme , Hänfling Bernd
Published: August 2018

Accurate, cost-effective monitoring of fish is required to assess the quality of lakes under the European Water Framework Directive (WFD). Recent studies have shown that environmental DNA (eDNA) metabarcoding is an effective and non-invasive method, which can provide semi-quantitative information on fish communities in large lakes.

This study further investigated the potential of eDNA metabarcoding as a tool for WFD status assessment by collecting and analysing water samples from eight Welsh lakes and six meres in Cheshire, England, with well described fish faunas. Water samples (N= 252) were assayed using two mitochondrial DNA regions (Cytb and 12S rRNA).

eDNA sampling indicated the presence of very similar species in the lakes compared to those expected on the basis of existing and historical information. In total, 24 species were detected with a total of 111 species occurrences in the lakes studied using eDNA. Secondly, there was a significant positive correlation between expected faunas and eDNA data in terms of confidence of species occurrence (Spearman’sr= 0.74,df= 109,p<; 0.001). Thirdly, eDNA data can estimate relative abundance with the standard five-level classification scale (“DAFOR”). Lastly, four ecological fish communities were characterised using eDNA data which agrees with the pre-defined lake types according to environmental characteristics.

Synthesis and applications. This study provides further evidence that eDNA metabarcoding could be a powerful and non-invasive monitoring tool for WFD purpose in a wide range of lake types, considerably outperforming other methods for community level analysis.
Investigating functional brain network integrity using a traditional and novel diagnostic system for neurodevelopmental disorders
Authors: Dajani Dina R. , Burrows Catherine A. , Odriozola Paola , Baez Adriana , Nebel Mary Beth , Mostofsky Stewart H. , Uddin Lucina Q.
Published: August 2018

Background

Current diagnostic systems for neurodevelopmental disorders do not have clear links to underlying neurobiology, limiting their utility in identifying targeted treatments for individuals. Several factors contribute to this issue, including the use of small samples in neuroimaging research and heterogeneity within diagnostic categories. Here, we aimed to investigate differences in functional brain network integrity between traditional diagnostic categories (autism spectrum disorder [ASD], attention-deficit/hyperactivity disorder [ADHD], typically developing [TD]) and carefully consider the impact of comorbid ASD and ADHD on functional brain network integrity in a large sample. We also assess the neurobiological validity of a novel, potential alternative nosology based on behavioral measures of executive function.

Method

Five-minute resting-state fMRI data were obtained from 168 children (128 boys, 40 girls) with ASD, ADHD, comorbid ASD and ADHD, and TD children. Independent component analysis and dual regression were used to compute within- and between-network functional connectivity metrics at the individual level.

Results

No significant group differences in within- nor between-network functional connectivity were observed between traditional diagnostic categories (ASD, ADHD, TD) even when stratified by comorbidity (ASD+ADHD, ASD, ADHD, TD). Similarly, subgroups classified by executive functioning levels showed no group differences.

Conclusions

Using clinical diagnosis and behavioral measures of executive function, no group differences were observed among the categories examined. Therefore, we suggest that brain imaging metrics may more effectively define clinical subgroups than behavioral metrics, and may contribute to the establishment of a neurobiologically valid nosology for neurodevelopmental disorders.
Quantitative mass spectrometry to interrogate proteomic heterogeneity in metastatic lung adenocarcinoma and validate a novel somatic mutation CDK12-G879V
Authors: Zhang Xu , Nguyen Khoa Dang , Rudnick Paul , Roper Nitin , Kawaler Emily , Maity Tapan K. , Asasthi Shivangi , Gao Shaojian , Biswas Romi , Venugopalan Abhilash , Cultraro Constance M. , Fenyö David , Guha Udayan
Published: August 2018

Lung cancer is the leading cause of cancer death both in men and women. Tumor heterogeneity is an impediment to targeted treatment of all cancers, including lung cancer. Here, we sought to characterize changes in tumor proteome and phosphoproteome by longitudinal, prospective collection of tumor tissue of an exceptional responder lung adenocarcinoma patient who survived with metastatic lung adenocarcinoma for more than seven years with HER2-directed therapy in combination with chemotherapy. We employed “Super-SILAC” and TMT labeling strategies to quantify the proteome and phosphoproteome of a lung metastatic site and ten different metastatic progressive lymph nodes collected across a span of seven years, including five lymph nodes procured at autopsy. We identified specific signaling networks enriched in lung compared to the lymph node metastatic sites. We correlated the changes in protein abundance with changes in copy number alteration (CNA) and transcript expression. To further interrogate the mass spectrometry data, patient-specific database was built incorporating all the somatic variants identified by whole genome sequencing (WGS) of genomic DNA from the lung, one lymph node metastatic site and blood. An extensive validation pipeline was built for confirmation of variant peptides. We validated 360 spectra corresponding to 55 germline and 6 somatic variant peptides. Targeted MRM assays demonstrated expression of two novel variant somatic peptides, CDK12-G879V and FASN-R1439Q, with expression in lung and lymph node metastatic sites, respectively. CDK12 G879V mutation likely results in a nonfunctional CDK12 kinase and chemotherapy susceptibility in lung metastatic sites. Knockdown of CDK12 in lung adenocarcinoma cells results in increased chemotherapy sensitivity, explaining the complete resolution of the lung metastatic sites in this patient.
A pipeline for rapidly generating genetically engineered mouse models of pancreatic cancer using invivoCRISPRCas9 mediated somatic recombination
Authors: Ideno Noboru , Yamaguchi Hiroshi , Okumara Takashi , Huang Jonathon , Brun Mitchel J. , Ho Michelle L. , Suh Junghae , Gupta Sonal , Maitra Anirban , Ghosh Bidyut
Published: August 2018

Genetically engineered mouse models (GEMMs) that recapitulate the major genetic drivers in pancreatic ductal adenocarcinoma (PDAC) have provided unprecedented insights into the pathogenesis of this lethal neoplasm. Nonetheless, generating an autochthonous model is an expensive, time consuming and labor intensive process, particularly when tissue specific expression or deletion of compound alleles are involved. In addition, many of the current PDAC GEMMs cause embryonic, pancreas-wide activation or loss of driver alleles, neither of which reflects the cognate human disease scenario. The advent of CRISPR/Cas9 based gene editing can potentially circumvent many of the aforementioned shortcomings of conventional breeding schema, but ensuring the efficiency of gene editingin vivoremains a challenge. Here we have developed a pipeline for generating PDAC GEMMs of complex genotypes with high efficiency using a single “workhorse” mouse strain expressing Cas9 in the adult pancreas under ap48promoter. Using adeno-associated virus (AAV) mediated delivery of multiplexed guide RNAs (sgRNAs) to the adult murine pancreas ofp48-Cre; LSL-Cas9mice, we confirm our ability to express an oncogenicKrasG12Dallele through homology-directed repair (HDR), in conjunction with CRISPR-induced disruption of cooperating alleles (Trp53, Lkb1andArid1A). The resulting GEMMs demonstrate a spectrum of precursor lesions (pancreatic intraepithelial neoplasia [PanIN] or Intraductal papillary mucinous neoplasm [IPMN] with eventual progression to PDAC. Next generation sequencing of the resulting murine PDAC confirms HDR of oncogenicKrasG12Dallele at the endogenous locus, and insertion deletion (“indel”) and frameshift mutations of targeted tumor suppressor alleles. By using a single “workhorse” mouse strain and optimal AAV serotype forin vivogene editing with combination of driver alleles, we have created a facile autochthonous platform for interrogation of the PDAC genome.
Analysis of Polygenic Score Usage and Performance in Diverse Human Populations
Authors: Duncan LE , Shen H , Gelaye B , Ressler KJ , Feldman MW , Peterson RE , Domingue BW
Published: August 2018

Studies examining relationships between genotypic and phenotypic variation have historically been carried out on people of European ancestry. Efforts are underway to address this limitation, but until they succeed, the legacy of a Euro-centric bias will continue to hinder research, including the use of polygenic scores, which are individual-level metrics of genetic risk. Ongoing debate surrounds the generalizability of polygenic scores based on genome-wide association studies (GWAS) conducted in European ancestry samples, to non-European ancestry samples. We analyzed the first decade of polygenic scoring studies (2008-2017, inclusive), and found that 67% of studies included exclusively European ancestry participants and another 19% included only East Asian ancestry participants. Only 3.8% of studies were carried out on samples of African, Hispanic, or Indigenous peoples. We find that effect sizes for European ancestry-derived polygenic scores are only 36% as large in African ancestry samples, as in European ancestry samples (t=−10.056, df=22, p=5.5×10−10). Analyzing global populations, we show that relationships between height polygenic scores and height are highly dependent on methodological choices in polygenic score construction, highlighting the need for caution in interpreting population level differences in distributions of polygenic scores, as currently calculated. These findings bolster the rationale for large-scale GWAS in diverse human populations and highlight the need for better handling of linkage disequilibrium and variant frequencies when applying scores to non-European samples.
Nascent chromatin occupancy profiling reveals locus and factor specific chromatin maturation dynamics behind the DNA replication fork
Authors: Gutiérrez Mónica P. , MacAlpine Heather K. , MacAlpine David M.
Published: August 2018

Proper regulation and maintenance of the epigenome is necessary to preserve genome function. However, in every cell division, the epigenetic state is disassembled and then re-assembled in the wake of the DNA replication fork. Chromatin restoration on nascent DNA is a complex and regulated process that includes nucleosome assembly and remodeling, deposition of histone variants, and the re-establishment of transcription factor binding. To study the genome-wide dynamics of chromatin restoration behind the DNA replication fork, we developed Nascent Chromatin Occupancy Profiles (NCOPs) to comprehensively profile nascent and mature chromatin at nucleotide resolution. While nascent chromatin is inherently less organized than mature chromatin, we identified locus specific differences in the kinetics of chromatin maturation that were predicted by the epigenetic landscape, including the histone variant H2A.Z which marked loci with rapid maturation kinetics. The chromatin maturation at origins of DNA replication was dependent on whether the origin underwent initiation or was passively replicated from distal-originating replication forks suggesting distinct chromatin assembly mechanisms between activated and disassembled pre-replicative complexes. Finally, we identified sites that were only occupied transiently by DNA-binding factors following passage of the replication fork which may provide a mechanism for perturbations of the DNA replication program to shape the regulatory landscape of the genome.
Bacterial predator-prey coevolution selects on virulence-associated prey defences
Authors: Nair Ramith R , Vasse Marie , Wielgoss Sébastien , Sun Lei , Yu Yuen-Tsu Nicco , Velicer Gregory J
Published: August 2018

The most recent version of this paper has been removed owing to copyright violation. Earlier versions of the paper remain available.
Viral Infection Skews Immunoglobulin Light Chain Repertoire Diversity
Authors: Schwartz John C. , Murtaugh Michael P.
Published: August 2018

Antibody responses are fundamentally important to effector and memory mechanisms of disease resistance. Antibody repertoire diversity and its response to natural infection is poorly understood, yet is a prerequisite for molecular and structural elucidation of functionally protective immunity to viral infections. Using a swine model of mammalian viral infection, we observed marked changes following infection with the major porcine pathogen, porcine reproductive and respiratory syndrome virus (PRRSV). Deep sequencing of >516,000 light chain VJ mRNA genes showed that, similar to humans, swine utilize both lambda and kappa loci equivalently. However, V and J gene usage were highly restricted; ≥99% of lambda light chains were IGLV3 and IGLV8 family members joined to IGLJ2 or IGLJ3, and 100% of kappa locus transcripts were IGKV1 or IGKV2 with only IGKJ2. Complementarity-determining region (CDR) variation was limited. Nevertheless, total diversity richness estimates were 2.3 × 105 for lambda and 1.5 × 105 for kappa, due in part to extensive germline variation in framework regions and allelic variation. Infection by PRRSV reduced total richness due to expression of several highly abundant clonal populations. Antibody light chain repertoires differed substantially among individuals, thus illustrating extensive potential variation in immune response in outbred populations. These findings demonstrate that individual variation in light chain repertoires may be an important component of variable antibody responses to infection and vaccination, and that swine are a relevant model of human antibody diversification in which the immune response capacity is critical to understanding individual variation in immune protection against disease.

Conflict of interest statement

The authors declare no conflicts of interest.

Highlights

λ and κ light chain diversity is equivalent to heavy chain diversity

High diversity is present despite limited gene segment usage

PRRSV infection increases abundance of dominant λ and κ VJ clones

High levels of variation are present among animals
Short Term Evolutionary Dynamics ofEscherichia Coliin Different Carbon Environments
Authors: Choudhury Debika , Saini Supreet
Published: August 2018

Starting from a parentalE. coliK-12 MG1655 strain, we evolve cells in five different carbon environments-glucose, arabinose, xylose, rhamnose, and a mixture of these four sugars (in a predefined ratio) for approximately 2,000 generations. At the end of the adaptation period, we quantify and compare growth dynamics of the strains in a variety of environments. The evolved strains show no specialized adaptation towards growth in the carbon medium in which they were evolved. Rather, in all environments, the evolved strains exhibited a reduced lag phase and an increased growth rate. Sequencing results reveal that these dynamical properties are not introduced via mutations in the precise loci associated with utilization of the sugar in which the bacterium was evolved in. These phenotypic changes are rather likely introduced via mutationselsewhere onthe genome. Sugar systems are known to exhibit hierarchy in utilization. Evolution in a defined environment, in our experimental framework, does not alter this hierarchy.
Gene expression plasticity and frontloading promote thermotolerance inPocilloporacorals
Authors: Brener-Raffalli K. , Vidal-Dupiol J. , Adjeroud M. , Rey O. , Romans P. , Bonhomme F. , Pratlong M. , Haguenauer A. , Pillot R. , Feuillassier L. , Claereboudt M. , Magalon H. , Gélin P. , Pontarotti P. , Aurelle D. , Mitta G. , Toulza E.
Published: August 2018

Ecosystems worldwide are suffering from climate change. Coral reef ecosystems are globally threatened by increasing sea surface temperatures. However, gene expression plasticity provides the potential for organisms to respond rapidly and effectively to environmental changes, and would be favored in variable environments. In this study, we investigated the thermal stress response inPocilloporacoral colonies from two contrasting environments by exposing them to heat stress. We compared the physiological state, bacterial and Symbionaceae communities (using 16S and ITS2 metabarcoding), and gene expression levels (using RNA-Seq) between control conditions and heat stress (the temperature just below the first signs of compromised health). Colonies from both thermal regimes remained apparently normal and presented open and colored polyps during heat stress, with no change in bacterial and Symbionaceae community composition. In contrast, they differed in their transcriptomic responses. The colonies from Oman displayed a more plastic transcriptome, but some genes had a higher basal expression level (frontloading) compared to the less thermotolerant colonies from New Caledonia. In terms of biological functions, we observed an increase in the expression of stress response genes (including induction of tumor necrosis factor receptors, heat shock proteins, and detoxification of reactive oxygen species), together with a decrease in the expression of genes involved in morpho-anatomical functions. Gene regulation (transcription factors, mobile elements, histone modifications and DNA methylation) appeared to be overrepresented in the Oman colonies, indicating possible epigenetic regulation. These results show that transcriptomic plasticity and frontloading can be co-occurring processes in corals confronted to highly variable thermal regimes.
Acetate and hypertonic stress stimulate organelle membrane fission using distinct phosphatidylinositol signals
Authors: Patel Dipti , Brett Christopher Leonard
Published: August 2018

Organelle morphology reflects an equilibrium between membrane fusion and fission that determines size, shape and copy number. By studying the yeast vacuole as a model, the conserved molecular mechanisms responsible for organelle fusion have been revealed. However, a detailed understanding of vacuole fission and how these opposing processes respond to the cell cycle, osmoregulation or metabolism to change morphology remain elusive. Thus, herein we describe a new fluorometric assay to measure vacuole fission in vitro. For proof-of-concept, we use this assay to confirm that acetate, a key intermediary metabolite, triggers vacuole fission in vitro and show that it also blocks homotypic vacuole fusion. The basis of this effect is distinct from hypertonic stress, a known trigger of fission and inhibitor of fusion that inactivates the Rab-GTPase Ypt7: Treatment with the phosphatidylinositol-kinase inhibitor wortmannin or the catalytic domain of the Rab-GAP (GTPase Activating Protein) Gyp1 reveal that fission can be triggered by Ypt7 inactivation alone in absence of hypertonic stress, placing it upstream of PI-3,5-P2synthesis and osmosis required for membrane scission. Whereas acetate seems to block PI-4-kinase to possibly increase the pool of PI on vacuole membranes needed to synthesize sufficient PI-3,5-P2for fission. Thus, we speculate that both PI-4-P and PI-3-P arms of PI-P signaling drive changes in membrane fission and fusion responsible altering vacuole morphology in response to cellular metabolism or osmoregulation.

GRAPHICAL ABSTRACT
Origins and geographic diversification of African rice (Oryza glaberrima)
Authors: Veltman Margaretha A. , Flowers Jonathan M. , van Andel Tinde R. , Schranz M. Eric
Published: August 2018

Rice is a staple food for the majority of our world’s growing population. Whereas Asian rice (Oryza sativaL.) has been extensively studied, the exact origins of African rice (Oryza glaberrimaSteud.) are still contested. Previous studies have supported either a centric or a non-centric origin of African rice domestication. Here we review the evidence for both scenarios through a critical reassessment of 206 whole genome sequences of domesticated and wild African rice. While genetic diversity analyses support a severe bottleneck caused by domestication, signatures of recent and strong positive selection do not unequivocally point to candidate domestication genes, suggesting that domestication proceeded differently than in Asian rice – either by selection on different alleles, or different modes of selection. Population structure analysis revealed five genetic clusters localising to different geographic regions. Isolation by distance was identified in the coastal populations, which could account for parallel adaptation in geographically separated demes. Although genome-wide phylogenetic relationships support an origin in the eastern cultivation range followed by diversification along the Atlantic coast, further analysis of domestication genes shows distinct haplotypes in the southwest - suggesting that at least one of several key domestication traits might have originated there. These findings shed new light on an old controversy concerning plant domestication in Africa by highlighting the divergent roots of African rice cultivation, including a separate centre of domestication activity in the Guinea Highlands. We thus suggest that the commonly accepted centric origin of African rice must be reconsidered in favour of a non-centric or polycentric view.
Spatio-temporal variability of soil nutrients and the responses of growth during growth stages of winter wheat in the north of China
Authors: Bao-wei Su , Geng-xing Zhao , Chao Dong
Published: August 2018

Study on soil nutrient variability and its effect on the growth and development of crop under traditional tillage mode is the foundation to comprehensively implement the precision agriculture policy on the field scale and crop excellent management. In this paper, a winter wheat field of 28.5 hm2 under traditional cultivation model in Tianzhuang town of Huantai county was selected as the research area. Sampling by mesh point method (60×60m), the variation characteristics of soil available nitrogen (AN), available phosphorus (AP) and available potassium (AK) in the before sowing, reviving stage, jointing stage, filling stage of winter wheat were analyzed by the method of geostatistics and GIS. At the same time, Pearson correlation analysis was used to study the response of wheat growth and development to soil nutrient variation. As the growth period goes by, 1) each nutrient showed low-high-low and moderate variability. AN and AK had the highest content at reviving stage, while AP at jointing stage, as turning point. The order of variability of each nutrient was AN>AP>AK. 2) The difference of nutrient variation first increased and then decreased, and showed medium to strong spatial correlation.

Three nutrients in the before sowing stage were strong spatial correlation, and the reviving stage was medium spatial correlation, to the jointing and filling stages, AN was medium spatial correlation, AP and AK were strong spatial correlation. The spatial correlation of each nutrients was the weakest in the reviving stage, and AN was the strongest in the before sowing stage, while AP and AK were strongest in the jointing stage. The spatial correlation of each soil nutrients decreased from before sowing to reviving stage, jointing stage to filling stage, and the spatial correlation increased from reviving stage to jointing stage. 3) Soil nutrient content first increased and then decreased, and the grade of nutrient gradually decreased. 4) The correlation between soil nutrients and wheat growth was gradually increasing. AN had the highest correlation with wheat growth, followed by AK and AP lowest. The effect of soil nutrients on the growth of wheat at the reviving stage was higher than that of the current nutrient, and the growth of wheat at jointing stage was mainly influenced by the current nutrient, while the growth of wheat at the filling period was both influenced by the nutrient content of the last and the current period; the date to supplement fertilizer should be postponed properly. In this study, the soil nutrient dynamics and its influence on the growth of wheat during the winter wheat growth period under the traditional field model were well understood, which could provide a theoretical basis for the precision management of soil nutrients in the northern winter wheat area with relatively uniform planting environment and cultivation management.
Quantitative Assessment of Colorectal Cancer Progression: a Comparative Study of Linear and Nonlinear Microscopy Techniques
Authors: Adur J. , Erbes L. , Bianchi M. , Ruff S. , Zeitoune A. , Izaguirre M.F. , Cesar C.L. , Carvahlo H.F. , Casco V.H.
Published: August 2018

BACKGROUND AND AIMS

Colorectal cancer (CRC) is a disease that can be prevented if is diagnosed and treated at pre-invasive stages. Thus, the monitoring of colonic cancer progression can improve the early diagnosis and detection of malignant lesions in the colon. This monitoring should be performed with appropriate image techniques and be accompanied by proper quantification to minimize subjectivity. We have monitored the mice CRC progression by image deconvolution, two-photon emission fluorescence (TPEF) and second harmonic generation (SHG) microscopies and present different quantization indices for diagnosis.

METHODS

The Azoxymethane (AOM) / dextran sodium sulfate (DSS) protocol was used. 35 eight-week old male BALB/cCmedc mice were used and distal colon segments were dissected at day zero and fourth, eighth, sixteen, and twenty weeks after injection. These segments were observed with linear and nonlinear optical microscopies and several parameters were used for quantification.

RESULTS

Crypt diameter higher than 0.08 mm and increased fluorescence signal intensity in linear images; as well as aspect relation above 0.7 and altered organization reflexed by high-energy values obtained from SHG images, away from those obtained in normal tissues.

CONCLUSION

The combination of linear and nonlinear signals improve the detection and classification of pathological changes in crypt morphology/distribution and collagen fiber structure/arrangement. In combination with standard screening approaches for CRC, the proposed methods improve the detection of the disease in its early stages, thereby increasing the chances of successful treatment.
Activation of TAp73 and inhibition of thioredoxin reductase for improved cancer therapy inTP53 mutant pancreatic tumors
Authors: Acedo Pilar , Fernandes Aristi , Zawacka-Pankau Joanna
Published: August 2018

The p73 is a tumor suppressor that compensates for p53 loss and induces apoptosis in tumors in response to genotoxic stress or small-molecule treatments.

Pancreatic ductal adenocarcinoma (PDAC) has a late onset of the disease, responds poorly to the existing therapies and has very low overall survival rates.

Here, using drug-repurposing approach, we found that protoporphyrin IX (PpIX) and benzoporphyrin derivative monoacid ring A (BPD) activate p73 and induce apoptosis in pancreatic cancer cells. PpIX and BPD induce reactive oxygen species and inhibit thioredoxin reductase 1 (TrxR1). Thus, PpIX and BPD target cancer cells’ vulnerabilities namely activate TAp73 tumor suppressor and inhibit oncogenic TrxR1. Our findings, may contribute to faster repurposing of PpIX and BPD to treat pancreatic tumors.

Lay Abstract

Despite the efforts, pancreatic cancer remains among the most aggressive tumors. Late diagnoses often linked with the asymptomatic disease progression make it extremely difficult to cure. We have used drugs that are already in clinics and applied in photodynamic therapy of cancer and showed that the compounds induce death of cancer cells. The mechanism is via activation of p73 tumor suppressor and inhibition oncogenic thioredoxin reductase. Molecules that in parallel induce two pathways leading to cell death might be very promising candidates for improved cancer therapy in pancreatic cancer patients.
Predicting protein-peptide interaction sites using distant protein complexes as structural templates
Authors: Johansson-Åkhe Isak , Mirabello Claudio , Wallner Björn
Published: August 2018

Protein-peptide interactions play an important role in major cellular processes, and are associated with several human diseases. To understand and potentially regulate these cellular function and diseases it is important to know the molecular details of the interactions. However, because of peptide flexibility and the transient nature of protein-peptide interactions, peptides are difficult to study experimentally. Thus, computational methods for predicting structural information about protein-peptide interactions are needed. Here we present InterPep, a pipeline for predicting protein-peptide interaction sites. It is a novel pipeline that, given a protein structure and a peptide sequence, utilizes structural template matches, sequence information, random forest machine learning, and hierarchical clustering to predict what region of the protein structure the peptide is most likely to bind. When tested on its ability to predict binding sites, InterPep successfully pinpointed 255 of 502 (50.7%) binding sites in experimentally determined structures at rank 1 and 348 of 502 (69.3%) among the top five predictions using only structures with no significant sequence similarity as templates. InterPep is a powerful tool for identifying peptide-binding sites; with a precision of 80% at a recall of 20% it should be an excellent starting point for docking protocols or experiments investigating peptide interactions. The source code for InterPred is available athttp://wallnerlab.org/InterPep/