bluuebunny/crossref_metadata_2025_split huggingface dataset:
Filaggrin and Periostin Expression Is Altered in Eosinophilic Esophagitis and Normalized With Treatment
Authors: Politi Ekaterini , Angelakopoulou Aspasia , Grapsa Dimitra , Zande Maria , Stefanaki Kalliopi , Panagiotou Ioanna , Roma Eleftheria , Syrigou Ekaterini 
Published: September 2016

ABSTRACTObjectives:Previous data have suggested that filaggrin (FLG) and periostin (POSTN) genes may be dysregulated in eosinophilic esophagitis (EoE). We aimed to further evaluate the expression patterns of FLG and POSTN proteins in esophageal tissue samples of patients with EoE, as compared to those of patients with gastroesophageal reflux disease (GERD) and normal controls.Methods:A total of 61 prospectively collected cases, including 40 children with EoE and 21 children with GERD, and a control group of 14 sex‐ and age‐matched healthy children were enrolled. Patients with EoE were treated with skin testing–driven elimination diet and/or corticosteroids. The immunohistochemical expression of FLG and POSTN was evaluated in esophageal biopsies obtained from patients and controls, and the results were correlated with EoE‐related clinicopathological parameters.Results:Positive FLG and negative POSTN staining were observed in all esophageal biopsies from normal controls. In contrast, FLG and POSTN stained negative and positive, respectively, in all pretreatment biopsies obtained from patients with EoE, whereas FLG and POSTN stained positive in 57.1% and 95.2% of GERD cases, respectively (P < 0.001). A statistically significant decrease of the proportion of cases with negative FLG and positive POSTN staining was observed from the first (pretreatment) to the second (post‐treatment) biopsy in the subgroup of patients with EoE (P < 0.001 in both correlations).Conclusions:FLG and POSTN expression may be downregulated and upregulated, respectively, in the esophageal mucosa of patients with active EoE, and these changes may be restored with treatment in a significant percentage of cases.
Anatomical Relationships of Burch Colposuspension Sutures
Authors: Kinman Casey L. , Agrawal Anubhav , Deveneau Nicolette E. , Meriwether Kate V. , Herring Nicole R. , Francis Sean L. 
Published: September 2016

Objectives
The prevalent use of minimally invasive midurethral slings for the treatment of stress urinary incontinence in the last several decades has resulted in fewer Burch procedures being performed and diminished surgical experience in performing the Burch colposuspension. However, recent antimesh media has resulted in more patients requesting nonmesh anti-incontinence procedures and a subsequent need for surgeons to refamiliarize themselves with the Burch procedure and its relevant anatomy. The objective of this study was to evaluate the relationships of Burch sutures to surrounding neurovascular anatomic structures in the human cadaver.

Methods
The retropubic space of 11 unembalmed female cadavers was dissected, and a Burch procedure performed. The distance from the Burch sutures’ location through both Cooper’s ligament and the vagina to the obturator neurovascular bundle and external iliac vessels was measured.

Results
The mean distance from the most lateral stitch in Cooper’s ligament to the obturator bundle was 25.9 ± 7.6 mm and to the external iliac vessels was 28.9 ± 9.3 mm, and in some instances, these structures were less than 1.5 cm away.

Conclusions
The obturator bundle and external iliac lie, on average, within 3 cm of sutures placed during a Burch colposuspension. Knowledge of these anatomical relationships is valuable when dissecting the space of Retzius and placing sutures for a Burch to avoid injury.
Perioperative Complications and Cost of Vaginal, Open Abdominal, and Robotic Surgery for Apical Vaginal Vault Prolapse
Authors: Anand Mallika , Weaver Amy L. , Fruth Kristin M. , Borah Bijan J. , Klingele Christopher J. , Gebhart John B. 
Published: September 2016

Objectives
To determine the rate of perioperative complications and cost associated with Mayo-McCall culdoplasty (MMC), open abdominal sacrocolpopexy (ASC), and robotic sacrocolpopexy (RSC) for posthysterectomy vaginal vault prolapse.

Methods
We retrospectively searched for the records of patients undergoing posthysterectomy apical vaginal prolapse surgery (MMC, ASC, or RSC) between January 1, 2000, and June 30, 2012, at our institution. For all patients identified, perioperative complications, length of hospital stay, and inpatient costs to patients were abstracted from the medical records and compared by procedure. Inverse–probability-of-procedure weighting using propensity scores was used to obtain less-biased comparisons of outcomes between procedures.

Results
A total of 512 patients met the inclusion criteria (174 MMC, 237 ASC, and 101 RSC). Using inverse-probability weighting, the MMC group had a significantly lower intraoperative complication rate (3.3% vs 11.6% for ASC, 3.4% vs 24.1% for RSC), median operative time (94 vs 217 min for ASC, 100 vs 228 min for RSC), and median cost (US $8,776 vs $12,695 for ASC, US $8,773 vs $13,107 for RSC) than the ASC and RSC groups (all P < 0.01). In addition, the MMC group had significantly fewer postoperative grade 3+ complications than the RSC group (1.1% vs 9.4%, P < 0.01).

Conclusions
In the treatment of posthysterectomy vaginal vault prolapse, MMC is associated with decreased non–urinary tract infection, less perioperative morbidity, and lower cost to patients compared with sacrocolpopexy.
Current management of low-grade gliomas
Authors: Hottinger Andreas F. , Hegi Monika E. , Baumert Brigitta G. 
Published: September 2016

Purpose of review
The management of patients suffering from low-grade gliomas (LGGs) remains a challenge in absence of a definite curative therapy. The median survival is highly variable, from 2 years (high-risk disease) to over 15 years (low risk). The aim of this review is to provide a practical step-by-step evaluation of the available treatment options for patients with LGGs.

Recent findings
Next to clinical prognostic markers, both the isocitrate dehydrogenase (IDH) mutation status and the status of 1p/19q codeletion are key prognostic factors for the optimal management of patients with LGG. Two recent randomized phase III clinical trials were performed in LGGs. They first compared the efficacy of radiation versus temozolomide (TMZ) chemotherapy in high-risk LGGs. The second trial compared radiation versus radiation combined with procarbazine, lomustine and vincristine chemotherapy.

Summary
Regarding molecular prognostic factors, IDH wild-type LGGs have the worst prognosis, independent of therapy, whereas patients with mutated IDH, codeleted 1p/19q LGGs fared best regarding progression-free survival (PFS). In high-risk LGGs, PFS is similar regardless of whether patients have been treated with radiation or TMZ. In the second trial, patients who were treated with combination radiation and chemotherapy showed significant longer overall survival.
Shedding light on biology of bacterial cells
Authors: Schneider Johannes P. , Basler Marek 
Published: September 2016

To understand basic principles of living organisms one has to know many different properties of all cellular components, their mutual interactions but also their amounts and spatial organization. Live-cell imaging is one possible approach to obtain such data. To get multiple snapshots of a cellular process, the imaging approach has to be gentle enough to not disrupt basic functions of the cell but also have high temporal and spatial resolution to detect and describe the changes. Light microscopy has become a method of choice and since its early development over 300 years ago revolutionized our understanding of living organisms. As most cellular components are indistinguishable from the rest of the cellular contents, the second revolution came from a discovery of specific labelling techniques, such as fusions to fluorescent proteins that allowed specific tracking of a component of interest. Currently, several different tags can be tracked independently and this allows us to simultaneously monitor the dynamics of several cellular components and from the correlation of their dynamics to infer their respective functions. It is, therefore, not surprising that live-cell fluorescence microscopy significantly advanced our understanding of basic cellular processes. Current cameras are fast enough to detect changes with millisecond time resolution and are sensitive enough to detect even a few photons per pixel. Together with constant improvement of properties of fluorescent tags, it is now possible to track single molecules in living cells over an extended period of time with a great temporal resolution. The parallel development of new illumination and detection techniques allowed breaking the diffraction barrier and thus further pushed the resolution limit of light microscopy. In this review, we would like to cover recent advances in live-cell imaging technology relevant to bacterial cells and provide a few examples of research that has been possible due to imaging.
This article is part of the themed issue ‘The new bacteriology’.
When pathogenic bacteria meet the intestinal microbiota
Authors: Rolhion Nathalie , Chassaing Benoit 
Published: September 2016

The intestinal microbiota is a large and diverse microbial community that inhabits the intestinal tract, containing about 100 trillion bacteria from 500–1000 distinct species that, collectively, provide multiple benefits to the host. The gut microbiota contributes to nutrient absorption and maturation of the immune system, and also plays a central role in protection of the host from enteric bacterial infection. On the other hand, many enteric pathogens have developed strategies in order to be able to outcompete the intestinal community, leading to infection and/or chronic diseases. This review will summarize findings describing the complex relationship occurring between the intestinal microbiota and enteric pathogens, as well as how future therapies can ultimately benefit from such discoveries.
This article is part of the themed issue ‘The new bacteriology’.
InhibitingMycobacterium tuberculosiswithin and without
Authors: Cole Stewart T. 
Published: September 2016

Tuberculosis remains a scourge of global health with shrinking treatment options due to the spread of drug-resistant strains ofMycobacterium tuberculosis. Intensive efforts have been made in the past 15 years to find leads for drug development so that better, more potent drugs inhibiting new targets could be produced and thus shorten treatment duration. Initial attempts focused on repurposing drugs that had been developed for other therapeutic areas but these agents did not meet their goals in clinical trials. Attempts to find new lead compounds employing target-based screens were unsuccessful as the leads were inactive againstM. tuberculosis. Greater success was achieved using phenotypic screening against live tubercle bacilli and this gave rise to the drugs bedaquiline, pretomanid and delamanid, currently in phase III trials. Subsequent phenotypic screens also uncovered new leads and targets but several of these targets proved to be promiscuous and inhibited by a variety of seemingly unrelated pharmacophores. This setback sparked an interest in alternative screening approaches that mimic the disease state more accurately. Foremost among these were cell-based screens, often involving macrophages, as these should reflect the bacterium's niche in the host more faithfully. A major advantage of this approach is its ability to uncover functions that are central to infection but not necessarily required for growthin vitro. For instance, inhibition of virulence functions mediated by the ESX-1 secretion system severely attenuates intracellularM. tuberculosis, preventing intercellular spread and ultimately limiting tissue damage. Cell-based screens have highlighted the druggability of energy production via the electron transport chain and cholesterol metabolism. Here, I review the scientific progress and the pipeline, but warn against over-optimism due to the lack of industrial commitment for tuberculosis drug development and other socio-economic factors.This article is part of the themed issue ‘The new bacteriology’.
Molecular phenotyping of infection-associated small non-coding RNAs
Authors: Barquist Lars , Westermann Alexander J. , Vogel Jörg 
Published: September 2016

Infection is a complicated balance, with both pathogen and host struggling to tilt the result in their favour. Bacterial infection biology has relied on forward genetics for many of its advances, defining phenotype in terms of replication in model systems. However, many known virulence factors fail to produce robust phenotypes, particularly in the systems most amenable to genetic manipulation, such as cell-culture models. This has particularly been limiting for the study of the bacterial regulatory small RNAs (sRNAs) in infection. We argue that new sequencing-based technologies can work around this problem by providing a ‘molecular phenotype’, defined in terms of the specific transcriptional dysregulation in the infection system induced by gene deletion. We illustrate this using the example of our recent study of the PinT sRNA using dual RNA-seq, that is, simultaneous RNA sequencing of host and pathogen during infection. We additionally discuss how other high-throughput technologies, in particular genetic interaction mapping using transposon insertion sequencing, may be used to further dissect molecular phenotypes. We propose a strategy for how high-throughput technologies can be integrated in the study of non-coding regulators as well as bacterial virulence factors, enhancing our ability to rapidly generate hypotheses with regards to their function.
This article is part of the themed issue ‘The new bacteriology’.
Logistic proliferation of cells in scratch assays is delayed
Authors: Jin Wang , Shah Esha T , Penington Catherine J , McCue Scott W , Maini Philip K , Simpson Matthew J 
Published: September 2016

AbstractScratch assays are used to study how a population of cells recolonises a vacant region on a two-dimensional substrate after a cell monolayer is scratched. These experiments are used in many applications including drug design for the treatment of cancer and chronic wounds. To provide insights into the mechanisms that drive scratch assays, solutions of continuum reaction–diffusion models have been calibrated to data from scratch assays. These models typically include a logistic source term to describe carrying capacity-limited proliferation, however the choice of using a logistic source term is often made without examining whether it is valid. Here we study the proliferation of PC-3 prostate cancer cells in a scratch assay. All experimental results for the scratch assay are compared with equivalent results from a proliferation assay where the cell monolayer is not scratched. Visual inspection of the time evolution of the cell density away from the location of the scratch reveals a series of sigmoid curves that could be naively calibrated to the solution of the logistic growth model. However, careful analysis of the per capita growth rate as a function of density reveals several key differences between the proliferation of cells in scratch and proliferation assays. Our findings suggest that the logistic growth model is valid for the entire duration of the proliferation assay. On the other hand, guided by data, we suggest that there are two phases of proliferation in a scratch assay; at short time we have adisturbance phasewhere proliferation is not logistic, and this is followed by agrowth phasewhere proliferation appears to be logistic. These two phases are observed across a large number of experiments performed at different initial cell densities. Overall our study shows that simply calibrating the solution of a continuum model to a scratch assay might produce misleading parameter estimates, and this issue can be resolved by making a distinction between the disturbance and growth phases. Repeating our procedure for other scratch assays will provide insight into the roles of the disturbance and growth phases for different cell lines and scratch assays performed on different substrates.
A fast multi-locus random-SNP-effect EMMA for genome-wide association studies
Authors: Wen Yang-Jun , Zhang Hanwen , Zhang Jin , Feng Jian-Ying , Huang Bo , Dunwell Jim M. , Zhang Yuan-Ming , Wu Rongling 
Published: September 2016

AbstractAlthough the mixed linear model (MLM) such as efficient mixed model association (EMMA), has been widely used in genome-wide association studies (GWAS), relatively little is known about fast and efficient algorithms to implement multi-locus GWAS. To address this issue, we report a fast multi-locus random-SNP-effect EMMA (FASTmrEMMA). In this method, a new matrix transformation was constructed to obtain a new genetic model that includes only quantitative trait nucleotide (QTN) variation and normal residual error; letting the number of nonzero eigenvalues be one and fixing the polygenic-to-residual variance ratio was used to increase computing speed. All the putative QTNs with the ≤0.005 P-values in the first step of the new method were included in one multi-locus model for true QTN detection. Owing to the multi-locus feature, the Bonferroni correction is replaced by a less stringent selection criterion. Results from analyses of both simulated and real data showed that FASTmrEMMA is more powerful in QTN detection, model fit and robustness, has less bias in QTN effect estimation, and requires less running time than the current single- and multi-locus methodologies for GWAS, such as E-BAYES, SUPER, EMMA, CMLM and ECMLM. Therefore, FASTmrEMMA provides an alternative for multi-locus GWAS.
TheMstncmpt-Dl1abcmutation impairs secretion of promyostatin
Authors: Vásárhelyi Viktor , Trexler Mária , Patthy László 
Published: September 2016

AbstractHypermuscularity of Compact mouse is caused by a 12-bp deletion in the myostatin gene, but the molecular basis of decreased myostatin activity is unclear since the deletion does not affect the integrity of the growth factor domain. In the present work we show that the deletion causes misfolding and impaired secretion of myostatin precursor with concomitant decrease in myostatin activity. We suggest that some modifier genes that influence the expression of the Compact phenotype of myostatin mutantMstnCmpt-dl1Abcmice may exert their action through their role in the Unfolded Protein Response.
Treadmilling by FtsZ filaments drives peptidoglycan synthesis and bacterial cell division
Authors: Bisson Filho Alexandre W. , Hsu Yen-Pang , Squyres Georgia R. , Kuru Erkin , Wu Fabai , Jukes Calum , Dekker Cees , Holden Seamus , VanNieuwenhze Michael S. , Brun Yves V. , Garner Ethan C. 
Published: September 2016

AbstractHow bacteria produce a septum to divide in two is not well understood. This process is mediated by periplasmic cell-wall producing enzymes that are positioned by filaments of the cytoplasmic membrane-associated actin FtsA and the tubulin FtsZ (FtsAZ). To understand how these components act in concert to divide cells, we visualized their movements relative to the dynamics of cell wall synthesis during cytokinesis. We find that the division septum is built at discrete sites that move around the division plane. Furthermore, FtsAZ filaments treadmill in circumferential paths around the division ring, pulling along the associated cell-wall-synthesizing enzymes. We show that the rate of FtsZ treadmilling controls both the rate of cell wall synthesis and cell division. The coupling of both the position and activity of the cell wall synthases to FtsAZ treadmilling guides the progressive insertion of new cell wall, synthesizing increasingly small concentric rings to divide the cell.One-sentence summaryBacterial cytokinesis is controlled by circumferential treadmilling of FtsAZ filaments that drives the insertion of new cell wall.
The Opiliones Tree of Life: shedding light on harvestmen relationships through transcriptomics
Authors: Fernándeza Rosa , Sharma Prashant , Tourinho Ana L.M. , Giribet Gonzalo 
Published: September 2016

AbstractOpiliones are iconic arachnids with a Paleozoic origin and a diversity that reflects ancient biogeographical patterns dating back at least to the times of Pangea. Due to interest in harvestman diversity, evolution and biogeography, their relationships have been thoroughly studied using morphology and PCR-based Sanger approaches to systematics. More recently, two studies utilized transcriptomics-based phylogenomics to explore their basal relationships and diversification, but sampling was limiting for understanding deep evolutionary patterns, as they lacked good taxon representation at the family level. Here we analyze a set of the 14 existing transcriptomes with 40 additional ones generated for this study, representing ca. 80% of the extant familial diversity in Opiliones. Our phylogenetic analyses, including a set of data matrices with different gene occupancy and evolutionary rates, and using a multitude of methods correcting for a diversity of factors affecting phylogenomic data matrices, provide a robust and stable Opiliones tree of life, where most families are precisely placed. Our dating analyses also using alternative calibration points, methods, and analytical parameters provide well-resolved old divergences, consistent with ancient regionalization in Pangea in some groups, and Pangean vicariance in others. The integration of state-of-the-art molecular techniques and analyses, together with the broadest taxonomic sampling to date presented in a phylogenomic study of harvestmen, provide new insights into harvestmen interrelationships, as well as a general overview of the general biogeographic patterns of this ancient arthropod group.
GTPase activity-coupled treadmilling of the bacterial tubulin FtsZ organizes septal cell-wall synthesis
Authors: Yang Xinxing , Lyu Zhixin , Miguel Amanda , McQuillen Ryan , Huang Kerwyn Casey , Xiao Jie 
Published: September 2016

AbstractThe bacterial tubulin FtsZ is the central component of the division machinery, coordinating an ensemble of proteins involved in septal cell-wall synthesis to ensure successful constriction. How cells achieve this coordination is unknown. We used a combination of imaging, genetic and biochemical approaches to demonstrate that inEscherichia colicells FtsZ exhibits dynamic treadmilling predominantly determined by its GTPase activity, and that the treadmilling dynamics directs processive movement of the septal cell-wall synthesis machinery. In FtsZ mutants with severely reduced treadmilling, the spatial distribution of septal synthesis and the molecular composition and ultrastructure of the septal cell wall are substantially altered. Thus, the treadmilling of FtsZ provides a novel and robust mechanism for achieving uniform septal cell-wall synthesis to enable correct new pole morphology.One-sentence summaryThe bacterial tubulin FtsZ uses GTP hydrolysis to power treadmilling, driving processive synthesis of the septal cell wall.
The appressorium ofMagnaporthe oryzaeremains mitotically active during post-penetration hyphal growth in rice cells
Authors: Jones Kiersun , Jenkinson Cory B. , Zhu Jie , Dorhmi Sara , Khang Chang Hyun 
Published: September 2016

AbstractTo investigate the mitotic dynamics of an appressorium, we used time-lapse confocal imaging of a fluorescence-based mitotic reporter strain ofMagnaporthe oryzae. We present evidence that: (i) appressoria remain viable and mitotically active after host penetration, (ii) appressorial mitosis, like invasive hyphal mitosis, is semi-closed, (iii) sister chromatids separate within the appressorium, (iv) a mitotic appressorial nucleus undergoes extreme constriction and elongation as it migrates through the penetration peg in a manner analogous to mitosis during cell-to-cell movement of invasive hyphae. These results provide new insight into the potential roles of the appressorium after host penetration and highlight the unique mitotic dynamics during rice blast infection.