bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gini coefficients for measuring the distribution of sexually transmitted infections among individuals with different levels of sexual activity
Authors: Gsteiger Sandro , Low Nicola , Sonnenberg Pam , Mercer Catherine H , Althaus Christian L 
Published: October 2018

AbstractObjectivesGini coefficients have been used to describe the distribution of Chlamydia trachomatis (CT) infections among individuals with different levels of sexual activity. The objectives of this study were to investigate Gini coefficients for different sexually transmitted infections (STIs), and to determine how STI control interventions might affect the Gini coefficient over time.MethodsWe used population-based data for sexually experienced women from two British National Surveys of Sexual Attitudes and Lifestyles (Natsal-2: 1999-2001; Natsal-3: 2010-2012) to calculate Gini coefficients for CT, Mycoplasma genitalium (MG), and human papillomavirus (HPV) types 6, 11, 16 and 18. We applied bootstrap methods to assess uncertainty and to compare Gini coefficients for different STIs. We then used a mathematical model of STI transmission to study how control interventions affect Gini coefficients.ResultsGini coefficients for CT and MG were 0.33 (95% confidence interval (CI): 0.18-0.49) and 0.16 (95% CI: 0.02-0.36), respectively. The relatively small coefficient for MG suggests a longer infectious duration compared with CT. The coefficients for HPV types 6, 11, 16 and 18 ranged from 0.15-0.38. During the decade between Natsal-2 and Natsal-3, the Gini coefficient for CT did not change. The transmission model shows that higher STI treatment rates are expected to reduce prevalence and increase the Gini coefficient of STIs. In contrast, increased condom use reduces STI prevalence but does not affect the Gini coefficient.ConclusionsGini coefficients for STIs can help us to understand the distribution of STIs in the population, according to level of sexual activity, and could be used to inform STI prevention and treatment strategies.Key messagesThe Gini coefficient can be used to describe the distribution of STIs in a population, according to different levels of sexual activity.Gini coefficients for Chlamydia trachomatis (CT) and human papillomavirus (HPV) type 18 appear to be higher than for Mycoplasma genitalium and HPV 6, 11 and 16.Mathematical modelling suggests that CT screening interventions should reduce prevalence and increase the Gini coefficient, whilst condom use reduces prevalence without affecting the Gini coefficient.Changes in Gini coefficients over time could be used to assess the impact of STI prevention and treatment strategies.
Measures of neural similarity
Authors: Bobadilla-Suarez S. , Ahlheim C. , Mehrotra A. , Panos A. , Love B. C. 
Published: October 2018

AbstractOne fundamental question is what makes two brain states similar. For example, what makes the activity in visual cortex elicited from viewing a robin similar to a sparrow? One common assumption in fMRI analysis is that neural similarity is described by Pearson correlation. However, there are a host of other possibilities, including Minkowski and Mahalanobis measures, with each differing in its mathematical, theoretical, neural computational assumptions. Moreover, the operable measures may vary across brain regions and tasks. Here, we evaluated which of several competing similarity measures best captured neural similarity. Our technique uses a decoding approach to assess the information present in a brain region and the similarity measures that best correspond to the classifier’s confusion matrix are preferred. Across two published fMRI datasets, we found the preferred neural similarity measures were common across brain regions, but differed across tasks. Moreover, Pearson correlation was consistently surpassed by alternatives.
Attenuating the DNA damage response to double strand breaks restores function in models of CNS neurodegeneration
Authors: Tuxworth Richard I. , Taylor Matthew J. , Anduaga Ane Martin , Hussien-Ali Alaa , Chatzimatthaiou Sotiroula , Longland Joanne , Thompson Adam M. , Almutiri Sharif , Alifragis Pavlos , Kyriacou Charalambos P. , Kysela Boris , Ahmed Zubair 
Published: October 2018

AbstractDNA double-strand breaks are a feature of many acute and long-term neurological disorders, including neurodegeneration, following neurotrauma and after stroke. Persistent activation of the DNA damage response in response to double strand breaks contributes to neural dysfunction and pathology as it can force post-mitotic neurons to re-enter the cell cycle leading to senescence or apoptosis. Mature, non-dividing neurons may tolerate low levels of DNA damage, in which case muting the DNA damage response might be neuroprotective. Here, we show that attenuating the DNA damage response by targeting the meiotic recombination 11, Rad50, Nijmegen breakage syndrome 1 complex, which is involved in double strand break recognition, is neuroprotective in three neurodegeneration models in Drosophila and prevents Aβ1-42-induced loss of synapses in embryonic hippocampal neurons. Attenuating the DNA damage response after optic nerve injury is also neuroprotective to retinal ganglion cells and promotes dramatic regeneration of their neurites both in vitro and in vivo. Dorsal root ganglion neurons similarly regenerate when the DNA damage response is targeted in vitro and in vivo and this strategy also induces significant restoration of lost function after spinal cord injury. We conclude that muting the DNA damage response in the nervous system is neuroprotective in multiple neurological disorders. Our results point to new therapies to maintain or repair the nervous system.
Solving the riddle of the evolution of Shine-Dalgarno based translation in chloroplasts
Authors: Weiner Iddo , Shahar Noam , Marcu Pini , Yacoby Iftach , Tuller Tamir 
Published: October 2018

AbstractThe chloroplast, a photosynthetic organelle found in all plant and algae species, originates from an ancient event in which a cyanobacterium was engulfed by a larger eukaryote. Thus, modern chloroplasts still harbor a bacterial-like genome and carry out all stages of gene expression, including mRNA translation by a 70S ribosome. However, the Shine-Dalgarno model, which predominantly regulates translation initiation by base-pairing between the ribosomal RNA and the mRNA in model bacteria genera, was reported to have ambiguous effects on chloroplast gene expression. Here we show that while the Shine-Dalgarno motif is clearly conserved in proteobacterial mRNAs, its general absence from chloroplast mRNAs is observed in cyanobacteria as well, promoting the idea that the evolutionary process of reducing the centrality of the Shine-Dalgarno mechanism began well before plastid endosymbiosis. As plastid ribosomal RNA anti-Shine-Dalgarno elements are highly similar to their bacterial counterparts, these sites alone cannot explain the decline in plastid Shine-Dalgarno generality. However, by computational simulation we show that upstream point mutations modulate the local structure of ribosomal RNA in chloroplasts, creating significantly tighter structures around the anti-Shine-Dalgarno locus, which in-turn reduce the probability of ribosome binding via the Shine-Dalgarno mechanism. To validate our model, we expressed a mCherry gene harboring a Shine-Dalgarno motif in the Chlamydomonas reinhardtii chloroplast. We show that co-expressing it with a 16S ribosomal RNA, modified according to our model, significantly enhances its expression compared to co-expression with an endogenous 16S gene.Significance statementChloroplasts are fascinating intracellular organelles which have evolved from an ancient cyanobacterium engulfed by a larger eukaryote. Surprisingly, the canonical mechanism regulating bacterial translation initiation – Shine-Dalgarno – has been shown to play a reduced role in chloroplasts. Here, we show that mutations upstream from the anti-Shine-Dalgarno element decrease the probability of spontaneous ribosome binding by modulating the secondary structure of the ribosomal RNA. These mutations constitute a regulatory step which acclimates the Shine-Dalgarno mechanism to the translational regulation regime of chloroplasts. Interestingly, we show that these chloroplast features occur in modern cyanobacteria as well, promoting the idea that they have evolved prior to endosymbiosis.
Harmonization of resting-state functional MRI data across multiple imaging sites via the separation of site differences into sampling bias and measurement bias
Authors: Yamashita Ayumu , Yahata Noriaki , Itahashi Takashi , Lisi Giuseppe , Yamada Takashi , Ichikawa Naho , Takamura Masahiro , Yoshihara Yujiro , Kunimatsu Akira , Okada Naohiro , Yamagata Hirotaka , Matsuo Koji , Hashimoto Ryuichiro , Okada Go , Sakai Yuki , Morimoto Jun , Narumoto Jin , Shimada Yasuhiro , Kasai Kiyoto , Kato Nobumasa , Takahashi Hidehiko , Okamoto Yasumasa , Tanaka Saori C , Kawato Mitsuo , Yamashita Okito , Imamizu Hiroshi 
Published: October 2018

AbstractWhen collecting large neuroimaging data associated with psychiatric disorders, images must be acquired from multiple sites because of the limited capacity of a single site. However, site differences represent the greatest barrier when acquiring multi-site neuroimaging data. We utilized a traveling-subject dataset in conjunction with a multi-site, multi-disorder dataset to demonstrate that site differences are composed of biological sampling bias and engineering measurement bias. Effects on resting-state functional MRI connectivity because of both bias types were greater than or equal to those because of psychiatric disorders. Furthermore, our findings indicated that each site can sample only from among a subpopulation of participants. This result suggests that it is essential to collect large neuroimaging data from as many sites as possible to appropriately estimate the distribution of the grand population. Finally, we developed a novel harmonization method that removed only the measurement bias by using traveling-subject dataset and achieved the reduction of the measurement bias by 29% and the improvement of the signal to noise ratios by 40%.
Motile curved bacteria are Pareto-optimal
Authors: Schuech Rudi , Hoehfurtner Tatjana , Smith David , Humphries Stuart 
Published: October 2018

AbstractCurved-rods are a ubiquitous bacterial phenotype, but the fundamental question of why they are shaped this way remains unanswered. Throughin silicoexperiments, we assessed freely swimming straight- and curved-rod bacteria of a wide diversity of equal-volume shapes parameterized by elongation and curvature, and predicted their performances in tasks likely to strongly influence overall fitness. Performance tradeoffs between these tasks lead to a variety of shapes that are Pareto-optimal, including coccoids, all straight rods, and a range of curvatures. Comparison with an extensive morphological survey of motile curved-rod bacteria indicates that the vast majority of species fall within the Pareto-optimal region of morphospace. This result is consistent with evolutionary tradeoffs between just three tasks: efficient swimming, chemotaxis, and low cell construction cost. We thus reveal the underlying selective pressures driving morphological diversity in a wide-spread component of microbial ecosystems.Significance StatementBacteria exhibit a bewildering diversity of morphologies but despite their impact on nearly all aspects of life, they are frequently classified into a few general categories, usually just ‘spheres’ and ‘rods’. Curved-rod bacteria are one simple variation and are widespread, particularly in the ocean. However, why so many species have evolved this shape is unknown. We show that curvature can increase swimming efficiency, revealing a widely-applicable selective advantage. Furthermore, we show that the distribution of cell lengths and curvatures observed across bacteria in nature are predicted by evolutionary tradeoffs between three tasks influenced by shape: efficient swimming, the ability to detect chemical gradients, and reduced cost of cell construction. We therefore reveal shape as an important component of microbial fitness.
Unraveling Tumor-Immune Heterogeneity in Advanced Ovarian Cancer Uncovers Immunogenic Effect of Chemotherapy
Authors: Jiménez-Sánchez Alejandro , Cybulska Paulina , Lavigne Katherine , Walther Tyler , Nikolovski Ines , Mazaheri Yousef , Weigelt Britta , Chi Dennis S. , Park Kay J. , Hollmann Travis , Couturier Dominique-Laurent , Vargas Alberto , Brenton James D. , Sala Evis , Snyder Alexandra , Miller Martin L. 
Published: October 2018

ABSTRACTIn metastatic cancer, the role of heterogeneity at the tumor-immune microenvironment, its molecular underpinnings and clinical relevance remain largely unexplored. To understand tumor-immune dynamics at baseline and upon chemotherapy treatment, we performed unbiased pathway and cell type-specific immunogenomics analysis of treatment-naive (38 samples from 8 patients) and paired chemotherapy treated (80 paired samples from 40 patients) high-grade serous ovarian cancer (HGSOC) samples. Whole transcriptome analysis and image-based quantification of T cells from treatment-naive tumors revealed ubiquitous variability in immune signaling and distinct immune microenvironments co-existing within the same individuals and within tumor deposits at diagnosis. To systematically explore cell type composition of the tumor microenvironment using bulk mRNA, we derived consensus immune and stromal cell gene signatures by intersecting state-of-the-art deconvolution methods, providing improved accuracy and sensitivity when compared to HGSOC immunostaining and leukocyte methylation data sets. Cell-type deconvolution and pathway analyses revealed that Myc and Wnt signaling associate with immune cell exclusion in untreated HGSOC. To evaluate the effect of chemotherapy on the intrinsic tumor-immune heterogeneity, we compared site-matched and site-unmatched tumors before and after neoadjuvant chemotherapy. Transcriptomic and T-cell receptor sequencing analyses showed that site-matched samples had increased cytotoxic immune activation and oligoclonal expansion of T cells after chemotherapy, which was not seen in site-unmatched samples where heterogeneity could not be accounted for. These results demonstrate that the tumor-immune interface in advanced HGSOC is intrinsically heterogeneous, and thus requires site-specific analysis to reliably unmask the impact of therapy on the tumor-immune microenvironment.
QuBiT: A quantitative tool for epithelial tubes reveals cell dynamics and unexpected patterns of organization during Drosophila tracheal morphogenesis
Authors: Yang Ran , Li Eric , Mani Madhav , Beitel Greg J. 
Published: October 2018

AbstractBiological tubes are essential for animal survival, and their functions are critically dependent on tube shape. Analyzing the contributions of cell shape and organization to the morphogenesis of small tubes has been hampered by the limitations of existing programs in quantifying cell geometry on highly curved tubular surfaces and calculating tube-specific parameters. We therefore developed QuBiT (QuantitativeTool forBiologicalTubes) and used it to analyze morphogenesis during embryonic Drosophila tracheal (airway) development. We find that there are previously unknown anterior-to-posterior (A-P) gradients of cell orientation and aspect ratio, and that there is periodicity in the organization of cells in the main tube. Furthermore, cell intercalation during development dampens an A-P gradient of the number of the number of cells per cross-section of the tube, but these intercalation events do not change the patterns of cell connectivity. These unexpected findings demonstrate the importance of a computational tool for analyzing the morphogenesis of small diameter biological tubes.
Galectin-1 promotes the invasion of bladder cancer urothelia through their matrix milieu
Authors: Balakrishnan A. , Pally D , Gondkar K. , Naito S. , Sidransky D. , Chatterjee A. , Kumar P. , Bhat R. 
Published: October 2018

AbstractThe progression of carcinoma of the urinary bladder involves migration of cancer epithelia through their surrounding tissue matrix microenvironment. This was experimentally confirmed when a gender- and grade-diverse set of bladder cancer cell lines were cultured in pathomimetic three-dimensional laminin-rich environments. The high-grade cells, particularly female, formed multicellular invasive morphologies in 3D. In comparison, low- and intermediate-grade counterparts showed growth-restricted phenotypes. A proteomic approach combining mass spectrometry and bioinformatics analysis identified the estrogen-driven lactose-binding lectin Galectin-1 (GAL-1) as a putative candidate that could drive this invasion. Expression ofLGALS1, the gene encoding GAL-1 showed an association with tumor grade progression in bladder cell lines. Immunohisto- and cyto-chemical experiments suggested greater extracellular levels of GAL-1 in 3D cultures of high-grade bladder cells and cancer tissues. High levels of GAL-1 associated with increased proliferation- and adhesion- of bladder cancer cells when grown on laminin-rich matrices. Pharmacological inhibition and Gal-1 knockdown in high-grade female cells decreased their adhesion to, and viability on, laminin-rich substrata. Higher GAL-1 also correlated with reduced E-cadherin and increased N-cadherin levels in consonance with a mesenchymal-like phenotype that we observed in 3D culture. The inhibition of GAL-1 reversed the stellate invasive phenotype to a more growth-restricted one in high-grade cells embedded within both basement-membrane-like and stromal collagenous matrix scaffolds. Finally, inhibition of GAL-1 specifically altered cell surface sialic acids, suggesting the mechanism by which the levels of GAL-1 may underlie the aggression and poor prognosis of invasive bladder cancer, especially in women.
Lmx1b influences correct post-mitotic coding of mesodiencephalic dopaminergic neurons
Authors: Wever Iris , Barrientos Pablo Largo , Hoekstra Elisa J. , Smidt Marten P. 
Published: October 2018

AbstractThe Lim Homeobox transcription factor 1 beta (LMX1b) has been identified as one of the transcription factors important for the development of mesodiencephalic dopaminergic (mdDA) neurons. During early development, Lmx1b is essential for induction and maintenance of the Isthmic Organizer (IsO), and genetic ablation results in the disruption of inductive activity from the IsO and loss of properly differentiated mdDA neurons.To study the downstream targets of Lmx1b without affecting the IsO, we generated a conditional model in which Lmx1b was selectively deleted in Pitx3 expressing cells from embryonic day (E)13 onward. Supporting previous data, no significant changes could be observed in general dopamine (DA) marks, like Th, Pitx3 and Vmat2 at E14.5. However, in depth analysis by means of RNA-sequencing revealed that Lmx1b is important for the expression level of survival factors En1 and En2 and for the repression of mdDA subset mark Ahd2 during (late) development. Interestingly, the regulation of Ahd2 by Lmx1b was found to be Pitx3 independent, since Pitx3 levels were not altered in Lmx1b conditional knock-outs (cKO) and Ahd2 expression was also up-regulated in Lmx1b/Pitx3 double mutants compared to Pitx3 mutants. Further analysis of Lmx1b cKOs showed that post-mitotic deletion of Lmx1b additional leads to a loss of TH+ cells at 3 months age both in the VTA and SNc. Remarkably, different cell types were affected in the SNc and the VTA. While TH+AHD2+ cells were lost the SNc, TH+AHD2- neurons were affected in the VTA, reflected by a loss of Cck expression, indicating that Lmx1b is important for the survival of a sub-group of mdDA neurons.
Type III secretion system ofPseudomonas aeruginosaaffects mucin gene expression via NF-κB and AKT signaling in human carcinoma epithelial cells and a pneumonia mouse model
Authors: Park Ji-Won , Shin In-Sik , Oh Sei-Ryang , Ha Un-Hwan , Ahn Kyung-Seop 
Published: October 2018

AbstractThe type III secretion system (T3SS) inPseudomonas aeruginosahas been linked to severe disease and poor clinical outcomes in animal and human studies. Of the various T3SS effector genes, ExoS and ExoT showed mutually exclusive distributions, and these two genes showed varied virulence. We aimed to investigate whether the ExoS and ExoT effector proteins ofP. aeruginosaaffect the expression of the proinflammatory mediators Muc7, Muc13, Muc15, and Muc19 via the NF-κB and AKT signaling pathways. To understand the role of the T3SS, we used AExoS, AExoT, and T3SS transcriptional activator ExsA mutants (ExsA∷Ω), as well as A549 cells stimulated withP. aeruginosastrain K (PAK). We investigated the effects of ΔExoS, ΔExoT, and ExsA∷Ω on the development of pneumonia in a mouse model and on Muc7, Muc13, Muc15, and Muc19 production in A549 cells. ΔExoS and ΔExoT markedly decreased the neutrophil count in the bronchoalveolar lavage fluid, with a reduction in Muc7, Muc13, Muc15, and Muc19 expression ΔExoS andΔExoT reduced NF-κB and AKT phosphorylation, together with Muc7, Muc13, Muc15, and Muc19 expression in PAK-infected mice and A549 cells. In conclusion,P. aeruginosainfection induced the expression of Mucus, and theP. aeruginosaT3SS appeared to be a key player in Muc7, Muc13, Muc15, and Muc19 expression, which is further controlled by NF-κB and AKT signaling. These findings might be useful to devise a novel therapeutic approach for the treatment of chronic pulmonary infections by targeting ExoS and ExoT.Author SummaryPseudomonas aeruginosais a ubiquitous gram-negative bacterium causing serious infections. Many clinical isolates ofP. aeruginosahave a specialized apparatus for injecting toxins into eukaryotic cells, namely, the type III secretion system (T3SS). The T3SS is a syringe-like apparatus on the bacterial surface, with 4 effector toxins: ExoS, ExoT, ExoY, and ExoU. We investigated the effect of ExoS and ExoT of the T3SS ofP. aeruginosaK strain (PAK). Mucus plays a vital role in protecting the lungs from environmental factors, but conversely, in muco-obstructive airway disease, mucus becomes pathologic. We showed that infection with ExoS and ExoT induced Muc7, Muc13, Muc15, and Muc19 expression in host cells. PAK clinical strains induce proinflammatory cytokine production through the T3SS, and this involves NF-κB and SP1/AKT activation in pneumonia mouse models. Mucus induction in response to ExoS and ExoT infection relied on NF-κB and SP1/AKT activation. Our findings highlight the roles of Muc7, Muc13, Muc15, and Muc19 in inducing proinflammatory cytokine expression during ExoS and ExoT exposure in PAK infections, paving the way for a novel therapeutic approach for the treatment of pulmonary infections.