bluuebunny/crossref_metadata_2025_split huggingface dataset:
Damage Repair Versus Aging in Biofilms
Authors: Wright Robyn J. , Clegg Robert J. , Coker Timothy L. R. , Kreft Jan-Ulrich 
Published: January 2020

ABSTRACTThe extent of senescence due to damage accumulation (or aging) is evidently evolvable as it varies hugely between species and is not universal, suggesting that its fitness advantages depend on life history and environment. In contrast, repair of damage is present in all organisms studied. Repair and segregation of damage have not always been considered as alternatives, despite the fundamental trade-off between investing resources into repair or growth. For unicellular organisms, unrepaired damage could be divided asymmetrically between daughter cells, leading to aging of one and rejuvenation of the other. Repair of unicells has been shown to be advantageous in well-mixed environments such as chemostats. However, most microorganisms live in spatially structured systems such as biofilms with gradients of environmental conditions and cellular physiology as well as clonal population structure. We asked whether this clonal structure might favor aging by damage segregation as this can be seen as a division of labor strategy, akin to the germline soma division in multicellular organisms. We used an individual-based model with a newly developed adaptive repair strategy where cells respond to their current intracellular damage levels by investing into repair machinery accordingly. We found that the new adaptive repair strategy was advantageous whenever efficient and optimal, both in biofilms and chemostats. Thus, biofilms do not favor a germline soma-like division of labor between daughter cells in terms of damage segregation. We suggest that damage segregation is only beneficial when active and effective, extrinsic mortality is high and a degree of multicellularity is present.IMPORTANCEDamage is an inevitable consequence of life, leading to a trade-off between allocating resources into damage repair or into growth whilst allowing aging,i.e., segregation of damage upon cell division. Few studies considered repair as an alternative to aging. Moreover, all previous studies merely considered well-mixed environments, although the vast majority of unicellular organisms live in spatially structured environments, exemplified by biofilms, and fitness advantages in well-mixed systems often turn into disadvantages in spatially structured systems. We compared the fitness consequences of aging versus damage repair in biofilms with an individual-based model implementing an adaptive repair mechanism based on sensing damage. We found that aging is not beneficial. Instead, it is useful as a stress response to deal with damage that failed to be repaired when (i) clearly asymmetric cell division is feasible; (ii) extrinsic mortality is high; and (iii) a degree of multicellularity is present.
In vitrocharacterization of protein effector export in the bradyzoite stage ofToxoplasma gondii
Authors: Mayoral Joshua , Shamamian Peter , Weiss Louis M. 
Published: January 2020

ABSTRACTThe ubiquitous parasiteToxoplasma gondiiexhibits an impressive ability to maintain a chronic infection of its host for prolonged periods. Despite this, little is known regarding if and howT. gondiibradyzoites, a quasi-dormant life-stage residing within intracellular cysts, manipulate the host cell so as to maintain a persistent infection. A previous proteomic study of the cyst wall, an amorphous layer of proteins that forms underneath the cyst membrane, identified MYR1 as a putative cyst wall proteinin vitro. As MYR1 is known to be involved in the translocation of parasite derived effector proteins into the host cell, we sought to determine whether parasites transitioning toward the bradyzoite life stage retain the capacity to translocate proteins via this pathway. By epitope tagging the endogenous loci of four known effectors that translocate from the parasitophorous vacuole into the host cell nucleus, we show by immunofluorescence that most effectors accumulate in the host nucleus at early but not late timepoints post-infection during the tachyzoite to bradyzoite transition and when parasites farther along the bradyzoite differentiation continuum invade a new host cell. We demonstrate that the suppression of interferon-gamma (IFN-γ) signaling, previously shown to be mediated by the effector TgIST, also occurs in the context of prolonged infection with bradyzoites, and that TgIST export is a process that occurs beyond the early stages of host cell infection. These findings have important implications as to how this highly successful parasite maintains a persistent infection of its host.IMPORTANCEToxoplasmabradyzoites persist within tissue cysts and are refractory to current treatments, serving as a reservoir for acute complications in settings of compromised immunity. Much remains to be understood regarding how this life-stage successfully establishes and maintains a persistent infection. In this study, we investigated whether the export of parasite effector proteins into the host cell occurs during the development ofin vitrotissue cysts. We quantified the presence of four previously described effectors in host cell nuclei at different timepoints post-bradyzoite differentiation and found that they accumulate largely during the early stages of infection. Despite a decline in nuclear accumulation, we found that one of these effectors still mediates its function after prolonged infection with bradyzoites and provide evidence that this effector is exported beyond early infection stages. These findings suggest that effector export from within developing tissue cysts provides one potential mechanism by which this parasite achieves chronic infection.
Diagnostic accuracy of physical examination to detect the pelvic fractures among the blunt trauma patients; systematic review and meta-analysis
Authors: Okada Yohei , Nishioka Norihiro , Tsujimoto Yasushi 
Published: January 2020

AbstractBackgroundThe study aims to perform systematic review and meta-analysis to identify the diagnostic accuracy of physical examination for pelvic fracture among the blunt trauma patients.MethodWe will perform a systematic review and meta-analysis for diagnostic test accuracy (DTA). We will include all reports on the diagnostic accuracy of physical examinations for detecting pelvic fractures. We will include the studies designed as prospective or retrospective observational (cohort or cross-sectional) studies or secondary analysis of randomized controlled trials. The target participants are blunt trauma patients with potential pelvic injury. The target condition is pelvic fracture. The index test being investigated is physical examination for pelvic fracture. The reference standard is X-ray or computed tomography to confirm the target condition. We will search MEDLINE, EMBASE and The Cochrane Library inclusive of Cochrane Controlled Trials Register. Two authors will independently screen the study eligibility and extract data. Screening will be a two-step process with initial title/abstract screening followed by full-text screening. We will evaluate the risk of bias independently by two investigators and reported according to the QUADAS-2 tool. In the meta-analysis, we will use a bivariate random-effects model to report the summary receiver operating characteristic (SROC) point (summary values for sensitivity and specificity) and the 95% confidence region around the summary ROC point.Trial registrationThis review is submitted with University hospital medical information network clinical trial registry (UMIN-CTR) [UMIN000038785].
Dissecting the collateral damage of antibiotics on gut microbes
Authors: Maier Lisa , Goemans Camille V. , Pruteanu Mihaela , Wirbel Jakob , Kuhn Michael , Cacace Elisabetta , Banerjee Tisya , Anderson Exene Erin , Milanese Alessio , Löber Ulrike , Forslund Sofia K. , Patil Kiran Raosaheb , Zeller Georg , Bork Peer , Typas Athanasios 
Published: January 2020

AbstractAntibiotics are used for fighting pathogens, but also target our commensal bacteria as a side effect, disturbing the gut microbiota composition and causing dysbiosis and disease1-3. Despite this well-known collateral damage, the activity spectrum of the different antibiotic classes on gut bacteria remains poorly characterized. Having monitored the activities of >1,000 marketed drugs on 38 representative species of the healthy human gut microbiome4, we here characterize further the 144 antibiotics therein, representing all major classes. We determined >800 Minimal Inhibitory Concentrations (MICs) and extended the antibiotic profiling to 10 additional species to validate these results and link to available data on antibiotic breakpoints for gut microbes. Antibiotic classes exhibited distinct inhibition spectra, including generation-dependent effects by quinolones and phylogeny-independence by β-lactams. Macrolides and tetracyclines, two prototypic classes of bacteriostatic protein synthesis inhibitors, inhibited almost all commensals tested. We established that both kill different subsets of prevalent commensal bacteria, and cause cell lysis in specific cases. This species-specific activity challenges the long-standing divide of antibiotics into bactericidal and bacteriostatic, and provides a possible explanation for the strong impact of macrolides on the gut microbiota composition in animals5-8and humans9-11. To mitigate the collateral damage of macrolides and tetracyclines on gut commensals, we exploited the fact that drug combinations have species-specific outcomes in bacteria12and sought marketed drugs, which could antagonize the activity of these antibiotics in abundant gut commensal species. By screening >1,000 drugs, we identified several such antidotes capable of protecting gut species from these antibiotics without compromising their activity against relevant pathogens. Altogether, this study broadens our understanding of antibiotic action on gut commensals, uncovers a previously unappreciated and broad bactericidal effect of prototypical bacteriostatic antibiotics on gut bacteria, and opens avenues for preventing the collateral damage caused by antibiotics on human gut commensals.
Increased likelihood of heat-induced large wildfires in the Mediterranean Basin
Authors: Ruffault J , Curt T , Moron V , Trigo RM , Mouillot F , Koutsias N , Pimont F , Martin-StPaul NK , Barbero R , Dupuy J-L , Russo A , Belhadj-Kheder C 
Published: January 2020

AbstractWildfire activity is expected to increase across the Mediterranean Basin because of climate change. However, the effects of future climate changes on the combinations of atmospheric conditions that promote large wildfires remain largely unknown. Using a fire-weather based classification of wildfires, we show that future climate scenarios point to an increase in the frequency and severity of two heat-induced fire-weather types that have been responsible for a majority of record-breaking wildfire events. Heat-induced fire-weather types are characterized by compound dry warm conditions and occur in the summer during heatwaves, either under moderate (sudden heatwavetype) or intense (hot droughttype) drought. Heat-induced fire weather is projected to increase in frequency by 14% by the end of the century (2071-2100) under the RCP4.5 scenario, and by 30% under the RCP8.5. These findings suggest that the frequency and extent of large wildfires will increase throughout the Mediterranean Basin, with far-reaching impacts.
Cell-type specific impact of glucocorticoid receptor activation on the developing brain
Authors: Cruceanu Cristiana , Dony Leander , Krontira Anthi C. , Fischer David S. , Roeh Simone , Di Giaimo Rossella , Kyrousi Christina , Arloth Janine , Czamara Darina , Martinelli Silvia , Wehner Stefanie , Breen Michael S. , Koedel Maik , Sauer Susann , Rex-Haffner Monika , Cappello Silvia , Theis Fabian J. , Binder Elisabeth B. 
Published: January 2020

AbstractA fine-tuned balance of glucocorticoid receptor (GR) activation is essential for organ formation, with disturbances influencing health outcomes. Excess GR-activationin uterohas been linked to brain-related negative outcomes, with unclear underlying mechanisms, especially regarding cell-type specific effects. To address this, we used anin vitromodel of fetal human brain, induced pluripotent-stem-cell-derived cerebral organoids, and mapped GR-activation effects using single-cell transcriptomics across development. Interestingly, neurons showed targeted regulation of differentiation- and maturation-related transcripts, suggesting a delay of these processes upon GR-activation. Uniquely in neurons, differentially-expressed transcripts were significantly enriched for genes associated with behavior-related phenotypes and disorders. This suggests that aberrant GR-activation could impact proper neuronal maturation, leading to increased disease susceptibility, through neurodevelopmental processes at the interface of genetic susceptibility and environmental exposure.
Sequence learning in a single trial: a spiking neurons model based on hippocampal circuitry
Authors: Coppolino S. , Migliore M. 
Published: January 2020

ABSTRACTIn contrast with our everyday experience using brain circuits, it can take a prohibitively long time to train a computational system to produce the correct sequence of outputs in the presence of a series of inputs. This suggests that something important is missing in the way in which models are trying to reproduce basic cognitive functions. In this work, we introduce a new neuronal network architecture that is able to learn, in a single trial, an arbitrary long sequence of any known objects. The key point of the model is the explicit use of mechanisms and circuitry observed in the hippocampus, which allow the model to reach a level of efficiency and accuracy that, to the best of our knowledge, is not possible with abstract network implementations. By directly following the natural system’s layout and circuitry, this type of implementation has the additional advantage that the results can be more easily compared to experimental data, allowing a deeper and more direct understanding of the mechanisms underlying cognitive functions and dysfunctions, and opening the way to a new generation of learning architectures.
Required concentration index quantifies effective drug combinations against hepatitis C virus infection
Authors: Kakizoe Yusuke , Koizumi Yoshiki , Ikoma Yukino , Ohashi Hirofumi , Wakita Takaji , Iwami Shingo , Watashi Koichi 
Published: January 2020

ABSTRACTSuccessful clinical drug development requires rational design of combination treatments based on preclinical data. Anti-HCV drugs exhibit significant diversity in antiviral effect. Dose-response assessments can be used to determine parameters profiling the diverse antiviral effect during combination treatment. In the current study, a combined experimental and mathematical approaches were used to compare and score different combinations of anti-hepatitis C virus (HCV) treatments. A “required concentration index” was generated and used to rank the antiviral profile of possible double- and triple-drug combinations against HCV genotype 1 and 2. Rankings varied based on target HCV genotype. Interestingly, multidrug (double and triple) treatment not only augmented antiviral activity, but also reduced genotype-specific efficacy, suggesting another advantage of multidrug treatment. The current study provides a quantitative method for profiling drug combinations against viral genotypes, to better inform clinical drug development.
Hemoglobin Non-equilibrium Oxygen Dissociation Curve
Authors: Scrima Rosella , Fugetto Sabino , Capitanio Nazzareno , Gatti Domenico L. 
Published: January 2020

AbstractAbnormal hemoglobins can have major consequences for tissue delivery of oxygen. Correct diagnosis of hemoglobinopathies with altered oxygen affinity requires a determination of hemoglobin oxygen dissociation curve (ODC), which relates the hemoglobin oxygen saturation to the partial pressure of oxygen in the blood. Determination of the ODC of human hemoglobin is typically carried out under conditions in which hemoglobin is in equilibrium with O2at each partial pressure. However, in the human body due to the fast transit of RBCs through tissues hemoglobin oxygen exchanges occur under non-equilibrium conditions. We describe the determination of non-equilibrium ODC, and show that under these conditions Hb cooperativity has two apparent components in the Adair, Perutz, and MWC models of Hb. The first component, which we callsequential cooperativity, accounts for ∼70% of Hb cooperativity, and emerges from the constraint of sequential binding that is shared by the three models. The second component, which we callconformational cooperativity, accounts for ∼30% of Hb cooperativity, and is due either to a conformational equilibrium between low affinity and high affinity tetramers (as in the MWC model), or to a conformational change from low to high affinity once two of the tetramer sites are occupied (Perutz model).
A flexible workflow for simulating transcranial electric stimulation in healthy and lesioned brains
Authors: Kalloch Benjamin , Bazin Pierre-Louis , Villringer Arno , Sehm Bernhard , Hlawitschka Mario 
Published: January 2020

AbstractSimulating transcranial electric stimulation is actively researched as knowledge about the distribution of the electrical field is decisive for understanding the variability in the elicited stimulation effect. Several software pipelines comprehensively solve this task in an automated manner for standard use-cases. However, simulations for non-standard applications such as uncommon electrode shapes or the creation of head models from non-optimized T1-weighted imaging data and the inclusion of irregular structures are more difficult to accomplish.We address these limitations and suggest a comprehensive workflow to simulate transcranial electric stimulation based on open-source tools. The workflow covers the head model creation from MRI data, the electrode modeling, the modeling of anisotropic conductivity behavior of the white matter, the numerical simulation and visualization.Skin, skull, air cavities, cerebrospinal fluid, white matter, and gray matter are segmented semi-automatically from T1-weighted MR images. Electrodes of arbitrary number and shape can be modeled. The meshing of the head model is implemented in a way to preserve feature edges of the electrodes and is free of topological restrictions of the considered structures of the head model. White matter anisotropy can be computed from diffusion-tensor imaging data.Our solver application was verified analytically and by contrasting tDCS simulation results with another simulation pipeline (SimNIBS 3.0). An agreement in both cases underlines the validity of our workflow.Our suggested solutions facilitate investigations of irregular structures in patients (e.g. lesions, implants) or of new electrode types. For a coupled use of the described workflow, we provide documentation and disclose the full source code of the developed tools.
Rapid detection of Pecan Root-Knot Nematode,Meloidogyne partityla, in laboratory and field conditions using loop-mediated isothermal amplification
Authors: Waliullah Sumyya , Bell Jessica , Stackhouse Tammy , Jagdale Ganpati , Hajihassani Abolfazl , Brenneman Timothy , Ali Md Emran 
Published: January 2020

AbstractMeloidogyne partitylais the dominant root-knot nematode (RKN) species parasitizing pecan in Georgia. This species is known to cause a reduction in root growth and a decline in yields from mature pecan trees. Rapid and accurate diagnosis of this RKN is required to control this nematode disease and reduce losses in pecan production. In this study, a loop-mediated isothermal amplification (LAMP) method was developed for simple, rapid and on-site detection ofM. partitylain infested plant roots and validated to detect the nematode in laboratory and field conditions. Specific primers were designed based on the sequence distinction of internal transcribed spacer (ITS)-18S/5.8S ribosomal RNA gene betweenM. partitylaand otherMeloidogynespp. The LAMP detection technique could detect the presence ofM. partitylagenomic DNA at a concentration as low as 1 pg, and no cross reactivity was found with DNA from other major RKN species such asM. javanica,M. incognitaandM. arenaria, andM. hapla. We also conducted a traditional morphology-based diagnostic assay and conventional polymerase chain reaction (PCR) assay to determine which of these techniques was less time consuming, more sensitive, and convenient to use in the field. The LAMP assay provided more rapid results, amplifying the target nematode species in less than 60 min at 65°C, with results 100 times more sensitive than conventional PCR (~2-3 hrs). Morphology-based, traditional diagnosis was highly time-consuming (2 days) and more laborious than conventional PCR and LAMP assays. These features greatly simplified the operating procedure and made the assay a powerful tool for rapid, on-site detection of pecan RKN,M. partityla. The LAMP assay will facilitate accurate pecan nematode diagnosis in the field and contribute to the management of the pathogen.
The effect of exercise on the protein profile of rat knee joint intra- and extra-articular ligaments
Authors: Kharaz Yalda A. , Birch Helen L. , Chester Alexandra , Alchorne Eleanor , Simpson Deborah , Clegg Peter , Comerford Eithne 
Published: January 2020

AbstractInjuries to the intra-articular knee joint ligament (anterior cruciate ligament (ACL)) together with the extra-articular medial collateral ligament (MCL) result in significant joint instability, pain and immobility for the affected individual. Moderate endurance type exercise has been shown to increase ligament strength, however little is known on the effect of short-term high intensity exercise regimes such as treadmill training on the ACL and MCL and whether they may be beneficial to the extracellular matrix (ECM) structure of these ligaments. This study aimed to identify the effect of short-term high intensity exercise on the proteome of the rat ACL and MCL using mass spectrometry. Sprague Dawley male rats (n=12) were split into equal groups of control and exercise animals, which were subjected to high intensity training and followed by proteomic analysis of the ACL and MCL. Knee joint and ligament health was assessed using OARSI scoring or using a validated histological scoring system. Histopathological analyses demonstrated no significant changes in the ACL, MCL or cartilage of the knee joint, indicating that the exercise regime used in this study did not have substantial impact on tissue structure and health of several tissues within the rat knee joint. Some proteins were found to be significantly more abundant in the ACL in the exercised group than the control group. However, no proteins with a significantly different expression were identified between MCL control and MCL exercised groups. The majority of proteins expressed at higher levels in the ACL exercise group were cytoskeletal proteins, ribosomal proteins and enzymes. Several matrisomal proteins were also more abundant such as collagen proteins and proteoglycans in ACL exercise group. In conclusion, our results indicate that short-term high intensity exercise has an impact on ACL ECM protein expression, with the majority of differential expressed proteins being cellular proteins such as actins, ribosomal and heat shock proteins, indicative of metabolic and molecular responses. Further study is necessary to determine the impact of these short-term changes on ligament structure and function.