bluuebunny/crossref_metadata_2025_split huggingface dataset:
Semantic coding in the occipital cortex of early blind individuals
Authors: Abboud Sami , Engemann Denis A. , Cohen Laurent 
Published: February 2019

AbstractThe visual cortex of early blind individuals is reorganized to support cognitive functions distinct from vision. Research suggests that one such prominent function is language. However, it is unknown whether the visual cortex of blind individuals codes for word meaning. We addressed this question by comparing neuronal activity evoked by a semantic decision task, using magnetoencephalography (MEG), between 12 early blind and 14 sighted participants otherwise comparable with regard to gender, age and education. We found that average brain responses to thousands of auditory word stimuli followed similar time courses in blind and sighted participants. However, in blind participants only, we found a sustained enhancement of activity in the visual cortex. Moreover, across the whole brain, we found an effect of semantic category from about 400 ms after word onset. Strikingly, in blind participants, semantic categories were discriminable starting 580 ms after word onset from signal captured by sensors sensitive to the visual cortex. We replicated the analyses in time windows locked to stimulus onset and behavioral response, using both classical hypothesis testing and machine learning for single-trial classification. Semantic decisions were well classified in all participants (AUC ∼ 0.60), but generalization capacity across participants was found reduced in the blind group due to a larger variability of discriminative patterns. In conclusion, our findings suggest that brain plasticity reorganizes the semantic system of blind individuals, and extends semantic computation into the visual cortex.
Closed loop motor-sensory dynamics in human vision
Authors: Gruber Liron , Ahissar Ehud 
Published: February 2019

AbstractVision is obtained with a continuous motion of the eyes. The kinematic analysis of eye motion, during any visual or ocular task, typically reveals two (kinematic) components: saccades, which quickly replace the visual content in the retinal fovea, and drifts, which slowly scan the image after each saccade. While the saccadic exchange of regions of interest (ROIs) is commonly considered to be included in motor-sensory closed-loops, it is commonly assumed that drifts function in an open-loop manner, that is, independent of the concurrent visual input. Accordingly, visual perception is assumed to be based on a sequence of open-loop processes, each initiated by a saccade-triggered retinal snapshot. Here we directly challenged this assumption by testing the dependency of drift kinematics on concurrent visual inputs using real-time gaze-contingent-display. Our results demonstrate a dependency of the trajectory on the concurrent visual input, convergence of speed to condition-specific values and maintenance of selected drift-related motor-sensory controlled variables, all strongly indicative of drifts being included in a closed-loop brain-world process, and thus suggesting that vision is inherently a closed-loop process.Author summaryOur eyes do not function like cameras; it has long been known that we are actively scanning our visual environment in order to see. Moreover, it is commonly accepted that our fast eye movements, saccades, are controlled by the brain and are affected by the sensory input. However, our slow eye movements, the ocular drifts, are often ignored when visual acquisition is analyzed. Accordingly, visual processing is typically assumed to be based on computations performed on saccade-triggered snapshots of the retinal state. Our work strongly challenges this model and provides significant evidence for an alternative model, a cybernetic one. We show that the dynamics of the ocular drifts do not allow, and cannot be explained by, open loop visual acquisition. Instead, our results suggest that visual acquisition is part of a closed-loop process, which dynamically and continuously links the brain to its environment.
PROTEIN THERMAL STABILITY ENGINEERING USING HOTMUSIC
Authors: Pucci Fabrizio , Kwasigroch Jean Marc , Rooman Marianne 
Published: February 2019

AbstractThe rational design of enzymes is a challenging research field, which plays an important role in the optimization of a wide series of biotechnological processes. Computational approaches allow to screen all possible amino acid substitutions in a target protein and to identify a subset likely to have the desired properties. They can thus be used to guide and restrict the huge, time-consuming, search in sequence space to reach protein optimality. Here we present HoTMuSiC, a tool that predicts the impact of point mutations on the protein melting temperature, which uses the experimental or modelled protein structure as sole input, and is available at dezyme.com. Its main advantages include accuracy and speed, which makes it a perfect instrument for thermal stability engineering projects aiming to design new proteins that feature increased heat resistance or remain active and stable in non-physiological conditions. We set up a HoTMuSiC-based pipeline, which uses additional information to avoid mutations of functionally important residues, identified as being too well conserved among homologous proteins or too close to annotated functional sites. The efficiency of this pipeline is successfully demonstrated on Rhizomucor miehei lipase.
Translating antibiotic prescribing into antimicrobial resistance in the environment: a hazard characterisation case study
Authors: Singer Andrew C. , Xu Qiuying , Keller Virginie D.J. 
Published: February 2019

AbstractThe use and misuse of antibiotics in humans, animals and agriculture since penicillin’s mass production in 1942 has contributed to the current global crisis of drug-resistant infections. Often overlooked are the unintended consequences of such widespread antibiotic use, such as the chronic environmental release of unmetabolised, bioactive antibiotics and antibiotic-resistance genes found in human and animals waste, particularly during and immediately after antibiotic treatment. Here, we report on the potential impact on antibiotic resistance gene selection in rivers from the antibiotic prescribing practice of the National Health Service (NHS) of England. Macrolide and fluoroquinolone prescription data from 2015/16 were used to model the concentrations of antibiotics in a highly populous, sewage-impacted English catchment. Predicted antibiotic concentrations in the river were compared against predicted no-effect concentrations (PNEC) to assess the hazard of antibiotic resistance selection. The study revealed that PNECs for macrolides and fluoroquinolones were exceeded in 63% and 73% of the length of the modelled River Thames catchment, respectively. Potential reductions in macrolide and fluoroquinolone prescriptions (e.g., 4% and 20%) were not shown to translate into meaningful reductions in the hazard of AMR selection in the river. Reductions in macrolide and fluoroquinolone prescribing of 77% and 85%, respectively, were necessary to alleviate the AMR selection hazard from 90+% of the modelled river catchment. Improved antibiotic stewardship, alone, is unlikely to alleviate the identified challenge. Action is needed to substantially reduce antibiotic prescribing, stimulate and implement innovation in sewage-treatment, reduce non-antibiotic drivers of antibiotic resistance (e.g., biocides, metals), and consider regulating antibiotic-resistance DNA as a pollutant.
Predicting Empathy from Resting Brain Connectivity
Authors: Christov-Moore Leonardo , Reggente Nicco , Douglas Pamela K. , Feusner Jamie D. , Iacoboni Marco 
Published: February 2019

AbstractRecent studies suggest that individual differences in empathic concern may be mediated by continuous interactions between self-other resonance and cognitive control networks. To test this hypothesis, we used machine learning to examine whether resting fMRI connectivity (i.e. the degree of synchronous BOLD activity across multiple cortical areas in the absence of task demands) of resonance and control networks could predict trait empathy (n=58). Indeed, resonance and control networks’ interconnectivity predicted empathic concern. Empathic concern was also predicted by connectivity within the somatomotor network. In light of numerous reported sex differences in empathy, we controlled for biological sex and also studied separately what aspect of these features could predict participants’ sex. Sex was best predicted by the interconnectivity of the visual system with the resonance, somatomotor, and cingulo-opercular network, as well as the somatomotor-control network connectivity. These findings confirm that variation in empathic responses to others reflects characteristic network properties detectable regardless of task demands. Furthermore, network properties of the visual system may be a locus of sex differences previously unaccounted for in empathy research. Finally, these findings suggest that it may be possible to assess empathic predispositions in individuals without needing to perform conventional empathy assessments.
Hearing loss promotes schizophrenia-relevant brain and behavioral abnormalities in a mouse model of human 22q11.2 Deletion Syndrome
Authors: Zinnamon Fhatarah A. , Harrison Freya G. , Wenas Sandra S. , Meyer Arne F. , Liu Qing , Wang Kuan Hong , Linden Jennifer F. 
Published: February 2019

ABSTRACTHearing loss has been implicated as a risk factor for schizophrenia, but it is not known whether this association arises from common etiology, top-down influences (e.g., social isolation), bottom-up neurobiological mechanisms, or combinations of these factors. Patients with 22q11.2 Deletion Syndrome (22q11.2DS) have a 25-30% risk of developing schizophrenia, and also suffer frequent hearing loss. Here, we used the Df1/+ mouse model of 22q11.2DS to investigate the relationship between hearing loss and susceptibility to schizophrenia-relevant brain and behavioral abnormalities. Df1/+ mice have a multi-gene deletion analogous to the chromosomal microdeletion that causes human 22q11.2DS, and like human 22q11.2DS patients exhibit high rates of hearing loss arising primarily from susceptibility to middle ear inflammation. We found that hearing loss in Df1/+ mice affected schizophrenia-relevant endophenotypes, including electrophysiological measures of central auditory gain and behavioral measures of auditory sensorimotor gating. Moreover, PV+ inhibitory interneurons, another marker for schizophrenia pathology, were significantly reduced in density in auditory cortex but not secondary motor cortex of Df1/+ mice with hearing loss. These results reveal bottom-up neurobiological mechanisms through which peripheral hearing loss arising from the 22q11.2 deletion may promote the emergence of schizophrenia-relevant auditory brain and behavioral abnormalities, and also suggest a link between conductive hearing loss and reduced PV+ interneuron density in the auditory cortex.SIGNIFICANCE STATEMENTHearing loss is a known risk factor for schizophrenia. Deletion of chromosomal locus 22q11.2 is associated with both schizophrenia and hearing loss in humans. In the Df1/+ mouse model of human 22q11.2 Deletion Syndrome, we find that hearing loss shapes measures that are considered schizophrenia-relevant endophenotypes, such as central auditory gain and auditory sensorimotor gating. Moreover, we report a reduction in density of PV+ inhibitory interneurons in the auditory cortex, but not secondary motor cortex, of Df1/+ mice with hearing loss. These results suggest mechanisms through which hearing loss associated with the 22q11.2 deletion may promote emergence of schizophrenia-relevant auditory brain and behavioral abnormalities and indicate that conductive hearing loss may influence PV+ interneuron density in the auditory cortex.
Adaptive stress response induced by toluene increasesSporothrix schenckiivirulence and host immune response
Authors: Téllez-Martínez Damiana , Batista-Duharte Alexander , Silva Vinicius Paschoalini , Fuentes Deivys Portuondo , Ferreira Lucas Souza , Polesi Marisa Campos , Barcelós Costa Caroline , Carlos Iracilda Zeppone 
Published: February 2019

ABSTRACTEnvironmental factors modify the physiology of microorganisms, allowing their survival in extreme conditions. However, the influence of chemical contaminants on fungal virulence has been little studied. Sporotrichosis is an emergent fungal disease caused bySporothrix schenckii,a soil-inhabiting fungus that has been found in polluted environments. Here, we evaluated the adaptive stress response ofS. schenckiiinduced by toluene, a key soil contaminant. The effect on fungal virulence and host immune response was also assessed. The fungus survived up to 0.10% toluene in liquid medium. Greater production of melanosomes and enhanced activity superoxide dismutase, associated to increased tolerance to H2O2were observed in toluene-exposed fungi. Intraperitoneal infection of mice withS. schenckiitreated with either 0, 0.01 or 0.1% of toluene, resulted in greater fungal burden at day 7 post-infection in spleen and liver in the groups infected with fungus treated with toluene 0.1%. A higher production of Il-1β, TNF-α, IL-10 and nitric oxyde by peritoneal macrophages and IFNγ, IL-4 and IL-17 by splenocytes was also observed in that group. Our findings showed that morphological and functional changes induced by toluene leads to increasedS. schenckiivirulence and antifungal host immune response in our model.
Cellular heterogeneity during mouse pancreatic ductal adenocarcinoma progression at single-cell resolution
Authors: Hosein Abdel Nasser , Huang Huocong , Wang Zhaoning , Parmar Kamalpreet , Du Wenting , Huang Jonathan , Maitra Anirban , Olson Eric , Verma Udit , Brekken Rolf A. 
Published: February 2019

AbstractBackground & AimsPancreatic ductal adenocarcinoma (PDA) is a major cause of cancer-related death with limited therapeutic options available. This highlights the need for improved understanding of the biology of PDA progression. The progression of PDA is a highly complex and dynamic process featuring changes in cancer cells and stromal cells; however, a comprehensive characterization of PDA cancer cell and stromal cell heterogeneity during disease progression is lacking. In this study, we aimed to profile cell populations and understand their phenotypic changes during PDA progression.MethodsWe employed single-cell RNA sequencing technology to agnostically profile cell heterogeneity during different stages of PDA progression in genetically engineered mouse models.ResultsOur data indicate that an epithelial-to-mesenchymal transition of cancer cells accompanies tumor progression. We also found distinct populations of macrophages with increasing inflammatory features during PDA progression. In addition, we noted the existence of three distinct molecular subtypes of fibroblasts in the normal mouse pancreas, which ultimately gave rise to two distinct populations of fibroblasts in advanced PDA, supporting recent reports on intratumoral fibroblast heterogeneity. Our data also suggest that cancer cells and fibroblasts are dynamically regulated by epigenetic mechanisms.ConclusionThis study systematically outlines the landscape of cellular heterogeneity during the progression of PDA. It strongly improves our understanding of the PDA biology and has the potential to aid in the development of therapeutic strategies against specific cell populations of the disease.
Quantification of alterations in diffusion measures of white matter integrity associated with healthy aging
Authors: Molloy Ciara J. , Nugent Sinead , Bokde Arun L.W. 
Published: February 2019

AbstractThis study aimed to evaluate the linear association of age with diffusion tensor imaging (DTI) measures of white matter such as fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). We assessed patterns of overlap between linear correlations of age with FA with RD, MD and AD to characterize the process of white matter degeneration observed with ageing. 79 healthy adults aged between 18 and 75 took part in the study. The DTI data were based on 61 directions acquired with a b-value of 2000. There was a statistically significant negative linear correlation of age with FA and AD and a positive linear correlation with RD and MD, and AD. The forceps minor tract showed largest percentage of voxels with an association of age with FA, RD and AD, and the anterior thalamic radiation with MD. We found 5 main patterns of overlap: FA alone (15.95%); FA and RD (31.90%); FA and AD (12.99%); FA, RD and AD (27.37%); FA RD, and MD (6.94%). Patterns of overlap between diffusion measures may reflect underlying biological changes with healthy ageing such as loss of myelination, axonal damage, as well as mild microstructural and chronic white matter impairments. This study may provide information about causes of degeneration in specific regions of the brain, and how this may affect healthy brain functioning in older adults.
Facilitating Replication and Reproducibility in Team Science: The ‘projects’ R Package
Authors: Krieger Nikolas I. , Perzynski Adam T. , Dalton Jarrod E. 
Published: February 2019

AbstractThe contemporary scientific community places a growing emphasis on the reproducibility of research. TheprojectsR package is a free, open-source endeavor created in the interest of facilitating reproducible research workflows. It adds to existing software tools for reproducible research and introduces several practical features that are helpful for scientists and their collaborative research teams. For each individual project, it supplies an intuitive framework for storing raw and cleaned study data sets, and provides script templates for protocol creation, data cleaning, data analysis and manuscript development. Internal databases of project and author information are generated and displayed, and manuscript title pages containing author lists and their affiliations are automatically generated from the internal database. File management tools allow teams to organize multiple projects. When used on a shared file system, multiple researchers can harmoniously contribute to the same project in a less punctuated manner, reducing the frequency of misunderstandings and the need for status updates.
Effects of decreased Rac activity and malignant state on oral squamous cell carcinoma
Authors: Al-Shareef Hani , Matsuoka Yudai , Kogo Mikihiko , Nakahara Hirokazu 
Published: February 2019

AbstractRac proteins, members of the Rho family of small GTP-binding proteins, have been implicated in transducing a number of signals for various biological mechanisms, including cell cytoskeleton organization, transcription, proliferation, migration, and cancer cell motility. Among human cancers, Rac proteins are highly activated by either overexpression of the genes, up-regulation of the protein, or by mutations that allow the protein to elude normal regulatory signaling pathways. Rac proteins are involved in controlling cell survival and apoptosis. The effects of Rac inhibition by the Rac-specific small molecule inhibitor NSC23766 or by transfection of dominant negative Rac (Rac-DN) were examined on three human-derived oral squamous cell carcinoma cell lines that exhibit different malignancy grades, OSC-20 (grade 3), OSC-19 (grade 4C), and HOC313 (grade 4D). Upon suppression of Rac, OSC-19 and HOC313 cells showed significant decreases in Rac activity and resulted in condensation of the nuclei and up- regulation of c-Jun N-terminal kinase (JNK), leading to caspase-dependent apoptosis. In contrast, OSC-20 cells showed only a slight decrease in Rac activity, which resulted in slight activation of JNK and no change in the nuclei. Fibroblasts treated with NSC23766 also showed only a slight decrease in Rac activity with no change in the nuclei or JNK activity. Our results indicated that apoptosis elicited by the inhibition of Rac depended on the extent of decreased Rac activity and the malignant state of the squamous cell carcinoma. In addition, activation of JNK strongly correlated with apoptosis. Rac inhibition may represent a novel therapeutic approach for cancer treatment.
Cipla-Medpro acquisition: the pre- and post-merger story
Authors: Saxena Nishant , Ungerer Marius 
Published: February 2019

Title
Cipla-Medpro acquisition: the pre- and post-merger story.

Learning outcomes
The learning outcomes are as follows: to develop a deeper understanding of the pre- and post-merger factors that should be considered in an M&A transaction; to develop an appreciation of the human capital and organisation cultural aspects involved in cross-country M&A’s; to develop an understanding of the role of leaders and an integration team to make an M&A realise the intended value; and to develop a sensitivity for doing an M&A in a developing country like South Africa.

Case overview/synopsis
This case study creates opportunities for discussing both pre-merger and post-merger dynamics to create a sensitivity that multiple factors contribute to a successful merger and acquisition strategic move. It is intended for classroom discussion only and does not represent correct or incorrect handling of the situation.

Complexity academic level
The complexity is MBA level. This case is primarily focussed on M&A’s as part of a course in Strategic Management (MBA level) but can also be considered for a course on Strategic HRM.

Supplementary materials
Teaching Notes are available for educators only.

Subject code
CSS: 11 Strategy.
Adoption and non-adoption motivational risk beliefs in the use of mobile services for health promotion
Authors: Cocosila Mihail , Turel Ofir 
Published: February 2019

PurposeThe purpose of this paper is to validate empirically a theoretical model that integrates an innovative construct capturing consumers’ non-adoption risk belief associated with not using a mobile service designed to support them in a non-leisure activity.Design/methodology/approachA theoretical model contrasting perceived non-adoption risk to perceived adoption risk of a mobile service supporting health promotion was developed and tested with a sample of potential consumers in North America.FindingsResults show that non-adoption risk is a moderately strong antecedent of motivational factors in contrast to adoption risk that hinders the acceptance of a mobile service supporting health promotion.Research limitations/implicationsHealthcare is a highly sensitive social sector, so possible negative consequences of not using the support of a mobile service are an additional motivation for adopting this service. Future research should test the role of non-adoption risk in other contexts of technology use, including non-leisure settings.Practical implicationsMaking potential users see the possible negative consequences of not using a mobile service designed to support them in a non-leisure activity increases their motivation and, subsequently, intention to use the service.Social implicationsEducational efforts to making consumers see the risks of not using a supporting technology application appear to be justified.Originality/valueThis study demonstrates the significant role of non-adoption risk belief that captures the negative consequences individuals may perceive if they fail to use as expected a mobile service application designed specifically to help them.