Miracle-dz/UniFAR-FTUs huggingface dataset:
Tractography of the Spider Monkey (Ateles geoffroyi) Corpus Callosum Using Diffusion Tensor Magnetic Resonance Imaging

The objective of this research was to describe the organization, connectivity and microstructure of the corpus callosum of the spider monkey (Ateles geoffroyi). Non-invasive magnetic resonance imaging and diffusion-tensor imaging were obtained from three subjects using a 3T Philips scanner. We hypothesized that the arrangement of fibers in spider monkeys would be similar to that observed in other non-human primates. A repeated measure (n = 3) of fractional anisotropy values was obtained of each subject and for each callosal subdivision. Measurements of the diffusion properties of corpus callosum fibers exhibited a similar pattern to those reported in the literature for humans and chimpanzees. No statistical difference was reached when comparing this parameter between the different CC regions (p = 0.066). The highest fractional anisotropy values corresponded to regions projecting from the corpus callosum to the posterior cortical association areas, premotor and supplementary motor cortices. The lowest fractional anisotropy corresponded to projections to motor and sensory cortical areas. Analyses indicated that approximately 57% of the fibers projects to the frontal cortex and 43% to the post-central cortex. While this study had a small sample size, the results provided important information concerning the organization of the corpus callosum in spider monkeys.
Groα‐mediated recruitment of neutrophils is required for elicitation of contact hypersensitivity

The factors mediating recruitment of immune T cells to challenge sites during contact hypersensitivity (CHS) responses remain unclear. To investigate the role of chemokines during elicitation of CHS, the temporal expression of chemokine genes in hapten‐challenged ears was tested. KC (the murine homologoue of Groα) was expressed 30 min following hapten challenge in naive and hapten‐sensitized mice. A rabbit KC‐specific antiserum inhibited elicitation of CHS when administered to sensitized mice prior to hapten challenge. Injecting either neutrophils or immune CD8+ T cells into the ear tissue of immune animals before hapten challenge circumvented the KC antiserum‐mediated inhibition of CHS. Neutrophil depletion also inhibited CHS and was circumvented by injecting either neutrophils or hapten‐primed CD8+ T cells into ears of sensitized mice followed by specific hapten challenge. These results indicate that KC‐directed neutrophil infiltration of hapten challenge sites is required for elicitation of CHS and suggest that neutrophils mediate recruitment of the hapten‐specific CD8+ T cells that subsequently produce cytokines mediating the hypersensitivity response.
On the Relation between the Small World Structure and Scientific Activities

The modern science has become more complex and interdisciplinary in its nature which might encourage researchers to be more collaborative and get engaged in larger collaboration networks. Various aspects of collaboration networks have been examined so far to detect the most determinant factors in knowledge creation and scientific production. One of the network structures that recently attracted much theoretical attention is called small world. It has been suggested that small world can improve the information transmission among the network actors. In this paper, using the data on 12 periods of journal publications of Canadian researchers in natural sciences and engineering, the co-authorship networks of the researchers are created. Through measuring small world indicators, the small worldiness of the mentioned network and its relation with researchers’ productivity, quality of their publications, and scientific team size are assessed. Our results show that the examined co-authorship network strictly exhibits the small world properties. In addition, it is suggested that in a small world network researchers expand their team size through getting connected to other experts of the field. This team size expansion may result in higher productivity of the whole team as a result of getting access to new resources, benefitting from the internal referring, and exchanging ideas among the team members. Moreover, although small world network is positively correlated with the quality of the articles in terms of both citation count and journal impact factor, it is negatively related with the average productivity of researchers in terms of the number of their publications.
Variation in the Frequency and Extent of Hybridization between Leucosceptrum japonicum and L. stellipilum (Lamiaceae) in the Central Japanese Mainland

Variations in the frequency and extent of hybridization among mixed populations located in the same contact zone provide natural laboratories for the study of extrinsic reproductive isolation maintaining species integrity. In this study, we examined the pattern of hybridization between L. japonicum and L. stellipilum among mixed populations in different localities of a contact zone. The genetic structures from three sympatric populations and six mixed populations in the hybrid zone, and five reference populations far from the contact zone, were characterized using 10 neutral nuclear microsatellite markers. Evidence from genetic distance-based clustering analysis, the frequency distribution of admixture proportion values, and the hybrid category assignment approaches indicated that the frequency and extent of hybridization varied considerably among populations in the contact zone between L. japonicum and L. stellipilum. One likely explanation is that variation in exogenous (ecological) selection among populations might contribute to differences in frequency and extent of hybridization. The present study will facilitate future research exploring the evolution of reproductive isolation between L. japonicum and L. stellipilum.
Impact of the access tunnel engineering on catalysis is strictly ligand‐specific

The traditional way of rationally engineering enzymes to change their biocatalytic properties utilizes the modifications of their active sites. Another emerging approach is the engineering of structural features involved in the exchange of ligands between buried active sites and the surrounding solvent. However, surprisingly little is known about the effects of mutations that alter the access tunnels on the enzymes’ catalytic properties, and how these tunnels should be redesigned to allow fast passage of cognate substrates and products. Thus, we have systematically studied the effects of single‐point mutations in a tunnel‐lining residue of a haloalkane dehalogenase on the binding kinetics and catalytic conversion of both linear and branched haloalkanes. The hotspot residue Y176 was identified using computer simulations and randomized through saturation mutagenesis, and the resulting variants were screened for shifts in binding rates. Strikingly, opposite effects of the substituted residues on the catalytic efficiency toward linear and branched substrates were observed, which was found to be due to substrate‐specific requirements in the critical steps of the respective catalytic cycles. We conclude that not only the catalytic sites, but also the access pathways must be tailored specifically for each individual ligand, which is a new paradigm in protein engineering and de novo protein design. A rational approach is proposed here to address more effectively the task of designing ligand‐specific tunnels using computational tools.
ATTI: Workload-Aware Query Adaptive OcTree Based Trajectory Index

The GPS trajectory databases serve as bases for many intelligent applications that need to extract some trajectories for future processing or mining. When doing such tasks, spatio-temporal range queries based methods, which find all sub-trajectories within the given spatial extent and time interval, are commonly used. However, the history trajectory indexes of such methods suffer from two problems. First, temporal and spatial factors are not considered simutaneously, resulting in low performance when processing spatio-temporal queries. Second, the efficiency of indexes is sensitive to query size. The query performance changes dramatically as the query size changed. This paper proposes workload-aware Adaptive OcTree based Trajectory clustering Index (ATTI) aiming at optimizing trajectory storage and index performance. The contributions are three-folds. First, the distribution and time delay of the trajectory storage are introduced into the cost model of spatio-temporal range query; Second, the distribution of spatial division is dynamically adjusted based on GPS update workload; Third, the query workload adaptive mechanism is proposed based on virtual OcTree forest. A wide range of experiments are carried out over Microsoft GeoLife project dataset, and the results show that query delay of ATTI could be about 50% shorter than that of the nested index. key words: spatial-temporal database, trajectory, workload-aware, adaptive
Both live and dead Enterococci activate Caenorhabditis elegans host defense via immune and stress pathways

ABSTRACT The innate immune response of the nematode Caenorhabditis elegans has been extensively studied and a variety of Toll-independent immune response pathways have been identified. Surprisingly little, however, is known about how pathogens activate the C. elegans immune response. Enterococcus faecalis and Enterococcus faecium are closely related enterococcal species that exhibit significantly different levels of virulence in C. elegans infection models. Previous work has shown that activation of the C. elegans immune response by Pseudomonas aeruginosa involves P. aeruginosa-mediated host damage. Through ultrastructural imaging, we report that infection with either E. faecalis or E. faecium causes the worm intestine to become distended with proliferating bacteria in the absence of extensive morphological changes and apparent physical damage. Genetic analysis, whole-genome transcriptional profiling, and multiplexed gene expression analysis demonstrate that both enterococcal species, whether live or dead, induce a rapid and similar transcriptional defense response dependent upon previously described immune signaling pathways. The host response to E. faecium shows a stricter dependence upon stress response signaling pathways than the response to E. faecalis. Unexpectedly, we find that E. faecium is a C. elegans pathogen and that an active wild-type host defense response is required to keep an E. faecium infection at bay. These results provide new insights into the mechanisms underlying the C. elegans immune response to pathogen infection.
CD28 stimulates tyrosine phosphorylation, cellular redistribution and catalytic activity of the inositol lipid 5‐phosphatase SHIP

The D‐3 phosphoinositide lipids phosphatidylinositol 3,4,5‐trisphophate [PtdIns(3,4,5)P3] and phosphatidylinositol 3,4‐bisphosphate [PtdIns(3,4)P2] represent upstream components of a major signaling pathway that is strongly activated by the T cell costimulatory molecule CD28. A major route for degradation of PtdIns(3,4,5)P3 (and hence, regulation of PtdIns(3,4,5)P3‐driven effector pathways), involves its conversion to PtdIns(3,4)P2 by the 145‐kDa SH2‐containing inositol (poly)phosphate 5‐phosphatase (SHIP). In this study, we demonstrate using the murine T cell hybridoma DC27.1, that SHIP is strongly tyrosine phosphorylated after ligation of CD28 by either mAb or the natural ligand B7.1. Ligation of CD3 also stimulates SHIP tyrosine phosphorylation and an additive effect on tyrosine phosphorylation of SHIP is observed when both CD3 and CD28 are ligated. The tyrosine phosphorylation of SHIP in response to CD28 ligation correlates with a marked redistribution of SHIP from the cytosol to the plasma membrane, as well as an increase in the in vitro 5‐phosphatase activity associated with SHIP immunoprecipitates derived from CD28‐stimulated cells. However, we have been unable to detect a direct association between CD28 and SHIP, so the mechanisms by which CD28 exerts the observed effects on SHIP remain unclear. This is the first demonstration that SHIP is a biochemical target for CD28 and suggests that SHIP may be involved in the regulation of T cell activation.
Galleria mellonella: A model of infection to discern novel mechanisms of pathogenesis of non-toxigenic Vibrio parahaemolyticus strains

ABSTRACT Vibrio parahaemolyticus is a leading cause of raw seafood-associated bacterial gastroenteritis in the world. Its pathogenesis is likely to be multifactorial, although the most characteristic virulence-associated factors are the toxins TDH and TRH, in addition to the Type-III Secretion System-2, which codes for diverse effectors involved in cytotoxicity and enterotoxicity. However, diarrhea cases produced by clinical strains lacking all of these main virulence factors (non-toxigenic strains) have been reported in many countries and they can represent up to 9-10% of the clinical isolations. So far, although there have been significant advances in the description of the virulence factors of V. parahaemolyticus, the ability of non-toxigenic strains to cause illness is still not completely understood. To elucidate this question it is necessary to have adequate infection models. The susceptibility of G. mellonella to the infection with non-toxigenic strains seems to be the response to identifying new virulence factors and consequently providing new insights into mechanisms of the virulence of non-toxigenic strains. This new model means an invaluable contribution to public health, since the understanding of virulence in strains lacking the traditional major toxins is essential to detect these strains present in waters and marine products and avoid possible food-borne infection.
Signal and Noise in the Perception of Facial Emotion Expressions

Human interactions are replete with emotional exchanges, and hence, the ability to decode others’ emotional expressions is of great importance. The present research distinguishes between the emotional signal (the intended emotion) and noise (perception of secondary emotions) in social emotion perception and investigates whether these predict the quality of social interactions. In three studies, participants completed laboratory-based assessments of emotion recognition ability and later reported their perceptions of naturally occurring social interactions. Overall, noise perception in the recognition task was associated with perceiving more negative emotions in others and perceiving interactions more negatively. Conversely, signal perception of facial emotion expressions was associated with higher quality in social interactions. These effects were moderated by relationship closeness in Greece but not in Germany. These findings suggest that emotion recognition as assessed in the laboratory is a valid predictor of social interaction quality. Thus, emotion recognition generalizes from the laboratory to everyday life.
The Novel Small Molecule Inhibitor, OSU-T315, Suppresses Vestibular Schwannoma and Meningioma Growth by Inhibiting PDK2 Function in the AKT Pathway Activation.

Activation of PKB/AKT signaling, which requires PDK1 and PDK2 function, drives Vestibular Schwannoma (VS) and meningioma growth. PDK2 function is defined as a molecule that phosphorylates AKT-Ser473. Integrin-Linked Kinase (ILK) functions as PDK2 in PKB/AKT activation in many cancers; therefore, we hypothesized that OSU-T315, a small molecule ILK inhibitor, will inhibit the ILK-PDK2 function in PKB/AKT signaling activation in VS and meningioma cell growth. OSU-T315 decreased cell viability at IC50 < 2μM in VS (HEI193) and meningioma (Ben-Men-1) cell lines, in primary cells at < 3. 5μM, while in normal primary Schwann cells at 7. 1μM. OSU-T315 inhibits AKT signaling by decreasing phosphorylation at AKT-Ser473, AKT-Thr308, ILK-Ser246 and ILK-Thr173. In addition, OSU-T315 affected the phosphorylation or expression levels of AKT downstream proliferation effectors as well as autophagy markers. Flow cytometry shows that OSU-T315 increased the percentage of cells arrested at G2/M for both, HEI193 (39.99%) and Ben-Men-1 (26.96%) cells, compared to controls (21.54%, 8.47%). Two hours of OSU-T315 treatment increased cell death in both cell lines (34.3%, 9.1%) versus untreated (12.1%, 8.1%). Though longer exposure increased cell death in Ben-Men-1, TUNEL assays showed that OSU-T315 does not induce apoptosis. OSU-T315 was primarily cytotoxic for HEI193 and Ben-Men-1 inducing a dysregulated autophagy. Our studies suggest that OSU-T315 has translational potential as a chemotherapeutic agent against VS and meningioma.
An In Vivo Study on Brain Microstructure in Biological and Chronological Ageing

This study aimed to investigate whether magnetization transfer imaging (MTI) parameters of cortical gray and white matter and subcortical gray matter structures differ between subjects enriched for human familial longevity and control subjects to provide a thorough description of the brain phenotype of familial longevity. Moreover, we aimed to describe cerebral ageing effects on MTI parameters in an elderly cohort. All subjects were included from the Leiden Longevity Study and underwent 3 Tesla MTI of the brain. In total, 183 offspring of nonagenarian siblings, who are enriched for familial factors of longevity, were contrasted with 163 environmentally and age-matched controls. No differences in cortical and subcortical gray matter and white matter MTI parameters were found between offspring and control subjects using histogram-based and voxel-wise analyses. Cortical gray matter and white matter MTI parameters decreased with increasing chronological age (all p < 0.001). Decrease of white matter magnetization transfer ratio (MTR) was homogeneous throughout the whole mean white matter skeleton except for parts of the callosal splenium and partly the posterior limb of the internal capsule and superior region of the corona radiata (p < 0.05). Mean MTR of subcortical gray matter structures decreased with increasing age (p amygdala, caudate nucleus and putamen < 0.001; p pallidum = 0.001, p thalamus = 0.002). In conclusion, the brain phenotype of human familial longevity is - at a mean age of 66 years - not characterized by preserved macromolecular brain tissue integrity.
Microglial immune response is impaired against the neurotropic fungus Lomentospora prolificans

Lomentospora (Scedosporium) prolificans is an opportunistic pathogen capable of causing invasive infections in immunocompromised patients. The fungus is able to disseminate via the bloodstream finally arriving at the central nervous system producing neurological symptoms and, in many cases, patient death. In this context, microglial cells, which are the resident immune cells in the central nervous system, may play an important role in these infections. However, this aspect of anti‐L. prolificans immunity has been poorly researched to date. Thus, the interactions and activity of microglial cells against L. prolificans were analysed, and the results show that there was a remarkable impairment in their performance regarding phagocytosis, the development of oxidative burst, and in the production of pro‐inflammatory cytokines, compared with macrophages. Interestingly, L. prolificans displays great growth also when challenged with immune cells, even when inside them. We also proved that microglial phagocytosis of the fungus is highly dependent on mannose receptor and especially on dectin‐1. Taken together, these data provide evidence for an impaired microglial response against L. prolificans and contribute to understanding the pathobiology of its neurotropism.
Health‐related quality of life and patient burden in patients with split‐thickness skin graft donor site wounds

Split‐thickness skin grafting is a common procedure to treat different kinds of wounds. This systematic, multicentre, observational, cross‐sectional study of adult patients with split‐thickness skin graft (STSG) donor site wounds was conducted to evaluate quality of life (QoL) impairments caused by donor site wounds following split‐thickness skin grafting. Therefore, 112 patients from 12 wound centres in Germany were examined based on patient and physician questionnaires as well as a physical examination of the donor site wound. Most indications for skin grafting were postsurgical treatment (n = 51; 42.5%) and chronic wounds (n = 47; 39.2%). European QoL visual analoque scale (EQ VAS) averaged 64.7 ± 23.3, European QoL 5 dimensions (EQ‐5D) averaged 77.4 ± 30.0.
Non-Destructive Inspection System for Welding Processes by applying Data Fusion

Welding processes are influenced by many parameters. By applying multimodal data fusion of multichannel image data and signals of various welding parameter, the correlation of these and their influence on weld seam imperfections are investigated. The application of a multispectral area camera array enables a new approach on non-destructive testing particularly supported by the passive thermography. The results show the different cooling behaviour of several welding imperfections, such as porosity, and present the relation between incorrect welding parameters and imperfections.
An Efficient and Comprehensive Strategy for Genetic Diagnostics of Polycystic Kidney Disease

Renal cysts are clinically and genetically heterogeneous conditions. Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent life-threatening genetic disease and mainly caused by mutations in PKD1. The presence of six PKD1 pseudogenes and tremendous allelic heterogeneity make molecular genetic testing challenging requiring laborious locus-specific amplification. Increasing evidence suggests a major role for PKD1 in early and severe cases of ADPKD and some patients with a recessive form. Furthermore it is becoming obvious that clinical manifestations can be mimicked by mutations in a number of other genes with the necessity for broader genetic testing. We established and validated a sequence capture based NGS testing approach for all genes known for cystic and polycystic kidney disease including PKD1. Thereby, we demonstrate that the applied standard mapping algorithm specifically aligns reads to the PKD1 locus and overcomes the complication of unspecific capture of pseudogenes. Employing careful and experienced assessment of NGS data, the method is shown to be very specific and equally sensitive as established methods. An additional advantage over conventional Sanger sequencing is the detection of copy number variations (CNVs). Sophisticated bioinformatic read simulation increased the high analytical depth of the validation study and further demonstrated the strength of the approach. We further raise some awareness of limitations and pitfalls of common NGS workflows when applied in complex regions like PKD1 demonstrating that quality of NGS needs more than high coverage of the target region. By this, we propose a time- and cost-efficient diagnostic strategy for comprehensive molecular genetic testing of polycystic kidney disease which is highly automatable and will be of particular value when therapeutic options for PKD emerge and genetic testing is needed for larger numbers of patients.