Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeting the Interplay Between Cancer Fibroblasts, Mesenchymal Stem Cells, and Cancer Stem Cells in Desmoplastic Cancers

Malignant tumors are highly heterogeneous and likely contain a subset of cancer cells termed cancer stem cells (CSCs). CSCs exist in a dynamic equilibrium with their microenvironments and the CSC phenotype is tightly regulated by both cell-intrinsic and cell-extrinsic factors including those derived from their surrounding cells or stroma. Many human solid tumors like breast, lung, colorectal and pancreatic cancers are characterized by a pronounced stromal reaction termed “the desmoplastic response. ” Carcinoma-associated fibroblasts (CAFs) derived either from resident fibroblasts or tumor-infiltrating mesenchymal stem cells (MSCs) are a major component of the stroma in desmoplastic cancers. Recent studies identified subpopulations of CAFs proficient in secreting a plethora of factors to foster CSCs, tumor growth, and invasion. In addition, cytotoxic therapy can lead to the enrichment of functionally perturbed CAFs, which are endowed with additional capabilities to enhance cancer stemness, leading to treatment resistance and tumor aggressiveness. When recruited into the tumor stroma, bone-marrow-derived MSCs can promote cancer stemness by secreting a specific set of paracrine factors or converting into pro-stemness CAFs. Thus, blockade of the crosstalk of pro-stemness CAFs and MSCs with CSCs may provide a new avenue to improving the therapeutic outcome of desmoplastic tumors. This up-to-date, in-depth and balanced review describes the recent progress in understanding the pro-stemness roles of CAFs and tumor-infiltrating MSCs and the associated paracrine signaling processes. We emphasize the effects of systemic chemotherapy on the CAF/MSC–CSC interplay. We summarize various promising and novel approaches in mitigating the stimulatory effect of CAFs or MSCs on CSCs that have shown efficacies in preclinical models of desmoplastic tumors and highlight the unique advantages of CAF- or MSC-targeted therapies. We also discuss potential challenges in the clinical development of CSC- or MSC-targeted therapies and propose CAF-related biomarkers that can guide the next-generation clinical studies.
Adaptation and Transfer of Robot Motion Policies for Close Proximity Human-Robot Interaction

In the context of human-robot collaboration in close proximity, safety and comfort are the two important aspects to achieve joint tasks efficiently. For safety, the robot must be able to avoid dynamic obstacles such as a human arm with high reliability. For comfort, the trajectories and avoidance behavior of the robot need to be predictable to the humans. Moreover, these two aspects might be different from person to person or from one task to another. This work presents a framework to generate predictable motions with dynamic obstacle avoidance for the robot interacting with the human by using policy improvement method. The trajectories are generated using Dynamic Motion Primitives with an additional potential field term that penalizes trajectories that may lead to collisions with obstacles. Furthermore, human movements are predicted using a data-driven approach for proactive avoidance. A cost function is defined which measures different aspects that affect the comfort and predictability of human co-workers (e.g., human response time, joint jerk). This cost function is then minimized during human-robot interaction by the means of policy improvement through black-box optimization to generate robot trajectories that adapt to human preferences and avoid obstacles. User studies are performed to evaluate the trust and comfort of human co-workers when working with the robot. In addition, the studies are also extended to various scenarios and different users to analyze the task transferability. This improves the learning performance when switching to a new task or the robot has to adapt to a different co-worker.
Physics Teachers' Acceptance of Multimedia Applications—Adaptation of the Technology Acceptance Model to Investigate the Influence of TPACK on Physics Teachers' Acceptance Behavior of Multimedia Applications

Although multimedia applications can undeniably have a positive impact on the learning success of students, they are not used by all physics teachers. The study presented in this paper examines the influence of technological knowledge of physics teachers on their acceptance behaviour by adding TPACK of a physics teacher, as an additional variable to an adapted technology acceptance model (TAM). In addition, the TAM has been adapted to study the acceptance of multimedia applications of physics teachers in physics education. For this purpose, both, the design features were adapted and items were reworded to adjust them to the usage of multimedia applications in school and teaching context. While the first part of the study evaluates the changes of the TAM, the second part of the study deals with the extension of the TAM by the factor TPACK. TPACK acts as a superordinate moderator variable, which has a highly significant influence on the adapted TAM’s design features “perceived ease of use“, “perceived usefulness for pupils“ and the “personal job relevance assessment“. Interestingly, the results of the study show that TPACK has no significant influence on the "perceived personal usefulness" of multimedia applications in physics teaching. Nevertheless, the prediction of the acceptance behaviour of multimedia applications in physics teaching can be improved by extending the adapted TAM2/UTAUT model by TPACK.
Cellular and Transcriptional Responses of Resistant and Susceptible Cultivars of Alfalfa to the Root Lesion Nematode, Pratylenchus penetrans

The root lesion nematode (RLN), Pratylenchus penetrans, is a migratory species that attacks a broad range of crops, including alfalfa. High levels of infection can reduce alfalfa forage yields and lead to decreased cold tolerance. Currently, there are no commercially certified varieties with RLN resistance. Little information on molecular interactions between alfalfa and P. penetrans, that would shed light on mechanisms of alfalfa resistance to RLN, is available. To advance our understanding of the host–pathogen interactions and to gain biological insights into the genetics and genomics of host resistance to RLN, we performed a comprehensive assessment of resistant and susceptible interactions of alfalfa with P. penetrans that included root penetration studies, ultrastructural observations, and global gene expression profiling of host plants and the nematode. Several gene-candidates associated with alfalfa resistance to P. penetrans and nematode parasitism genes encoding nematode effector proteins were identified for potential use in alfalfa breeding programs or development of new nematicides. We propose that preformed or constitutive defenses, such as significant accumulation of tannin-like deposits in root cells of the resistant cultivar, could be a key to nematode resistance, at least for the specific case of alfalfa-P. penetrans interaction.
Monitoring of Marine Mammal Strandings Along French Coasts Reveals the Importance of Ship Strikes on Large Cetaceans: A Challenge for the European Marine Strategy Framework Directive

The marine traffic has evolved to ever more big and fast ships increasing substantially the pressure on marine fauna. Ship strike is nowadays identified as a major threat on large cetaceans inducing significant additional mortalities. However, estimation of ship strike rates is still challenging notably because such events occurred generally far offshore and collision between large ships and whales go often unnoticed by ship crew. The monitoring of marine mammal strandings remain one the most efficient way to evaluate the problem. In France, a national coordinated network collected data and samples on stranded marine mammals since 1972 along the Mediterranean and Atlantic French coasts. We examined stranding data, including photography and necropsy reports, collected between 1972 and 2017 with the aim to provide a comprehensive review of confirmed collision records of large whales in France. During this period, a total of 51 ship strikes were identified which represents the first identified causes of mortality for large whale in France. It has increased since 1972 with 7 records during the first decade to reach 22 stranded animals observed between 2005 and 2017. This issue appears particularly critical in the Mediterranean Sea where one in five stranded whales showed evidence of ship strike. This review of collision records highlights the risk of a negative impact of this anthropogenic pressure on the dynamic of whale populations in Europe, suggesting that ship strike rates could not allow achieving the Good Environmental Status of marine mammal populations required by the European Marine Strategy Framework Directive.
Homomeric and Heteromeric Aβ Species Exist in Human Brain and CSF Regardless of Alzheimer’s Disease Status and Risk Genotype

Background: A fundamental question in Alzheimer’s disease (AD) is whether amyloid-β (Aβ) peptides and their deposition in the brain signify a direct pathological role or they are mere outcome of the disease pathophysiological events affecting neuronal function. It is therefore important to decipher their physiological role in the brain. So far, the overwhelming focus has been on the potential toxicity of Aβ, often studied outside the crucial AD characteristics, i.e.: (i) the slow, decades-long disease progression that precedes clinical symptoms; (ii) the link to apolipoprotein-E ε4 allele as major risk factor; (iii) the selective early degeneration of cholinergic neurons. Previous studies, in vitro and cerebrospinal fluid (CSF) only, indicated one possible native function of Aβ peptides is the allosteric modulation of acetylcholine homeostasis, via molecular interactions between Aβ, apolipoprotein-E, and the acetylcholine-degrading enzymes, cholinesterases, resulting in the formation of acetylcholine-hydrolyzing complexes (BAβACs). Methods: Here, by combining sucrose-density gradient fractionation of post-mortem brains and in-house developed sensitive ELISA assays on the obtained fractions, we investigated the presence, levels and molecular interactions between Aβ, apolipoprotein-E and cholinesterases for the first time in brain tissues. We examined three distinct brain regions of Alzheimer and non-demented subjects, plus a large number of Alzheimer CSF samples. Results: We report that both monomeric and oligomeric (homomeric and heteromeric) forms of Aβ peptides are present in the brain of Alzheimer and non-demented individuals. Heteromeric Aβ was found in stable complexes with apolipoprotein-E and/or cholinesterases, irrespective of APOE genotype or disease status, arguing in favor of a physiological dynamic formation and function for these complexes in the brain. The patterns and molecular sizes of the detected soluble Aβ forms were closely matched between CSF and brain samples. This evinces that the detected Aβ-apolipoprotein-E complexes and BAβACs in CSF most likely originate from the interstitial fluids of the brain. Conclusions: In conclusion, both light homomeric Aβ oligomers and heteromeric Aβ-ApoE and BAβACs are present and readily detectable in the brain, regardless of disease status and APOE4 genotype. Deeper knowledge of the physiological function of Aβ is crucial for better understanding the early pathological events that decades later lead to manifestation of AD.
Use of Recurrence Quantification Analysis to Examine Associations Between Changes in Text Structure Across an Expressive Writing Intervention and Reductions in Distress Symptoms in Women With Breast Cancer

The current study presents an exploratory analysis of using Recurrence Quantification Analysis (RQA) to analyze text data from an Expressive Writing Intervention (EWI) for Danish women treated for Breast Cancer. The analyses are based on the analysis of essays from a subsample with the average age 54.6 years (SD = 9.0), who completed questionnaires for cancer-related distress (IES) and depression symptoms (BDI-SF). The results show a significant association between an increase in recurrent patterns of text structure from first to last writing session and a decrease in cancer-related distress at three months post-intervention. Furthermore, the change in structure from first to last essay displayed a moderate, but significant correlation with change in cancer-related distress from baseline to nine months post-intervention. The results suggest that changes in recurrence patterns of text structure might be an indicator of cognitive restructuring that leads to amelioration of cancer-specific distress.
Event-Related Desynchronization/Synchronization in Spinocerebellar Ataxia Type 3

Introduction: Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant, cerebellar degeneration predominant disease caused by excessive CAG repeats. We examined event-related dysynchronization/synchronization (ERD/ERS) in patients with SCA3. Methods: We assessed ERD/ERS of self-paced voluntary hand movements in 15 patients with genetically proven SCA3 in comparison with healthy controls. Results: In ERS, a significant interaction effect between group, frequency, and period (F = 1.591; p = 0.005; ρI = 0.86) was observed. The post-hoc two-tailed independent t-test showed significant differences in high beta and low beta ERS. By contrast, in ERD, no apparent differences were observed in the pattern of patients with SCA3 in comparison with healthy controls (F = 1.01; p = 0.442). Conclusion: The study revealed a decreased ERS in patients with SCA3, especially at the frequency of 20–30 Hz. This study elucidates the significant role of cerebellum in motor control.
Mechanistic Insight Into the Activation of the NLRP3 Inflammasome by Neisseria gonorrhoeae in Macrophages

Gonorrhea is a type III legal communicable disease caused by Neisseria gonorrhoeae (NG), one of the most common sexually transmitted bacteria worldwide. NG infection can cause urethritis or systemic inflammation and may lead to infertility or other complications. The NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome is a protein complex composed of NLRP3, apoptosis-associated speck-like protein and caspase-1 and is an important part of the cellular machinery controlling the release of interleukin (IL)-1β and IL-18 and the pathogenesis of numerous infectious diseases. It has been reported that NG infection activates the NLRP3 inflammasome; however, the underlying mechanism remain unclear. In this report, the signaling pathways involved in the regulation of NG-mediated NLRP3 inflammasome activation in macrophages were studied. The results indicated that viable NG, but not heat-killed or freeze/thaw-killed NG, activated the NLRP3 inflammasome in macrophages through toll-like receptor 2, but not toll-like receptor 4. NG infection provided the priming signal to the NLRP3 inflammasome that induced the expression of NLRP3 and IL-1β precursor through the nuclear factor kappa B and mitogen-activated protein kinase pathways. In addition, NG infection provided the activation signal to the NLRP3 inflammasome that activated caspase-1 through P2X7 receptor-dependent potassium efflux, lysosomal acidification, mitochondrial dysfunction, and reactive oxygen species production pathways. Furthermore, we demonstrated that NLRP3 knockout increased phagocytosis of bacteria by macrophages and increases the bactericidal activity of macrophages against NG. These findings provide potential molecular targets for the development of anti-inflammatory drugs that could ameliorate NG-mediated inflammation.
Directly Sequenced Genomes of Contemporary Strains of Syphilis Reveal Recombination-Driven Diversity in Genes Encoding Predicted Surface-Exposed Antigens

Syphilis, caused by Treponema pallidum subsp. pallidum (TPA), remains an important public health problem with an increasing worldwide prevalence. Despite recent advances in in vitro cultivation, genetic variability of this pathogen during infection is poorly understood. Here, we present contemporary and geographically diverse complete treponemal genome sequences isolated directly from patients using a methyl-directed enrichment prior to sequencing. This approach reveals that approximately 50% of the genetic diversity found in TPA is driven by inter- and/or intra-strain recombination events, particularly in strains belonging to one of the defined genetic groups of syphilis treponemes: Nichols-like strains. Recombinant loci were found to encode putative outer-membrane proteins and the recombination variability was almost exclusively found in regions predicted to be at the host-pathogen interface. Genetic recombination has been considered to be a rare event in treponemes, yet our study unexpectedly showed that it occurs at a significant level and may have important impacts in the biology of this pathogen, especially as these events occur primarily in the outer membrane proteins. This study reveals the existence of strains with different repertoires of surface-exposed antigens circulating in the current human population, which should be taken into account during syphilis vaccine development.
Salmonella Pathogenicity Island 1 (SPI-1) and Its Complex Regulatory Network

Salmonella species can infect a diverse range of birds, reptiles, and mammals, including humans. The type III protein secretion system (T3SS) encoded by Salmonella pathogenicity island 1 (SPI-1) delivers effector proteins required for intestinal invasion and the production of enteritis. The T3SS is regarded as the most important virulence factor of Salmonella. SPI-1 encodes transcription factors that regulate the expression of some virulence factors of Salmonella, while other transcription factors encoded outside SPI-1 participate in the expression of SPI-1-encoded genes. SPI-1 genes are responsible for the invasion of host cells, regulation of the host immune response, e.g., the host inflammatory response, immune cell recruitment and apoptosis, and biofilm formation. The regulatory network of SPI-1 is very complex and crucial. Here, we review the function, effectors, and regulation of SPI-1 genes and their contribution to the pathogenicity of Salmonella.
Dentate Gyrus Peroxiredoxin 6 Levels Discriminate Aged Unimpaired From Impaired Rats in a Spatial Memory Task

Similar to humans, the normal aged rat population is not homogeneous in terms of cognitive function. Two distinct subpopulations of aged Sprague–Dawley rats can be identified on the basis of spatial memory performance in the hole-board paradigm. It was the aim of the study to reveal protein changes relevant to aging and spatial memory performance. Aged impaired (AI) and unimpaired (AU) male rats, 22–24 months old were selected from a large cohort of 160 animals; young animals served as control. Enriched synaptosomal fractions from dentate gyrus from behaviorally characterized old animals were used for isobaric tags labeling based quantitative proteomic analysis. As differences in peroxiredoxin 6 (PRDX6) levels were a pronounced finding, PRDX6 levels were also quantified by immunoblotting. AI showed impaired spatial memory abilities while AU performed comparably to young animals. Our study demonstrates substantial quantitative alteration of proteins involved in energy metabolism, inflammation and synaptic plasticity during aging. Moreover, we identified protein changes specifically coupled to memory performance of aged rats. PRDX6 levels clearly differentiated AI from AU and levels in AU were comparable to those of young animals. In addition, it was observed that stochasticity in protein levels increased with age and discriminate between AI and AU groups. Moreover, there was a significantly higher variability of protein levels in AI. PRDX6 is a member of the PRDX family and well-defined as a cystein-1 PRDX that reduces and detoxifies hydroxyperoxides. It is well-known and documented that the aging brain shows increased active oxygen species but so far no study proposed a potential target with antioxidant activity that would discriminate between impaired and unimpaired memory performers. Current data, representing so far the largest proteomics data set in aging dentate gyrus (DG), provide the first evidence for a probable role of PRDX6 in memory performance.
Effects of Lengthening Velocity During Eccentric Training on Vastus Lateralis Muscle Hypertrophy

Eccentric loading is an effective stimulus for muscle hypertrophy and strength gains, however, the effect of lengthening velocity is under debate. The purpose of the current study was to investigate the influence of muscle lengthening velocity during eccentric training on muscle hypertrophy and strength gains at a given overall loading volume. Forty-seven participants were randomly assigned to a control (n = 14, age: 26.9 ± 4.1 years) and an experimental group (n = 33, age: 27.1 ± 4.4 years). Each leg of the participants in the experimental group was randomly assigned to one of the four eccentric training protocols with different angular velocities (i.e., 45, 120, 210, and 300°/s). Both the magnitude of loading (100% of the isometric maximum) and overall time under tension was matched between the protocols. The training was performed for 33 sessions, 3 times per week with 5 training sets per session. Before and after the intervention, the maximum isometric knee extension moments were measured in all groups using dynamometry, vastus lateralis (VL) muscle anatomical cross-sectional area, and VL muscle volume were measured in the experimental group using magnetic resonance imaging. Data was analyzed in a mixed-design analysis of variance. After the training intervention, the maximum knee joint moments increased in the experimental group (14.2%, p < 0.05) but not the control group. VL anatomical cross-sectional area and VL muscle volume increased significantly (p < 0.05) in the experimental group (5.1 and 5.7%, respectively), but we did not find any significant differences between the four training protocols in all investigated parameters (p > 0.05). The present study provides evidence that muscle hypertrophy and strength gains after eccentric exercise is velocity-independent when load magnitude and overall time under tension are matched between conditions. This is likely due to the similar mechanical demand for the muscle induced by the loading conditions of all four training protocols. The better control of motion and the potentially decreased joint loading compared to high lengthening velocity contractions support the application of slow eccentric exercises in special populations like elderly and people with neurological and musculoskeletal diseases.
ArxA From Azoarcus sp. CIB, an Anaerobic Arsenite Oxidase From an Obligate Heterotrophic and Mesophilic Bacterium

Arsenic is a toxic element widely distributed in nature, but numerous bacteria are able to resist its toxicity mainly through the ars genes encoding an arsenate reductase and an arsenite efflux pump. Some “arsenotrophic” bacteria are also able to use arsenite as energy supplier during autotrophic growth by coupling anaerobic arsenite oxidation via the arx gene products to nitrate respiration or photosynthesis. Here, we have demonstrated that Azoarcus sp. CIB, a facultative anaerobic β-proteobacterium, is able to resist arsenic oxyanions both under aerobic and anaerobic conditions. Genome mining, gene expression, and mutagenesis studies revealed the presence of a genomic island that harbors the ars and arx clusters involved in arsenic resistance in strain CIB. Orthologous ars clusters are widely distributed in the genomes of sequenced Azoarcus strains. Interestingly, genetic and metabolic approaches showed that the arx cluster of the CIB strain encodes an anaerobic arsenite oxidase also involved in the use of arsenite as energy source. Hence, Azoarcus sp. CIB represents the prototype of an obligate heterotrophic bacterium able to use arsenite as an extra-energy source for anaerobic cell growth. The arsenic island of strain CIB supports the notion that metabolic and energetic skills can be gained by genetic mobile elements.