julilili42/papers huggingface dataset:
MET currents and otoacoustic emissions from mice with a detached tectorial membrane indicate the extracellular matrix regulates Ca2+ near stereocilia
2021-02-10

Key points The aim was to determine whether detachment of the tectorial membrane (TM) from the organ of Corti in Tecta/Tectb −/− mice affects the biophysical properties of cochlear outer hair cells (OHCs). Tecta/Tectb −/− mice have highly elevated hearing thresholds, but OHCs mature normally. Mechanoelectrical transducer (MET) channel resting open probability ( P o ) in mature OHC is ∼50% in endolymphatic [Ca 2+ ], resulting in a large standing depolarizing MET current that would allow OHCs to act optimally as electromotile cochlear amplifiers. MET channel resting P o in vivo is also high in Tecta/Tectb −/− mice, indicating that the TM is unlikely to statically bias the hair bundles of OHCs. Distortion product otoacoustic emissions (DPOAEs), a readout of active, MET‐dependent, non‐linear cochlear amplification in OHCs, fail to exhibit long‐lasting adaptation to repetitive stimulation in Tecta/Tectb −/− mice. We conclude that during prolonged, sound‐induced stimulation of the cochlea the TM may determine the extracellular Ca 2+ concentration near the OHC's MET channels. Abstract The tectorial membrane (TM) is an acellular structure of the cochlea that is attached to the stereociliary bundles of the outer hair cells (OHCs), electromotile cells that amplify motion of the cochlear partition and sharpen its frequency selectivity. Although the TM is essential for hearing, its role is still not fully understood. In Tecta/Tectb −/− double knockout mice, in which the TM is not coupled to the OHC stereocilia, hearing sensitivity is considerably reduced compared with that of wild‐type animals. In vivo , the OHC receptor potentials, assessed using cochlear microphonics, are symmetrical in both wild‐type and Tecta/Tectb −/− mice, indicating that the TM does not bias the hair bundle resting position. The functional maturation of hair cells is also unaffected in Tecta/Tectb −/− mice, and the resting open probability of the mechanoelectrical transducer (MET) channel reaches values of ∼50% when the hair bundles of mature OHCs are bathed in an endolymphatic‐like Ca 2+ concentration (40 μM) in vitro . The resultant large MET current depolarizes OHCs to near –40 mV, a value that would allow optimal activation of the motor protein prestin and normal cochlear amplification. Although the set point of the OHC receptor potential transfer function in vivo may therefore be determined primarily by endolymphatic Ca 2+ concentration, repetitive acoustic stimulation fails to produce adaptation of MET‐dependent otoacoustic emissions in vivo in the Tecta/Tectb −/− mice. Therefore, the TM is likely to contribute to the regulation of Ca 2+ levels around the stereocilia, and thus adaptation of the OHC MET channel during prolonged sound stimulation.
Unraveling the Molecular Tumor-Promoting Regulation of Cofilin-1 in Pancreatic Cancer
2021-02-10

Cofilin-1 (CFL1) overexpression in pancreatic cancer correlates with high invasiveness and shorter survival. Besides a well-documented role in actin remodeling, additional cellular functions of CFL1 remain poorly understood. Here, we unraveled molecular tumor-promoting functions of CFL1 in pancreatic cancer. For this purpose, we first show that a knockdown of CFL1 results in reduced growth and proliferation rates in vitro and in vivo, while apoptosis is not induced. By mechanistic modeling we were able to predict the underlying regulation. Model simulations indicate that an imbalance in actin remodeling induces overexpression and activation of CFL1 by acting on transcription factor 7-like 2 (TCF7L2) and aurora kinase A (AURKA). Moreover, we could predict that CFL1 impacts proliferation and apoptosis via the signal transducer and activator of transcription 3 (STAT3). These initial model-based regulations could be substantiated by studying protein levels in pancreatic cancer cell lines and human datasets. Finally, we identified the surface protein CD44 as a promising therapeutic target for pancreatic cancer patients with high CFL1 expression.
EEG Data Quality: Determinants and Impact in a Multicenter Study of Children, Adolescents, and Adults with Attention-Deficit/Hyperactivity Disorder (ADHD)
2021-02-10

Electroencephalography (EEG) represents a widely established method for assessing altered and typically developing brain function. However, systematic studies on EEG data quality, its correlates, and consequences are scarce. To address this research gap, the current study focused on the percentage of artifact-free segments after standard EEG pre-processing as a data quality index. We analyzed participant-related and methodological influences, and validity by replicating landmark EEG effects. Further, effects of data quality on spectral power analyses beyond participant-related characteristics were explored. EEG data from a multicenter ADHD-cohort (age range 6 to 45 years), and a non-ADHD school-age control group were analyzed (ntotal = 305). Resting-state data during eyes open, and eyes closed conditions, and task-related data during a cued Continuous Performance Task (CPT) were collected. After pre-processing, general linear models, and stepwise regression models were fitted to the data. We found that EEG data quality was strongly related to demographic characteristics, but not to methodological factors. We were able to replicate maturational, task, and ADHD effects reported in the EEG literature, establishing a link with EEG-landmark effects. Furthermore, we showed that poor data quality significantly increases spectral power beyond effects of maturation and symptom severity. Taken together, the current results indicate that with a careful design and systematic quality control, informative large-scale multicenter trials characterizing neurophysiological mechanisms in neurodevelopmental disorders across the lifespan are feasible. Nevertheless, results are restricted to the limitations reported. Future work will clarify predictive value.
Successful talent development in popular game sports in Switzerland: The case of ice hockey
2021-02-10

There is continuing discussion in talent research on the best approach to developing sporting expertise through learning activities during early sport participation. Among other concepts, the specialized sampling model describes a pathway between early specialization and early sampling and yields promising results in Swiss football. As successful constellations of early sport participation might be affected by sport-specific constraints (e.g., age of peak performance, selection pressure, and physiological/psychological requirements), other popular game sports may show similar promising pathways. This study investigates whether ice hockey, another popular game sport in Switzerland, shows similar successful constellations of early sport participation. A sample of 98 former Swiss junior national team players born between 1984 and 1994 reported on early sport participation through a retrospective questionnaire. Using the person-oriented Linking of Clusters after removal of a Residue (LICUR) method, volumes of in-club practice, free play, and activities besides ice hockey until 12 years of age were analyzed, along with player’s age at initial club participation. The results indicate that ice hockey enthusiasts with the most free play and above-average in-club practice had a greater chance of reaching professional level compared to other groups. This implies that high domain specificity with varied sampling experiences is the most promising approach to developing sporting expertise in ice hockey. As similar results were previously found in Swiss football, comparable sport-specific constraints might indeed require similar constellations of learning activities during early sport participation. Therefore, in popular game sports in Switzerland, the specialized sampling model seems to be most promising.
Epidemiology of dengue fever in Gabon: Results from a health facility-based fever surveillance in Lambaréné and its surroundings
2021-02-10

Background In Africa, information on dengue is limited to outbreak reports and focused on some countries with continuing transmission in West and East Africa. To estimate the proportion of dengue-positive cases among febrile patients and identify clinical indicators of dengue cases, we conducted passive facility-based fever surveillance in a catchment area population of 70,000 residents of Lambaréné and its surroundings in Gabon. Methods Non-malarial febrile patients with current fever or history of fever (≤7 days) between 1 and 55 years of age, were enrolled at Albert Schweitzer Hospital (ASH). Acute (visit 1, day of enrollment) and convalescent blood samples were collected between 10 and 21 days after enrollment. Acute/convalescent samples were tested with IgM/IgG ELISA, and a selected subset of acute samples with RT-PCR. Results Among 682 non-malarial febrile patients enrolled, 119 (17.4%) were identified as dengue-positive (94 dengue-confirmed and 25 dengue-probable cases). Of these dengue-positive cases, 14 were confirmed with PCR, and based on serotyping, two infections were identified to be DENV-2 and two were DENV-3. The majority of our enrolled patients were &lt;25 years of age and close to 80% of our dengue-positive cases were &lt;15 years of age. In adjusted analyses, retro-orbital pain and abdominal pain were 2.7 and 1.6 times more frequently found among dengue-positive cases, compared to non-dengue cases. Conclusion Lambaréné is not considered dengue-endemic. However, one in six non-malarial febrile episodes was found to be dengue-positive in the study period. Dengue should be considered more frequently in clinicians’ diagnosis among non-malarial febrile patients in Lambaréné. Given the lack of data on dengue in Gabon, additional prospective and longitudinal studies would help to further define the burden and patterns of dengue for improved case detection.
Laparoscopic Peritoneal Wash Cytology-Derived Primary Human Mesothelial Cells for In Vitro Cell Culture and Simulation of Human Peritoneum
2021-02-10

Peritoneal mucosa of mesothelial cells line the abdominal cavity, surround intestinal organs and the female reproductive organs and are responsible for immunological integrity, organ functionality and regeneration. Peritoneal diseases range from inflammation, adhesions, endometriosis, and cancer. Efficient technologies to isolate and cultivate healthy patient-derived mesothelial cells with maximal purity enable the generation of capable 2D and 3D as well as in vivo-like microfluidic cell culture models to investigate pathomechanisms and treatment strategies. Here, we describe a new and easily reproducible technique for the isolation and culture of primary human mesothelial cells from laparoscopic peritoneal wash cytology. We established a protocol containing multiple washing and centrifugation steps, followed by cell culture at the highest purity and over multiple passages. Isolated peritoneal mesothelial cells were characterized in detail, utilizing brightfield and immunofluorescence microscopy, flow cytometry as well as Raman microspectroscopy and multivariate data analysis. Thereby, cytokeratin expression enabled specific discrimination from primary peritoneal human fibroblasts. Raman microspectroscopy and imaging were used to study morphology and biochemical properties of primary mesothelial cell culture compared to cryo-fixed and cryo-sectioned peritoneal tissue.
Paired-pulse measures (SICI, SICF, ICF, LICI, LCD)
2021-02-10

Abstract Paired-pulse transcranial magnetic stimulation (TMS) techniques provide an opportunity to examine and better understand the excitatory and inhibitory circuitry in the human cortex in health and disease. Typically, a conditioning stimulus is applied and the effect on cortical excitability is inferred by the change in motor evoked potential (MEP) amplitude elicited by a test stimulus delivered shortly (milliseconds) thereafter. This approach has revealed a range of distinct, but generally overlapping, excitatory and inhibitory phenomena, which have been characterized according to their temporal and pharmacological profile, activation threshold, and various other properties. These phenomena have provided new pathophysiological insights into neurological and psychiatric disorders, and paired-pulse TMS measures have demonstrated clinical diagnostic utility. More recently, via implementation of TMS-evoked electroencephalography (TMS-EEG), paired-pulse TMS protocols have started to expand into nonmotor regions.
The interactive role of subjective attitudinal ambivalence, knowledge, and certainty for attitude stability: The case of driving electric vehicles
2021-02-10

Research has investigated how each of numerous indicators of attitude strength separately affect an attitude's stability, resistance to persuasion, and utility in predicting behavior. More recent studies, however, have revealed interactive effects of attitude certainty and objective ambivalence. High (vs. low) certainty strengthened an attitude low in objective ambivalence (e.g., higher resistance to persuasion and attitude stability) but weakened an attitude high in objective ambivalence (e.g., lower resistance and stability). Extending these findings, we show that attitude certainty also moderates the effect of an attitude high or low in subjective ambivalence on attitude stability. Moreover, we generalize an interaction perspective on indicators of attitude strength by showing that attitude knowledge also interacts with ambivalence and certainty regarding attitude stability. Findings are discussed in regard to the interplay of different strength indicators more generally.
Nonclassical Nucleation—Role of Metastable Intermediate Phase in Crystal Nucleation: An Editorial Prefix
2021-02-10

Classical nucleation theory (CNT), which was established about 90 years ago, represents the most commonly used theory in describing nucleation processes. For a fluid-to-solid phase transition, CNT states that the solutes in a supersaturated solution reversibly form small clusters. Once a cluster reaches its critical size, it becomes thermodynamically stable and is favored for further growth. One of the most important assumptions of CNT is that the nucleation process is described by one reaction coordinate and all order parameters proceed simultaneously. Recent studies in experiments, computer simulations, and theory have revealed nonclassical features in the early stage of nucleation. In particular, the decoupling of order parameters involved during a fluid-to-solid transition leads to the so-called two-step nucleation mechanism, in which a metastable intermediate phase (MIP) exists in parallel to the initial supersaturated solution and the final crystals. These MIPs can be high-density liquid phases, mesoscopic clusters, or preordered states. In this Special Issue, we focus on the role of the various MIPs in the early stage of crystal nucleation of organic materials, metals and alloys, aqueous solutions, minerals, colloids, and proteins, and thus on various scenarios of nonclassical pathways of crystallization.
Cortical silent period
2021-02-10

Abstract The cortical silent period (cSP) refers to a period of suppression or silencing of ongoing electromyographic (EMG) activity during voluntary muscle contraction induced by a magnetic stimulus over the contralateral primary motor cortex. This chapter summarizes the physiological basis of the cSP, discusses technical aspects and recommendations on how to record and analyze it, and provides an overview of useful clinical applications. Evidence is presented that multiple spinal mechanisms are implicated in the initial part of the cSP, but some may be also active further on, whereas long-lasting cortical inhibitory mechanisms operate throughout the entire cSP, with an emphasis during its later part. The cSP is a highly relevant and clinically useful tool to assess inhibitory corticomotoneuronal mechanisms in health and disease.
Pharmacology of TMS measures
2021-02-10

Abstract Application of a single dose of a central nervous system (CNS) active drug with a defined mode of action has been proven useful to explore pharmaco-physiological properties of transcranial magnetic stimulation (TMS)-evoked electromyographic (EMG) measures of motor cortical excitability. With this approach, it is possible to demonstrate that TMS-EMG measures reflect axonal, or excitatory or inhibitory synaptic excitability in distinct interneuron circuits. On the other hand, the array of pharmaco-physiologically well-characterized TMS-EMG measures can be employed to study the effects of a drug with unknown or multiple modes of action, and hence to determine its main mode of action at the systems level of the motor cortex. Acute drug effects may be rather different from chronic drug effects, and these differences can also be studied in TMS experiments. Moreover, TMS or repetitive TMS (rTMS) may induce changes in endogenous neurotransmitter or neuromodulator systems. This offers the opportunity to study neurotransmission along defined neuronal projections. Finally, more recently, TMS-evoked electroencephalographic (EEG) responses have been developed to study cortical excitability and connectivity. Pharmaco-physiological testing can be employed to also characterize these TMS-EEG measures. All these aspects of the pharmacology of TMS measures in healthy subjects will be reviewed in this chapter.
Photoelectron spectroscopy reveals molecular diffusion through physisorbed template layers on Au(111)
2021-02-10

Abstract Molecular exchange processes in organic heterostructures are often detrimental to the performance of nano-optoelectronic devices. Bilayers of vacuum sublimed organic semiconductors on inorganic substrates can serve as reductionist model for organic–organic interfaces and the coupling strength of the template layer on the substrate is a decisive factor for possible molecular exchange. We use density-functional theory modelling and x-ray photoelectron spectroscopy to show that the coupling of the pentacene oxo-derivatives 6,13-pentacenequinone (P2O) and 5,7,12,14-pentacenetetrone (P4O) with Au(111) is weak. Consequently, as shown by ultraviolet photoelectron spectroscopy, subsequently deposited copper-phthalocyanine (CuPc) diffuses through the template layers to the Au(111) substrate.
Day labourers in Munich’s train station district – from exploitation to human trafficking and forced labour? Pracownicy jednodniowi w rejonie dworca kolejowego w Monachium – pomiędzy wykorzystaniem a handlem ludźmi i pracą przymusową?
2021-02-10

In the beginning of the 21st century, a day labourer market was established in the southern main station district of Munich. In August 2013, the market aroused negative public attention due to a petition from local businesspeople. Since then, the day labourers have been subject to surveillance and banishment. In 2019, a significant amendment to the Illegal Employment Act made day labourer markets illegal. It is known that day labourers offer their own labour to employers, who frequently deprive them of the agreed wage. This practice poses the question of whether these exploitative working conditions amount to human trafficking, forced labour, or labour exploitation. This question is explored in a case study analysis based on talks with day labourers and interviews with different actors in Munich’s train station district.
Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3–90 years
2021-02-11

Abstract Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta‐Analysis (ENIGMA) Consortium to examine age‐related trajectories inferred from cross‐sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3–90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter‐individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age‐related morphometric patterns.
Germanium nanospheres for ultraresolution picotensiometry of kinesin motors
2021-02-11

Kinesin takes substeps Simultaneously measuring the nanoscale motion and forces that molecular machines generate provides insights into how they work mechanically to fulfill their cellular function. To study these machines, Sudhakar et al. developed germanium semiconductor nanospheres as probes for so-called optical tweezers. With these high–refractive index nanospheres, they improved the resolution of optical tweezers and discovered that the motor kinesin takes 4-nanometer substeps. Further, instead of detaching from their microtubule track under load, motors slid back on it, enabling rapid reengagement in transport. The new technology will allow investigation of a range of other proteins and their behaviors at nanometer scales. Science , this issue p. eabd9944
Hybrid Urban Borderlands – Redevelopment Efforts and Shifting Boundaries In and Around Downtown San Diego
2021-02-11

In recent years, far-reaching urbanization and gentrification processes have been taking place in and around downtown San Diego. These have been accompanied not just by structural upheavals, but by social changes that still await in-depth analysis. In the context of San Diego's inner-city redevelopment, urban research can profit from a border-theoretical approach, initiating a geography of urban boundaries focused on change processes and the redrawing, shifting, and dissolution of boundaries. Although urban neighborhoods are particularly characterized by differentiation, ambiguity, and fragmentation, border-theoretical findings have rarely been applied on this level. Against this background, the article traces processes of social "ordering" and "othering," and the shifting of individual-subjective demarcations in the inner-ring suburbs of San Diego—the former warehouse district East Village and the adjacent Mexican-American community neighborhood Barrio Logan. A methodological triangulation of interviews, participatory observations, and cartographic and photographic visualizations illustrates the outward thrust and adaption of multi-dimensional boundaries between the downtown area and the urbanizing first ring—phenomena of what we have called "hybrid urban borderlands." Aimed primarily at creating a wider understanding of urbanization processes in San Diego's inner-ring, our project opens up further differentiations in the field of border studies across its disciplinary boundary to urban research.