Thalamic but Not Subthalamic Neuromodulation Simplifies Word Use in Spontaneous Language

Several investigations have shown language impairments following electrode implantation surgery for Deep Brain Stimulation (DBS) in movement disorders. The impact of the actual stimulation, however, differs between DBS targets with further deterioration in formal language tests induced by thalamic DBS in contrast to subtle improvement observed in subthalamic DBS. Here, we studied speech samples from interviews with participants treated with DBS of the thalamic ventral intermediate nucleus (VIM) for essential tremor (ET), or the subthalamic nucleus (STN) for Parkinson’s disease (PD), and healthy volunteers (each n = 13). We analyzed word frequency and the use of open and closed class words. Active DBS increased word frequency in case of VIM, but not STN stimulation. Further, relative to controls, both DBS groups produced fewer open class words. Whereas VIM DBS further decreased the proportion of open class words, it was increased by STN DBS. Thus, VIM DBS favors the use of relatively common words in spontaneous language, compatible with the idea of lexical simplification under thalamic stimulation. The absence or even partial reversal of these effects in patients receiving STN DBS is of interest with respect to biolinguistic concepts suggesting dichotomous thalamic vs. basal ganglia roles in language processing.Peer Reviewe

Generation and Labeling of Murine Bone Marrow-derived Dendritic Cells with Qdot Nanocrystals for Tracking Studies

Dendritic cells (DCs) are professional antigen presenting cells (APCs) found in peripheral tissues and in immunological organs such as thymus, bone marrow, spleen, lymph nodes and Peyer's patches 1-3. DCs present in peripheral tissues sample the organism for the presence of antigens, which they take up, process and present in their surface in the context of major histocompatibility molecules (MHC). Then, antigen-loaded DCs migrate to immunological organs where they present the processed antigen to T lymphocytes triggering specific immune responses. One way to evaluate the migratory capabilities of DCs is to label them with fluorescent dyes 4

Dendritic Cells The Tumor Microenvironment and the Challenges for an Effective Antitumor Vaccination

Many clinical trials have been carried out or are in progress to assess the therapeutic potential of dendritic-cell- (DC-) based vaccines on cancer patients, and recently the first DC-based vaccine for human cancer was approved by the FDA. Herewith, we describe the general characteristics of DCs and different strategies to generate effective antitumor DC vaccines. In recent years, the relevance of the tumor microenvironment in the progression of cancer has been highlighted. It has been shown that the tumor microenvironment is capable of inactivating various components of the immune system responsible for tumor clearance. In particular, the effect of the tumor microenvironment on antigen-presenting cells, such as DCs, does not only render these immune cells unable to induce specific immune responses, but also turns them into promoters of tumor growth. We also describe strategies likely to increase the efficacy of DC vaccines by reprogramming the immunosuppressive nature of the tumor microenvironment

Tracing embodied word production in persons with Parkinson’s disease in distinct motor conditions

Embodied cognition theories posit direct interactions between sensorimotor and mental processing. Various clinical observations have been interpreted in this controversial framework, amongst others, low verb generation in word production tasks performed by persons with Parkinson's disease (PD). If this were the consequence of reduced motor simulation of prevalent action semantics in this word class, reduced PD pathophysiology should result in increased verb production and a general shift of lexical contents towards particular movement-related meanings. 17 persons with PD and bilateral deep brain stimulation (DBS) of the subhtalamic nucleus (STN) and 17 healthy control persons engaged in a semantically unconstrained, phonemic verbal fluency task, the former in both DBS-off and DBS-on states. The analysis referred to the number of words produced, verb use, and the occurrence of different dimensions of movement-related semantics in the lexical output. Persons with PD produced fewer words than controls. In the DBS-off, but not in the DBS-on condition, the proportion of verbs within this reduced output was lower than in controls. Lowered verb production went in parallel with a semantic shift: in persons with PD in the DBS-off, but not the DBS-on condition, the relatedness of produced words to own body-movement was lower than in controls. In persons with PD, DBS induced-changes of the motor condition appear to go along with formal and semantic shifts in word production. The results are compatible with the idea of some impact of motor system states on lexical processing

Toll-Like Receptors as Novel Therapeutic Targets for Ovarian Cancer

Ovarian cancer (OC) is an aggressive disease that affects approximately 1 in 70 women and has a poor prognosis (<50%, 5-year survival rate), in part because it is often diagnosed at a late stage. There are three main types of OC: neoplasms of surface epithelial, germ cell, or stromal origin, with surface epithelial tumors comprising about 80% of all OCs. In addition to improving diagnostics, it is necessary to develop more effective treatments for epithelial-origin OC. Here, we describe the paradoxical roles of toll-like receptor (TLR) signaling in the progression of cancer and discuss how its modulation may result in decreased tumor growth and metastasis via the attenuation of proangiogenic cytokines and potentiation of proapoptotic factors. In particular, it has been found that TLR activity can behave like a “double-edged sword”, as its signaling pathways have been implicated as having both tumor-suppressive and tumor-promoting effects. With particular emphasis on OC, we discuss the need to consider the signaling details of TLRs and associated proteins in the multiple cell types present in the tumor milieu to achieve safe and effective design of TLR-based cancer therapies

Many Roads Lead to Digital Transformation: A Configurational Perspective on Digital Competence Elements

Organizations need to develop digital competences to utilize digital technologies to succeed in digital transformation. Yet, current efforts on organizational strategies to develop digital competences, i.e., digital M&A or appointing a CDO, have been conducted in isolation. However, following digital ecodynamics, material, organizational and environmental factors are in fact interwoven. We aim to cater to this confluence by taking a configurational perspective on digital competence development and its effect on digital transformation. We integrate prior findings of digital competence on (1) the firm level and the role of knowledge resources, (2) the leadership level and competence of the firm’s upper echelon, and (3) the role of contextual complexities in the form of the firm’s environment and structure. Subsequently, we employ fsQCA on a unique dataset. Thereby, we disentangle the multifaceted complexity of digital transformation and provide more fine-grained conceptual insights into the phenomena

Landscape of stimulation-responsive chromatin across diverse human immune cells.

A hallmark of the immune system is the interplay among specialized cell types transitioning between resting and stimulated states. The gene regulatory landscape of this dynamic system has not been fully characterized in human cells. Here we collected assay for transposase-accessible chromatin using sequencing (ATAC-seq) and RNA sequencing data under resting and stimulated conditions for up to 32 immune cell populations. Stimulation caused widespread chromatin remodeling, including response elements shared between stimulated B and T cells. Furthermore, several autoimmune traits showed significant heritability in stimulation-responsive elements from distinct cell types, highlighting the importance of these cell states in autoimmunity. Allele-specific read mapping identified variants that alter chromatin accessibility in particular conditions, allowing us to observe evidence of function for a candidate causal variant that is undetected by existing large-scale studies in resting cells. Our results provide a resource of chromatin dynamics and highlight the need to characterize the effects of genetic variation in stimulated cells

Anti-cancer and anti-trypanosomal properties of alkaloids from the root bark of Zanthoxylum leprieurii Guill and Perr

Purpose: To isolate the anti-cancer and anti-trypanosomal principles of Zanthoxylum leprieurii, a medicinally versatile wild tropical plant used for managing tumours, African trypanosomiasis, and inflammation in southeastern Nigeria. Methods: The pure compounds were isolated using chromatographic methods. The structural elucidation of the pure compounds was based on their NMR (1D and 2D) and mass spectral data as well as chemical test results. Structure-activity relationships were based on the structural differences among the compounds. The cytotoxicity of the extracts and compounds (1, 2, 3, and 4) was evaluated in HeLa (human cervix adenocarcinoma) cell line while the trypanocidal activities were evaluated on Trypanosoma brucei brucei. Results: Two acridone alkaloids, 1-hydroxy-3-methoxy-10-methylacridin-9 (10H)-one, named fabiocinine (1), and 1-hydroxy-2,3-dimethoxy-10-methylacridin-9 (10H)-one (arborinine, 2), together with a furoquinoline alkaloid, skimmianine (3), and a chelerythrine derivative, 6-acetonyl-5,6-dihydrochelerythrine (4) were isolated from the root bark of Zanthoxylum leprieurii. Skimmianine (3) exhibited cytotoxicity and anti-trypanosomal IC50 of 12.8 and 13.2 µg/mL respectively (p less than 0.05). Compound (1) and arborinine (2) were selectively cytotoxic to HeLa cells with cytotoxicity IC50 of 28.49 and 62.71 µg/mL, respectively, while (4) did not show significant activity (p less than 0.05). Conclusion: Zanthoxylum leprieurii root bark contains cytotoxic and trypanocidal compounds, and is thus a potential source of anti-cancer and anti-trypanosomal leads

Blühstreifen und Ackerbegleitflora fördern Nützlinge im Kohlanbau

In einer Feldstudie in den Jahren 2016 und 2018 wurde untersucht, ob Blühstreifen der Saatmischung «Nützlinge Kohlanbau» am Rand von Kohlfeldern im Schweizer Mittelland räuberische Nützlinge (Laufund Kurzflügelkäfer sowie Spinnen) und Bestäuber (Schwebfliegen und Bienen) fördern können. In beiden Untersuchungsjahren war die Artenvielfalt der spontanen und angesäten Ackerbegleitflora in den Blühstreifen durchschnittlich doppelt so hoch wie in den Kohlfeldern. Fallenfänge im Zentrum von acht Kohlfeldern und in den dazugehörigen Blühstreifen am Rand zeigten 2016, dass durch die gesteigerte Artenvielfalt der Begleitpflanzen Bienen, Laufkäfer und Spinnen gefördert wurden. Zudem wurde festgestellt, dass ein hoher Bodendeckungsgrad der spontanen Ackerbegleitflora die Schwebfliegen förderte. Im Jahr 2018 zeigte der Direktvergleich zwischen Blühstreifen und den Rändern von sechs Kohlfeldern, dass signifikant mehr Bienenindividuen und -arten und marginal mehr Kurzflügel- und Laufkäferarten in den Blühstreifen vorkamen. Sowohl 2016 als auch 2018 wurden über 90 Arten ausschliesslich in den Blühstreifen festgestellt, rund doppelt so viele wie in den Kohlflächen. Biodiversitätsförderflächen bieten einen periodischen Lebensraum für diverse räuberische Nützlinge und Bestäuber und können somit die positiven Effekte der spontanen Ackerbegleitflora stärken, was eine ökologische Aufwertung von Produktionsflächen im Kohlanbau ermöglicht