bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nanoscale organization of Actin Filaments in the Red Blood Cell Membrane Skeleton
Authors: Nowak Roberta B. , Alimohamadi Haleh , Pestonjamasp Kersi , Rangamani Padmini , Fowler Velia M. 
Published: March 2021

AbstractRed blood cell (RBC) shape and deformability are supported by a planar network of short actin filament (F-actin) nodes interconnected by long spectrin molecules at the inner surface of the plasma membrane. Spectrin-F-actin network structure underlies quantitative modelling of forces controlling RBC shape, membrane curvature and deformation, yet the nanoscale organization of F-actin nodes in the networkin situis not understood. Here, we examined F-actin distribution in RBCs using fluorescent-phalloidin labeling of F-actin imaged by multiple microscopy modalities. Total internal reflection fluorescence (TIRF) and Zeiss Airyscan confocal microscopy demonstrate that F-actin is concentrated in multiple brightly stained F-actin foci ∼200-300 nm apart interspersed with dimmer F-actin staining regions. Live cell imaging reveals dynamic lateral movements, appearance and disappearance of F-actin foci. Single molecule STORM imaging and computational cluster analysis of experimental and synthetic data sets indicate that individual filaments are non-randomly distributed, with the majority as multiple filaments, and the remainder sparsely distributed as single filaments. These data indicate that F-actin nodes are non-uniformly distributed in the spectrin-F-actin network and necessitate reconsideration of current models of forces accounting for RBC shape and membrane deformability, predicated upon uniform distribution of F-actin nodes and associated proteins across the micron-scale RBC membrane.
Post discharge persistent symptoms after COVID-19 in rheumatic and musculoskeletal diseases
Authors: Leon Leticia , Perez-Sancristobal Ines , Garcia Alfredo Madrid , Pedraza Leticia Lopez , Colomer Jose Ignacio , Lara Sergio Lerma , Bermejo Pia Lois , Mucientes Arkaitz , Rodriguez-Rodriguez Luis , Fernandez-Gutierrez Benjamin , Abasolo Lydia 
Published: March 2021

ABSTRACTOBJECTIVESTo describe persistent symptoms and consequences in Rheumatic and Musculoskeletal diseases (RMD) discharged from the hospital after Covid-19; to assess the roll of autoimmune rheumatic diseases (ARD) compared to and non-autoimmune rheumatic and musculoskeletal diseases (NARD) on persistent symptoms and consequences.METHODSWe performed a cross-sectional observational study. RMD attended at a rheumatology outpatient clinic in Madrid with Covid-19 that required hospital admission were included. The main outcomes were persistence of symptoms and health consequences related to Covid19 after discharge. Independent variable was RMD group (ARD and NARD) and covariates were sociodemographic, clinical, and treatments. We ran a multivariable logistic regression model to assess the risk by RMD group on main outcomes.RESULTSWe included 105 patients and 51.5% had ARD. 68.57% reported at least one persistent symptom. The most frequent were dyspnea, fatigue, and chest pain. 31 patients had consequences. Lung damage was found in 11.4% of the patients, 18% had blood test abnormalities (10% lymphopenia), two died, one developed central retinal vein occlusion and one patient developed optic neuritis. 11 patients required readmission due to Covid-19 problems (16.7% ARD vs 3.9% NARD; p=0.053). No statistically significant differences by RMD groups were found in the final models.CONCLUSIONMany RMD patients have persistent symptoms, similar to other populations. This study also highlights that lung damage is the most frequent consequence. ARD compared to NARD does not seem to differ in terms of persistent symptoms or consequences, although ARD might have a greater number of readmissions due to Covid-19.
Ameliorating Emotional Attention through Modulation of Neural Oscillations with Transcranial Alternating Current Stimulation
Authors: Liu Shuang , He Yuchen , Guo Dongyue , Liu Xiaoya , Hao Xinyu , Hu Pengchong , Ming Dong 
Published: March 2021

AbstractBackgroundNumerous clinical reports suggest that psychopathy like schizophrenia, anxiety and depressive disorder is accompanied by early attentional abnormalities in emotional information processing. In the past decade, the efficacy of transcranial alternating current stimulation (tACS) in changing emotional functioning has been repeatedly observed and has demonstrated a causal relationship between endogenous oscillations and emotional processing. However, tACS effects on emotional attention have not yet been tested.MethodsA total of 53 healthy participants were randomized to 2 groups, and they were subjected to active or sham tACS at individual alpha frequency (IAF) in the bilaterally dorsolateral prefrontal cortex (dlPFC). Participants and received this treatment for 20 min durations daily for 7 consecutive days. On days 1 and 7, electroencephalogram (EEG) recording of 8 minute resting with eyes open and closed. Responses to a facial emotion identification task were also recorded to measure alpha changes and event-related potential (ERP) alterations.ResultsOn day 7 after tACS, the active group showed a more clear elevation in alpha power at rest, especially in open state around stimulation area, compared to the sham group. ERPs revealed a significant larger P200 amplitude after active stimulation (p< 0.05), indicating attentional improvement in facial emotion processing. Additionally, a notable positive correlation (p< 0.05) between alpha power and P200 amplitude was found, providing an electrophysiological interpretation regarding the role of tACS in emotional attention modulation. In addition, the IAF-tACS showed an obvious advantage in alpha entrainment compared to an additional 10 Hz-tACS.ConclusionsThese results support a seminal outcome for the effect of IAF-tACS on emotional attention modulation, demonstrating a feasible and individual-specific therapy for neuropsychiatric disorders related to emotion processing, especially regarding oscillatory disturbances.
Systematic exploration ofEscherichia coliphage-host interactions with the BASEL phage collection
Authors: Maffei Enea , Shaidullina Aisylu , Burkolter Marco , Druelle Valentin , Willi Luc , Estermann Fabienne , Michaelis Sarah , Hilbi Hubert , Thaler David S. , Harms Alexander 
Published: March 2021

AbstractBacteriophages, the viruses infecting bacteria, hold great potential for the treatment of multidrug-resistant bacterial infections and other applications due to their unparalleled diversity and recent breakthroughs in their genetic engineering. However, fundamental knowledge of molecular mechanisms underlying phage-host interactions is mostly confined to a few traditional model systems and did not keep pace with the recent massive expansion of the field. The true potential of molecular biology encoded by these viruses has therefore remained largely untapped, and phages for therapy or other applications are often still selected empirically. We therefore sought to promote a systematic exploration of phage-host interactions by composing a well-assorted library of 66 newly isolated phages infecting the model organismEscherichia colithat we share with the community as the BASEL collection (BActeriophage SElection for your Laboratory). This collection is largely representative of naturalE. coliphage diversity and was intensively characterized phenotypically and genomically alongside ten well-studied traditional model phages. We experimentally determined essential host receptors of all phages, quantified their sensitivity to eleven defense systems across different layers of bacterial immunity, and matched these results to the phages’ host range across a panel of pathogenic enterobacterial strains. Our results reveal clear patterns in the distribution of phage phenotypes and genomic features that highlight systematic differences in the potency of different immunity systems and point towards the molecular basis of receptor specificity in several phage groups. Strong trade-offs were detected between fitness traits like broad host recognition and resistance to bacterial immunity that might drive the divergent adaptation of different phage groups to specific niches. We envision that the BASEL collection will inspire future work exploring the biology of bacteriophages and their hosts by facilitating the discovery of underlying molecular mechanisms as the basis for an effective translation into biotechnology or therapeutic applications.
Expansion-Assisted Iterative-FISH defines lateral hypothalamus spatio-molecular organization
Authors: Wang Yuhan , Eddison Mark , Fleishman Greg , Weigert Martin , Xu Shengjin , Henry Fredrick E. , Wang Tim , Lemire Andrew L. , Schmidt Uwe , Yang Hui , Rokicki Konrad , Goina Cristian , Svoboda Karel , Myers Eugene W. , Saalfeld Stephan , Korff Wyatt , Sternson Scott M. , Tillberg Paul W. 
Published: March 2021

AbstractDetermining the spatial organization and morphological characteristics of molecularly defined cell types is a major bottleneck for characterizing the architecture underpinning brain function. We developedExpansion-Assisted IterativeFluorescenceInSituHybridization (EASI-FISH) to survey gene expression in brain tissue, as well as a turnkey computational pipeline to rapidly process large EASI-FISH image datasets. EASI-FISH was optimized for thick brain sections (300 µm) to facilitate reconstruction of spatio-molecular domains that generalize across brains. Using the EASI-FISH pipeline, we investigated the spatial distribution of dozens of molecularly defined cell types in the lateral hypothalamic area (LHA), a brain region with poorly defined anatomical organization. Mapping cell types in the LHA revealed nine novel spatially and molecularly defined subregions. EASI-FISH also facilitates iterative re-analysis of scRNA-Seq datasets to determine marker-genes that further dissociated spatial and morphological heterogeneity. The EASI-FISH pipeline democratizes mapping molecularly defined cell types, enabling discoveries about brain organization.Highlights-EASI-FISH enables robust gene expression profiling in thick brain slices-A turnkey analysis pipeline for facile analysis of large EASI-FISH image datasets-EASI-FISH reveals novel subregions of the lateral hypothalamus-Identification of rare cell types based on morphological and spatial heterogeneity
Spatial patterns in functional brain connectomes reflect acute and chronic cannabis use
Authors: Ramaekers JG , Mason NL , Toennes SW , Theunissen EL , Amico E 
Published: March 2021

AbstractResting state fMRI has been employed to identify alterations in functional connectivity within or between brain regions following acute and chronic exposure to Δ9-tetrahydrocannabinol (THC), the psychoactive component in cannabis. Most studies focused a priori on a limited number of local brain areas or circuits, without considering the impact of cannabis on wholebrain network organization. The present study attempted to identify changes in the wholebrain human functional connectome as assessed with ultra-high field (7T) resting state scans of occasional (N=12) and chronic cannabis users (N=14) during placebo and following vaporization of cannabis. Two distinct data-driven methodologies, i.e. network-based statistics (NBS) and connICA, were used to identify changes in functional connectomes associated with acute cannabis intoxication and chronic cannabis use. Both methodologies revealed a broad state of hyperconnectivity within the entire range of major brain networks in chronic cannabis users compared to occasional cannabis users, which might be reflective of an adaptive network reorganization following prolonged cannabis exposure. The connICA methodology also extracted a distinct spatial connectivity pattern of hypoconnectivity involving the dorsal attention, limbic, subcortical and cerebellum networks and of hyperconnectivity between the default mode and ventral attention network, that was associated with the feeling of subjective high during THC intoxication across both user groups. Whole-brain network approaches identified spatial patterns in functional brain connectomes that distinguished acute from chronic cannabis use, and offer an important utility for probing the interplay between short and long-term alterations in functional brain dynamics when progressing from occasional to chronic use of cannabis.
Cyclodextrins increase membrane tension and are universal activators of mechanosensitive channels
Authors: Cox Charles D , Zhang Yixiao , Zhou Zijing , Walz Thomas , Martinac Boris 
Published: March 2021

AbstractThe bacterial mechanosensitive channel of small conductance, MscS, has been extensively studied to understand how mechanical forces are converted into the conformational changes that underlie mechanosensitive (MS) channel gating. We showed that lipid removal by β-cyclodextrin can mimic membrane tension. Here, we show that all cyclodextrins (CDs) can activate reconstitutedE. coliMscS, that MscS activation by CDs depends on CD-mediated lipid removal, and that the CD amount required to gate MscS scales with the channel’s sensitivity to membrane tension. CD-mediated lipid removal ultimately causes MscS desensitization, which we show is affected by the lipid environment. CDs can also activate the structurally unrelated MscL. While many MS channels respond to membrane forces, generalized by the ‘force-from-lipids’ principle, their different molecular architectures suggest that they use unique ways to convert mechanical forces into conformational changes. CDs emerge as a universal tool for the structural and functional characterization of unrelated MS channels.
An unusually long 5’UTR of ATP dependent cold shock DEAD-box RNA helicase genecsdAnegatively regulates its own expression inEscherichia coli
Authors: Jana Soma , Datta Partha P. 
Published: March 2021

AbstractCold-shockDEAD-box proteinA(CsdA) is an ATP dependant cold shock DEAD-box RNA helicase. It is a major cold shock protein needed for the cold adaptation inEscherichia coli. Although the CsdA has been studied at the protein level, further studies are necessary to understand its mechanisms of gene regulations. In this regard, we have constructed a promoter less vector with the ORF of a GFP reporter and found that the promoter of thecsdAgene resides far upstream (more than 800 bases) of its coding region. Furthermore, ourin vivodeletion experiment has confirmed the existence of this extraordinarily long 5’UTR. Our results show that it represses its own expression. In addition, the short peptide encoding (26 aa)yrbNgene resides within this 5’UTR as an operon with 8 overlapping nucleotides with thecsdAcoding region. Besides, we observed that thecsdAgene expression may also occur along with immediate upstream (180 nucleotides)nlpIgene both at 37°C and 15°C and from thepnpgene (1173 nucleotides upstream) only during cold. In conclusion,csdAgene has operon feature like prokaryotes, in contrast, it also contains an extraordinarily long 5’UTR, found in eukaryotes.
Probing adaptation and spontaneous firing in human auditory-nerve fibers with far-field peri-stimulus time responses
Authors: Huet Antoine , Batrel Charlène , Dubernard Xavier , Kleiber Jean-Charles , Desmadryl Gilles , Venail Frédéric , Liberman M. Charles , Nouvian Régis , Puel Jean-Luc , Bourien Jérôme 
Published: March 2021

AbstractInformation in sound stimuli is conveyed from sensory hair cells to the cochlear nuclei by the firing of auditory nerve fibers (ANFs). For obvious ethical reasons, single unit recordings from the cochlear nerve have never been performed in human, thus functional hallmarks of ANFs are unknown. By filtering and rectifying the electrical signal recorded at the round window of gerbil cochleae, we reconstructed a peri-stimulus time response (PSTR), with a waveform similar to the peri-stimulus time histograms (PSTHs) recorded from single ANFs. Pair-by-pair analysis of simultaneous PSTR and PSTH recordings in gerbil provided a model to predict the rapid adaptation and spontaneous discharge rates (SR) in a population of ANFs according to their location in the cochlea. We then probed the model in the mouse, in which the SR-based distribution of ANFs differs from the gerbil. We show that the PSTR-based predictions of the rapid adaptation time constant and mean SR across frequency again matched those obtained by recordings from single ANFs. Using PSTR recorded from the human cochlear nerve in 8 normal-hearing patients who underwent cerebellopontine angle surgeries for a functional cranial-nerve disorders (trigeminal neuralgia or hemifacial spasm), we predicted a rapid adaptation of about 3 milliseconds and a mean SR of 23 spikes/s in the 4 kHz frequency range in human ANFs. Together, our results support the use of PSTR as a promising diagnostic tool to map the auditory nerve in humans, thus opening new avenues to better understanding neuropathies, tinnitus, and hyperacusis.
The role of meaning in service innovation: a conceptual exploration
Authors: Kustrak Korper Ana , Holmlid Stefan , Patrício Lia 
Published: March 2021

PurposeThe purpose of this paper is to introduce the concept of meaning as a relevant but missing link in understanding the building blocks of service innovation informed by service-dominant (S-D) logic. In exploring the role of meaning in service innovation, especially related to new value propositions, resource integration and new value cocreation, the authors suggest using the conceptualization of meaning within human-centered design, which has an established body of knowledge on addressing how actors engage and interact.Design/methodology/approachThe paper builds an actionable conceptual framework that relates meaning to central tenets of service innovation, such as resource integration, value propositions and cocreation of value. It delineates the central building blocks of service innovation and conceptually integrates them with meaning to explain the underlying mechanisms of service innovation related both to its development and adoption.FindingsThe findings highlight how and why meaning precedes value creation and directs resource integration. Indicating that meaning is driven by experience of earlier interactions it delineates its relationships with new value formation and positions resource interpretation as a driver of this process.Originality/valueThis paper extends the understanding of service innovation in relation to S-D logic, with meaning as a conceptual link to aspects of S-D logic that claim a phenomenological nature. Meaning contributes to S-D logic by providing an understanding of how beneficiaries form intentions to engage in value creation and resource integration. Additionally, by integrating service and design research domains, this paper suggests possibilities for multidisciplinary contributions in future research.
Mastocytosis in the skin accompanied by pseudo‐Kaposi’s sarcoma
Authors: Vergara‐de‐la‐Campa Laura , Torrado Inés , Recuero‐Pradillo María , Torrelo Antonio , Gironella Mercedes , Pardal Emilia , Godoy Ana Cristina , Matito Almudena , Pérez‐Hortet Cristina , Mollejo Manuela , Álvarez‐Twöse Iván 
Published: March 2021

AbstractMastocytosis is a heterogeneous group of diseases characterized by abnormal proliferation of neoplastic mast cells in the skin and/or other extracutaneous tissues. Most patients with skin involvement can be subclassified into one of the three subtypes of cutaneous mastocytosis currently recognized by the World Health Organization (i.e., mastocytoma, maculopapular cutaneous mastocytosis and diffuse cutaneous mastocytosis); however, some patients may occasionally present with atypical skin lesions that cannot be ascribed to any of these disease subtypes. Here, we report three patients diagnosed with mastocytosis and an unusual cutaneous involvement mimicking Kaposi’s sarcoma. Skin biopsies showed neoplastic mast cell infiltrates together with features commonly seen in acroangiodermatitis, and immunohistochemistry for human herpesvirus 8 was negative. One patient fulfilled the criteria for aggressive systemic mastocytosis, showed no response to cytoreductive therapy, and died because of disease progression. The remaining two patients had indolent and smoldering systemic mastocytosis, respectively, but they showed several features associated with an unfavorable prognosis such as extensive involvement of the hematopoiesis by the KIT D816V mutation, increased serum β2‐microglobulin, and decreased serum lactate dehydrogenase. The presence of pseudo‐Kaposi’s sarcoma skin lesions is an uncommon finding in mastocytosis which may alert physicians to the possible existence of underlying features indicative of a poor prognosis.
Economic Aspects of Loneliness in Australia
Authors: Kung Claryn S. J. , Kunz Johannes S. , Shields Michael A. 
Published: March 2021

AbstractWe highlight the problem of loneliness, and argue that it is not only a public health issue but also an economic problem. We provide a brief review of findings from the key literature on the associations between loneliness, mental and physical health, and healthcare costs; and then present some evidence on its trends, the extent of socioeconomic inequalities and its links with health and healthcare usage, in Australia. We hope to encourage further economics research on loneliness, and related issues of social isolation and poor social support, to aid the design of policies and interventions to reduce loneliness.
‘You Have to Withstand That Because You Have Come for What You Have Come for’: Barriers and facilitators to antiretroviral treatment access among older South Africans living with HIV
Authors: Schatz Enid , Knight Lucia , Mukumbang Ferdinand C. , Teti Michelle , Myroniuk Tyler W. 
Published: March 2021

ABSTRACTNationwide rollout of antiretroviral treatment (ART) is increasing the number of older persons living with HIV (OPLWH) in South Africa. Yet, little is known about how the sociological aspects of ageing – stigma, finances and family dynamics – impact access to ART. Qualitative interviews with 23 persons aged 50‐plus living near Cape Town highlight the barriers and facilitators to the acceptability, affordability and availability of ART access among OPLWH. Key age‐related barriers included perceived shame of sexuality and disclosing HIV status to others, perceived disrespect by clinical staff, affording transportation to clinics and pre‐existing co‐morbidities. Key age‐related facilitators included family moral and financial support, particularly from children and grandchildren, and access to social grants. Importantly, many barriers and facilitators had feedback loops, for example social grants reduced transportation barriers to clinics when ageing and poor health limited mobility. As the population living with HIV ages, it is critical to assess the ways ageing, as a social process, impacts ART access and to address these to improve older persons’ HIV care.