bluuebunny/crossref_metadata_2025_split huggingface dataset:
High throughput imaging of nanoscale extracellular vesicles by scanning electron microscopy for accurate size-based profiling and morphological analysis
Authors: Cavallaro Sara , Hååg Petra , Viktorsson Kristina , Krozer Anatol , Fogel Kristina , Lewensohn Rolf , Linnros Jan , Dev Apurba 
Published: January 2021

ABSTRACTNanoscale extracellular vesicle (EVs) have been found to play a key role in intercellular communication, offering opportunities for both diagnostics and therapeutics. However, lying below the diffraction limit and also being highly heterogeneous in their size, morphology and abundance, these vesicles pose significant challenges for their physical characterization. Here, we present a direct visual approach for their accurate morphological and size-based profiling by using scanning electron microscopy (SEM). To achieve that, we methodically examined various process steps and developed a protocol to improve the throughput, conformity and image quality while preserving the shape of EVs. The investigation was performed with small EVs (sEVs) isolated from a non-small cell lung cancer (NSCLC) cell line H1975 as well as from a human serum, and the results were compared with those obtained from nanoparticle tracking analysis (NTA). While the comparison of the sEV size distributions showed good agreement between the two methods for large sEVs (diameter >70 nm), the microscopy based approach showed a better capacity for analyses on smaller vesicles, with higher sEV counts compared to NTA. In addition, we demonstrated the possibility of identifying non-EV particles based on size and morphological features. The study also showed process steps that can generate artifacts bearing resemblance with sEVs. The results therefore present a simple way to use a widely available microscopy tool for accurate and high throughput physical characterization of EVs.
Actin fence therapy with exogenous V12Rac1 protects against Acute Lung Injury
Authors: Gusarova Galina A. , Das Shonit R. , Islam Mohammad N. , Westphalen Kristin , Jin Guangchun , O.Shmarakov Igor , Li Li , Bhattacharya Sunita , Bhattacharya Jahar 
Published: January 2021

AbstractHigh mortality in Acute Lung Injury (ALI) results from sustained proinflammatory signaling by alveolar receptors, such as TNFα receptor type 1 (TNFR1). Factors that determine the sustained signaling are not known. Unexpectedly, optical imaging of live alveoli revealed a major TNFα-induced surge of alveolar TNFR1 due to a Ca2+-dependent mechanism that decreased the cortical actin fence. Mouse mortality due to inhaled LPS was associated with cofilin activation, actin loss and the TNFR1 surge. The constitutively active form of the GTPase, Rac1 (V12Rac1), given intranasally as a non-covalent construct with a cell-permeable peptide, enhanced alveolar F-actin and blocked the TNFR1 surge. V12Rac1 also protected against ALI-induced mortality resulting from intranasal (i.n.) instillation of LPS, or ofPseudomonas aeruginosa. We propose a new therapeutic paradigm in which actin enhancement by exogenous Rac1 strengthens the alveolar actin fence, protecting against proinflammatory receptor hyperexpression, hence blocking ALI.
The VTA-BLA-NAc circuit for sex reward inhibited by VTA GABAergic neurons under stress in male mice
Authors: Sun Linshan , You Jingjing , Cui Minghu , Sun Fengjiao , Wang Jiangong , Wang Wentao , Wang Dan , Liu Dunjiang , Xu Zhicheng , Qiu Changyun , Liu Bin , Yan Haijing 
Published: January 2021

AbstractAnhedonia, inability to experience pleasure from rewarding or enjoyable activities, is the prominent symptom of depression that involves dysfunction of the reward processing system. Both genetic predisposition and life events are thought to increase the risk for depression, in particular life stress. The cellular mechanism underlying stress modulating the reward processing neural circuits and subsequently disrupting reward-related behaviors remains elusive. We identify the VTA-BLA-NAc pathway as being activated by sex reward. Blockade of this circuit induces depressive-like behaviors, while reactivation of VTA neurons associated with sexual rewarding experience acutely ameliorates the impairment of reward-seeking behaviors induced by chronic restraint stress. Our histological and electrophysiological results show that the VTA neuron subpopulation responding to restraint stress inhibits the responsiveness of the VTA dopaminergic neurons to sexual reward. Together, these results reveal the cellular mechanism by which stress influences the brain reward processing system and provide a potential target for depression treatment.
In-silico studies of Neurocognitive and Neuropharmacological effect of Bacopa monnieri (L.)
Authors: Sangeet Satyam , Khan Arshad 
Published: January 2021

ABSTRACTDifferent Indian therapeutic plants have picked up consideration for their restorative properties against neurodevelopmental disorders lately.Bacopa monnieri (B. monnieri), being one of them, finds its utilization significantly in the treatment of cognition and learning. Despite the fact that it possesses such great capacity to treat neurological issues, how precisely it confers its influence is muddled. This study makes a stride towards knowing which phytochemical is significantly associated with grantingB. monnieriwith therapeutic properties. The docking investigation and the molecular simulation studies proposes that there is no single phytochemical included that impartsB. monnieria significant medicinal effect. It is really the blend of dominant part of natural phytochemicals present inB. monnierithat bestows the anti-neurological activity toB. monnieri.The ADME studies shows the convergence of properties of phytochemicals ofB. monnieriwith that of commercially available drugs which suggests that phytochemicals ofB. monnierican used as a potential drug source to treat neurodegenerative and neurodevelopmental disorders.
Nuclear stabilisation of p53 requires a functional nucleolar surveillance pathway
Authors: Hannan Katherine M. , Soo Priscilla , Wong Mei S. , Lee Justine K. , Hein Nadine , Evers Maurits , Wysoke Kira D. , Williams Tobias D. , Montellese Christian , Smith Lorey K. , Al-Obaidi Sheren J. , Núñez-Villacís Lorena , Poh Perlita , Pavy Megan , He Jin-Shu , Parsons Kate M. , Diesch Jeannine , Burgio Gaetan , Ferreira Rita , Feng Zhi-Ping , Gould Cathryn M. , Madhamshettiwar Piyush B. , Flygare Johan , Gonda Thomas J. , Simpson Kaylene J. , Kutay Ulrike , Pearson Richard B. , Engel Christoph , Watkins Nicholas J. , Hannan Ross D. , George Amee J. 
Published: January 2021

AbstractThe nucleolar surveillance pathway (NSP) monitors nucleolar fidelity and responds to nucleolar stresses (i.e., inactivation of ribosome biogenesis) by mediating the inhibitory binding of ribosomal proteins (RPs) to mouse double minute 2 homolog (MDM2), a nuclear-localised E3 ubiquitin ligase, which results in p53 accumulation. Inappropriate activation of the NSP has been implicated in the pathogenesis of collection of human diseases termed “ribosomopathies”, while drugs that selectively activate the NSP are now in trials for cancer. Despite the clinical significance, the precise molecular mechanism(s) regulating the NSP remain poorly understood. Using genome-wide loss of function screens, we demonstrate the ribosome biogenesis (RiBi) axis as the most potent class of genes whose disruption stabilises p53. Furthermore, we identified a novel suite of genes critical for the NSP, including a novel mammalian protein implicated in 5S ribonucleoprotein particle (5S-RNP) biogenesis, HEATR3. By selectively disabling the NSP, we unexpectedly demonstrate that a functional NSP is required for the ability of all nuclear acting stresses tested, including DNA damage, to robustly induce p53 accumulation. Together, our data demonstrates that the NSP has evolved as the dominant central integrator of stresses that regulate nuclear p53 abundance, thus ensuring RiBi is hardwired to cellular proliferative capacity.
Hearing loss is associated with delayed neural responses to continuous speech
Authors: Gillis Marlies , Decruy Lien , Vanthornhout Jonas , Francart Tom 
Published: January 2021

AbstractWe investigated the impact of hearing loss on the neural processing of speech. Using a forward modeling approach, we compared the neural responses to continuous speech of 14 adults with sensorineural hearing loss with those of age-matched normal-hearing peers.Compared to their normal-hearing peers, hearing-impaired listeners had increased neural tracking and delayed neural responses to continuous speech in quiet. The latency also increased with the degree of hearing loss. As speech understanding decreased, neural tracking decreased in both populations; however, a significantly different trend was observed for the latency of the neural responses. For normal-hearing listeners, the latency increased with increasing background noise level. However, for hearing-impaired listeners, this increase was not observed.Our results support the idea that the neural response latency indicates the efficiency of neural speech processing. Hearing-impaired listeners process speech in silence less efficiently than normal-hearing listeners. Our results suggest that this reduction in neural speech processing efficiency is a gradual effect which occurs as hearing deteriorates. Moreover, the efficiency of neural speech processing in hearing-impaired listeners is already at its lowest level when listening to speech in quiet, while normal-hearing listeners show a further decrease in efficiency when the noise level increases.From our results, it is apparent that sound amplification does not solve hearing loss. Even when listing to speech in silence at a comfortable loudness, hearing-impaired listeners process speech less efficiently.
α-catenin links integrin adhesions to F-actin to regulate ECM mechanosensing and rigidity-dependence
Authors: Mukherjee Abhishek , Melamed Shay , Damouny-Khoury Hana , Amer Malak , Feld Lea , Nadjar-Boger Elisabeth , Sheetz Michael P. , Wolfenson Haguy 
Published: January 2021

AbstractBoth cell-cell and cell-matrix adhesions are regulated by mechanical signals, but the mechanobiological processes that mediate the crosstalk between these structures are poorly understood. Here we show that α- catenin, a mechanosensitive protein that is classically associated with cadherin-based adhesions, directly interacts with and regulates integrin adhesions. α-catenin is recruited to the edges of mesenchymal cells, where it interacts with F-actin. This is followed by mutual retrograde flow of α-catenin and F-actin from the cell edge, during which α-catenin interacts with vinculin within integrin adhesions. This interaction affects adhesion maturation, stress-fiber assembly, and force transmission to the matrix. In epithelial cells, α-catenin is present in cell-cell adhesions and absent from cell-matrix adhesions. However, when these cells undergo epithelial-to-mesenchymal transition, α-catenin transitions to cell-matrix adhesions, where it facilitates proper mechanosensing. This is highlighted by the ability of α-catenin-depleted cells to grow on soft matrices. These results suggest a dual role of α-catenin in mechanosensing, through both cell-cell and cell-matrix adhesions.
The pseudouridine synthase dyskerin binds to cytoplasmic H/ACA-box snoRNA retaining transcripts affecting nuclear hormone receptor dependence
Authors: Zacchini Federico , Venturi Giulia , De Sanctis Veronica , Bertorelli Roberto , Ceccarelli Claudio , Santini Donatella , Taffurelli Mario , Penzo Marianna , Treré Davide , Inga Alberto , Dassi Erik , Montanaro Lorenzo 
Published: January 2021

ABSTRACTDyskerin is a nuclear protein involved in H/ACA box snoRNA-guided uridine modification of RNA. Since its defective function induces specific alterations in gene expression, we sought to unbiasedly identify mRNAs regulated by dyskerin. We found that dyskerin depletion affects the expression or the association with polysomes of selected mRNA isoforms characterized by the retention of H/ACA box snoRNA-containing introns. These snoRNA retaining transcripts (snoRTs) are bound by dyskerin and can interact with cytoplasmic ribosomes. We then characterized the cytoplasmic dyskerin RNA interactome finding both H/ACA box snoRTs and protein-coding transcripts. Since a fraction of these latter transcripts is involved in the nuclear hormone receptor binding, we tested to see if this specific activity is affected by dyskerin. Results indicate that dyskerin dysregulation may alter the dependence on nuclear hormone receptor ligands in breast cancer. Our work suggests a cytoplasmic function for dyskerin which could affect mRNA post-transcriptional networks relevant for nuclear hormone receptor functions.
Different autotrophic enrichments yield efficient inocula for biocathodic applications
Authors: Gülay Arda , Jensen Marlene Mark , Sicheritz-Pontén Thomas , Smets Barth F. 
Published: January 2021

AbstractThe uptake of extracellular electrons from cathodes by microbes is a recently discovered phenomenon. However, current knowledge on the diversity of microbes accepting extracellular electrons and populating biocathodes is scarce. Research is required to explore the distribution of extracellular electron uptake metabolism in the tree of life across microbial guilds. Here we characterize the electron uptake ability of microbial guilds enriched on H2, S2O32-, or CH4and NH4+from the same inoculum taken from a groundwater treatment sand-filter. We hypothesized that functional microbes having dense outer membrane cytochromes in their native pathway, such as pathways of NH4+, CH4, S2O32-and H2, can perform extracellular electron uptake. We aimed of addressing the following questions: (1) Are there any known microbial member of anticipated function performing extracellular electron transfer? (2) How does electron uptake efficiency vary between the different functional guilds? (3) How is the dissipated electron energy distributed across metabolisms? We developed and applied a novel pipeline to identify taxa utilizing direct electron energy and utilizing secondary microbial products. We report the putative direct electron uptake metabolism of types belonging toMethylomonas, UBA6140, andNitrosomonas. Furthermore, members ofStreptococcaceae, Rhizobiaceae, Streptococcus, Brevundimonas, Chryseobacterium, andPseudomonasare detected as electroactive taxa. Our results reveal novel insights into the diversity, electrochemical activity, and metabolism of taxa performing direct electron uptake.
Combined scanning small-angle X-ray scattering and holography probes multiple length scales in cell nuclei
Authors: Wittmeier Andrew , Cassini Chiara , Töpperwien Mareike , Denz Manuela , Hagemann Johannes , Osterhoff Markus , Salditt Tim , Köster Sarah 
Published: January 2021

X-rays are emerging as a complementary probe to visible-light photons and electrons for imaging biological cells. By exploiting their small wavelength and high penetration depth, it is possible to image whole, intact cells and resolve subcellular structures at nanometer resolution. A variety of X-ray methods for cell imaging have been devised for probing different properties of biological matter, opening up various opportunities for fully exploiting different views of the same sample. Here, a combined approach is employed to study cell nuclei of NIH-3T3 fibroblasts. Scanning small-angle X-ray scattering is combined with X-ray holography to quantify length scales, aggregation state, and projected electron and mass densities of the nuclear material. Only by joining all this information is it possible to spatially localize nucleoli, heterochromatin and euchromatin, and physically characterize them. It is thus shown that for complex biological systems, like the cell nucleus, combined imaging approaches are highly valuable.
Aggressive Boards and CEO Turnover
Authors: AGHAMOLLA CYRUS , HASHIMOTO TADASHI 
Published: January 2021

ABSTRACTThis study investigates a communication game between a CEO and a board of directors where the CEO's career concerns can potentially impede value‐increasing informative communication. By adopting a policy of aggressive boards (excessive replacement), shareholders can facilitate communication between the CEO and the board. The results are in contrast to the multitude of models which generally find that management‐friendly boards improve communication, and help to explain empirical results concerning CEO turnover. The results also provide the following novel predictions concerning variation in CEO turnover: (1) there is greater CEO turnover in firms or industries where CEO performance is relatively more difficult to assess; (2) the board is more aggressive in their replacement of the CEO in industries or firms where the board's advisory role is more salient; and (3) there is comparatively less CEO turnover in firms or industries where the variance of CEO talent is high.
Emergency physicians' role in telemedicine care during the coronavirus disease pandemic: Experiences from Taiwan
Authors: Chu Chien‐Ming , Wang Tsung‐Hsi , Lee Hsin‐Chung , Lin Chaou‐Shune , Feng Cho‐Chao 
Published: January 2021

AbstractTaiwan's response to the coronavirus disease pandemic received international recognition. Among various epidemic control measures, telemedicine services are provided for people under home quarantine. Although this service presents no policy, cost or equipment problems, the medical needs of people under home quarantine are diverse. Further, there are no clear guidelines regarding which specialists should be included in a multidisciplinary team. Moreover, many physicians are unwilling to participate in telemedicine, creating a big challenge for hospitals providing these services. Emergency physicians (EPs) have unique experiences in crisis management and can provide a number of effective public health measures. We advocate that EPs should be the first specialists to contact patients in a multidisciplinary team. Currently, there is a lack of literature on this subject, and Taiwan's epidemic control experience is used as an example to prove our viewpoint and provide recommendations for future EPs.
Diffusion‐weighted whole‐body imaging with background suppression (DWIBS) is effective and economical for detection of metastasis or recurrence of lung cancer
Authors: Usuda Katsuo , Iwai Shun , Yamagata Aika , Iijima Yoshihito , Motono Nozomu , Matoba Munetaka , Doai Mariko , Yamada Sohsuke , Ueda Yoshimichi , Hirata Keiya , Uramoto Hidetaka 
Published: January 2021

AbstractBackgroundDiffusion‐weighted whole‐body imaging with background suppression (DWIBS) is used for the diagnosis and staging of cancers. The medical cost of an MR examination including DWIBS is $123, which is 80% less expensive than the cost ($798) of F18‐fluorodeoxyglucose positron emission tomography/computed tomography (FDG‐PET/CT) examination.MethodsThis study examined the efficacy of DWIBS for relapses after lung cancer resection. A total of 55 patients who had pulmonary resection of lung cancer, postoperative computed tomography (CT) every six months, and DWIBS and FDG‐PET/CT (every year) were enrolled in this study. If a metastatic lesion was detected on CT scan, DWIBS and FDG‐PET/CT were also used.ResultsA total of 55 patients who underwent pulmonary resections for lung cancer, and had CT, DWIBS and FDG‐PET/CT examination during follow‐up after pulmonary resection were enrolled in this study. Lung cancer in 32 patients relapsed. Postoperative radiographic examinations revealed pulmonary metastases in 17 patients, bone metastases in seven, liver metastases in five, lymph node metastases in five, pleural metastases in four, metastases to the chest wall in two, brain metastases in two, adrenal gland metastasis in one, and renal metastasis in one. The mean apparent diffusion coefficient (ADC) value of the relapse was 0.9 to 1.70 × 10−3 mm2/s. The accuracy 0.98 (54/55) of DWIBS for detecting multiple metastatic lesions was likely to be higher than 0.94 (52/55) of CT or 0.94 (52/55) of FDG‐PET/CT, but there were no significant differences.ConclusionsDWIBS can detect multiple metastatic lesions throughout the entire body and differentiate malignancy from benignity in only one examination. DWIBS has benefits of diagnostic accuracy and is less expensive in medical costs for the detection of a relapse. DWIBS could potentially replace FDG‐PET/CT after lung cancer resection.
Higher osimertinib introduction rate achieved by multiple repeated rebiopsy after acquired resistance to first/second generation EGFR‐TKIs
Authors: Ninomaru Taira , Hata Akito , Kokan Chiyuki , Okada Hideaki , Tomimatsu Hirotaka , Ishida Jun 
Published: January 2021

AbstractBackgroundIndication for treatment with osimertinib after first/second generation (1/2G) epidermal growth factor receptor‐tyrosine kinase inhibitor (EGFR‐TKI) resistance depends on T790M mutation detected by rebiopsy. The aim of our study was to analyze the data on clinical practice at our hospital where histological rebiopsy is actively carried out multiple times.MethodsWe retrospectively reviewed our electronic medical records of EGFR‐mutant non‐small cell lung cancer (NSCLC) patients to examine clinical rebiopsy situation, T790M detection rate, osimertinib introduction rate and associated outcomes.ResultsAmong 95 patients with EGFR‐mutant NSCLC, 72 patients received 1/2G EGFR‐TKIs. Of 60 with progressive disease on 1/2G EGFR‐TKIs, 50 (83%) underwent rebiopsy. T790M was detected in 40 (80%) of 50, resulting in a 79% osimertinib introduction rate, as one patient refused osimertinib. T790M was detected by first rebiopsy in 18 (36%) of 50 patients, and by second or subsequent rebiopsy in 22 (44%). Median time to treatment failure of T790M‐positive patients at first rebiopsy was 22.6 (95% confidence interval [CI]: 10.2–32.8) months, and those at multiple repeated rebiopsy was 20.9 (95% CI: 8.6–not reached) months (p = 0.64). Median overall survival (OS) in osimertinib introduced group was 92.5 (95% CI: 62.9–not reached), while in nonosimertinib median OS was 39.0 months (95% CI: 22.2–not reached) (p = 0.04).ConclusionsT790M detection rate was increased by multiple repeated rebiopsy, achieving a higher osimertinib introduction rate. This higher introduction rate could contribute to better prognosis of EGFR‐mutant NSCLC patients.
Transformation from adenocarcinoma to squamous cell lung carcinoma with MET amplification after lorlatinib resistance: A case report
Authors: Ueda Shoko , Shukuya Takehito , Hayashi Takuo , Suzuki Mario , Kondo Akihide , Arai Yuta , Takeshige Tomohito , Ninomiya Hironori , Takahashi Kazuhisa 
Published: January 2021

AbstractTo date, several studies have described the mechanism of resistance to first‐ or second‐generation anaplastic lymphoma kinase (ALK) inhibitors. Secondary ALK mutations, ALK gene amplification, and other bypass signal activations (i.e., KRAS mutation, EGFR mutation, amplification of KIT, and increased autophosphorylation of EGFR) are known as resistance mechanisms. However, little has been previously reported on acquired resistance mechanisms to lorlatinib. Here, we report a case of a patient with ALK‐positive lung adenocarcinoma that acquired resistance to lorlatinib during treatment for brain metastasis and showed histological transformation to squamous cell carcinoma with MET amplification. We also review the previous literature on the resistance mechanism to ALK inhibitors.