bluuebunny/crossref_metadata_2025 huggingface dataset:
Learning the distribution of single-cell chromosome conformations in bacteria reveals emergent order across genomic scales
Authors: Messelink Joris J. B. , van Teeseling Muriel C. F. , Janssen Jacqueline , Thanbichler Martin , Broedersz Chase P.
Published: March 2021

The order and variability of bacterial chromosome organization, contained within the distribution of chromosome conformations, are unclear. Here, we develop a fully data-driven maximum entropy approach to extract single-cell 3D chromosome conformations from Hi–C experiments on the model organism Caulobacter crescentus. The predictive power of our model is validated by independent experiments. We find that on large genomic scales, organizational features are predominantly present along the long cell axis: chromosomal loci exhibit striking long-ranged two-point axial correlations, indicating emergent order. This organization is associated with large genomic clusters we term Super Domains (SuDs), whose existence we support with super-resolution microscopy. On smaller genomic scales, our model reveals chromosome extensions that correlate with transcriptional and loop extrusion activity. Finally, we quantify the information contained in chromosome organization that may guide cellular processes. Our approach can be extended to other species, providing a general strategy to resolve variability in single-cell chromosomal organization.
Nanostructure of nickel-promoted indium oxide catalysts drives selectivity in CO2 hydrogenation
Authors: Frei Matthias S. , Mondelli Cecilia , García-Muelas Rodrigo , Morales-Vidal Jordi , Philipp Michelle , Safonova Olga V. , López Núria , Stewart Joseph A. , Ferré Daniel Curulla , Pérez-Ramírez Javier
Published: March 2021

Metal promotion in heterogeneous catalysis requires nanoscale-precision architectures to attain maximized and durable benefits. Herein, we unravel the complex interplay between nanostructure and product selectivity of nickel-promoted In2O3in CO2hydrogenation to methanol through in-depth characterization, theoretical simulations, and kinetic analyses. Up to 10 wt.% nickel, InNi3patches are formed on the oxide surface, which cannot activate CO2but boost methanol production supplying neutral hydrogen species. Since protons and hydrides generated on In2O3drive methanol synthesis rather than the reverse water-gas shift but radicals foster both reactions, nickel-lean catalysts featuring nanometric alloy layers provide a favorable balance between charged and neutral hydrogen species. For nickel contents >10 wt.%, extended InNi3structures favor CO production and metallic nickel additionally present produces some methane. This study marks a step ahead towards green methanol synthesis and uncovers chemistry aspects of nickel that shall spark inspiration for other catalytic applications.
Fault zone heterogeneities explain depth-dependent pattern and evolution of slow earthquakes in Cascadia
Authors: Luo Yingdi , Liu Zhen
Published: March 2021

Slow earthquakes including tremor and slow-slip events are recent additions to the conventional earthquake family and have a close link to megathrust earthquakes. Slow earthquakes along the Cascadia subduction zone display a diverse behavior at different spatiotemporal scales and an intriguing increase of events frequency with depth. However, what causes such variability, especially the depth-dependent behavior is not well understood. Here we build on a heterogeneous asperities-in-matrix fault model that incorporates differential pore pressure in a rate-and-state friction framework to investigate the underlying processes of the observed episodic tremor and slow-slip (ETS) variability. We find that the variations of effective normal stress (pore pressure) is one important factor in controlling ETS behavior. Our model reproduces the full complexity of ETS patterns and the depth-frequency scaling that agree quantitatively well with observations, suggesting that fault zone heterogeneities can be one viable mechanism to explain a broad spectrum of transient fault behaviors.
1/f-noise-free optical sensing with an integrated heterodyne interferometer
Authors: Jin Ming , Tang Shui-Jing , Chen Jin-Hui , Yu Xiao-Chong , Shu Haowen , Tao Yuansheng , Chen Antony K. , Gong Qihuang , Wang Xingjun , Xiao Yun-Feng
Published: March 2021

Optical evanescent sensors can non-invasively detect unlabeled nanoscale objects in real time with unprecedented sensitivity, enabling a variety of advances in fundamental physics and biological applications. However, the intrinsic low-frequency noise therein with an approximately 1/f-shaped spectral density imposes an ultimate detection limit for monitoring many paramount processes, such as antigen-antibody reactions, cell motions and DNA hybridizations. Here, we propose and demonstrate a 1/f-noise-free optical sensor through an up-converted detection system. Experimentally, in a CMOS-compatible heterodyne interferometer, the sampling noise amplitude is suppressed by two orders of magnitude. It pushes the label-free single-nanoparticle detection limit down to the attogram level without exploiting cavity resonances, plasmonic effects, or surface charges on the analytes. Single polystyrene nanobeads and HIV-1 virus-like particles are detected as a proof-of-concept demonstration for airborne biosensing. Based on integrated waveguide arrays, our devices hold great potentials for multiplexed and rapid sensing of diverse viruses or molecules.
Cellular macromolecules-tethered DNA walking indexing to explore nanoenvironments of chromatin modifications
Authors: Chen Feng , Bai Min , Cao Xiaowen , Xue Jing , Zhao Yue , Wu Na , Wang Lei , Zhang Dexin , Zhao Yongxi
Published: March 2021

Exploring spatial organization and relationship of diverse biomolecules within cellular nanoenvironments is important to elucidate the fundamental processes of life. However, it remains methodologically challenging. Herein, we report a molecular recognition mechanism cellular macromolecules-tethered DNA walking indexing (Cell-TALKING) to probe the nanoenvironments containing diverse chromatin modifications. As an example, we characterize the nanoenvironments of three DNA modifications around one histone posttranslational modification (PTM). These DNA modifications in fixed cells are labeled with respective DNA barcoding probes, and then the PTM site is tethered with a DNA walking probe. Cell-TALKING can continuously produce cleavage records of any barcoding probes nearby the walking probe. New 3’-OH ends are generated on the cleaved barcoding probes to induce DNA amplification for downstream detections. Combining fluorescence imaging, we identify various combinatorial chromatin modifications and investigate their dynamic changes during cell cycles. We also explore the nanoenvironments in different cancer cell lines and clinical specimens. In principle, using high-throughput sequencing instead of fluorescence imaging may allow the detection of complex cellular nanoenvironments containing tens of biomolecules such as transcription factors.
Small extracellular vesicles derived from interferon-γ pre-conditioned mesenchymal stromal cells effectively treat liver fibrosis
Authors: Takeuchi Suguru , Tsuchiya Atsunori , Iwasawa Takahiro , Nojiri Shunsuke , Watanabe Takayuki , Ogawa Masahiro , Yoshida Tomoaki , Fujiki Katsunori , Koui Yuta , Kido Taketomo , Yoshioka Yusuke , Fujita Mayu , Kikuta Junichi , Itoh Tohru , Takamura Masaaki , Shirahige Katsuhiko , Ishii Masaru , Ochiya Takahiro , Miyajima Atsushi , Terai Shuji
Published: March 2021

Mesenchymal stromal cells (MSCs) are used for ameliorating liver fibrosis and aiding liver regeneration after cirrhosis; Here, we analyzed the therapeutic potential of small extracellular vesicles (sEVs) derived from interferon-γ (IFN-γ) pre-conditioned MSCs (γ-sEVs). γ-sEVs effectively induced anti-inflammatory macrophages with high motility and phagocytic abilities in vitro, while not preventing hepatic stellate cell (HSC; the major source of collagen fiber) activation in vitro. The proteome analysis of MSC-derived sEVs revealed anti-inflammatory macrophage inducible proteins (e.g., annexin-A1, lactotransferrin, and aminopeptidase N) upon IFN-γ stimulation. Furthermore, by enabling CX3CR1+ macrophage accumulation in the damaged area, γ-sEVs ameliorated inflammation and fibrosis in the cirrhosis mouse model more effectively than sEVs. Single cell RNA-Seq analysis revealed diverse effects, such as induction of anti-inflammatory macrophages and regulatory T cells, in the cirrhotic liver after γ-sEV administration. Overall, IFN-γ pre-conditioning altered sEVs resulted in efficient tissue repair indicating a new therapeutic strategy.
Micro-RNA miR-542-3p suppresses decidualization by targeting ILK pathways in human endometrial stromal cells
Authors: Qu Xinlan , Fang Yuan , Zhuang Siying , Zhang Yuanzhen
Published: March 2021

Decidualization of human endometrial stromal cells (HESCs) is a vital step for successful pregnancy. However, the process by which micro-RNAs (miRNAs) regulate decidualization remains elusive. Our current study was designed to identify the mechanism of miRNA miR-542-3p and its potential targets in regulating decidualization. The results showed that miR-542-3p was down-regulated in HESCs. Luciferase assay confirmed that integrin-linked kinase (ILK) is a direct target of miR-542-3p. Overexpression of miR-542-3p resulted in decreased ILK and downstream transforming growth factor β1 (TGF-β1) and SMAD family member 2 (SMAD2) expression. Additional expression of ILK attenuates the miR542-3p-induced down-regulation of TGF-β1 and SMAD2, changes properties such as suppression of proliferation and invasion, and induction of apoptosis, thereby affecting the differentiation of HESCs. Moreover, miR-542-3p overexpression caused down-regulation of the angiogenic factors vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9), and the supernatant of HESCs overexpressing miR-542-3p inhibited the formation of tubular structures in human umbilical vein endothelial cells (HUVECs), suggesting that miR-542-3p inhibits angiogenesis of HUVECs. Furthermore, in our mouse model, following injection of miR-542-3p mimic into the endometrium of mice at pregnancy day 8 (D8), we found decreased miR-542-3p expression and loss of embryo implantation sites. In conclusion, miR-542-3p can affect the process of endometrial decidualization by down-regulating ILK. The present study adds further understanding of the process and regulation of decidualization.
Core–shell hydrogel microcapsules enable formation of human pluripotent stem cell spheroids and their cultivation in a stirred bioreactor
Authors: Fattahi Pouria , Rahimian Ali , Slama Michael Q. , Gwon Kihak , Gonzalez-Suarez Alan M. , Wolf Jadon , Baskaran Harihara , Duffy Caden D. , Stybayeva Gulnaz , Peterson Quinn P. , Revzin Alexander
Published: March 2021

Cellular therapies based on human pluripotent stem cells (hPSCs) offer considerable promise for treating numerous diseases including diabetes and end stage liver failure. Stem cell spheroids may be cultured in stirred bioreactors to scale up cell production to cell numbers relevant for use in humans. Despite significant progress in bioreactor culture of stem cells, areas for improvement remain. In this study, we demonstrate that microfluidic encapsulation of hPSCs and formation of spheroids. A co-axial droplet microfluidic device was used to fabricate 400 μm diameter capsules with a poly(ethylene glycol) hydrogel shell and an aqueous core. Spheroid formation was demonstrated for three hPSC lines to highlight broad utility of this encapsulation technology. In-capsule differentiation of stem cell spheroids into pancreatic β-cells in suspension culture was also demonstrated.
Global phylogeography of a pantropical mangrove genus Rhizophora
Authors: Takayama Koji , Tateishi Yoichi , Kajita Tadashi
Published: March 2021

Rhizophorais a key genus for revealing the formation process of the pantropical distribution of mangroves. In this study, in order to fully understand the historical scenario ofRhizophorathat achieved pantropical distribution, we conducted phylogeographic analyses based on nucleotide sequences of chloroplast and nuclear DNA as well as microsatellites for samples collected worldwide. Phylogenetic trees suggested the monophyly of each AEP and IWP lineages respectively except forR. samoensisandR. × selala. The divergence time between the two lineages was 10.6 million years ago on a dated phylogeny, and biogeographic stochastic mapping analyses supported these lineages separated following a vicariant event. These data suggested that the closure of the Tethys Seaway and the reduction in mangrove distribution followed by Mid-Miocene cooling were key factors that caused the linage diversification. Phylogeographic analyses also suggested the formation of the distinctive genetic structure at the AEP region across the American continents around Pliocene. Furthermore, long-distance trans-pacific dispersal occurred from the Pacific coast of American continents to the South Pacific and formed F1 hybrid, resulting in gene exchange between the IWP and AEP lineages after 11 million years of isolation. Considering the phylogeny and phylogeography with divergence time, a comprehensive picture of the historical scenario behind the pantropical distribution ofRhizophorais updated.
Geographical distribution of the dispersal ability of alien plant species in China and its socio-climatic control factors
Authors: Zhou Quanlai , Wu Jing , Cui Xue , Li Xuehua , Liu Zhimin , Musa Ala , Ma Qun , Yu Haibin , Liang Wei , Jiang Shaoyan , Wang Yongcui
Published: March 2021

Dispersal ability is important for the introduction, establishment, and spread of alien plant species. Therefore, determination of the geographical distribution of the dispersal ability of such species, and the relationship between dispersal ability and socio-climatic factors are essential to elucidate the invasion strategies of the alien plant species. Analytic hierarchy process and inventory, risk rank, and dispersal mode data available on Chinese alien plant species were used to determine their dispersal ability, the geographical distribution thereof, and the relationship between socio-climatic factors and dispersal ability. High-risk alien plant species had a higher natural dispersal ability (or several natural dispersal modes) but a lower anthropogenic dispersal ability (or few anthropogenic dispersal modes) than low-risk alien plant species. The geographical distribution of the dispersal ability of the alien plant species showed an inverse relationship with species density. Alien plant species with low dispersal ability (i.e., with fewer dispersal modes and distribution in the southeast) showed a tendency to adapt to environments with mild climates, while those with high dispersal ability (i.e., with more disposal nodes and distribution in the northwest) showed a tendency to adapt to harsh environments. It is essential for land managers and policy makers to understand the geographical distribution of the dispersal ability of alien plant species and their socio-climatic control factors to formulate strategies to control the natural and anthropogenic dispersal of such plants.
Scale-up fermentation of Escherichia coli for the production of recombinant endoglucanase from Clostridium thermocellum
Authors: Shahzadi Iram , Al-Ghamdi Maryam A. , Nadeem Muhammad Shahid , Sajjad Muhammad , Ali Asif , Khan Jalaluddin Azam , Kazmi Imran
Published: March 2021

Endoglucanase (EC 3.2.1.4) catalysing the hydrolysis of β-1.4-glycosidic linkage of cellulose molecules is an enzyme of tremendous industrial importance. The present study describes a response surface methodology based predicted model to deduce a set of fermentation conditions for optimum growth and activity of recombinant endoglucanase in E. coli BL21 (DE3). Numerous significant parameters including fermentation media composition, temperature (Celsius), pH and agitation rate (rpm) were analysed systemically by employing central composite design. This effort reports highly efficient recombinant endoglucanase overproduction (6.9 gl−1 of biomass) with 30% expression by E. coli in modified M9NG media incubated at 37 °C and pH 7 agitated at 200 rpm. Addition of 3 mM glucose and 24 mM glycerol in the M9NG media has shown positive effect on the enzyme yield and activity. The CMCase activity experimentally estimated was found to be 1185 U/mg with the optimized parameters. The outcomes of both the responses by the predicted quadratic model were found in consensus with the obtained values. Our results well depicted the favourable conditions to further scale-up the volumetric yield of other relevant recombinant enzymes and proteins.
Cerebrospinal fluid findings in patients with psychotic symptoms—a retrospective analysis
Authors: Rattay Tim W. , Martin Pascal , Vittore Debora , Hengel Holger , Cebi Idil , Tünnerhoff Johannes , Stefanou Maria-Ioanna , Hoffmann Jonatan F. , von der Ehe Katrin , Klaus Johannes , Vonderschmitt Julia , Herrmann Matthias L. , Bombach Paula , Al Barazi Hazar , Zeltner Lena , Richter Janina , Hesse Klaus , Eckstein Kathrin N. , Klingberg Stefan , Wildgruber Dirk
Published: March 2021

In current international classification systems (ICD-10, DSM5), the diagnostic criteria for psychotic disorders (e.g. schizophrenia and schizoaffective disorder) are based on symptomatic descriptions since no unambiguous biomarkers are known to date. However, when underlying causes of psychotic symptoms, like inflammation, ischemia, or tumor affecting the neural tissue can be identified, a different classification is used ("psychotic disorder with delusions due to known physiological condition" (ICD-10: F06.2) or psychosis caused by medical factors (DSM5)). While CSF analysis still is considered optional in current diagnostic guidelines for psychotic disorders, CSF biomarkers could help to identify known physiological conditions. In this retrospective, partly descriptive analysis of 144 patients with psychotic symptoms and available CSF data, we analyzed CSF examinations' significance to differentiate patients with specific etiological factors (F06.2) from patients with schizophrenia, schizotypal, delusional, and other non-mood psychotic disorders (F2). In 40.3% of all patients, at least one CSF parameter was out of the reference range. Abnormal CSF-findings were found significantly more often in patients diagnosed with F06.2 (88.2%) as compared to patients diagnosed with F2 (23.8%, p < 0.00001). A total of 17 cases were identified as probably caused by specific etiological factors (F06.2), of which ten cases fulfilled the criteria for a probable autoimmune psychosis linked to the following autoantibodies: amphiphysin, CASPR2, CV2, LGl1, NMDA, zic4, and titin. Two cases presented with anti-thyroid tissue autoantibodies. In four cases, further probable causal factors were identified: COVID-19, a frontal intracranial tumor, multiple sclerosis (n = 2), and neurosyphilis. Twenty-one cases remained with "no reliable diagnostic classification". Age at onset of psychotic symptoms differed between patients diagnosed with F2 and F06.2 (p = 0.014), with the latter group being older (median: 44 vs. 28 years). Various CSF parameters were analyzed in an exploratory analysis, identifying pleocytosis and oligoclonal bands (OCBs) as discriminators (F06.2 vs. F2) with a high specificity of > 96% each. No group differences were found for gender, characteristics of psychotic symptoms, substance dependency, or family history. This study emphasizes the great importance of a detailed diagnostic workup in diagnosing psychotic disorders, including CSF analysis, to detect possible underlying pathologies and improve treatment decisions.
Assessing adaptive requirements and breeding potential of spelt under Mediterranean environment
Authors: Curzon Arie Y. , Kottakota Chandrasekhar , Nashef Kamal , Abbo Shahal , Bonfil David J. , Reifen Ram , Bar-El Shimrit , Rabinovich On , Avneri Asaf , Ben-David Roi
Published: March 2021

The rising demand for spelt wheat (Triticum aestivum ssp. spelta) as a high-value grain crop has raised interest in its introduction into non-traditional spelt growing areas. This study aimed to assess adaptive constrains of spelt under short Mediterranean season. At first screening of a wide spelt collection for phenology and allelic distribution at the photoperiod (PPD) and vernalization (VRN) loci was done. In addition an in-depth phenotypic evaluation of a selected panel (n = 20) was performed, including agronomically important traits and concentration of grain mineral (GMC) and grain protein (GPC) content. Results from both wide screening and in-depth in panel (group of 18 spelt lines and two bread wheat lines) evaluation shows that the major adaptive constraint for spelt under Mediterranean conditions is late heading, caused by day length sensitivity, as evident from phenology and allelic profile (PPD and VRN). All lines carrying the photoperiod-sensitive allele (PPD-D1b) were late flowering (> 120DH). Based on the panel field evaluations those consequently suffer from low grain yield and poor agronomic performances. As for minerals, GMC for all but Zn, significantly correlated with GPC. In general, GMC negatively correlated with yield which complicated the assessment of GMC per-se and challenge the claim for higher mineral content in spelt grains. The exceptions were, Fe and Zn, which did not correlate with yield. Spelt lines showing high Fe and Zn concentration in a high-yield background illustrate their potential for spelt wheat breeding. Improving spelt adaptation to Mediterranean environments could be mediated by introducing the insensitive-PPD-D1a allele to spelt wheat background. Following this breeding path spelt could better compete with bread wheat under short season with limited and fluctuating rain fall.
Gastrectomy for stage IV gastric cancer: a comparison of different treatment strategies from the SEER database
Authors: Desiderio Jacopo , Sagnotta Andrea , Terrenato Irene , Annibale Bruno , Trastulli Stefano , Tozzi Federico , D’Andrea Vito , Bracarda Sergio , Garofoli Eleonora , Fong Yuman , Woo Yanghee , Parisi Amilcare
Published: March 2021

In the West, more than one third of newly diagnosed subjects show metastatic disease in gastric cancer (mGC) with few care options available. Gastrectomy has recently become a subject of debate, with some evidence showing advantages in survival beyond the sole purpose of treatment tumor-related complications. We investigated the survival benefit of different strategies in mGC patients, focusing on the role and timing of gastrectomy. Data were extracted from the SEER database. Groups were determined according to whether patients received gastrectomy, chemotherapy, supportive care. Patients receiving a multimodality treatment were further divided according to timing of surgery, whether performed before (primary gastrectomy, PG) or after chemotherapy (secondary gastrectomy, SG). 16,596 patients were included. Median OS was significantly higher (p < 0.001) in the SG (15 months) than in the PG (13 months), gastrectomy alone (6 months), and chemotherapy (7 months) groups. In the multivariate analysis, SG showed better OS (HR = 0.22, 95%CI = 0.18–0.26, p < 0.001) than PG (HR = 0.25, 95%CI = 0.23–0.28, p < 0.001), gastrectomy (HR = 0.40, 95%CI = 0.36–0.44, p < 0.001), and chemotherapy (HR = 0.42, 95%CI = 0.4–0.44, p < 0.001). The survival benefits persisted even after the PSM analysis. This study shows survival advantages of gastrectomy as multimodality strategy after chemotherapy. In selected patients, SG can be proposed to improve the management of stage IV disease.
Left posterior temporal cortex is sensitive to syntax within conceptually matched Arabic expressions
Authors: Matar Suhail , Dirani Julien , Marantz Alec , Pylkkänen Liina
Published: March 2021

During language comprehension, the brain processes not only word meanings, but also the grammatical structure—the “syntax”—that strings words into phrases and sentences. Yet the neural basis of syntax remains contentious, partly due to the elusiveness of experimental designs that vary structure independently of meaning-related variables. Here, we exploit Arabic’s grammatical properties, which enable such a design. We collected magnetoencephalography (MEG) data while participants read the same noun-adjective expressions with zero, one, or two contiguously-written definite articles (e.g., ‘chair purple’; ‘the-chair purple’; ‘the-chair the-purple’), representing equivalent concepts, but with different levels of syntactic complexity (respectively, indefinite phrases: ‘a purple chair’; sentences: ‘The chair is purple.’; definite phrases: ‘the purple chair’). We expected regions processing syntax to respond differently to simple versus complex structures. Single-word controls (‘chair’/‘purple’) addressed definiteness-based accounts. In noun-adjective expressions, syntactic complexity only modulated activity in the left posterior temporal lobe (LPTL), ~ 300 ms after each word’s onset: indefinite phrases induced more MEG-measured positive activity. The effects disappeared in single-word tokens, ruling out non-syntactic interpretations. In contrast, left anterior temporal lobe (LATL) activation was driven by meaning. Overall, the results support models implicating the LPTL in structure building and the LATL in early stages of conceptual combination.
The impact of viremia on organ failure, biomarkers and mortality in a Swedish cohort of critically ill COVID-19 patients
Authors: Järhult Josef D. , Hultström Michael , Bergqvist Anders , Frithiof Robert , Lipcsey Miklos
Published: March 2021

The spread of virus via the blood stream has been suggested to contribute to extra-pulmonary organ failure in Coronavirus disease 2019 (COVID-19). We assessed SARS-CoV-2 RNAemia (RNAemia) and the association between RNAemia and inflammation, organ failure and mortality in critically ill COVID-19 patients. We included all patients with PCR verified COVID-19 and consent admitted to ICU. SARS-CoV-2 RNA copies above 1000/ml measured by PCR in plasma was defined as RNAemia and used as surrogate for viremia. In this cohort of 92 patients 59 (64%) were invasively ventilated. RNAemia was found in 31 patients (34%). Hypertension and corticosteroid treatment was more common in patients with RNAemia. Extra-pulmonary organ failure biomarkers and the extent of organ failure were similar in patients with and without RNAemia, but the former group had more renal replacement therapy and higher mortality (26 vs 16%; 35 vs 16%, respectively, p = 0.04). RNAemia was not an independent predictor of death at 30 days after adjustment for age. SARS-CoV2 RNA copies in plasma is a common finding in ICU patients with COVID-19. Although viremia was not associated with extra pulmonary organ failure it was more common in patients who did not survive to 30 days after ICU admission.

Trial registration: ClinicalTrials NCT04316884.
Comparison of three different types of exercises for selective contractions of supra- and infrahyoid muscles
Authors: Chang Min Cheol , Park Sungwon , Cho Joo Young , Lee Byung Joo , Hwang Jong-Moon , Kim KwanMyung , Park Donghwi
Published: March 2021

Several exercise methods, such as the Shaker exercise, tongue press exercise, chin tuck against resistance (CTAR) exercise, and submandibular push exercise, have been introduced to strengthen the muscles involved in swallowing. In this study, we compared the effectiveness of the CTAR, submandibular push, and Shaker exercises for the induction of selective supra- and infrahyoid muscle contractions using surface electromyography (EMG). This study is a prospective non-randomized controlled study. Twenty-five healthy subjects and 20 patients experiencing swallowing difficulty were enrolled. During the three different types of exercises, the root mean square (RMS) values of the sternocleidomastoid (SCM), suprahyoid (anterior belly of the digastric and mylohyoid muscles), and infrahyoid (sternothyroid and thyrohyoid muscles) muscles were analyzed using surface EMG. Differences in the activity of swallowing muscles among the three different exercises were analyzed using one-way repeated measured analysis of variance. In terms of both the maximum and mean RMS values of the suprahyoid muscle, the submandibular push exercise showed a larger RMS value than the CTAR and Shaker exercises in healthy subjects (p < 0.05). In terms of both the maximum and mean RMS values of the suprahyoid muscle, the Shaker exercise and submandibular push exercise showed a larger RMS value than the CTAR exercise in patients with swallowing difficulty (p < 0.05). The submandibular push exercise may be effective as a swallowing muscle exercise owing to its superiority in inducing selective contractions of the supra- and infrahyoid muscles. The CTAR and Shaker exercises are also effective in this regard.
Statistics of seismicity to investigate the Campi Flegrei caldera unrest
Authors: Tramelli A. , Godano C. , Ricciolino P. , Giudicepietro F. , Caliro S. , Orazi M. , De Martino P. , Chiodini G.
Published: March 2021

The knowledge of the dynamic of the Campi Flegrei calderic system is a primary goal to mitigate the volcanic risk in one of the most densely populated volcanic areas in the world. From 1950 to 1990 Campi Flegrei suffered three bradyseismic crises with a total uplift of 4.3 m. After 20 years of subsidence, the uplift started again in 2005 accompained by a low increment of the seismicity rate. In 2012 an increment in the seismic energy release and a variation in the gas composition of the fumaroles of Solfatara (in the central area of the caldera) were recorded. Since then, a slow and progressive increase in phenomena continued until today. We analyze the INGV - Osservatorio Vesuviano seismic catalogue of Campi Flegrei from 2000 to 2020 in order to look for any variation in the seismic parameters and compare them with geochemical monitored ones. A remarkable correlation between independent variables of earthquake cumulative number, CO/CO2 values and vertical ground deformation reveals a likely common origin. Moreover the correlation between all the variables here analysed enlightens that the same origin can cause the temporal behavior of all these variables. We interpret the seismological, geochemical and geodetic observable in terms of the injection of magmatic fluids into the hydrothermal system or its pressurization.
Near-surface real-time seismic imaging using parsimonious interferometry
Authors: Hanafy Sherif M. , Hoteit Hussein , Li Jing , Schuster Gerard T.
Published: March 2021

Results are presented for real-time seismic imaging of subsurface fluid flow by parsimonious refraction and surface-wave interferometry. Each subsurface velocity image inverted from time-lapse seismic data only requires several minutes of recording time, which is less than the time-scale of the fluid-induced changes in the rock properties. In this sense this is real-time imaging. The images are P-velocity tomograms inverted from the first-arrival times and the S-velocity tomograms inverted from dispersion curves. Compared to conventional seismic imaging, parsimonious interferometry reduces the recording time and increases the temporal resolution of time-lapse seismic images by more than an order-of-magnitude. In our seismic experiment, we recorded 90 sparse data sets over 4.5 h while injecting 12-tons of water into a sand dune. Results show that the percolation of water is mostly along layered boundaries down to a depth of a few meters, which is consistent with our 3D computational fluid flow simulations and laboratory experiments. The significance of parsimonious interferometry is that it provides more than an order-of-magnitude increase of temporal resolution in time-lapse seismic imaging. We believe that real-time seismic imaging will have important applications for non-destructive characterization in environmental, biomedical, and subsurface imaging.
Underrated primary biogenic origin and lifetime of atmospheric formic and acetic acid
Authors: Lee Xinqing , Huang Daikuan , Liu Qi , Liu Xueyan , Zhou Hui , Wang Qian , Ma Yuena
Published: March 2021

Formic and acetic acids are ubiquitous in the troposphere, playing an important role in the atmospheric chemistry. Recent model studies ended up with substantial low bias on their tropospheric budgets presumably due to a large missing biogenic source derived most likely from photochemical oxidation of long-lived volatile organic compound(s), i.e., a secondary biogenic emission. Here, by studying the stable carbon isotope composition of formic and acetic acid in couple in the troposphere and relevant sources, we find the gap relates to primary biogenic emission and atmospheric lifetime of the acids. We show the primary biogenic emission is only second to the secondary biogenic emission as a strong source. Marine emission is the least one yet present in all the tropospheric environments except some local air. Long-distance transport of this origin indicates the lifetime over 5 days for both acids. Our results indicate that recent simulations underrated both primary biogenic emission and the lifetime. These underestimations would inevitably bias low the modeled results, especially in the low and free troposphere where primary biogenic emission and lifetime has the most pronounced influence, respectively.
Discovery of novel antituberculosis agents among 3-phenyl-5-(1-phenyl-1H-[1,2,3]triazol-4-yl)-[1,2,4]oxadiazole derivatives targeting aminoacyl-tRNA synthetases
Authors: Rybak Mariia Yu. , Balanda Anatoliy O. , Yatsyshyna Anna P. , Kotey Igor. M. , Starosyla Sergiy A. , Bdzhola Volodymyr G. , Lukash Lubov L. , Yarmoluk Sergiy M. , Tukalo Michael A. , Volynets Galyna P.
Published: March 2021

Antibiotic resistance is a major problem of tuberculosis treatment. This provides the stimulus for the search of novel molecular targets and approaches to reduce or forestall resistance emergence inMycobacterium tuberculosis. Earlier, we discovered a novel small-molecular inhibitor among 3-phenyl-5-(1-phenyl-1H-[1,2,3]triazol-4-yl)-[1,2,4]oxadiazoles targeting simultaneously two enzymes—mycobacterial leucyl-tRNA synthetase (LeuRS) and methionyl-tRNA synthetase (MetRS), which are promising molecular targets for antibiotic development. Unfortunately, the identified inhibitor does not reveal antibacterial activity towardM. tuberculosis. This study aims to develop novel aminoacyl-tRNA synthetase inhibitors among this chemical class with antibacterial activity toward resistant strains ofM. tuberculosis. We performed molecular docking of the library of 3-phenyl-5-(1-phenyl-1H-[1,2,3]triazol-4-yl)-[1,2,4]oxadiazole derivatives and selected 41 compounds for investigation of their inhibitory activity toward MetRS and LeuRS in aminoacylation assay and antibacterial activity towardM. tuberculosisstrains using microdilution assay. In vitro screening resulted in 10 compounds active against MetRS and 3 compounds active against LeuRS. Structure-related relationships (SAR) were established. The antibacterial screening revealed 4 compounds active towardM. tuberculosismono-resistant strains in the range of concentrations 2–20 mg/L. Among these compounds, only one compound27has significant enzyme inhibitory activity toward mycobacterial MetRS (IC50 = 148.5 µM). The MIC for this compound towardM. tuberculosisH37Rv strain is 12.5 µM. This compound is not cytotoxic to human HEK293 and HepG2 cell lines. Therefore, 3-phenyl-5-(1-phenyl-1H-[1,2,3]triazol-4-yl)-[1,2,4]oxadiazole derivatives can be used for further chemical optimization and biological research to find non-toxic antituberculosis agents with a novel mechanism of action.
New insights into the molecular mechanism behind mannitol and erythritol fructosylation by β-fructofuranosidase from Schwanniomyces occidentalis
Authors: Rodrigo-Frutos David , Jiménez-Ortega Elena , Piedrabuena David , Ramírez-Escudero Mercedes , Míguez Noa , Plou Francisco J. , Sanz-Aparicio Julia , Fernández-Lobato María
Published: March 2021

The β-fructofuranosidase from Schwanniomyces occidentalis (Ffase) is a useful biotechnological tool for the fructosylation of different acceptors to produce fructooligosaccharides (FOS) and fructo-conjugates. In this work, the structural determinants of Ffase involved in the transfructosylating reaction of the alditols mannitol and erythritol have been studied in detail. Complexes with fructosyl-erythritol or sucrose were analyzed by crystallography and the effect of mutational changes in positions Gln-176, Gln-228, and Asn-254 studied to explore their role in modulating this biocatalytic process. Interestingly, N254T variant enhanced the wild-type protein production of fructosyl-erythritol and FOS by $$\sim$$
∼
30% and 48%, respectively. Moreover, it produced neokestose, which represented $$\sim$$
∼
27% of total FOS, and yielded 31.8 g l−1 blastose by using glucose as exclusive fructosyl-acceptor. Noteworthy, N254D and Q176E replacements turned the specificity of Ffase transferase activity towards the synthesis of the fructosylated polyols at the expense of FOS production, but without increasing the total reaction efficiency. The results presented here highlight the relevance of the pair Gln-228/Asn-254 for Ffase donor-sucrose binding and opens new windows of opportunity for optimizing the generation of fructosyl-derivatives by this enzyme enhancing its biotechnological applicability.
Uncertainty about the risks associated with microplastics among lay and topic-experienced respondents
Authors: Thiele Christina J. , Hudson Malcolm D.
Published: March 2021

Microplastics are contaminants of emerging concern but there is currently a lack of evidence on actual risks relating to them, despite claims in media and scientific articles. Research on people’s perceptions on microplastics is in its infancy. Here we present part of a larger survey about people’s perceptions of issues with microplastics. Our analysis of 1681 responses across the globe to an online questionnaire demonstrates a certain level of uncertainty, not only in lay people but also respondents who study/work on the topic of plastics and microplastics as a pollutant. This uncertainty ranges from level of concern about microplastics as an environmental issue to existing evidence for effects. Further, there is some discrepancy between risk perception and state of the research. Some of this may be driven by scientific work with some serious limitations in reporting and methods. This highlights the need for fact-checking of circulating information about microplastics, but also for addressing the discordance between ecotoxicological risk and how risk is framed within the scientific community.
Gate-controlled amplifiable ultraviolet AlGaN/GaN high-electron-mobility phototransistor
Authors: Baek Seung-Hye , Lee Gun-Woo , Cho Chu-Young , Lee Sung-Nam
Published: March 2021

Gate-controlled amplifiable ultraviolet phototransistors have been demonstrated using AlGaN/GaN high-electron-mobility transistors (HEMTs) with very thin AlGaN barriers. In the AlGaN/GaN HEMTs, the dark current between the source and drain increases with increasing thickness of the AlGaN barrier from 10 to 30 nm owing to the increase in piezoelectric polarization-induced two-dimensional electron gas (2-DEG). However, the photocurrent of the AlGaN/GaN HEMT decreases with increasing thickness of the AlGaN barrier under ultraviolet exposure conditions. It can be observed that a thicker AlGaN barrier exhibits a much higher 2-DEG than the photogenerated carriers at the interface between AlGaN and GaN. In addition, regardless of the AlGaN barrier thickness, the source–drain dark current increases as the gate bias increases from − 1.0 to + 1.0 V. However, the photocurrent of the phototransistor with the 30 nm thick AlGaN barrier was not affected by the gate bias, whereas that of the phototransistor with 10 nm thick AlGaN barrier was amplified from reduction of the gate bias. From these results, we suggest that by controlling the gate bias, a thin AlGaN barrier can amplify/attenuate the photocurrent of the AlGaN/GaN HEMT-based phototransistor.
Effects of low occlusal loading on the neuromuscular behavioral development of cortically-elicited jaw movements in growing rats
Authors: Aung Phyo Thura , Kato Chiho , Fujita Akiyo , Abe Yasunori , Ogawa Takuya , Ishidori Hideyuki , Okihara Hidemasa , Kokai Satoshi , Ono Takashi
Published: March 2021

The effect of altered occlusal force on masticatory-related neuromuscular control, which projects from the anterior part of the cortical masticatory area (A-CMA), during growth remains unclear. This study sought to evaluate the effect of occlusal hypofunction on neuromuscular development of jaw muscle activities and cortically-induced rhythmic jaw movements (RJMs) in growing rats. Sixty-four 2-week-old male albino Wistar rats were divided into the control (fed normal diet) and experimental (fed soft diet) groups soon after weaning. Electromyographic activity was recorded at 5, 7, 9, and 11 weeks from the right masseter and anterior digastric along with RJMs. We found a significantly longer onset latency and smaller peak-to-peak amplitude in the experimental group than that in the control group. The RJMs showed an increase in gape size and lateral excursion until up to 9 weeks in both groups. However, both the average gape size and lateral excursion were significantly smaller in the experimental group than that in the control group after 9 weeks. The jaw movement pattern also showed a significant decrease at the maximum opening period in the experimental group. Our findings indicate that inadequate occlusal function during growth alters neuromuscular control of masticatory behaviors and impairs the pattern of RJMs.
The effectiveness of Rutin for prevention of surgical induced endometriosis development in a rat model
Authors: Talebi Hatef , Farahpour Mohammad Reza , Hamishehkar Hamed
Published: March 2021

Apoptosis and antioxidant mechanisms are pathways for the treatment of endometriosis (Endo). Rutin (Rtn) is an antioxidant flavonol that induces apoptosis. This study, for first time, was conducted to evaluate the effects of rutin on Endo through apoptosis and antioxidant mechanisms. The experimental Endo was induced in 24 rats and then the animals were subdivided into Endo-sole, 3000 and 6000 µg/kg rutin (Rtn-3000 and Rtn-6000) and vitamin C groups. After 4 weeks, the expression of Bcl2, Bax, anti Pro Caspase-9, cleaved Caspase-9, pro PARP, pro Cleaved PARP, Pro PARP, pro mTOR and mTOR were assessed by western blotting technique. The protein concentrations of malondialdehyde (MDA), total antioxidant capacity, and super oxide dismutase and gutathione peroxidase were also evaluated. TUNEL staining was also used for the detection of apoptosis. Caspase-9 and concentration of antioxidants were higher in the treated groups compared to Endo-sole group (P < 0.05). The results also showed that rutin decreased the expression of Bcl2 and MDA concentration (P < 0.05). The results for TUNEL staining showed that the animals treated with Rtn-6000 and vitamin C showed higher apoptosis. Rutin induces apoptosis by the expression of Bcl-2, Bax and caspase and also antioxidant activity by increasing antioxidants concentrations.
Hoxd13/Bmp2-mediated mechanism involved in zebrafish finfold design
Authors: Castro João , Beviano Vanessa , Paço Ana , Leitão-Castro Joana , Cadete Francisco , Francisco Miguel , Freitas Renata
Published: March 2021

The overexpression of hoxd13a during zebrafish fin development causes distal endochondral expansion and simultaneous reduction of the finfold, mimicking the major events thought to have happened during the fin-to-limb transition in Vertebrates. We investigated the effect of hoxd13a overexpression on putative downstream targets and found it to cause downregulation of proximal fin identity markers (meis1 and emx2) and upregulation of genes involved in skeletogenesis/patterning (fbn1, dacha) and AER/Finfold maintenance (bmps). We then show that bmp2b overexpression leads to finfold reduction, recapitulating the phenotype observed in hoxd13a-overexpressing fins. In addition, we show that during the development of the long finfold in leot1/lofdt1 mutants, hoxd13a and bmp2b are downregulated. Our results suggest that modulation of the transcription factor Hoxd13 during evolution may have been involved in finfold reduction through regulation of the Bmp signalling that then activated apoptotic mechanisms impairing finfold elongation.
Contracting eastern African C4 grasslands during the extinction of Paranthropus boisei
Authors: Quinn Rhonda L. , Lepre Christopher J.
Published: March 2021

The extinction of the Paranthropus boisei estimated to just before 1 Ma occurred when C4 grasslands dominated landscapes of the Eastern African Rift System (EARS). P. boisei has been characterized as an herbivorous C4 specialist, and paradoxically, its demise coincided with habitats favorable to its dietary ecology. Here we report new pedogenic carbonate stable carbon (δ13CPC) and oxygen (δ18OPC) values (nodules = 53, analyses = 95) from an under-sampled interval (1.4–0.7 Ma) in the Turkana Basin (Kenya), one of the most fossiliferous locales of P. boisei. We combined our new results with published δ13CPC values from the EARS dated to 3–0 Ma, conducted time-series analysis of woody cover (ƒWC), and compared the EARS ƒWC trends to regional and global paleo-environmental and -climatic datasets. Our results demonstrate that the long-term rise of C4 grasslands was punctuated by a transient but significant increase in C3 vegetation and warmer temperatures, coincident with the Mid-Pleistocene Transition (1.3–0.7 Ma) and implicating a short-term rise in pCO2. The contraction of C4 grasslands escalated dietary competition amongst the abundant C4-feeders, likely influencing P. boisei’s demise.
In oxygen-deprived tumor cells ERp57 provides radioprotection and ensures proliferation via c-Myc, PLK1 and the AKT pathway
Authors: Ocklenburg Tobias , Neumann Fabian , Wolf Alexandra , Vogel Julia , Göpelt Kirsten , Baumann Melanie , Baumann Jennifer , Kranz Philip , Metzen Eric , Brockmeier Ulf
Published: March 2021

The disulfide isomerase ERp57, originally found in the endoplasmic reticulum, is located in multiple cellular compartments, participates in diverse cell functions and interacts with a huge network of binding partners. It was recently suggested as an attractive new target for cancer therapy due to its critical role in tumor cell proliferation. Since a major bottleneck in cancer treatment is the occurrence of hypoxic areas in solid tumors, the role of ERp57 in cell growth was tested under oxygen depletion in the colorectal cancer cell line HCT116. We observed a severe growth inhibition when ERp57 was knocked down in hypoxia (1% O2) as a consequence of downregulated c-Myc, PLK1, PDPK1 (PDK1) and AKT (PKB). Further, irradiation experiments revealed also a radiosensitizing effect of ERp57 depletion under oxygen deprivation. Compared to ERp57, we do not favour PDPK1 as a suitable pharmaceutical target as its efficient knockdown/chemical inhibition did not show an inhibitory effect on proliferation.