bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional maintenance of calcium store by ShcB adaptor protein in cerebellar Purkinje cells
Authors: Kakizawa Sho , Kishimoto Yasushi , Yamamoto Shinichiro , Onga Kazuko , Yasuda Kunihiko , Miyamoto Yoshiaki , Watanabe Masahiko , Sakai Ryuichi , Mori Nozomu 
Published: September 2020

AbstractIntracellular Ca2+ levels are changed by influx from extracellular medium and release from intracellular stores. In the central nervous systems, Ca2+ release is involved in various physiological events, such as neuronal excitability and transmitter release. Although stable Ca2+ release in response to stimulus is critical for proper functions of the nervous systems, regulatory mechanisms relating to Ca2+ release are not fully understood in central neurons. Here, we demonstrate that ShcB, an adaptor protein expressed in central neurons, has an essential role in functional maintenance of Ca2+ store in cerebellar Purkinje cells (PCs). ShcB-knockout (KO) mice showed defects in cerebellar-dependent motor function and long-term depression (LTD) at cerebellar synapse. The reduced LTD was accompanied with an impairment of intracellular Ca2+ release. Although the expression of Ca2+ release channels and morphology of Ca2+ store looked intact, content of intracellular Ca2+ store and activity of sarco/endoplasmic reticular Ca2+-ATPase (SERCA) were largely decreased in the ShcB-deficient cerebellum. Furthermore, when ShcB was ectopically expressed in the ShcB-KO PCs, the Ca2+ release and its SERCA-dependent component were restored. These data indicate that ShcB plays a key role in the functional maintenance of ER Ca2+ store in central neurons through regulation of SERCA activity.
Canagliflozin attenuates isoprenaline-induced cardiac oxidative stress by stimulating multiple antioxidant and anti-inflammatory signaling pathways
Authors: Hasan Raquibul , Lasker Shoumen , Hasan Ahasanul , Zerin Farzana , Zamila Mushfera , Chowdhury Faizul Islam , Nayan Shariful Islam , Rahman Md. Mizanur , Khan Ferdous , Subhan Nusrat , Alam Md. Ashraful 
Published: September 2020

AbstractThe antidiabetic drug canagliflozin is reported to possess several cardioprotective effects. However, no studies have investigated protective effects of canagliflozin in isoprenaline (ISO)-induced cardiac oxidative damage—a model mimicking sympathetic nervous system (SNS) overstimulation-evoked cardiac injuries in humans. Therefore, we investigated protective effects of canagliflozin in ISO-induced cardiac oxidative stress, and their underlying molecular mechanisms in Long-Evans rat heart and in HL-1 cardiomyocyte cell line. Our data showed that ISO administration inflicts pro-oxidative changes in heart by stimulating production of reactive oxygen species (ROS) and reactive nitrogen species (RNS). In contrast, canagliflozin treatment in ISO rats not only preserves endogenous antioxidants but also reduces cardiac oxidative stress markers, fibrosis and apoptosis. Our Western blotting and messenger RNA expression data demonstrated that canagliflozin augments antioxidant and anti-inflammatory signaling involving AMP-activated protein kinase (AMPK), Akt, endothelial nitric oxide synthase (eNOS), nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). In addition, canagliflozin treatment attenuates pro-oxidative, pro-inflammatory and pro-apoptotic signaling mediated by inducible nitric oxide synthase (iNOS), transforming growth factor beta (TGF-β), NADPH oxidase isoform 4 (Nox4), caspase-3 and Bax. Consistently, canagliflozin treatment improves heart function marker in ISO-treated rats. In summary, we demonstrated that canagliflozin produces cardioprotective actions by promoting multiple antioxidant and anti-inflammatory signaling.
Diffusible GRAPHIC to visualize morphology of cells after specific cell–cell contact
Authors: Kinoshita Nagatoki , Huang Arthur J. Y. , McHugh Thomas J. , Miyawaki Atsushi , Shimogori Tomomi 
Published: September 2020

AbstractThe ability to identify specific cell–cell contact in the highly heterogeneous mammalian body is crucial to revealing precise control of the body plan and correct function. To visualize local connections, we previously developed a genetically encoded fluorescent indicator, GRAPHIC, which labels cell–cell contacts by restricting the reconstituted green fluorescent protein (GFP) signal to the contact site. Here, we modify GRAPHIC to give the reconstituted GFP motility within the membrane, to detect cells that make contact with other specific cells. Removal of leucine zipper domains, located between the split GFP fragment and glycophosphatidylinositol anchor domain, allowed GFP reconstituted at the contact site to diffuse throughout the entire plasma membrane, revealing cell morphology. Further, depending on the structural spacers employed, the reconstituted GFP could be selectively targeted to N terminal (NT)- or C terminal (CT)-probe-expressing cells. Using these novel constructs, we demonstrated that we can specifically label NT-probe-expressing cells that made contact with CT-probe-expressing cells in an epithelial cell culture and in Xenopus 8-cell-stage blastomeres. Moreover, we showed that diffusible GRAPHIC (dGRAPHIC) can be used in neuronal circuits to trace neurons that make contact to reveal a connection map. Finally, application in the developing brain demonstrated that the dGRAPHIC signal remained on neurons that had transient contacts during circuit development to reveal the contact history. Altogether, dGRAPHIC is a unique probe that can visualize cells that made specific cell–cell contact.
Four meta-analyses across 164 studies on atypical footedness prevalence and its relation to handedness
Authors: Packheiser Julian , Schmitz Judith , Berretz Gesa , Carey David P. , Paracchini Silvia , Papadatou-Pastou Marietta , Ocklenburg Sebastian 
Published: September 2020

AbstractHuman lateral preferences, such as handedness and footedness, have interested researchers for decades due to their pronounced asymmetries at the population level. While there are good estimates on the prevalence of handedness in the population, there is no large-scale estimation on the prevalence of footedness. Furthermore, the relationship between footedness and handedness still remains elusive. Here, we conducted meta-analyses with four different classification systems for footedness on 145,135 individuals across 164 studies including new data from the ALSPAC cohort. The study aimed to determine a reliable point estimate of footedness, to study the association between footedness and handedness, and to investigate moderating factors influencing footedness. We showed that the prevalence of atypical footedness ranges between 12.10% using the most conservative criterion of left-footedness to 23.7% including all left- and mixed-footers as a single non-right category. As many as 60.1% of left-handers were left-footed whereas only 3.2% of right-handers were left-footed. Males were 4.1% more often non-right-footed compared to females. Individuals with psychiatric and neurodevelopmental disorders exhibited a higher prevalence of non-right-footedness. Furthermore, the presence of mixed-footedness was higher in children compared to adults and left-footedness was increased in athletes compared to the general population. Finally, we showed that footedness is only marginally influenced by cultural and social factors, which play a crucial role in the determination of handedness. Overall, this study provides new and useful reference data for laterality research. Furthermore, the data suggest that footedness is a valuable phenotype for the study of lateral motor biases, its underlying genetics and neurodevelopment.
The short isoform of extended synaptotagmin-2 controls Ca2+ dynamics in T cells via interaction with STIM1
Authors: Woo Jin Seok , Sun Zuoming , Srikanth Sonal , Gwack Yousang 
Published: September 2020

AbstractCa2+ release-activated Ca2+ (CRAC) channels elevate cytoplasmic Ca2+ concentration, which is essential for T cell activation, differentiation and effector functions. T cell receptor stimulation induces depletion of the endoplasmic reticulum (ER) Ca2+ stores, which is sensed by stromal interaction molecule 1 (STIM1). STIM1 translocates to the ER-plasma membrane (PM) junctions to interact with ORAI1, the pore subunit of the CRAC channels. Here, we show that two members of the extended synaptotagmin (E-Syt) family, E-Syt1, and the short isoform of E-Syt2 (E-Syt2S), contribute to activation of CRAC channels in T cells. Knockdown or deletion of both ESYT1 and ESYT2 reduced store-operated Ca2+ entry (SOCE) and ORAI1-STIM1 clustering in Jurkat T cells. Further, depletion of E-Syts in primary T cells decreased Ca2+ entry and cytokine production. While the ER-PM junctions were reduced in both HeLa and Jurkat T cells deleted for ESYT1 and ESYT2, SOCE was impaired only in Jurkat T cells, suggesting that the membrane-tethering function of E-Syts is distinct from their role in SOCE. Mechanistically, E-Syt2S, the predominant isoform of E-Syt2 in T cells, recruited STIM1 to the junctions via a direct interaction. This study demonstrates a membrane-tethering-independent role of E-Syts in activation of CRAC channels in T cells.
Blood collection technique, anticoagulants and storing temperature have minor effects on the isolation of polymorphonuclear neutrophils
Authors: Krabbe Julia , Beilmann Viktor , Alamzad-Krabbe Hanif , Böll Svenja , Seifert Anke , Ruske Nadine , Kraus Thomas , Martin Christian 
Published: September 2020

AbstractIn the isolation of polymorphonuclear neutrophils (PMNs) the technique and other external factors can have great influence on the quality and quantity of isolated neutrophils. To elucidate the influence of the blood collection technique, anticoagulants and storing temperature on isolated PMNs healthy volunteers provided blood samples with different needles and collection techniques, anticoagulants (EDTA, heparin, citrate) and storing temperatures (4, 22, 37 °C). From each blood sample PMNs were isolated and compared regarding number of PMNs and oxidative burst. The blood collection technique, anticoagulants and storing temperature had minor impact on isolated PMNs. All three tested cannulas and anticoagulants can be used to obtain blood samples for PMN isolation. For storing temperatures 37 °C should be preferred. Regarding time between the PMN isolation and the actual experiments, a time span of maximum 1 h should be targeted.
Inhibition of non-homologous end joining of gamma ray-induced DNA double-strand breaks by cAMP signaling in lung cancer cells
Authors: Noh Sung-Eun , Juhnn Yong-Sung 
Published: September 2020

AbstractDNA double-strand breaks (DSB) are formed by various exogenous and endogenous factors and are repaired by homologous recombination and non-homologous end joining (NHEJ). DNA-dependent protein kinase (DNA-PK) is the principal enzyme for NHEJ. We explored the role and the underlying mechanism of cAMP signaling in the NHEJ repair of DSBs resulted from gamma ray irradiation to non-small cell lung cancer (NSLC) cells. Activated cAMP signaling by expression of an activated stimulatory GTP-binding protein or by pretreatment with isoproterenol and prostaglandin E2, delayed the repair of DSBs resulted from gamma ray irradiation, and the delaying effects depended on protein kinase A (PKA). Activated cAMP signaling suppressed XRCC4 and DNA ligase IV recruitment into DSB foci, and reduced phosphorylation at T2609 in DNA-PK catalytic subunit (DNA-PKcs) with a concomitant increase in phosphorylation at S2056 in PKA-dependent ways following gamma ray irradiation. cAMP signaling decreased phosphorylation of T2609 by protein phosphatase 2A-dependent inhibition of ATM. We conclude that cAMP signaling delays the repair of gamma ray-induced DNA DSBs in NSLC cells by inhibiting NHEJ via PKA-dependent pathways, and that cAMP signaling differentially modulates DNA-PKcs phosphorylation at S2056 and T2609, which might contribute to the inhibition of NHEJ in NSLC cells.
The Xpert MTB/RIF Ultra assay detects Mycobacterium tuberculosis complex DNA in white rhinoceros (Ceratotherium simum) and African elephants (Loxodonta africana)
Authors: Goosen Wynand J. , Kerr Tanya J. , Kleynhans Léanie , Warren Robin M. , van Helden Paul D. , Persing David H. , Parsons Sven D. C. , Buss Peter , Miller Michele A. 
Published: September 2020

AbstractThe study describes the novel use of the Xpert MTB/RIF Ultra assay for detection of Mycobacterium tuberculosis complex (MTBC) DNA in samples from white rhinoceros (Ceratotherium simum) and African elephants (Loxodonta africana). Culture negative respiratory sample matrices were spiked to determine if the Ultra could detect MTBC DNA in rhinoceros and elephant samples. Rhinoceros bronchial alveolar lavage fluid (BALF) was found to have an inhibitory effect on the Ultra. In this study, the limit of detection (LOD) of M. tuberculosis H37Rv in all spiked animal samples were 2 CFU/ml compared to 15.6 CFU/ml for humans, while the LOD for M. bovis SB0121 was 30 CFU/ml compared to 143.4 CFU/ml for M. bovis BCG in humans. Screening was performed on stored tissue and respiratory samples from known MTBC-infected animals and MTBC DNA was detected in 92% of samples collected from six rhinoceros and two elephants. Conversely, 83% of culture-negative tissue and respiratory samples from uninfected animals tested negative on the Ultra. In conclusion, the Ultra assay appears to be a sensitive and rapid diagnostic test for the detection of MTBC DNA from tissue and respiratory samples collected from African elephants and rhinoceros. Furthermore, the Ultra assay could provide a new tool for the detection of MTBC in various sample types from other wildlife species.
Optimal number of faces for fast self-folding kirigami
Authors: Melo H. P. M. , Dias C. S. , Araújo N. A. M. 
Published: September 2020

AbstractThere is an increasing body of research studying how to obtain 3D structures at the microscale from the spontaneous folding of planar templates, using thermal fluctuations as the driving force. Here, combining numerical simulations and analytical calculations, we show that the total folding time of a regular pyramid is a non-monotonic function of the number of faces (N), with a minimum for five faces. The motion of each face is consistent with a Brownian process and folding occurs through a sequence of irreversible binding events between faces. The first one is well-described by a first-passage process in 2D, with a characteristic time that decays with N. By contrast, the subsequent binding events are first-passage processes in 1D and the time of the last one grows logarithmically with N. It is the interplay between these two different sets of events that explains the non-monotonic behavior. Implications in the self-folding of more complex structures are discussed.
Development of ultrasonic waveguide sensor for liquid level measurement in loop system
Authors: Dhayalan R. , Saravanan S. , Manivannan S. , Purna Chandra Rao B. 
Published: September 2020

This Letter presents an ultrasonic waveguide sensor for measuring fluctuations in a liquid level using leaky longitudinal wave L(0,2) in a coolant loop system. A 20% cold‐worked D9 fuel pin clad tube of 1000 mm long, 6.6 mm outer diameter and 0.45 mm wall thickness was used as a waveguide on which the L(0,2) mode was transmitted/received along the axial direction at 500 kHz. When the waveguide got introduced into a coolant loop and partially immersed in a non‐viscous liquid (water/liquid sodium), the amplitude of L(0,2) mode got reduced due to leakage. The rate of leakage depends on the characteristics of the waveguide and the embedding liquid medium. By utilising this physical property of L(0,2) mode, it is possible to predict the variations in liquid level during dynamic conditions. Experimental measurements were carried out on a mock‐up test loop in which water was used as embedding liquid and two artificial notches were made on the waveguide at different depths were used as reference levels. The time‐amplitude signals were monitored and the reflected energies from the bottom end of the waveguide and the notches were used as the threshold and reference amplitudes respectively for identification of water level.
Design of a multilayer dual‐band balanced‐to‐balanced SIW filtering power divider
Authors: Liu Yijie , Zhang Gang , Zheng Jian , Li Yujie , Li Zeling , Li Mingjia , Wang Enrong 
Published: September 2020

A new compact multilayer dual‐band balanced‐to‐balanced filtering power divider (FPD) based on substrate integrated waveguide (SIW) resonator is proposed in this Letter. Originating from the field distributions of resonant modes in the square SIW cavity, TE201 ‐mode and TE203 ‐mode are utilised to achieve desired differential‐mode (DM) transmission and high common‐mode (CM) suppression. Meanwhile, dual DM passbands are generated by reasonably coupling two SIW resonators in the back‐to‐back form with the help of four coupling apertures etched on the middle‐layer ground. Besides, a pair of isolated resistors is loaded at back‐diagonal regions of the upper‐layer SIW resonator, achieving high port‐to‐port isolation. For demonstration, a prototype dual‐band balanced‐to‐balanced SIW FPD operating at 11.0 and 18.4 GHz is ultimately designed, fabricated and tested. Good agreement between simulated and measured results is obtained, verifying the feasibility and validity of the design concept.
Saliva versus Plasma Therapeutic Drug Monitoring of Gentamicin in Jordanian Preterm Infants. Development of a Physiologically-Based Pharmacokinetic (PBPK) Model and Validation of Class II Drugs of Salivary Excretion Classification System
Authors: Idkaidek Nasir , Hamadi Salim , Bani-Domi Rabab , Al-Adham Ibrahim , Alsmadi Motasem , Awaysheh Faten , Aqrabawi Hisham , Al-Ghazawi Ahmad , Rabayah Ayman 
Published: September 2020

AbstractGentamicin has proven to be a very successful treatment for bacterial infection, but it also can cause adverse effects, especially ototoxicity, which is irreversible. Therapeutic drug monitoring (TDM) in saliva is a more convenient non-invasive alternative compared to plasma. A physiologically-based pharmacokinetic (PBPK) model of gentamicin was built and validated using previously-published plasma and saliva data. The validated model was then used to predict experimentally-observed plasma and saliva gentamicin TDM data in Jordanian pediatric preterm infant patients measured using sensitive LCMS/MS method. A correlation was established between plasma and saliva exposures. The developed PBPK model predicted previously reported gentamicin levels in plasma, saliva and those observed in the current study. A good correlation was found between plasma and saliva exposures. The PBPK model predicted that gentamicin in saliva is 5–7 times that in plasma, which is in agreement with observed results. Saliva can be used as an alternative for TDM of gentamicin in preterm infant patients. Exposure to gentamicin in plasma and saliva can reliably be predicted using the developed PBPK model in patients.
Pharmacokinetics and Tissue Distribution of Loratadine, Desloratadine
and Their Active Metabolites in Rat based on a Newly Developed LC-MS/MS
Analytical Method
Authors: Zhang Yuxin , Lu Yihua , Wang Lijuan , Tian Yuan , Zhang Zunjian 
Published: September 2020

AbstractLoratadine (LOR) and its major metabolite, desloratadine (DL) are new-generation
antihistamines. The hydroxylated metabolites of them, 6-OH-DL, 5-OH-DL and
3-OH-DL are also active because of their ability to inhibit binding of
pyrilamine to brain H1 receptors and a tendency for distributing to
specific immune-regulatory tissues. In this study, a new validated
LC-MS/MS method to simultaneously quantify LOR, DL, 6-OH-DL, 5-OH-DL and
3-OH-DL in plasma and tissues was established and applied to an investigation of
their pharmacokinetics and target-tissue distribution tendency for the first
time. Pharmacokinetics parameters in rat were measured and the results suggest
that the body’s exposure to active metabolites were much higher than to
the prodrug with LOR, but much lower with DL. The tissue distribution study
shows that LOR, DL and their active metabolites were widely distributed in the
liver, spleen, thymus, heart, adrenal glands and pituitary gland. For
immune-regulatory tissues, the concentrations of LOR, DL and their active
metabolites in the spleen were much higher than in the thymus, which is related
to the spleen, one of the sites where immune responses occur. LOR and its
metabolites might inhibit immune-mediated allergic inflammation through the
hypothalamic-pituitary-adrenal (HPA) axis. It was also found that the
concentration of LOR in the heart was highest after liver and adrenal glands
while those of DL, 6-OH-DL and 5-OH-DL in the liver, adrenal glands and spleen
were all higher than those in the heart, which suggests that LOR may have a
greater tendency to distribute in the heart than its metabolites.
Halogen–Lithium Exchange of Sensitive (Hetero)aromatic Halides under Barbier Conditions in a Continuous Flow Set-Up
Authors: Weidmann Niels , Nishimura Rodolfo H. V. , Knochel Paul , Harenberg Johannes H. 
Published: September 2020

AbstractA halogen–lithium exchange reaction of (hetero)aromatic halides performed in the presence of various electrophiles such as aldehydes, ketones, Weinreb amides, and imines using BuLi as exchange reagent and a commercially available flow set-up is reported. The organolithiums generated in situ were instantaneously trapped with various electrophiles (Barbier conditions) resulting in the formation of polyfunctional (hetero)arenes. This method enables the functionalization of (hetero)arenes containing highly sensitive functional groups such as esters­, which are not tolerated in batch conditions.
An Improved Synthesis of 3,6-Dihydro-as-indacene
Authors: Preite Marcelo , Molins Elies , Chávez Ivonne , Amshumali Mungalimane K. , Morales-Verdejo Cesar , Dibdalli Yuvaraja , Faúndez Rodrigo , Manriquez Juan M. 
Published: September 2020

AbstractThis contribution describes an updated synthetic route to 3,6-dihydro-as-indacene along with full characterization of all inter­mediates. The title compound is prepared by Mannich condensation of 2-methylfuran with formaldehyde and dimethylamine hydrochloride, quaternization of the resulting amine with methyl iodide, and conversion into the ammonium hydroxide salt by treatment with silver oxide in water. Subsequent Hoffmann elimination and [6,6]-cycloaddition through pyrolysis produces a furanocyclophane, which after photooxidation, intramolecular cycloaddition, and dehydration with sodium carbonate affords 2,3,6,7-tetrahydro-1,8-dione-as-indacene. Reduction of this diketone gives a mixture of alcohols, which after dehydration under slightly basic or acidic conditions produces 3,6-dihydro-as-indacene. The structure is confirmed by X-ray diffraction, and all intermediates are characterized by means of 1H and 13C NMR spectroscopy.