bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metalloproteinase 1 downregulation in neurofibromatosis 1: Therapeutic potential of antimalarial hydroxychloroquine and chloroquine
Authors: Tsuji Gaku , Takai-Yumine Ayako , Kato Takahiro , Furue Masutaka 
Published: May 2021

AbstractNeurofibromatosis type 1 is an autosomal dominant genetic disorder caused by mutation in the neurofibromin 1 (NF1) gene. Its hallmarks are cutaneous findings including neurofibromas, benign peripheral nerve sheath tumors. We analyzed the collagen and matrix metalloproteinase 1 (MMP1) expression in Neurofibromatosis 1 cutaneous neurofibroma and found excessive expression of collagen and reduced expression of MMP1. To identify new therapeutic drugs for neurofibroma, we analyzed phosphorylation of components of the Ras pathway, which underlies NF1 regulation, and applied treatments to block this pathway (PD184352, U0126, and rapamycin) and lysosomal processes (chloroquine (CQ), hydroxychloroquine (HCQ), and bafilomycin A (BafA)) in cultured Neurofibromatosis 1 fibroblasts. We found that downregulation of the MMP1 protein was a key abnormal feature in the neurofibromatosis 1 fibroblasts and that the decreased MMP1 was restored by the lysosomal blockers CQ and HCQ, but not by the blockers of the Ras pathway. Moreover, the MMP1-upregulating activity of those lysosomal blockers was dependent on aryl hydrocarbon receptor (AHR) activation and ERK phosphorylation. Our findings suggest that lysosomal blockers are potential candidates for the treatment of Neurofibromatosis 1 neurofibroma.
Copolymers incorporated with β-substituted acrylate synthesized by organo-catalyzed group-transfer polymerization
Authors: Imada Motosuke , Takenaka Yasumasa , Tsuge Takeharu , Abe Hideki 
Published: May 2021

AbstractVarious copolymers incorporated with β-substituted acrylates, such as alkyl crotonates (e.g., methyl crotonate (MC), ethyl crotonate (EC), isopropyl crotonate (iPC), and n-butyl crotonate (nBC)) and methyl cinnamate (MCin), were synthesized by group-transfer polymerization (GTP) using a silicon-based Lewis acid catalyst. In addition to β-substituted acrylates, α-substituted acrylates (e.g., methyl methacrylate (MMA) and n-butyl methacrylate (nBMA)) were examined as comonomers. Proton nuclear magnetic resonance (1H NMR) spectroscopy and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) characterizations of the obtained copolymers revealed that each monomer component was incorporated sufficiently. The thermal stabilities of the resulting copolymers were investigated by dynamic mechanical analysis (DMA), indicating that the glass-transition temperature (Tg) of the copolymers can be widely varied over a relatively high-temperature range by selecting the optimal comonomer. More specifically, the Tg values of poly(MC-random-EC) (MC/EC molar ratio = 50/50), poly(MC-random-nBC) (MC/nBC molar ratio = 50/50), poly(MC-random-MCin) (MC/MCin molar ratio = 54/46), and poly(nBC-random-MCin) (nBC/MCin molar ratio = 56/44) were 173, 130, 216, and 167 °C, respectively.
Analysis of diverse eukaryotes suggests the existence of an ancestral mitochondrial apparatus derived from the bacterial type II secretion system
Authors: Horváthová Lenka , Žárský Vojtěch , Pánek Tomáš , Derelle Romain , Pyrih Jan , Motyčková Alžběta , Klápšťová Veronika , Vinopalová Martina , Marková Lenka , Voleman Luboš , Klimeš Vladimír , Petrů Markéta , Vaitová Zuzana , Čepička Ivan , Hryzáková Klára , Harant Karel , Gray Michael W. , Chami Mohamed , Guilvout Ingrid , Francetic Olivera , Franz Lang B. , Vlček Čestmír , Tsaousis Anastasios D. , Eliáš Marek , Doležal Pavel 
Published: May 2021

AbstractThe type 2 secretion system (T2SS) is present in some Gram-negative eubacteria and used to secrete proteins across the outer membrane. Here we report that certain representative heteroloboseans, jakobids, malawimonads and hemimastigotes unexpectedly possess homologues of core T2SS components. We show that at least some of them are present in mitochondria, and their behaviour in biochemical assays is consistent with the presence of a mitochondrial T2SS-derived system (miT2SS). We additionally identified 23 protein families co-occurring with miT2SS in eukaryotes. Seven of these proteins could be directly linked to the core miT2SS by functional data and/or sequence features, whereas others may represent different parts of a broader functional pathway, possibly also involving the peroxisome. Its distribution in eukaryotes and phylogenetic evidence together indicate that the miT2SS-centred pathway is an ancestral eukaryotic trait. Our findings thus have direct implications for the functional properties of the early mitochondrion.
Cross-reactive serum and memory B-cell responses to spike protein in SARS-CoV-2 and endemic coronavirus infection
Authors: Song Ge , He Wan-ting , Callaghan Sean , Anzanello Fabio , Huang Deli , Ricketts James , Torres Jonathan L. , Beutler Nathan , Peng Linghang , Vargas Sirena , Cassell Jon , Parren Mara , Yang Linlin , Ignacio Caroline , Smith Davey M. , Voss James E. , Nemazee David , Ward Andrew B. , Rogers Thomas , Burton Dennis R. , Andrabi Raiees 
Published: May 2021

AbstractPre-existing immunity to seasonal endemic coronaviruses could have profound consequences for antibody responses to SARS-CoV-2, induced from natural infection or vaccination. A first step to establish whether pre-existing responses can impact SARS-CoV-2 infection is to understand the nature and extent of cross-reactivity in humans to coronaviruses. Here we compare serum antibody and memory B cell responses to coronavirus spike proteins from pre-pandemic and SARS-CoV-2 convalescent donors using binding and functional assays. We show weak evidence of pre-existing SARS-CoV-2 cross-reactive serum antibodies in pre-pandemic donors. However, we find evidence of pre-existing cross-reactive memory B cells that are activated during SARS-CoV-2 infection. Monoclonal antibodies show varying degrees of cross-reactivity with betacoronaviruses, including SARS-CoV-1 and endemic coronaviruses. We identify one cross-reactive neutralizing antibody specific to the S2 subunit of the S protein. Our results suggest that pre-existing immunity to endemic coronaviruses should be considered in evaluating antibody responses to SARS-CoV-2.
Sensing of joint and spinal bending or stretching via a retractable and wearable badge reel
Authors: Li Chengyu , Liu Di , Xu Chaoqun , Wang Ziming , Shu Sheng , Sun Zhuoran , Tang Wei , Wang Zhong Lin 
Published: May 2021

AbstractHuman motions, such as joint/spinal bending or stretching, often contain information that is useful for orthopedic/neural disease diagnosis, rehabilitation, and prevention. Here, we show a badge-reel-like stretch sensing device with a grating-structured triboelectric nanogenerator exhibiting a stretching sensitivity of 8 V mm−1, a minimum resolution of 0.6 mm, a low hysteresis, and a high durability (over 120 thousand cycles). Experimental and theoretical investigations are performed to define the key features of the device. Studies from human natural daily activities and exercise demonstrate the functionality of the sensor for real-time recording of knee/arm bending, neck/waist twisting, and so on. We also used the device in a spinal laboratory, monitoring human subjects’ spine motions, and validated the measurements using the commercial inclinometer and hunchback instrument. We anticipate that the lightweight, precise and durable stretch sensor applied to spinal monitoring could help mitigate the risk of long-term abnormal postural habits induced diseases.
BAD regulates mammary gland morphogenesis by 4E-BP1-mediated control of localized translation in mouse and human models
Authors: Githaka John Maringa , Tripathi Namita , Kirschenman Raven , Patel Namrata , Pandya Vrajesh , Kramer David A. , Montpetit Rachel , Zhu Lin Fu , Sonenberg Nahum , Fahlman Richard P. , Danial Nika N. , Underhill D. Alan , Goping Ing Swie 
Published: May 2021

AbstractElucidation of non-canonical protein functions can identify novel tissue homeostasis pathways. Herein, we describe a role for the Bcl-2 family member BAD in postnatal mammary gland morphogenesis. InBad3SAknock-in mice, where BAD cannot undergo phosphorylation at 3 key serine residues, pubertal gland development is delayed due to aberrant tubulogenesis of the ductal epithelium. Proteomic and RPPA analyses identify that BAD regulates focal adhesions and the mRNA translation repressor, 4E-BP1. These results suggest that BAD modulates localized translation that drives focal adhesion maturation and cell motility. Consistent with this, cells withinBad3SAorganoids contain unstable protrusions with decreased compartmentalized mRNA translation and focal adhesions, and exhibit reduced cell migration and tubulogenesis. Critically, protrusion stability is rescued by 4E-BP1 depletion. Together our results confirm an unexpected role of BAD in controlling localized translation and cell migration during mammary gland development.
Mismatch repair deficiency predicts response to HER2 blockade in HER2-negative breast cancer
Authors: Punturi Nindo B. , Seker Sinem , Devarakonda Vaishnavi , Mazumder Aloran , Kalra Rashi , Chen Ching Hui , Li Shunqiang , Primeau Tina , Ellis Matthew J. , Kavuri Shyam M. , Haricharan Svasti 
Published: May 2021

AbstractResistance to endocrine treatment occurs in ~30% of ER+ breast cancer patients resulting in ~40,000 deaths/year in the USA. Preclinical studies strongly implicate activation of growth factor receptor, HER2 in endocrine treatment resistance. However, clinical trials of pan-HER inhibitors in ER+/HER2− patients have disappointed, likely due to a lack of predictive biomarkers. Here we demonstrate that loss of mismatch repair activates HER2 after endocrine treatment in ER+/HER2− breast cancer cells by protecting HER2 from protein trafficking. Additionally, HER2 activation is indispensable for endocrine treatment resistance in MutL- cells. Consequently, inhibiting HER2 restores sensitivity to endocrine treatment. Patient data from multiple clinical datasets supports an association between MutL loss, HER2 upregulation, and sensitivity to HER inhibitors in ER+/HER2− patients. These results provide strong rationale for MutL loss as a first-in-class predictive marker of sensitivity to combinatorial treatment with endocrine intervention and HER inhibitors in endocrine treatment-resistant ER+/HER2− breast cancer patients.
Regulation of coordinated muscular relaxation in Drosophila larvae by a pattern-regulating intersegmental circuit
Authors: Hiramoto Atsuki , Jonaitis Julius , Niki Sawako , Kohsaka Hiroshi , Fetter Richard D. , Cardona Albert , Pulver Stefan R. , Nose Akinao 
Published: May 2021

AbstractTypical patterned movements in animals are achieved through combinations of contraction and delayed relaxation of groups of muscles. However, how intersegmentally coordinated patterns of muscular relaxation are regulated by the neural circuits remains poorly understood. Here, we identify Canon, a class of higher-order premotor interneurons, that regulates muscular relaxation during backward locomotion of Drosophila larvae. Canon neurons are cholinergic interneurons present in each abdominal neuromere and show wave-like activity during fictive backward locomotion. Optogenetic activation of Canon neurons induces relaxation of body wall muscles, whereas inhibition of these neurons disrupts timely muscle relaxation. Canon neurons provide excitatory outputs to inhibitory premotor interneurons. Canon neurons also connect with each other to form an intersegmental circuit and regulate their own wave-like activities. Thus, our results demonstrate how coordinated muscle relaxation can be realized by an intersegmental circuit that regulates its own patterned activity and sequentially terminates motor activities along the anterior-posterior axis.
Entanglement-assisted capacity regions and protocol designs for quantum multiple-access channels
Authors: Shi Haowei , Hsieh Min-Hsiu , Guha Saikat , Zhang Zheshen , Zhuang Quntao 
Published: May 2021

AbstractWe solve the entanglement-assisted (EA) classical capacity region of quantum multiple-access channels (MACs) with an arbitrary number of senders. As an example, we consider the bosonic thermal-loss MAC and solve the one-shot capacity region enabled by an entanglement source composed of sender-receiver pairwise two-mode squeezed vacuum states. The EA capacity region is strictly larger than the capacity region without entanglement-assistance. With two-mode squeezed vacuum states as the source and phase modulation as the encoding, we also design practical receiver protocols to realize the entanglement advantages. Four practical receiver designs, based on optical parametric amplifiers, are given and analyzed. In the parameter region of a large noise background, the receivers can enable a simultaneous rate advantage of 82.0% for each sender. Due to teleportation and superdense coding, our results for EA classical communication can be directly extended to EA quantum communication at half of the rates. Our work provides a unique and practical network communication scenario where entanglement can be beneficial.
Introducing a novel low energy gamma ray shield utilizing Polycarbonate Bismuth Oxide composite
Authors: Mehrara Rojin , Malekie Shahryar , Kotahi Seyed Mohsen Saleh , Kashian Sedigheh 
Published: May 2021

AbstractThe fabrication of different weight percentages of Polycarbonate-Bismuth Oxide composite (PC-Bi2O3), namely 0, 5, 10, 20, 30, 40, and 50 wt%, was done via the mixed-solution method. The dispersion state of the inclusions into the polymeric matrix was studied through XRD and SEM analyses. Also, TGA and DTA analyses were carried out to investigate the thermal properties of the samples. Results showed that increasing the amount of Bi2O3 into the polymer matrix shifted the glass transition temperature of the composites towards the lower temperatures. Then, the amount of mass attenuation coefficients of the samples were measured using a CsI(Tl) detector for different gamma rays of 241Am, 57Co, 99mTc, and 133Ba radioactive sources. It was obtained that increasing the concentration of the Bi2O3 fillers in the polycarbonate matrix resulted in increasing the attenuation coefficients of the composites significantly. The attenuation coefficient was enhanced twenty-three times for 50 wt% composite in 59 keV energy, comparing to the pure polycarbonate.
Directed evolution of Metarhizium fungus improves its biocontrol efficacy against Varroa mites in honey bee colonies
Authors: Han Jennifer O. , Naeger Nicholas L. , Hopkins Brandon K. , Sumerlin David , Stamets Paul E. , Carris Lori M. , Sheppard Walter S. 
Published: May 2021

AbstractEntomopathogenic fungi show great promise as pesticides in terms of their relatively high target specificity, low non-target toxicity, and low residual effects in agricultural fields and the environment. However, they also frequently have characteristics that limit their use, especially concerning tolerances to temperature, ultraviolet radiation, or other abiotic factors. The devastating ectoparasite of honey bees, Varroa destructor, is susceptible to entomopathogenic fungi, but the relatively warm temperatures inside honey bee hives have prevented these fungi from becoming effective control measures. Using a combination of traditional selection and directed evolution techniques developed for this system, new strains of Metarhizium brunneum were created that survived, germinated, and grew better at bee hive temperatures (35 °C). Field tests with full-sized honey bee colonies confirmed that the new strain JH1078 is more virulent against Varroa mites and controls the pest comparable to current treatments. These results indicate that entomopathogenic fungi are evolutionarily labile and capable of playing a larger role in modern pest management practices.
Optimization of sunflower head pectin extraction by ammonium oxalate and the effect of drying conditions on properties
Authors: Ma Xuemei , Yu Jiayi , Jing Jing , Zhao Qian , Ren Liyong , Hu Zhiyong 
Published: May 2021

AbstractPectin is a kind of natural and complex carbohydrates which is extensively used in food, chemical, cosmetic, and pharmaceutical industries. Fresh sunflower (Helianthus annuus L.) heads were utilized as a novel source of pectin extracted by ammonium oxalate. The conditions of the extraction process were optimized implementing the response surface methodology. Under optimal extraction parameters (extraction time 1.34 h, liquid–solid ratio 15:1 mL/g, ammonium oxalate concentration 0.76% (w/v)), the maximum experimental yield was 7.36%. The effect of spray-drying and freeze-drying on the physiochemical properties, structural characteristics, and antioxidant activities was investigated by FT-IR spectroscopy, high performance size exclusion chromatography, and X-ray diffraction. The results showed freeze-drying lead to decrease in galacturonic acid (GalA) content (76.2%), molecular weight (Mw 316 kDa), and crystallinity. The antioxidant activities of pectin were investigated utilizing the in-vitro DPPH and ABTS radical-scavenging systems. This study provided a novel and efficient extraction method of sunflower pectin, and confirmed that different drying processes had an effect on the structure and properties of pectin.
Impact of natural salt lick on the home range of Panthera tigris at the Royal Belum Rainforest, Malaysia
Authors: Lazarus Bryan Andrew , Che-Amat Azlan , Abdul Halim Shah Muhammad Muzammil , Hamdan Azwan , Abu Hassim Hasliza , Mustaffa Kamal Farina , Tengku Azizan Tengku Rinalfi Putra , Mohd Noor Mohd Hezmee , Mohamed Mustapha Noordin , Ahmad Hafandi 
Published: May 2021

AbstractNatural salt lick (sira) is a strategic localisation for ecological wildlife assemblage to exhibit geophagy which may act as a population dynamic buffer of prey and predators. Undoubtedly, many agree that geophagy at natural licks is linked to nutritional ecology, health and assembly places facilitating social interaction of its users. Overall, natural salt licks not only save energy of obtaining nutrient leading to health maintenance but also forms the basis of population persistence. The Royal Belum Rainforest, Malaysia (Royal Belum) is a typical tropical rainforest in Malaysia rich in wildlife which are mainly concentrated around the natural salt lick. Since this is one of the most stable fauna ecology forest in Malaysia, it is timely to assess its impact on the Malayan tiger (Panthera tigris) home range dynamics. The three-potential home ranges of the Malayan tiger in this rainforest were selected based on animal trails or foot prints surrounding the salt lick viz (e.g. Sira Kuak and Sira Batu; Sira Rambai and Sira Buluh and Sira Papan) as well as previous sightings of a Malayan tiger in the area, whose movement is dependent on the density and distribution of prey. Camera traps were placed at potential animal trails surrounding the salt lick to capture any encountered wildlife species within the area of the camera placements. Results showed that all home ranges of Malayan tiger were of no significance for large bodied prey availability such as sambar deer (Rusa unicolor), and smaller prey such as muntjacs (Muntiacus muntjac) and wild boar (Sus scrofa). Interestingly, all home range harbour the Malayan tiger as the only sole predator. The non-significance of prey availability at each home range is attributed to the decline of the Malayan tiger in the rainforest since tigers are dependant on the movement of its preferred prey surrounding natural salt licks. Thus, the information from this study offers fundamental knowledge on the importance of prey-predator interaction at salt lick which will help in designing strategy in rewilding or rehabilitation programs of the Malayan tiger at the Royal Belum Rainforest.
A bispecific antibody agonist of the IL-2 heterodimeric receptor preferentially promotes in vivo expansion of CD8 and NK cells
Authors: Harris Katherine E. , Lorentsen Kyle J. , Malik-Chaudhry Harbani K. , Loughlin Kaitlyn , Basappa Harish Medlari , Hartstein Sharon , Ahmil Ghenima , Allen Nicole S. , Avanzino Brian C. , Balasubramani Aarti , Boudreau Andrew A. , Chang Karen , Cuturi Maria-Cristina , Davison Laura M. , Ho Dennis M. , Iyer Suhasini , Rangaswamy Udaya S. , Sankaran Preethi , Schellenberger Ute , Buelow Roland , Trinklein Nathan D. 
Published: May 2021

AbstractThe use of recombinant interleukin-2 (IL-2) as a therapeutic protein has been limited by significant toxicities despite its demonstrated ability to induce durable tumor-regression in cancer patients. The adverse events and limited efficacy of IL-2 treatment are due to the preferential binding of IL-2 to cells that express the high-affinity, trimeric receptor, IL-2Rαβγ such as endothelial cells and T-regulatory cells, respectively. Here, we describe a novel bispecific heavy-chain only antibody which binds to and activates signaling through the heterodimeric IL-2Rβγ receptor complex that is expressed on resting T-cells and NK cells. By avoiding binding to IL-2Rα, this molecule circumvents the preferential T-reg activation of native IL-2, while maintaining the robust stimulatory effects on T-cells and NK-cells in vitro. In vivo studies in both mice and cynomolgus monkeys confirm the molecule’s in vivo biological activity, extended pharmacodynamics due to the Fc portion of the molecule, and enhanced safety profile. Together, these results demonstrate that the bispecific antibody is a safe and effective IL-2R agonist that harnesses the benefits of the IL-2 signaling pathway as a potential anti-cancer therapy.
Linking genome size variation to population phenotypic variation within the rotifer, Brachionus asplanchnoidis
Authors: Stelzer Claus-Peter , Pichler Maria , Hatheuer Anita 
Published: May 2021

AbstractEukaryotic organisms usually contain much more genomic DNA than expected from their biological complexity. In explaining this pattern, selection-based hypotheses suggest that genome size evolves through selection acting on correlated life history traits, implicitly assuming the existence of phenotypic effects of (extra) genomic DNA that are independent of its information content. Here, we present conclusive evidence of such phenotypic effects within a well-mixed natural population that shows heritable variation in genome size. We found that genome size is positively correlated with body size, egg size, and embryonic development time in a population of the monogonont rotifer Brachionus asplanchnoidis. The effect on embryonic development time was mediated partly by an indirect effect (via egg size), and a direct effect, the latter indicating an increased replication cost of the larger amounts of DNA during mitosis. Our results suggest that selection-based change of genome size can operate in this population, provided it is strong enough to overcome drift or mutational change of genome size.