bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cooperation-based concept formation in male bottlenose dolphins
Authors: King Stephanie L. , Connor Richard C. , Krützen Michael , Allen Simon J. 
Published: April 2021

AbstractIn Shark Bay, Western Australia, male bottlenose dolphins form a complex nested alliance hierarchy. At the first level, pairs or trios of unrelated males cooperate to herd individual females. Multiple first-order alliances cooperate in teams (second-order alliances) in the pursuit and defence of females, and multiple teams also work together (third-order alliances). Yet it remains unknown how dolphins classify these nested alliance relationships. We use 30 years of behavioural data combined with 40 contemporary sound playback experiments to 14 allied males, recording responses with drone-mounted video and a hydrophone array. We show that males form a first-person social concept of cooperative team membership at the second-order alliance level, independently of first-order alliance history and current relationship strength across all three alliance levels. Such associative concepts develop through experience and likely played an important role in the cooperative behaviour of early humans. These results provide evidence that cooperation-based concepts are not unique to humans, occurring in other animal societies with extensive cooperation between non-kin.
Bioactive hierarchical silk fibers created by bioinspired self-assembly
Authors: Fan Linpeng , Li Jing-Liang , Cai Zengxiao , Wang Xungai 
Published: April 2021

AbstractArtificial recapitulation of the hierarchy of natural protein fibers is crucial to providing strategies for developing advanced fibrous materials. However, it is challenging due to the complexity of the natural environment. Inspired by the liquid crystalline spinning of spiders, we report the development of natural silk-like hierarchical fibers, with bundles of nanofibrils aligned in their long-axis direction, by self-assembly of crystallized silk fibroin (SF) droplets. The formation of self-assembled SF fibers is a process of coalesced droplets sprouting to form a branched fibrous network, which is similar to the development of capillaries in our body. The as-assembled hierarchical SF fibers are highly bioactive and can significantly enhance the spreading and growth of human umbilical vein endothelial cells compared to the natural SF fibers. This work could help to understand the natural silk spinning process of spiders and provides a strategy for design and development of advanced fibrous biomaterials for various applications.
One-hour coherent optical storage in an atomic frequency comb memory
Authors: Ma Yu , Ma You-Zhi , Zhou Zong-Quan , Li Chuan-Feng , Guo Guang-Can 
Published: April 2021

AbstractPhoton loss in optical fibers prevents long-distance distribution of quantum information on the ground. Quantum repeater is proposed to overcome this problem, but the communication distance is still limited so far because of the system complexity of the quantum repeater scheme. Alternative solutions include transportable quantum memory and quantum-memory-equipped satellites, where long-lived optical quantum memories are the key components to realize global quantum communication. However, the longest storage time of the optical memories demonstrated so far is approximately 1 minute. Here, by employing a zero-first-order-Zeeman magnetic field and dynamical decoupling to protect the spin coherence in a solid, we demonstrate coherent storage of light in an atomic frequency comb memory over 1 hour, leading to a promising future for large-scale quantum communication based on long-lived solid-state quantum memories.
Structural studies of phosphorylation-dependent interactions between the V2R receptor and arrestin-2
Authors: He Qing-Tao , Xiao Peng , Huang Shen-Ming , Jia Ying-Li , Zhu Zhong-Liang , Lin Jing-Yu , Yang Fan , Tao Xiao-Na , Zhao Ru-Jia , Gao Feng-Yuan , Niu Xiao-Gang , Xiao Kun-Hong , Wang Jiangyun , Jin Changwen , Sun Jin-Peng , Yu Xiao 
Published: April 2021

AbstractArrestins recognize different receptor phosphorylation patterns and convert this information to selective arrestin functions to expand the functional diversity of the G protein-coupled receptor (GPCR) superfamilies. However, the principles governing arrestin-phospho-receptor interactions, as well as the contribution of each single phospho-interaction to selective arrestin structural and functional states, are undefined. Here, we determined the crystal structures of arrestin2 in complex with four different phosphopeptides derived from the vasopressin receptor-2 (V2R) C-tail. A comparison of these four crystal structures with previously solved Arrestin2 structures demonstrated that a single phospho-interaction change results in measurable conformational changes at remote sites in the complex. This conformational bias introduced by specific phosphorylation patterns was further inspected by FRET and 1H NMR spectrum analysis facilitated via genetic code expansion. Moreover, an interdependent phospho-binding mechanism of phospho-receptor-arrestin interactions between different phospho-interaction sites was unexpectedly revealed. Taken together, our results provide evidence showing that phospho-interaction changes at different arrestin sites can elicit changes in affinity and structural states at remote sites, which correlate with selective arrestin functions.
Neurexins regulate presynaptic GABAB-receptors at central synapses
Authors: Luo Fujun , Sclip Alessandra , Merrill Sean , Südhof Thomas C. 
Published: April 2021

AbstractDiverse signaling complexes are precisely assembled at the presynaptic active zone for dynamic modulation of synaptic transmission and synaptic plasticity. Presynaptic GABAB-receptors nucleate critical signaling complexes regulating neurotransmitter release at most synapses. However, the molecular mechanisms underlying assembly of GABAB-receptor signaling complexes remain unclear. Here we show that neurexins are required for the localization and function of presynaptic GABAB-receptor signaling complexes. At four model synapses, excitatory calyx of Held synapses in the brainstem, excitatory and inhibitory synapses on hippocampal CA1-region pyramidal neurons, and inhibitory basket cell synapses in the cerebellum, deletion of neurexins rendered neurotransmitter release significantly less sensitive to GABAB-receptor activation. Moreover, deletion of neurexins caused a loss of GABAB-receptors from the presynaptic active zone of the calyx synapse. These findings extend the role of neurexins at the presynaptic active zone to enabling GABAB-receptor signaling, supporting the notion that neurexins function as central organizers of active zone signaling complexes.
Recommendations for acceleration of vaccine development and emergency use filings for COVID-19 leveraging lessons from the novel oral polio vaccine
Authors: Thiel Natalie , Selwyn Casey , Murphy Georgina , Simpson Shmona , Chakrabarti Ajoy C. 
Published: April 2021

AbstractA new oral polio vaccine, nOPV2, has become the first vaccine to pursue a WHO Emergency Use Listing. Many lessons were learned as part of the accelerated development plan and submission, which have been categorized under the following sections: regulatory, clinical development, chemistry manufacturing and controls, and post-deployment monitoring. Efforts were made to adapt findings from these studies to COVID-19 vaccine candidates. Specific concepts for accelerating COVID-19 vaccine development across multiple functional domains were also included. The goals of this effort were twofold: (1) to help familiarize vaccine developers with the EUL process; and (2) to provide general guidance for faster development and preparations for launch during the COVID-19 pandemic.
A multidimensional measure of polypharmacy for older adults using the Health and Retirement Study
Authors: Carr Ewan , Federman Alex , Dzahini Olubanke , Dobson Richard J. , Bendayan Rebecca 
Published: April 2021

AbstractPolypharmacy is commonly defined based on the number of medications taken concurrently using standard cut-offs, but several studies have highlighted the need for a multidimensional assessment. We developed a multidimensional measure of polypharmacy and compared with standard cut-offs. Data were extracted for 2141 respondents of the 2007 Prescription Drug Survey, a sub-study of the Health Retirement Study. Latent classes were identified based on multiple indicators of polypharmacy, including quantity, temporality and risk profile. A four-class model was selected based on fit statistics and clinical interpretability: ‘High risk, long-term’ (Class 1), ‘Low risk, long-term’ (Class 2), ‘High risk, short-term’ (Class 3), and ‘High risk for drug interactions, medium-term, regular’ (Class 4). Classes differed regarding sex, cohabitation, disability and multimorbidity. Participants in the ‘low risk’ class tended to be male, cohabitating, and reported fewer health conditions, compared to ‘high risk’ classes. Polypharmacy classes were compared to standard cut-offs (5+ or 9+ medications) in terms of overlap and mortality risk. The three ‘high risk’ classes overlapped with the groups concurrently taking 5+ and 9+ medications per month. However, the multidimensional measure further differentiated individuals in terms of risk profile and temporality of medication taking, thus offering a richer assessment of polypharmacy.
Nanoparticle composite TPNT1 is effective against SARS-CoV-2 and influenza viruses
Authors: Chang Sui-Yuan , Huang Kuo-Yen , Chao Tai-Ling , Kao Han-Chieh , Pang Yu-Hao , Lu Lin , Chiu Chun-Lun , Huang Hsin-Chang , Cheng Ting-Jen Rachel , Fang Jim-Min , Yang Pan-Chyr 
Published: April 2021

AbstractA metal nanoparticle composite, namely TPNT1, which contains Au-NP (1 ppm), Ag-NP (5 ppm), ZnO-NP (60 ppm) and ClO2 (42.5 ppm) in aqueous solution was prepared and characterized by spectroscopy, transmission electron microscopy, dynamic light scattering analysis and potentiometric titration. Based on the in vitro cell-based assay, TPNT1 inhibited six major clades of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with effective concentration within the range to be used as food additives. TPNT1 was shown to block viral entry by inhibiting the binding of SARS-CoV-2 spike proteins to the angiotensin-converting enzyme 2 (ACE2) receptor and to interfere with the syncytium formation. In addition, TPNT1 also effectively reduced the cytopathic effects induced by human (H1N1) and avian (H5N1) influenza viruses, including the wild-type and oseltamivir-resistant virus isolates. Together with previously demonstrated efficacy as antimicrobials, TPNT1 can block viral entry and inhibit or prevent viral infection to provide prophylactic effects against both SARS-CoV-2 and opportunistic infections.
Hyperoxia-activated circulating extracellular vesicles induce lung and brain injury in neonatal rats
Authors: Ali Anum , Zambrano Ronald , Duncan Matthew R. , Chen Shaoyi , Luo Shihua , Yuan Huijun , Chen Pingping , Benny Merline , Schmidt Augusto , Young Karen , Kerr Nadine , de Rivero Vaccari Juan Pablo , Keane Robert W. , Dietrich W. Dalton , Wu Shu 
Published: April 2021

AbstractHyperoxia-induced lung injury plays a key role in the development of bronchopulmonary dysplasia (BPD), characterized by inflammatory injury and impaired lung development in preterm infants. Although BPD is a predictor of poor neurodevelopmental outcomes, currently it is uncertain how lung injury contributes to brain injury in preterm infants. Extracellular vesicles (EVs) are a heterogeneous group of cell-derived membranous structures that regulate intercellular and inter-organ communications. Gasdermin D (GSDMD) has emerged as a key executor of inflammasome-mediated cell death and inflammation. In this study, we utilized a neonatal rat model of BPD to assess if hyperoxia stimulates lung release of circulating EVs and if these EVs induce lung and brain injury. We found that hyperoxia-exposed rats had elevated numbers of plasma-derived EVs compared to rats maintained in room air. These EVs also had increased cargos of surfactant protein C, a marker of type II alveolar epithelial cells (AEC), and the active (p30) form of GSDMD. When these EVs were adoptively transferred into normal newborn rats via intravenous injection, they were taken up both by lung and brain tissues. Moreover, EVs from hyperoxic animals induced not only the pathological hallmarks of BPD, but also brain inflammatory injury in recipient rats, as well as inducing cell death in cultured pulmonary vascular endothelial cells and neural stem cells (NSC). Similarly, hyperoxia-exposed cultured AEC-like cells released EVs that also contained increased GSDMD-p30 and these EVs induced pyroptotic cell death in NSC. Overall, these data indicate that hyperoxia-activated circulating EVs mediate a lung to brain crosstalk resulting in brain injury and suggest a mechanism that links lung injury and neurodevelopmental impairment in BPD infants.
The antiviral effect of metformin on zika and dengue virus infection
Authors: Farfan-Morales Carlos Noe , Cordero-Rivera Carlos Daniel , Osuna-Ramos Juan Fidel , Monroy-Muñoz Irma Eloisa , De Jesús-González Luis Adrián , Muñoz-Medina José Esteban , Hurtado-Monzón Arianna M. , Reyes-Ruiz José Manuel , del Ángel Rosa María 
Published: April 2021

AbstractThe Dengue (DENV) and zika (ZIKV) virus infections are currently a public health concern. At present, there is no treatment or a safe and effective vaccine for these viruses. Hence, the development of new strategies as host-directed therapy is required. In this sense, Metformin (MET), an FDA-approved drug used for the treatment of type 2 diabetes, has shown an anti-DENV effect in vitro by activating AMPK and reducing HMGCR activity. In this study, MET treatment was evaluated during in vitro and in vivo ZIKV infection and compared to MET treatment during DENV infection. Our results demonstrated that MET has a broad in vitro antiviral spectrum. MET inhibited ZIKV infection in different cell lines, but it was most effective in inhibiting DENV and yellow fever virus (YFV) infection in Huh-7 cells. However, the drug failed to protect against ZIKV infection when AG129 immunodeficient mice were used as in vivo model. Interestingly, MET increased DENV-infected male mice's survival time, reducing the severe signs of the disease. Together, these findings indicate that, although MET was an effective antiviral agent to inhibit in vitro and in vivo DENV infection, it could only inhibit in vitro ZIKV infection.
Detection of pro angiogenic and inflammatory biomarkers in patients with CKD
Authors: Jalal Diana , Sanford Bridget , Renner Brandon , Ten Eyck Patrick , Laskowski Jennifer , Cooper James , Sun Mingyao , Zakharia Yousef , Spitz Douglas , Dokun Ayotunde , Attanasio Massimo , Jones Kenneth , Thurman Joshua M. 
Published: April 2021

AbstractCardiovascular disease (CVD) is the most common cause of death in patients with native and post-transplant chronic kidney disease (CKD). To identify new biomarkers of vascular injury and inflammation, we analyzed the proteome of plasma and circulating extracellular vesicles (EVs) in native and post-transplant CKD patients utilizing an aptamer-based assay. Proteins of angiogenesis were significantly higher in native and post-transplant CKD patients versus healthy controls. Ingenuity pathway analysis (IPA) indicated Ephrin receptor signaling, serine biosynthesis, and transforming growth factor-β as the top pathways activated in both CKD groups. Pro-inflammatory proteins were significantly higher only in the EVs of native CKD patients. IPA indicated acute phase response signaling, insulin-like growth factor-1, tumor necrosis factor-α, and interleukin-6 pathway activation. These data indicate that pathways of angiogenesis and inflammation are activated in CKD patients’ plasma and EVs, respectively. The pathways common in both native and post-transplant CKD may signal similar mechanisms of CVD.
Master Blaster: an approach to sensitive identification of remotely related proteins
Authors: Janaki Chintalapati , Gowri Venkatraman S. , Srinivasan Narayanaswamy 
Published: April 2021

AbstractGenome sequencing projects unearth sequences of all the protein sequences encoded in a genome. As the first step, homology detection is employed to obtain clues to structure and function of these proteins. However, high evolutionary divergence between homologous proteins challenges our ability to detect distant relationships. In the past, an approach involving multiple Position Specific Scoring Matrices (PSSMs) was found to be more effective than traditional single PSSMs. Cascaded search is another successful approach where hits of a search are queried to detect more homologues. We propose a protocol, ‘Master Blaster’, which combines the principles adopted in these two approaches to enhance our ability to detect remote homologues even further. Assessment of the approach was performed using known relationships available in the SCOP70 database, and the results were compared against that of PSI-BLAST and HHblits, a hidden Markov model-based method. Compared to PSI-BLAST, Master Blaster resulted in 10% improvement with respect to detection of cross superfamily connections, nearly 35% improvement in cross family and more than 80% improvement in intra family connections. From the results it was observed that HHblits is more sensitive in detecting remote homologues compared to Master Blaster. However, there are true hits from 46-folds for which Master Blaster reported homologs that are not reported by HHblits even using the optimal parameters indicating that for detecting remote homologues, use of multiple methods employing a combination of different approaches can be more effective in detecting remote homologs. Master Blaster stand-alone code is available for download in the supplementary archive.
SARS pandemic exposure impaired early childhood development in China
Authors: Fan Yunfei , Wang Huiyu , Wu Qiong , Zhou Xiang , Zhou Yubo , Wang Bin , Han Yiqun , Xue Tao , Zhu Tong 
Published: April 2021

AbstractSocial and mental stressors associated with the pandemic of a novel infectious disease, e.g., COVID-19 or SARS may promote long-term effects on child development. However, reports aimed at identifying the relationship between pandemics and child health are limited. A retrospective study was conducted to associate the SARS pandemic in 2003 with development milestones or physical examinations among longitudinal measurements of 14,647 children. Experiencing SARS during childhood was associated with delayed milestones, with hazard ratios of 3.17 (95% confidence intervals CI: 2.71, 3.70), 3.98 (3.50, 4.53), 4.96 (4.48, 5.49), or 5.57 (5.00, 6.20) for walking independently, saying a complete sentence, counting 0–10, and undressing him/herself for urination, respectively. These results suggest relevant impacts from COVID-19 on child development should be investigated.
Diagnostic potential of hypoxia-induced genes in liquid biopsies of breast cancer patients
Authors: Peiró Carlos Henrique F. , Perez Matheus M. , de Aquino Glauco S. A. , Encinas Jéssica F. A. , Sousa Luiz Vinícius de A. , da Veiga Glaucia Luciano , del Giglio Auro , Fonseca Fernando L. A. , da Costa Aguiar Alves Beatriz 
Published: April 2021

AbstractIn tumor cells, higher expression of glucose transporter proteins (GLUT) and carbonic anhydrases (CAIX) genes is influenced by hypoxia-induced factors (HIF).Thus, we aimed to study the expression profile of these markers in sequential peripheral blood collections performed in breast cancer patients in order to verify their predictive potential in liquid biopsies. Gene expressions were analyzed by qPCR in tumor and blood samples from 125 patients and 25 healthy women. Differential expression was determined by the 2(−ΔCq) method. Expression of HIF-1α and GLUT1 in the blood of breast cancer patients is significantly higher (90–91 and 160–161 fold increased expression, respectively; p < 0.0001) than that found in healthy women. Their diagnostic power was confirmed by ROC curve. CAIX is also more expressed in breast cancer women blood, but its expression was detected only in a few samples. But none of these genes could be considered predictive markers. Therefore, evaluation of the expression of HIF-1α and GLUT1 in blood may be a useful laboratory tool to complement the diagnosis of breast cancer, in addition to being useful for follow-up of patients and of women with a family history of breast cancer.
Chronic intermittent ethanol promotes ventral subiculum hyperexcitability via increases in extrinsic basolateral amygdala input and local network activity
Authors: Bach Eva C. , Ewin Sarah E. , Baldassaro Alexandra D. , Carlson Hannah N. , Weiner Jeffrey L. 
Published: April 2021

AbstractThe hippocampus, particularly its ventral domain, can promote negative affective states (i.e. stress and anxiety) that play an integral role in the development and persistence of alcohol use disorder (AUD). The ventral hippocampus (vHC) receives strong excitatory input from the basolateral amygdala (BLA) and the BLA-vHC projection bidirectionally modulates anxiety-like behaviors. However, no studies have examined the effects of chronic alcohol on the BLA-vHC circuit. In the present study, we used ex vivo electrophysiology in conjunction with optogenetic approaches to examine the effects of chronic intermittent ethanol exposure (CIE), a well-established rodent model of AUD, on the BLA-vHC projection and putative intrinsic vHC synaptic plasticity. We discovered prominent BLA innervation in the subicular region of the vHC (vSub). CIE led to an overall increase in the excitatory/inhibitory balance, an increase in AMPA/NMDA ratios but no change in paired-pulse ratios, consistent with a postsynaptic increase in excitability in the BLA-vSub circuit. CIE treatment also led to an increase in intrinsic network excitability in the vSub. Overall, our findings suggest a hyperexcitable state in BLA-vSub specific inputs as well as intrinsic inputs to vSub pyramidal neurons which may contribute to the negative affective behaviors associated with CIE.