bluuebunny/crossref_metadata_2025_split huggingface dataset:
A high-throughput screening platform for Polycystic Kidney Disease (PKD) drug repurposing utilizing murine and human ADPKD cells
Authors: Asawa Rosita R. , Danchik Carina , Zakharov Alexey , Chen Yuchi , Voss Ty , Jadhav Ajit , Wallace Darren P. , Trott Josephine F. , Weiss Robert H. , Simeonov Anton , Martinez Natalia J. 
Published: March 2020

AbstractAutosomal dominant polycystic kidney disease (ADPKD) is one of the most common inherited monogenic disorders, characterized by a progressive decline in kidney function due in part to the formation of fluid-filled cysts. While there is one FDA-approved therapy, it is associated with potential adverse effects, and all other clinical interventions are largely supportive. Insights into the cellular pathways underlying ADPKD have revealed striking similarities to cancer. Moreover, several drugs originally developed for cancer have shown to ameliorate cyst formation and disease progression in animal models of ADPKD. These observations prompted us to develop a high-throughput screening platform of cancer drugs in a quest to repurpose them for ADPKD. We screened ~8,000 compounds, including compounds with oncological annotations, as well as FDA-approved drugs, and identified 155 that reduced the viability of Pkd1-null mouse kidney cells with minimal effects on wild-type cells. We found that 109 of these compounds also reduced in vitro cyst growth of Pkd1-null cells cultured in a 3D matrix. Moreover, the result of the cyst assay identified therapeutically relevant compounds, including agents that interfere with tubulin dynamics and reduced cyst growth without affecting cell viability. Because it is known that several ADPKD therapies with promising outcomes in animal models failed to be translated to human disease, our platform also incorporated the evaluation of compounds in a panel of primary ADPKD and normal human kidney (NHK) epithelial cells. Although we observed differences in compound response amongst ADPKD and NHK cell preparation, we identified 18 compounds that preferentially affected the viability of most ADPKD cells with minimal effects on NHK cells. Our study identifies attractive candidates for future efficacy studies in advanced pre-clinical models of ADPKD.
Characterization of serum small extracellular vesicles and their small RNA contents across humans, rats, and mice
Authors: Zhao Fengbo , Cheng Li , Shao Qian , Chen Zixing , Lv Xiufang , Li Jing , He Li , Sun Yufeng , Ji Qiuhong , Lu Peng , Ji Yuhua , Ji Juling 
Published: March 2020

AbstractSerum small extracellular vesicles (sEVs) have recently drawn considerable interest because of the diagnostic and therapeutic potential of their miRNAs content. However, the characteristics of human, mouse and rat serum sEVs and their differences in small RNA contents are still unknown. In this study, through nanoparticle tracking analysis and small RNA sequencing, we found that human, rat, and mouse serum sEVs exhibited distinct sizes and particle numbers as well as small RNA contents. Serum sEVs contained not only abundant miRNAs but also a large number of tRNA fragments. Most serum miRNAs existed both inside and outside of sEVs but were enriched in sEVs. Common serum sEV miRNAs (188 miRNAs) and species-specific serum sEV miRNAs (265, 58, and 159 miRNAs, respectively) were identified in humans, rats, or mice. The serum sEVs contained miRNAs from tissues and organs throughout the body, with blood cells as the main contributors. In conclusion, our findings confirmed the rationality of exploring serum sEV miRNAs as noninvasive diagnostic markers and revealed great differences in serum sEV small RNAs between humans, rats, and mice. Inadequate attention to these differences and the contribution of blood cells to serum sEV miRNAs could hinder the clinical translation of basic studies.
A Modified Magnified Analysis of Proteome (MAP) Method for Super-Resolution Cell Imaging that Retains Fluorescence
Authors: Woo Jiwon , Seo Jeong-Min , Lee Mirae , Kim Juyoung , Min Sol , Kim Sang-Tae , Ku Seockmo , Park Jeong-Yoon 
Published: March 2020

AbstractBiological systems consist of a variety of distinct cell types that form functional networks. Super-resolution imaging of individual cells is required for better understanding of these complex systems. Direct visualization of 3D subcellular and nano-scale structures in cells is helpful for the interpretation of biological interactions and system-level responses. Here we introduce a modified magnified analysis of proteome (MAP) method for cell super-resolution imaging (Cell-MAP) which preserves cell fluorescence. Cell-MAP expands cells more than four-fold while preserving their overall architecture and three-dimensional proteome organization after hydrogel embedding. In addition, Optimized-Cell-MAP completely preserves fluorescence and successfully allows for the observation of tagged small molecular probes containing peptides and microRNAs. Optimized-Cell-MAP further successfully applies to the study of structural characteristics and the identification of small molecules and organelles in mammalian cells. These results may give rise to many other applications related to the structural and molecular analysis of smaller assembled biological systems.
TmRelish is required for regulating the antimicrobial responses to Escherichia coli and Staphylococcus aureus in Tenebrio molitor
Authors: Keshavarz Maryam , Jo Yong Hun , Patnaik Bharat Bhusan , Park Ki Beom , Ko Hye Jin , Kim Chang Eun , Edosa Tariku Tesfaye , Lee Yong Seok , Han Yeon Soo 
Published: March 2020

AbstractRelish, a transcription factor, is a critical downstream component of the immune deficiency (Imd) pathway and regulates host defense against bacterial infection by mediating antimicrobial peptide (AMP) synthesis. Understanding the immunological function of the mealworm beetle, Tenebrio molitor Relish (TmRelish) will be instructive in understanding insect immunity. In the present study, full-length ORF of TmRelish was retrieved from T. molitor-expressed sequence tags and RNA-seq database. The predicted TmRelish amino acid sequence contained an N-terminal Rel-homology domain; an Ig-like, plexin, and transcription factor domain; ankyrin repeat motifs; a nuclear localization signal; and a C-terminal death domain and shared the highly conserved structure of the Relish proteins of other insect species. TmRelish mRNA was detected in all developmental stages of the insect; however, the highest levels were detected in the larval gut tissue and adult hemocytes. TmRelish mRNA level was upregulated in the fat body, hemocyte, and gut tissue 9 h after infection of T. molitor larvae by the gram-negative bacteria, Escherichia coli. Furthermore, TmRelish knockdown led to significantly higher mortality of the E. coli-infected larvae, and significantly lower mortality of larvae infected with Staphylococcus aureus or Candida albicans. To elucidate the possible cause of mortality, we measured AMP transcription in the fat body, hemocytes, gut, and Malpighian tubules (MTs) of T. molitor larvae. TmRelish knockdown suppressed the expression of nine AMP genes in the larval fat body and gut tissue during E. coli infection, suggesting that TmRelish positively regulates AMP expression in both immune-related tissues, in response to E. coli challenge. Furthermore, negative regulation of some AMPs by TmRelish in the MTs, gut and hemocytes in response to C. albicans infection suggests a crosstalk between the Toll and Imd pathways.
Silicon amendment induces synergistic plant defense mechanism against pink stem borer (Sesamia inferens Walker.) in finger millet (Eleusine coracana Gaertn.)
Authors: Jadhao Kundansing Rajpalsing , Bansal Anuradha , Rout Gyana R. 
Published: March 2020

AbstractSilicon (Si) uptake and accumulation in plants can mitigate various biotic stresses through enhanced plant resistance against wide range of herbivores. But the role of silicon in defense molecular mechanism still remains to be elucidated in finger millet. In the present study, we identified three silicon transporter genes viz.EcLsi1,EcLsi2, andEcLsi6involved in silicon uptake mechanism. In addition, the study also identified and characterized ten different Si transporters genes from finger millet through transcriptome assembly. The phylogenetic study revealed thatEcLsi1andEcLsi6 are homologs whileEcLsi2andEcLsi3 form another pair of homologs.EcLsi1andEcLsi6belong to family of NIP2s (Nod26-like major intrinsic protein),bona fidesilicon transporters, whereasEcLsi2andEcLsi3, an efflux Si transporter, belong to an uncharacterized anion transporter family having a significant identity with putative arsB transporter proteins. Further, the phylogenetic and topology analysis suggest thatEcLsi1andEcLsi2co-evolved during evolution while,EcLsi2andEcLsi3are evolved from eitherEcLsi1and/orEcLsi6by fusion or duplication event. Moreover, these silicon transporters are predicted to be localized in plasma membrane, but their structural differences indicate that they might have differences in their silicon uptake ability. Silicon amendment induces the synergistic defense mechanism by significantly increasing the transcript level of silicon transporter genes (EcLsi1,EcLsi2andEcLsi6) as well as defense hormone regulating genes (EcSAM,EcPALandEcLOX) at 72 hpi (hours of post infestation) in both stem and roots compared to non-silicon treated plants against pink stem borer in finger millet plants. This study will help to understand the molecular defense mechanism for developing strategies for insect pest management.
Second-line Hormonal Therapy for the Management of Metastatic Castration-resistant Prostate Cancer: a Real-World Data Study Using a Claims Database
Authors: Liu Jui-Ming , Lin Cheng-Chia , Liu Kuan-Lin , Lin Cheng-Feng , Chen Bing-Yu , Chen Tien-Hsing , Sun Chi-Chin , Wu Chun-Te 
Published: March 2020

AbstractWe evaluated the efficacy of second-line hormonal therapy for treatment of metastatic castration-resistant prostate cancer (mCRPC) in a real-world retrospective study. We conducted a population-based real-world cohort study of 258 mCRPC patients between 2014 and 2018 using the Chang Gung Research Database (CGRD) of Taiwan. The second-line hormonal therapy included abiraterone acetate and enzalutamide. The clinical efficacy outcomes were overall survival (OS) and prostate-specific antigen (PSA) doubling time. The median PSA level was also assessed. In total, 223 mCRPC patients who underwent second-line hormonal therapy met all of the inclusion and exclusion criteria for this study. Among them, 65 (29.1%) patients were in the PSA response group and 158 (70.9%) were in the non-response group. The median age was 72.9 years. The median OS was 12.3 months (range: 9.9–19.9 months) and 9.6 months (range: 5.3–15.9 months) in the response and non-response groups, respectively, and the respective PSA doubling times were 9.0 months (range: 4.4–11.6 months) and 3.9 months (range: 2.2–9.1 months), with a median follow-up period of 10.5 months. A significantly longer median OS was seen in the PSA response group. This real-world database study demonstrated that clinical outcomes of second-line hormonal therapy were better in patients with a PSA response. Further studies are warranted to achieve a better understanding of second-line hormonal therapy for mCRPC in Asian populations.
Increased genetic diversity from colony merging in termites does not improve survival against a fungal pathogen
Authors: Aguero Carlos M. , Eyer Pierre-André , Vargo Edward L. 
Published: March 2020

AbstractIn some species of social insects the increased genetic diversity from having multiple breeders in a colony has been shown to improve pathogen resistance. Termite species typically found colonies from single mated pairs and therefore may lack the flexibility to buffer pathogen pressure with increased genetic diversity by varying the initial number of reproductives. However, they can later increase group diversity through colony merging, resulting in a genetically diverse, yet cohesive, workforce. In this study, we investigate whether the increased group diversity from colony fusion benefits social immunity in the subterranean termite Reticulitermes flavipes. We confirm previous findings that colonies of R. flavipes will readily merge and we show that workers will equally groom nestmates and non-nestmates after merging. Despite this, the survival of these merged colonies was not improved after exposure to a fungal pathogen, but instead leveled to that of the more susceptible or the more resistant colony. Our study brings little support to the hypothesis that colony fusion may improve immunity through an increase of genetic diversity in R. flavipes. Instead, we find that following exposure to a lethal pathogen, one colony is heavily influential to the entire group’s survival after merging.
Combined effect of oxygen-scavenger packaging and UV-C radiation on shelf life of refrigerated tilapia (Oreochromis niloticus) fillets
Authors: Monteiro Maria Lúcia Guerra , Mársico Eliane Teixeira , Mutz Yhan da Silva , Castro Vinicius Silva , Moreira Rodrigo Vilela de Barros Pinto , Álvares Thiago da Silveira , Conte-Junior Carlos Adam 
Published: March 2020

AbstractThis study investigated the physicochemical, instrumental and bacterial parameters of tilapia fillets subjected to oxygen-scavenger packaging, alone or in combination with UV-C radiation at two doses (0.102 and 0.301 J/cm2), stored at 4 ± 1 °C for 23 days. The oxygen scavenger, both UV-C doses, and the oxygen scavenger combined with UV-C, independently of the dose, extended the shelf life in 5, 6 and 7 days, respectively, by decreasing the bacterial growth rate and the formation of degradation compounds (e.g., TVB-N and ammonia). Oxygen-scavenger packaging, alone or in combination with UV-C at 0.102 J/cm2 and 0.301 J/cm2 showed lower amounts of free amino acids (FAA; 34.39, 34.49 and 34.50 mg L-lysine/kg fish tissue, 3.63, 3.57 and 3.61 mg L- ornithine/kg fish tissue, 27.52, 27.63 and 27.67 mg L-arginine/kg fish tissue), biogenic amines (BA; 3.81, 3.87 and 3.89 mg cadaverine/kg fish tissue, 12.88, 12.91 and 12.86 mg putrescine/kg fish tissue, 2.41, 2.44 and 2.47 mg spermidine/kg fish tissue), redness (2.53, 2.55 and 2.59), yellowness (6.65, 6.69 and 6.72), lipid oxidation (1.52, 1.53 and 1.58 mg malondialdehyde/kg fish tissue) and protein oxidation (5.06, 5.11 and 5.18 nmol carbonyls/mg protein), with higher hardness (3273.41, 2652.98 and 2687.57 g) than control (air packaging; 41.97 mg L-lysine/kg fish tissue, 4.83 mg L- ornithine/kg fish tissue, 37.33 mg L-arginine/kg fish tissue, 4.82 mg cadaverine/kg fish tissue, 16.56 mg putrescine/kg fish tissue, 3.21 mg spermidine/kg fish tissue, 4.26 of redness, 8.17 of yellowness, 2.88 mg malondialdehyde/kg fish tissue, 9.44 nmol carbonyls/mg protein and 2092.58 g of hardness), respectively, on day 13 of storage when the control fillets were unfit for consumption (7 log CFU/g) (p < 0.05). However, in the same day of storage, both UV-C doses had similar values for BA (p > 0.05), higher amounts of FAA (44.28 and 44.13 mg L-lysine/kg fish tissue, 5.16 and 5.12 mg L- ornithine/kg fish tissue, 40.20 and 40.28 mg L-arginine/kg fish tissue), redness (4.86 and 5.33), yellowness (9.32 and 10.01), lipid oxidation (3.09 and 3.52 mg malondialdehyde/kg fish tissue) and protein oxidation (10.27 and 11.93 nmol carbonyls/mg protein), as well as lower hardness (1877.54 and 1767.39 g), respectively, than control fillets (p < 0.05). The combined preservation methods were the most effective in extending the shelf life and prolonging the physicochemical quality of the refrigerated tilapia fillets and the O2 scavenger proved to be a potential alternative to prevent the negative changes induced by both UV-C doses.
Continuous, noninvasive wireless monitoring of flow of cerebrospinal fluid through shunts in patients with hydrocephalus
Authors: Krishnan Siddharth R. , Arafa Hany M. , Kwon Kyeongha , Deng Yujun , Su Chun-Ju , Reeder Jonathan T. , Freudman Juliet , Stankiewicz Izabela , Chen Hsuan-Ming , Loza Robert , Mims Marcus , Mims Mitchell , Lee KunHyuck , Abecassis Zachary , Banks Aaron , Ostojich Diana , Patel Manish , Wang Heling , Börekçi Kaan , Rosenow Joshua , Tate Matthew , Huang Yonggang , Alden Tord , Potts Matthew B. , Ayer Amit B. , Rogers John A. 
Published: March 2020

AbstractHydrocephalus is a common disorder caused by the buildup of cerebrospinal fluid (CSF) in the brain. Treatment typically involves the surgical implantation of a pressure-regulated silicone tube assembly, known as a shunt. Unfortunately, shunts have extremely high failure rates and diagnosing shunt malfunction is challenging due to a combination of vague symptoms and a lack of a convenient means to monitor flow. Here, we introduce a wireless, wearable device that enables precise measurements of CSF flow, continuously or intermittently, in hospitals, laboratories or even in home settings. The technology exploits measurements of thermal transport through near-surface layers of skin to assess flow, with a soft, flexible, and skin-conformal device that can be constructed using commercially available components. Systematic benchtop studies and numerical simulations highlight all of the key considerations. Measurements on 7 patients establish high levels of functionality, with data that reveal time dependent changes in flow associated with positional and inertial effects on the body. Taken together, the results suggest a significant advance in monitoring capabilities for patients with shunted hydrocephalus, with potential for practical use across a range of settings and circumstances, and additional utility for research purposes in studies of CSF hydrodynamics.
Chimeric symbionts expressing a Wolbachia protein stimulate mosquito immunity and inhibit filarial parasite development
Authors: Epis Sara , Varotto-Boccazzi Ilaria , Crotti Elena , Damiani Claudia , Giovati Laura , Mandrioli Mauro , Biggiogera Marco , Gabrieli Paolo , Genchi Marco , Polonelli Luciano , Daffonchio Daniele , Favia Guido , Bandi Claudio 
Published: March 2020

AbstractWolbachia can reduce the capability of mosquitoes to transmit infectious diseases to humans and is currently exploited in campaigns for the control of arboviruses, like dengue and Zika. Under the assumption that Wolbachia-mediated activation of insect immunity plays a role in the reduction of mosquito vectorial capacity, we focused our attention on the Wolbachia surface protein (WSP), a potential inductor of innate immunity. We hypothesized that the heterologous expression of this protein in gut- and tissue-associated symbionts may reduce parasite transmission. We thus engineered the mosquito bacterial symbiont Asaia to express WSP (AsaiaWSP). AsaiaWSP induced activation of the host immune response in Aedes aegypti and Anopheles stephensi mosquitoes, and inhibited the development of the heartworm parasite Dirofilaria immitis in Ae. aegypti. These results consolidate previous evidence on the immune-stimulating property of WSP and make AsaiaWSP worth of further investigations as a potential tool for the control of mosquito-borne diseases.
Assembly of Dy60 and Dy30 cage-shaped nanoclusters
Authors: Luo Zhi-Rong , Wang Hai-Ling , Zhu Zhong-Hong , Liu Tong , Ma Xiong-Feng , Wang Hui-Feng , Zou Hua-Hong , Liang Fu-Pei 
Published: March 2020

AbstractRapid kinetics, complex and diverse reaction intermediates, and difficult screening make the study of assembly mechanisms of high-nuclearity lanthanide clusters challenging. Here, we synthesize a double-cage dysprosium cluster [Dy60(H2L1)24(OAc)71(O)5(OH)3(H2O)27]·6H2O·6CH3OH·7CH3CN (Dy60) by using a multidentate chelate-coordinated diacylhydrazone ligand. Two Dy30 cages are included in the Dy60 structure, which are connected via an OAc− moiety. The core of Dy60 is composed of 8 triangular Dy3 and 12-fold linear Dy3 units. We further change the alkali added in the reaction system and successfully obtain a single cage-shaped cluster [Dy30(H2L1)12(OAc)36(OH)4(H2O)12]·2OH·10H2O·12CH3OH·13CH3CN (Dy30) with a perfect spherical cavity, which could be considered an intermediate in Dy60 formation. Time-dependent, high-resolution electrospray ionization mass spectrometry (HRESI-MS) is used to track the formation of Dy60. A possible self-assembly mechanism is proposed. We track the formation of Dy30 and the six intermediate fragments are screened.
Topologically protected zero refraction of elastic waves in pseudospin-Hall phononic crystals
Authors: Huang Hongbo , Tan Zhuhua , Huo Shaoyong , Feng Luyang , Chen Jiujiu , Han Xu 
Published: March 2020

AbstractZero-angle refraction of elastic waves in metamaterials has attracted attention for its extraordinary wave collimation properties. However, earlier implementations relied on the specific flat equifrequency curve of the phononic crystals suffer from a narrow range of incident angles or operating bandwidths, which severely hinders the exploration and design of functional devices. Here, we propose an elastic near-zero refractive index metamaterial of a triangular lattice to realize topological zero refraction with arbitrary angles of incidence and wide working frequency range. Topological robustness of the zero-angle refraction of pseudospin-Hall edge state against defects is experimentally demonstrated. Furthermore, tunable wave mode conversion associated with the zero-angle refraction is revealed and discussed. These results provide a paradigm for the simultaneous control of the refraction properties of longitudinal and transverse waves that can be employed for designing the topological elastic antennas and elastic wave collimator.