bluuebunny/crossref_metadata_2025 huggingface dataset:
miR-27a is a master regulator of metabolic reprogramming and chemoresistance in colorectal cancer
Authors: Barisciano Giovannina , Colangelo Tommaso , Rosato Valeria , Muccillo Livio , Taddei Maria Letizia , Ippolito Luigi , Chiarugi Paola , Galgani Mario , Bruzzaniti Sara , Matarese Giuseppe , Fassan Matteo , Agostini Marco , Bergamo Francesca , Pucciarelli Salvatore , Carbone Annalucia , Mazzoccoli Gianluigi , Colantuoni Vittorio , Bianchi Fabrizio , Sabatino Lina
Published: March 2020

Background

Metabolic reprogramming towards aerobic glycolysis in cancer supports unrestricted cell proliferation, survival and chemoresistance. The molecular bases of these processes are still undefined. Recent reports suggest crucial roles for microRNAs. Here, we provide new evidence of the implication of miR-27a in modulating colorectal cancer (CRC) metabolism and chemoresistance.

Methods

A survey of miR-27a expression profile in TCGA-COAD dataset revealed that miR-27a-overexpressing CRCs are enriched in gene signatures of mitochondrial dysfunction, deregulated oxidative phosphorylation, mTOR activation and reduced chemosensitivity. The same pathways were analysed in cell lines in which we modified miR-27a levels. The response to chemotherapy was investigated in an independent cohort and cell lines.

Results

miR-27a upregulation in vitro associated with impaired oxidative phosphorylation, overall mitochondrial activities and slight influence on glycolysis. miR-27a hampered AMPK, enhanced mTOR signalling and acted in concert with oncogenes and tumour cell metabolic regulators to force an aerobic glycolytic metabolism supporting biomass production, unrestricted growth and chemoresistance. This latter association was confirmed in our cohort of patients and cell lines.

Conclusions

We disclose an unprecedented role for miR-27a as a master regulator of cancer metabolism reprogramming that impinges on CRC response to chemotherapy, underscoring its theragnostic properties.
53BP1 loss rescues embryonic lethality but not genomic instability of BRCA1 total knockout mice
Authors: Chen Jiyuan , Li Peng , Song Licun , Bai Long , Huen Michael S. Y. , Liu Yidan , Lu Lin-Yu
Published: March 2020

BRCA1 is critical for DNA double-strand break (DSB) repair by homologous recombination (HR). BRCA1 deficient mice are embryonic lethal. Previous studies have shown that 53BP1 knockout (KO) rescues embryonic lethality of BRCA1 hypomorphic mutant mice by restoring HR. Here, we show that 53BP1 KO can partially rescue embryonic lethality of BRCA1 total KO mice, but HR is not restored in BRCA1-53BP1 double knockout (DKO) mice. As a result, BRCA1-53BP1 DKO cells are extremely sensitive to PARP inhibitors (PARPi). In addition to HR deficiency, BRCA1-53BP1 DKO cells have elevated microhomology-mediated end joining (MMEJ) activity and G2/M cell cycle checkpoint defects, causing severe genomic instability in these cells. Interestingly, BRCA1-53BP1 DKO mice rapidly develop thymic lymphoma that is 100% penetrant, which is not observed in any BRCA1 mutant mice rescued by 53BP1 KO. Taken together, our study reveals that 53BP1 KO can partially rescue embryonic lethality caused by complete BRCA1 loss without rescuing HR-related defects. This finding suggests that loss of 53BP1 can support the development of cancers with silenced BRCA1 expression without causing PARPi resistance.
Depletion of ID3 enhances mesenchymal stem cells therapy by targeting BMP4 in Sjögren’s syndrome
Authors: Hu Lei , Xu Junji , Wu Tingting , Fan Zhipeng , Sun Lingyun , Liu Yi , Li Yan , Zhang Chunmei , Wang Jingsong , Ding Yaozhong , Wang Songlin
Published: March 2020

Mesenchymal stem cell (MSCs) transplantation has been used to treat Sjögren’s syndrome (SS) based on the immunoregulatory properties of MSCs. However, the effectiveness need improving and its underlying intrinsic mechanisms remain largely unknown. Here, we show that Id3 is upregulated in bone marrow-derived MSCs (BMMSCs) isolated from NOD/ShiLtJ mice, a widely used SS model, compared with ICR mice as control, suggesting that it functions in SS development and therapy. Transplantation of Id3-deficient BMMSCs rescues salivary gland function more effective than wild-type BMMSCs in NOD/ShiLtJ mice. Mechanistically, we show that ID3 negatively regulated BMP4 expression by preventing binding of basic helix–loop–helix protein E2A to the promoter of the Bmp4 gene. BMP4 in turn promoted PGE2 production in MSCs, and exhibited enhanced suppressive activities of T-cell proliferation and Th1 differentiation. Importantly, BMMSCs from SS patients showed significantly lower BMP4 and PGE2 expression than those from healthy individuals. Taken together, our findings revealed the targeting Id3 may be therapeutically useful for improving MSC immunoregulation and effectiveness of MSCs therapy for SS.
Identification of region-specific astrocyte subtypes at single cell resolution
Authors: Batiuk Mykhailo Y. , Martirosyan Araks , Wahis Jérôme , de Vin Filip , Marneffe Catherine , Kusserow Carola , Koeppen Jordan , Viana João Filipe , Oliveira João Filipe , Voet Thierry , Ponting Chris P. , Belgard T. Grant , Holt Matthew G.
Published: March 2020

Astrocytes, a major cell type found throughout the central nervous system, have general roles in the modulation of synapse formation and synaptic transmission, blood–brain barrier formation, and regulation of blood flow, as well as metabolic support of other brain resident cells. Crucially, emerging evidence shows specific adaptations and astrocyte-encoded functions in regions, such as the spinal cord and cerebellum. To investigate the true extent of astrocyte molecular diversity across forebrain regions, we used single-cell RNA sequencing. Our analysis identifies five transcriptomically distinct astrocyte subtypes in adult mouse cortex and hippocampus. Validation of our data in situ reveals distinct spatial positioning of defined subtypes, reflecting the distribution of morphologically and physiologically distinct astrocyte populations. Our findings are evidence for specialized astrocyte subtypes between and within brain regions. The data are available through an online database (https://holt-sc.glialab.org/), providing a resource on which to base explorations of local astrocyte diversity and function in the brain.
Determining the adsorption energies of small molecules with the intrinsic properties of adsorbates and substrates
Authors: Gao Wang , Chen Yun , Li Bo , Liu Shan-Ping , Liu Xin , Jiang Qing
Published: March 2020

Adsorption is essential for many processes on surfaces; therefore, an accurate prediction of adsorption properties is demanded from both fundamental and technological points of view. Particularly, identifying the intrinsic determinants of adsorption energy has been a long-term goal in surface science. Herein, we propose a predictive model for quantitative determination of the adsorption energies of small molecules on metallic materials and oxides, by using a linear combination of the valence and electronegativity of surface atoms and the coordination of active sites, with the corresponding prefactors determined by the valence of adsorbates. This model quantifies the effect of the intrinsic properties of adsorbates and substrates on adsorbate–substrate bonding, derives naturally the well-known adsorption-energy scaling relations, and accounts for the efficiency and limitation of engineering the adsorption energy and reaction energy. All involved parameters are predictable and thus allow the rapid rational design of materials with optimal adsorption properties.
A methylated lysine is a switch point for conformational communication in the chaperone Hsp90
Authors: Rehn Alexandra , Lawatscheck Jannis , Jokisch Marie-Lena , Mader Sophie L. , Luo Qi , Tippel Franziska , Blank Birgit , Richter Klaus , Lang Kathrin , Kaila Ville R. I. , Buchner Johannes
Published: March 2020

Methylation of a conserved lysine in C-terminal domain of the molecular chaperone Hsp90 was shown previously to affect its in vivo function. However, the underlying mechanism remained elusive. Through a combined experimental and computational approach, this study shows that this site is very sensitive to sidechain modifications and crucial for Hsp90 activity in vitro and in vivo. Our results demonstrate that this particular lysine serves as a switch point for the regulation of Hsp90 functions by influencing its conformational cycle, ATPase activity, co-chaperone regulation, and client activation of yeast and human Hsp90. Incorporation of the methylated lysine via genetic code expansion specifically shows that upon modification, the conformational cycle of Hsp90 is altered. Molecular dynamics simulations including the methylated lysine suggest specific conformational changes that are propagated through Hsp90. Thus, methylation of the C-terminal lysine allows a precise allosteric tuning of Hsp90 activity via long distances.
Structural basis of RNA polymerase I pre-initiation complex formation and promoter melting
Authors: Pilsl Michael , Engel Christoph
Published: March 2020

Transcription of the ribosomal RNA precursor by RNA polymerase (Pol) I is a prerequisite for the biosynthesis of ribosomes in eukaryotes. Compared to Pols II and III, the mechanisms underlying promoter recognition, initiation complex formation and DNA melting by Pol I substantially diverge. Here, we report the high-resolution cryo-EM reconstruction of a Pol I early initiation intermediate assembled on a double-stranded promoter scaffold that prevents the establishment of downstream DNA contacts. Our analyses demonstrate how efficient promoter-backbone interaction is achieved by combined re-arrangements of flexible regions in the ‘core factor’ subunits Rrn7 and Rrn11. Furthermore, structure-function analysis illustrates how destabilization of the melted DNA region correlates with contraction of the polymerase cleft upon transcription activation, thereby combining promoter recruitment with DNA-melting. This suggests that molecular mechanisms and structural features of Pol I initiation have co-evolved to support the efficient melting, initial transcription and promoter clearance required for high-level rRNA synthesis.
Molecularly tunable thin-film nanocomposite membranes with enhanced molecular sieving for organic solvent forward osmosis
Authors: Li Bofan , Japip Susilo , Chung Tai-Shung
Published: March 2020

Thin-film nanocomposites (TFN) functionalized with tunable molecular-sieving nanomaterials have been employed to tailor membranes, with an enhanced permeability and selectivity. Herein, water-soluble hollow cup-like macrocyclic molecules, sulfothiacalix[4]arene (STCAss) and sulfocalix[4]arene (SCA), are ionically bonded into the polyamide network to engineer the molecular-sieving properties of TFN membranes for organic solvent forward osmosis (OSFO). Introducing both STCAss and SCA into the polyamide network not only increases the free volume, but also reduces the thickness of the TFN layers. Combining with their molecularly tunable size of the lower cavities, both STCAss and SCA enable the TFN membranes to size exclusively reject the draw solutes, but only STCAss-functionalized membrane has an ethanol flux doubling the pristine one under the FO and PRO modes in OSFO processes; leading the functionalized polyamide network with remarkable improvements in OSFO performance. This study may provide insights to molecularly functionalize TFN membranes using multifunctional nano-fillers for sustainable separations.
A FinFET with one atomic layer channel
Authors: Chen Mao-Lin , Sun Xingdan , Liu Hang , Wang Hanwen , Zhu Qianbing , Wang Shasha , Du Haifeng , Dong Baojuan , Zhang Jing , Sun Yun , Qiu Song , Alava Thomas , Liu Song , Sun Dong-Ming , Han Zheng
Published: March 2020

Since its invention in the 1960s, one of the most significant evolutions of metal-oxide-semiconductor field effect transistors (MOS-FETs) would be the three dimensionalized version that makes the semiconducting channel vertically wrapped by conformal gate electrodes, also recognized as FinFET. During the past decades, the width of fin (W$${}_{{\rm{fin}}}$$fin) in FinFETs has shrunk from about 150 nm to a few nanometers. However, W$${}_{{\rm{fin}}}$$fin seems to have been levelling off in recent years, owing to the limitation of lithography precision. Here, we show that by adapting a template-growth method, different types of mono-layered two-dimensional crystals are isolated in a vertical manner. Based on this, FinFETs with one atomic layer fin are obtained, with on/off ratios reaching $$\sim\!\! 10^{7}$$~107. Our findings push the FinFET to the sub 1 nm fin-width limit, and may shed light on the next generation nanoelectronics for higher integration and lower power consumption.
Author Correction: Dynamic regulation of canonical TGFβ signalling by endothelial transcription factor ERG protects from liver fibrogenesis
Authors: Dufton Neil P. , Peghaire Claire R. , Osuna-Almagro Lourdes , Raimondi Claudio , Kalna Viktoria , Chauhan Abhishek , Webb Gwilym , Yang Youwen , Birdsey Graeme M. , Lalor Patricia , Mason Justin C. , Adams David H. , Randi Anna M.
Published: March 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Pseudo-Occlusion of the Internal Carotid Artery in Acute Ischemic Stroke: Clinical Outcome after Mechanical Thrombectomy
Authors: Jung Woo Sang , Lee Jin Soo , Solander Sten , Choi Jin Wook
Published: March 2020

Pseudo-occlusion (PO) of the cervical internal carotid artery (cICA) can be caused by distal ICA occlusion. We explored the clinical impact of PO after mechanical thrombectomy (MT). Patients who underwent MT to treat distal ICA occlusions between July 2012 and March 2018 were reviewed. A cICA-PO was defined as when single phase computed tomography angiography (CTA) revealed a gradual decline in contrast above the level of the carotid bulb. We investigated the relationship between a cICA-PO and outcome; we also explored the association between successful recanalization and outcome. Among 71 patients, 40 (56.3%) exhibited cICA-PO and more likely to experience poor outcomes (80.0% vs. 25.8%, P < 0.001), hemorrhagic transformation (32.5% vs. 9.6%, P = 0.01), and a lower rate of successful recanalization (65.0% vs. 90.3%, P = 0.014) than the non-PO group. In binary logistic regression, a cICA-PO was independently associated with a poor outcome (odds ratio, 4.278; 95% CI, 1.080–33.006; P = 0.045). In the cICA-PO group, all patients who failed recanalization (n = 15) experienced poor outcomes, as did 69.2% of patients in whom recanalization was successful (P = 0.018). cICA-POs are common and have worse outcomes than non-PO patients. Patients with cICA-POs are more likely to exhibit poor outcomes after MT, particularly when recanalization fails.
Quantitative 3D imaging parameters improve prediction of hip osteoarthritis outcome
Authors: Turmezei T. D. , Treece G. M. , Gee A. H. , Sigurdsson S. , Jonsson H. , Aspelund T. , Gudnason V. , Poole K. E. S.
Published: March 2020

Osteoarthritis is an increasingly important health problem for which the main treatment remains joint replacement. Therapy developments have been hampered by a lack of biomarkers that can reliably predict disease, while 2D radiographs interpreted by human observers are still the gold standard for clinical trial imaging assessment. We propose a 3D approach using computed tomography—a fast, readily available clinical technique—that can be applied in the assessment of osteoarthritis using a new quantitative 3D analysis technique called joint space mapping (JSM). We demonstrate the application of JSM at the hip in 263 healthy older adults from the AGES-Reykjavík cohort, examining relationships between 3D joint space width, 3D joint shape, and future joint replacement. Using JSM, statistical shape modelling, and statistical parametric mapping, we show an 18% improvement in prediction of joint replacement using 3D metrics combined with radiographic Kellgren & Lawrence grade (AUC 0.86) over the existing 2D FDA-approved gold standard of minimum 2D joint space width (AUC 0.73). We also show that assessment of joint asymmetry can reveal significant differences between individuals destined for joint replacement versus controls at regions of the joint that are not captured by radiographs. This technique is immediately implementable with standard imaging technologies.
RORγt may Influence the Microenvironment of Thyroid Cancer Predicting Favorable Prognosis
Authors: Cunha Lucas Leite , Morari Elaine Cristina , Nonogaki Suely , Bufalo Natassia Elena , da Assumpção Ligia Vera Montalli , Soares Fernando Augusto , Vassallo José , Ward Laura Sterian
Published: March 2020

We aimed to investigate the role of RORγt (Retinoic acid-related orphan receptor gamma) in the tumor microenvironment of differentiated thyroid carcinoma. We retrospectively analyzed 56 patients (48 papillary and 8 follicular thyroid carcinomas). Immunohistochemical expression of RORγt was compared to other immune markers previously investigated by our group, clinical and pathological information. All patients presented cytoplasmic expression of RORγt in thyroid tumor cells. Seven (12.5%) patients presented no nuclear expression of RORγt. Positivity was few (up to 10%) in 14 patients; 10 to 50% in 5 patients (8.9%); and more than 50% in 30 patients (53.6%). Nuclear RORγt positivity was associated with absence of distant metastasis at diagnosis (p = 0.013) and the need of less cumulative doses of radioactive iodine (p = 0.039). Patients whose tumors were positive for nuclear RORγt presented higher 10-years relapse-free survival rate than those patients who were negative for RORγt (p = 0.023). We classified the patients according to the clustering of immunological immunohistochemical markers. We were able to distinguish a subset (A) of 38 patients who presented high expression of nuclear RORγt and tended to be scarce in proinflammatory immune markers. Other 16 patients integrated a second subset (B) whose tumor microenvironment accumulated proinflammatory markers and presented low expression of nuclear nuclear RORγt. Distant metastasis at diagnosis were more frequent among patients from cluster B than from cluster A (p = 0.008). Our results reinforce that the expression of RORγt together with other immune markers might help predict the prognosis of patients with thyroid cancer and help individualize clinical management.
Social and Reproductive Behavior of Captive Malayan Tapirs’ (Tapirus indicus): Interactions with Maternal Experience and Environmental Conditions
Authors: Arumugam Kalai Arasi , Top Marina Mohd. , Ibrahim Wan Norhamidah Wan , Buesching Christina D. , Annavi Geetha
Published: March 2020

Malayan tapirs are listed as endangered and are bred in captivity under governmental management. The success of captive breeding programs varies and the underlying causes are unclear. Here, we investigate how tapir reproduction is affected by previous breeding experience, enclosure type/size and visitor numbers so that appropriate steps can be taken to achieve self-sustaining captive populations. Data on social and reproductive behaviors were collected from six tapirs (three males, three females), from different breeding centers in Peninsular Malaysia for 18 weeks. Results revealed that social and reproductive behavior of both sexes was significantly influenced by social and environmental conditions. Larger enclosure size tended to increase social and reproductive behaviors, whereas high number of visitors reduced initial interaction between males and females. No specific breeding month was confirmed; however, reproductive behaviors were highest in April. Overall, this study contributes to a better understanding of the relationships between social and reproductive behaviors, and captive environments on Malayan tapirs. In future, frequency of sexual interactions should be monitored regularly to identify animals exhibiting below-average frequency and who might, therefore, be prone to reproductive difficulties.
Shared Causal Paths underlying Alzheimer’s dementia and Type 2 Diabetes
Authors: Hu Zixin , Jiao Rong , Wang Panpan , Zhu Yun , Zhao Jinying , De Jager Phil , Bennett David A. , Jin Li , Xiong Momiao
Published: March 2020

Although Alzheimer’s disease (AD) is a central nervous system disease and type 2 diabetes MELLITUS (T2DM) is a metabolic disorder, an increasing number of genetic epidemiological studies show clear link between AD and T2DM. The current approach to uncovering the shared pathways between AD and T2DM involves association analysis; however such analyses lack power to discover the mechanisms of the diseases. As an alternative, we developed novel causal inference methods for genetic studies of AD and T2DM and pipelines for systematic multi-omic casual analysis to infer multilevel omics causal networks for the discovery of common paths from genetic variants to AD and T2DM. The proposed pipelines were applied to 448 individuals from the ROSMAP Project. We identified 13 shared causal genes, 16 shared causal pathways between AD and T2DM, and 754 gene expression and 101 gene methylation nodes that were connected to both AD and T2DM in multi-omics causal networks.
Classification models for Invasive Ductal Carcinoma Progression, based on gene expression data-trained supervised machine learning
Authors: Roy Shikha , Kumar Rakesh , Mittal Vaibhav , Gupta Dinesh
Published: March 2020

Early detection of breast cancer and its correct stage determination are important for prognosis and rendering appropriate personalized clinical treatment to breast cancer patients. However, despite considerable efforts and progress, there is a need to identify the specific genomic factors responsible for, or accompanying Invasive Ductal Carcinoma (IDC) progression stages, which can aid the determination of the correct cancer stages. We have developed two-class machine-learning classification models to differentiate the early and late stages of IDC. The prediction models are trained with RNA-seq gene expression profiles representing different IDC stages of 610 patients, obtained from The Cancer Genome Atlas (TCGA). Different supervised learning algorithms were trained and evaluated with an enriched model learning, facilitated by different feature selection methods. We also developed a machine-learning classifier trained on the same datasets with training sets reduced data corresponding to IDC driver genes. Based on these two classifiers, we have developed a web-server Duct-BRCA-CSP to predict early stage from late stages of IDC based on input RNA-seq gene expression profiles. The analysis conducted by us also enables deeper insights into the stage-dependent molecular events accompanying IDC progression. The server is publicly available at http://bioinfo.icgeb.res.in/duct-BRCA-CSP.
Backwash sediment record of the 2009 South Pacific Tsunami and 1960 Great Chilean Earthquake Tsunami
Authors: Riou Brieuc , Chaumillon Eric , Chagué Catherine , Sabatier Pierre , Schneider Jean-Luc , Walsh John-Patrick , Zawadzki Atun , Fierro Daniela
Published: March 2020

Following recent tsunamis, most studies have focused on the onshore deposits, while the offshore backwash deposits, crucial for a better understanding of the hydrodynamic processes during such events and offering an opportunity for sedimentary archives of past tsunamis, have mostly been omitted. Here, we present a unique sedimentary record of the backwash from two historical tsunamis sampled in a sheltered bay in American Samoa, namely the 2009 South Pacific Tsunami and the 1960 Great Chilean Earthquake Tsunami. Although not always concomitant with a marked grain size change, backwash deposits are identified by terrestrial geochemical and mineralogical signatures, associated with basal soft sediment micro-deformations. These micro-deformations, including asymmetric flame structures, are described for the first time in historic shallow marine backwash deposits and lead us to propose an improved depositional mechanism for tsunami backflow based on hyperpycnal currents. Moreover, this study brings a potential new criterion to the proxy toolkit for identifying tsunami backwash deposits, namely the basal soft sediment micro-deformations. We suggest that further studies focus on these micro-deformations in order to test the representability of this criterion for tsunami backwash deposits. Sheltered shallow marine environments in areas repeatedly impacted by tsunamis have a higher potential for the reconstruction of paleo-tsunami catalogs and should be preferentially investigated for coastal risk assessment.
Immunization with DNA prime-subunit protein boost strategy based on influenza H9N2 virus conserved matrix protein M1 and its epitope screening
Authors: Liu Fen , Wang Xueliang , Zheng Mei , Xiong Feifei , Liu Xueying , Zhou Linting , Tan Wensong , Chen Ze
Published: March 2020

Developing an effective universal influenza vaccine against influenza virus with highly conserved antigenic epitopes could induce a broad-spectrum immune response to prevent infection. The soluble protein M1 that can induce the M1 specific immune response was first confirmed in our previous study. In this study, we characterized the immune response induced by DNA prime-subunit protein boost strategy based on the relatively conserved matrix protein 1 (M1) in the BALB/c mouse model, and evaluated its protection ability against a lethal challenge of homologous H9N2 avian influenza virus (A/Chicken/Jiangsu/11/2002). The results showed that 100 μg DNA prime + 100 μg M1 subunit protein boost-strategy significantly increased antibody levels more than vaccination with M1 DNA or M1 subunit protein alone, and induced a more balanced Th1 / Th2 immune response, which not only can provide protection against the homologous virus but also can provide part of the cross-protection against the heterosubtypic PR8 H1N1 strain. In addition, we used an Elispot assay to preliminary screen the T cell epitope in M1 protein, and identified that p22 (M111–25VLSIIPSGPLKAEIA) epitope was the only immunodominant M1-specific CD4+T cell epitopes, which could be helpful in understanding the function of influenza virus T cell epitopes.
Prototyping Trastuzumab Docetaxel Immunoliposomes with a New FCM-Based Method to Quantify Optimal Antibody Density on Nanoparticles
Authors: Rodallec A. , Franco C. , Robert S. , Sicard G. , Giacometti S. , Lacarelle B. , Bouquet F. , Savina A. , Lacroix R. , Dignat-George F. , Ciccolini J. , Poncelet P. , Fanciullino R.
Published: March 2020

Developing targeted nanoparticles is a rising strategy to improve drug delivery in oncology. Antibodies are the most commonly used targeting agents. However, determination of their optimal number at the surface remains a challenging issue, mainly due to the difficulties in measuring precisely surface coating levels when prototyping nanoparticles. We developed an original quantitative assay to measure the exact number of coated antibodies per nanoparticle. Using flow cytometry optimized for submicron particle analysis and beads covered with known amounts of human IgG-kappa mimicking various amounts of antibodies, this new method was tested as part of the prototyping of docetaxel liposomes coated with trastuzumab against Her2+ breast cancer. This quantification method allowed to discriminate various batches of immunoliposomes depending on their trastuzumab density on nanoparticle surface (i.e., 330 (Immunoliposome-1), 480 (Immunoliposome-2) and 690 (Immunoliposome-3), p = 0.004, One-way ANOVA). Here we showed that optimal number of grafted antibodies on nanoparticles should be finely tuned and highest density of targeting agent is not necessarily associated with highest efficacy. Overall, this new method should help to better prototype third generation nanoparticles.
Latitudinal consistency of biomass size spectra - benthic resilience despite environmental, taxonomic and functional trait variability
Authors: Mazurkiewicz Mikołaj , Górska Barbara , Renaud Paul E. , Włodarska-Kowalczuk Maria
Published: March 2020

Global warming is expected to cause reductions in organism body size, a fundamental biological unit important in determining biological processes. Possible effects of increasing temperature on biomass size spectra in coastal benthic communities were investigated. We hypothesized higher proportions of smaller size classes in warmer conditions. Soft bottom infauna samples were collected in six Norwegian and Svalbard fjords, spanning wide latitudinal (60–81°N) and bottom water temperature gradients (from −2 to 8 °C). Investigated fjords differed in terms of environmental settings (e.g., pigments or organic carbon in sediments). The slopes of normalised biomass size spectra (NBSS) did not differ among the fjords, while the benthic biomass and NBSS intercepts varied and were related to chlorophyllaand δ13C in sediments. The size spectra based on both abundance and biomass remained consistent, regardless of the strong variability in macrofauna taxonomic and functional trait composition. Variable relationships between temperature and body size were noted for particular taxa. Our results indicate that while benthic biomass depends on the nutritional quality of organic matter, its partitioning among size classes is consistent and independent of environmental and biological variability. The observed size structure remains a persistent feature of studied communities and may be resilient to major climatic changes.
Social media, nature, and life satisfaction: global evidence of the biophilia hypothesis
Authors: Chang Chia-chen , Cheng Gwyneth Jia Yi , Nghiem Thi Phuong Le , Song Xiao Ping , Oh Rachel Rui Ying , Richards Daniel R. , Carrasco L. Roman
Published: March 2020

Humans may have evolved a need to connect with nature, and nature provides substantial cultural and social values to humans. However, quantifying the connection between humans and nature at a global scale remains challenging. We lack answers to fundamental questions: how do humans experience nature in different contexts (daily routines, fun activities, weddings, honeymoons, other celebrations, and vacations) and how do nature experiences differ across countries? We answer these questions by coupling social media and artificial intelligence using 31,534 social media photographs across 185 countries. We find that nature was more likely to appear in photographs taken during a fun activity, honeymoon, or vacation compared to photographs of daily routines. More importantly, the proportion of photographs with nature taken during fun activities is associated with national life satisfaction scores. This study provides global evidence of the biophilia hypothesis by showing a connection between humans and nature that contributes to life satisfaction and highlights how nature serves as background to many of our positive memories.
A Rationale for the Use of Clotted Vertebral Bone Marrow to Aid Tissue Regeneration Following Spinal Surgery
Authors: Salamanna F. , Contartese D. , Giavaresi G. , Sicuro L. , Barbanti Brodano G. , Gasbarrini A. , Fini M.
Published: March 2020

Vertebral body bone marrow aspirate (V-BMA), easily accessible simultaneously with the preparation of the site for pedicle screw insertion during spinal procedures, is becoming an increasingly used cell therapy approach in spinal surgery. However, the main drawbacks for V-BMA use are the lack of a standardized procedure and of a structural texture with the possibility of diffusion away from the implant site. The aim of this study was to evaluate, characterize and compare the biological characteristics of MSCs from clotted V-BMA and MSCs from whole and concentrate V-BMAs. MSCs from clotted V-BMA showed the highest cell viability and growth factors expression (TGF-β, VEGF-A, FGF2), the greatest colony forming unit (CFU) potency, cellular homogeneity, ability to differentiate towards the osteogenic (COL1AI, TNFRSF11B, BGLAP) and chondrogenic phenotype (SOX9) and the lowest ability to differentiate toward the adipogenic lineage (ADIPOQ) in comparison to all the other culture conditions. Additionally, results revealed that MSCs, differently isolated, expressed different level of HOX and TALE signatures and that PBX1 and MEIS3 were down-regulated in MSCs from clotted V-BMA in comparison to concentrated one. The study demonstrated for the first time that the cellular source inside the clotted V-BMA showed the best biological properties, representing an alternative and advanced cell therapy approach for patients undergoing spinal surgery.
Cannabidiol is an effective helper compound in combination with bacitracin to kill Gram-positive bacteria
Authors: Wassmann Claes Søndergaard , Højrup Peter , Klitgaard Janne Kudsk
Published: March 2020

The cannabinoid cannabidiol (CBD) is characterised in this study as a helper compound against resistant bacteria. CBD potentiates the effect of bacitracin (BAC) against Gram-positive bacteria (Staphylococcus species, Listeria monocytogenes, and Enterococcus faecalis) but appears ineffective against Gram-negative bacteria. CBD reduced the MIC value of BAC by at least 64-fold and the combination yielded an FIC index of 0.5 or below in most Gram-positive bacteria tested. Morphological changes in S. aureus as a result of the combination of CBD and BAC included several septa formations during cell division along with membrane irregularities. Analysis of the muropeptide composition of treated S. aureus indicated no changes in the cell wall composition. However, CBD and BAC treated bacteria did show a decreased rate of autolysis. The bacteria further showed a decreased membrane potential upon treatment with CBD; yet, they did not show any further decrease upon combination treatment. Noticeably, expression of a major cell division regulator gene, ezrA, was reduced two-fold upon combination treatment emphasising the impact of the combination on cell division. Based on these observations, the combination of CBD and BAC is suggested to be a putative novel treatment in clinical settings for treatment of infections with antibiotic resistant Gram-positive bacteria.
Human glutaredoxin-1 can transfer copper to isolated metal binding domains of the P1B-type ATPase, ATP7B
Authors: Maghool Shadi , Fontaine Sharon La , Roberts Blaine R. , Kwan Ann H. , Maher Megan J.
Published: March 2020

Intracellular copper (Cu) in eukaryotic organisms is regulated by homeostatic systems, which rely on the activities of soluble metallochaperones that participate in Cu exchange through highly tuned protein-protein interactions. Recently, the human enzyme glutaredoxin-1 (hGrx1) has been shown to possess Cu metallochaperone activity. The aim of this study was to ascertain whether hGrx1 can act in Cu delivery to the metal binding domains (MBDs) of the P1B-type ATPase ATP7B and to determine the thermodynamic factors that underpin this activity. hGrx1 can transfer Cu to the metallochaperone Atox1 and to the MBDs 5-6 of ATP7B (WLN5-6). This exchange is irreversible. In a mixture of the three proteins, Cu is delivered to the WLN5-6 preferentially, despite the presence of Atox1. This preferential Cu exchange appears to be driven by both the thermodynamics of the interactions between the proteins pairs and of the proteins with Cu(I). Crucially, protein-protein interactions between hGrx1, Atox1 and WLN5-6 were detected by NMR spectroscopy both in the presence and absence of Cu at a common interface. This study augments the possible activities of hGrx1 in intracellular Cu homeostasis and suggests a potential redundancy in this system, where hGrx1 has the potential to act under cellular conditions where the activity of Atox1 in Cu regulation is attenuated.
Cellular metabolic activity marker via selective turn-ON detection of transporter protein using nitrobenzoxadiazole-based fluorescent reporter
Authors: Dutta Tanoy , Pal Kaushik , Koner Apurba L.
Published: March 2020

A nitrobenzoxadiazole-based fluoroprobe (NBD-Bu) is designed to probe cellular metabolic activity in cancer and normal cells. NBD-Bu shows a significant fluorescence enhancement upon selective binding to the transport protein serum albumin in PBS buffer at ambient conditions. Encouraged by this finding, the site- specificity of NBD-Bu has been explored through a competitive displacement assay in the presence of site-specific markers such as warfarin and ibuprofen. Notably, even at micromolar concentrations, the probe possesses the ability to displace the site marker drug ibuprofen, efficiently. Subsequently, high-resolution fluorescence imaging results consolidated the potential of NBD-Bu for detection of abnormal cellular metabolic activity.
Going Beyond Rate Changes as the Sole Indicator for Dynamic Triggering of Earthquakes
Authors: Pankow Kristine L. , Kilb Debi
Published: March 2020

Remote earthquake triggering is a well-established phenomenon. Triggering is commonly identified from statistically significant increases in earthquake rate coincident with the passage of seismic energy. In establishing rate changes, short duration earthquake catalogs are commonly used, and triggered sequences are not typically analyzed within the context of background seismic activity. Using 500 mainshocks and four western USA 33-yearlong earthquake catalogs, we compare the ability of three different statistical methods to identify remote earthquake triggering. Counter to many prior studies, we find remote dynamic triggering is rare (conservatively, <2% of the time). For the mainshocks associated with remote rate increases, the spatial and temporal signatures of triggering differ. We find that a rate increase coincident in time with mainshock energy alone is insufficient to conclude that dynamic triggering occurred. To classify dynamically triggered sequences, we suggest moving away from strict statistical measurements and instead use a compatibility assessment that includes multiple factors, like spatial and temporal indicators.
Rapid isothermal duplex real-time recombinase polymerase amplification (RPA) assay for the diagnosis of equine piroplasmosis
Authors: Lei Rong , Wang Xinyi , Zhang Di , Liu Yize , Chen Qijun , Jiang Ning
Published: March 2020

Equine piroplasmosis (EP) is a severe disease of horses caused by the tick-borne protozoa Theileria equi (T. equi) and Babesia caballi (B. caballi). Infectious carriers are not always symptomatic, meaning there is a risk to non-enzootic areas. Regulatory tests for EP include sero-epidemiological methods for equine babesiosis, but these lack specificity due to cross-reactivity with other Babesia species. In this study, we present a real-time quantitative recombinase polymerase amplification (qRPA) method for fast simultaneous detection of both T. equi and B. caballi. In this method, primers and probes targeting the 18S rRNA gene of both T. equi and B. caballi, the ema-1 gene of T. equi and the bc48 gene of B. caballi were designed and evaluated. The sensitivity of qRPA was evaluated using the pUC57 plasmid DNA containing the target gene. For the pUC57-bc48 gene DNA, the R2 value was 0.983 for the concentration range 0.2 ng (4.1 × 107 DNA copies) to 2.0 fg (4.1 × 101 DNA copies). For the pUC57-ema gene DNA, the R2 value was 0.993 for the concentration range 0.2 ng (5.26 × 107 DNA copies) to 2.0 fg (5.26 × 102 DNA copies). For the pUC57-Bc18S gene DNA the R2 value was 0.976 for the concentration range 2.0 ng (4.21 × 108 DNA copies) to 2.0 fg (4.21 × 102 DNA copies). For the pUC57-Te18S gene DNA, the R2 value was 0.952 (Fig. S3b) for the concentration range 2.0 ng (4.16 × 108 DNA copies) to 2.0 fg (4.16 × 102 DNA copies). Furthermore, a duplex qRPA analysis was developed and optimized and the results showed that primers and probes targeting for the bc48 gene of B. caballi and the 18S rRNA gene of T. equi is the best combination for a duplex qRPA analysis in one reaction. The developed duplex qRPA assay has good specificity, and had negative amplification for several similar parasite. For DNA extracted from real horse blood specimens, this qRPA method has comparable sensitivity to traditional qPCR, but a simpler and more rapid operating process to obtain positive amplification. The qRPA, including the duplex strategy described here, could allow fast identification of the EP-causing T. equi and B. caballi, showing great potential for on-site EP screening of horses.
Compost Soil Microbial Fuel Cell to Generate Power using Urea as Fuel
Authors: Magotra Verjesh Kumar , Kumar Sunil , Kang T. W. , Inamdar Akbar I. , Aqueel Abu Talha , Im Hyunsik , Ghodake Gajanan , Shinde Surendra , Waghmode D. P. , Jeon H. C.
Published: March 2020

The acute problem of eutrophication increasing in the environment is due to the increase of industrial wastewater, synthetic nitrogen, urine, and urea. This pollutes groundwater, soil and creates a danger to aquatic life. Therefore, it is advantageous to use these waste materials in the form of urea as fuel to generate power using Microbial Fuel Cell (MFC). In this work, we studied the compost soil MFC(CSMFC) unlike typical MFC with urea from the compost as fuel and graphite as a functional electrode. The electrochemical techniques such as Cyclic Voltammetry, Chronoamperometry are used to characterise CSMFC. It is observed that the CSMFC in which the compost consists of urea concertation of 0.5 g/ml produces maximum power. Moreover, IV measurement is carried out using polarization curves in order to study its sustainability and scalability. Bacterial studies were also playing a significant role in power generation. The sustainability study revealed that urea is consumed in CSMFC to generate power. This study confirmed that urea has a profound effect on the power generation from the CSMFC. Our focus is to get power from the soil processes in future by using waste like urine, industrial wastewater, which contains much amount of urea.
Exercise intensity and physical fitness modulate lipoproteins profile during acute aerobic exercise session
Authors: Antunes B. M. , Rossi F. E. , Oyama L. M. , Rosa-Neto J. C. , Lira F. S.
Published: March 2020

Physical inactivity has emerged as an important cardiometabolic risk factor; however, the beneficial impacts of physical exercise according physical fitness status are still unclear. To analyze the lipoproteins and immune-endocrine response to acute aerobic exercise sessions performed at different intensities according physical fitness status and evaluated the gene expression in monocyte cells. Twelve individuals, divided into Low and High VO2max, performed three randomized acute exercise sessions at low (<60% VO2max), moderate (60–75% VO2max), and high (>90% VO2max) intensities. Blood samples were collected pre, immediately post, and 60 minutes post-exercise to analyze NEFA, triacylglycerol, non-HDL-c, HDL-c, PAI-1, leptin and adiponectin concentrations. Blood samples were collected from another set of twelve individuals for use in monocyte cell cultures to analyze L-CAT, CETP, and AMPK gene expressions. Low VO2max group pre-exercise exhibited higher postprandial leptin and total cholesterol concentrations than High VO2max group (p < 0.05). Exercise performed in high-intensity promoted a decreased leptin and NEFA levels (p < 0.05, for both), but for PAI-1 levels was decreased (p < 0.05) only for the Low VO2max group. Triacylglycerol levels decreased after all exercise sessions (p < 0.05) for both groups, and HDL-c exhibited decrease during moderate-intensity (p < 0.05), but this scenario was attenuated in Low VO2max group. Low VO2max individuals exhibit some metabolic-endocrine disruption, and acute aerobic exercise sessions performed at low, moderate, and high intensities are capable of modulating metabolic-endocrine parameters, mainly at high-intensity, in a physical fitness-dependent way, given that Low VO2max group was more responsive and seem to be able to appropriate more exercise-related benefits.
Evidence of trans-generational developmental modifications induced by simulated heat waves in an arthropod
Authors: Walzer A. , Formayer H. , Tixier M.-S.
Published: March 2020

Heat waves are considered to pose a greater risk to arthropods with their limited thermoregulation abilities than the increase of mean temperatures. Theoretically, within- and trans-generational modifications may allow populations to keep pace with rapidly occurring heat waves. Here, we evaluated this assumption using individuals of predatory miteAmblydromalus limonicusfrom the F1 and F2 generation, which were exposed to summer or simulated heat wave conditions during juvenile development. Independent of generation, survival and male body size were insensitive to heat waves. Heat stress elongated juvenile development of F1 males and females, and lowered the F1 female size at maturity indicating non-adaptive within-generational effects. Trans-generational modifications speeded up the development of F2 males and females and resulted in larger body size of F2 females deriving from the heat wave-experienced F1 generation. Faster F2 development should be adaptive, because it reduces the exposure time to heat waves and promotes an early beginning of mating activities. Being large at extreme high temperatures maybe a benefit for the F2 females, because large individuals are less vulnerable to dehydration and overheating. Thus, the potential fitness loss from reduced F1 growth should be compensated by increased fitness in the F2 indicating adaptive trans-generational modifications.
Adapting SureSelect enrichment protocol to the Ion Torrent S5 platform in molecular diagnostics of craniosynostosis
Authors: Bukowska-Olech Ewelina , Popiel Delfina , Koczyk Grzegorz , Sowińska-Seidler Anna , Socha Magdalena , Wojciechowicz Bartosz , Dawidziuk Adam , Larysz Dawid , Jamsheer Aleksander
Published: March 2020

Obtaining reliable and high fidelity next-generation sequencing (NGS) data requires to choose a suitable sequencing platform and a library preparation approach, which both have their inherent assay-specific limitations. Here, we present the results of successful adaptation of SureSelect hybridisation-based target enrichment protocol for the sequencing on the Ion Torrent S5 platform, which is designed to work preferably with amplicon-based panels. In our study, we applied a custom NGS panel to screen a cohort of 16 unrelated patients affected by premature fusion of the cranial sutures, i.e. craniosynostosis (CS). CS occurs either as an isolated malformation or in a syndromic form, representing a genetically heterogeneous and clinically variable group of disorders. The approach presented here allowed us to achieve high quality NGS data and confirmed molecular diagnosis in 19% of cases, reaching the diagnostic yield similar to some of the published research reports. In conclusion, we demonstrated that an alternative enrichment strategy for library preparations can be successfully applied prior to sequencing on the Ion Torrent S5 platform. Also, we proved that the custom NGS panel designed by us represents a useful and effective tool in the molecular diagnostics of patients with CS.
Expansion of the Sahara Desert and shrinking of frozen land of the Arctic
Authors: Liu Ye , Xue Yongkang
Published: March 2020

Expansion of the Sahara Desert (SD) and greening of the Arctic tundra-glacier region (ArcTG) have been hot subjects under extensive investigations. However, quantitative and comprehensive assessments of the landform changes in these regions are lacking. Here we use both observations and climate-ecosystem models to quantify/project changes in the extents and boundaries of the SD and ArcTG based on climate and vegetation indices. It is found that, based on observed climate indices, the SD expands 8% and the ArcTG shrinks 16% during 1950–2015, respectively. SD southern boundaries advance 100 km southward, and ArcTG boundaries are displaced about 50 km poleward in 1950–2015. The simulated trends based on climate and vegetation indices show consistent results with some differences probably due to missing anthropogenic forcing and two-way vegetation-climate feedback effect in simulations. The projected climate and vegetation indices show these trends will continue in 2015–2050.