bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatial Extent and Temporal Correlation of Chorus and Hiss: Statistical Results From Multipoint THEMIS Observations
Authors: Agapitov O. , Mourenas D. , Artemyev A. , Mozer F. S. , Bonnell J. W. , Angelopoulos V. , Shastun V. , Krasnoselskikh V.
Published: October 2018

The spatial localization of whistler mode waves, determined by their generation process, propagation, and damping, is important for assessing the efficiency of wave‐particle interactions and the dynamics of the radiation belts. We use 11 years of multipoint wave measurements in 2007–2017 from five Time History of Events and Macroscale Interactions during Substorms (THEMIS) spacecraft covering L = 2–10 at low magnetic latitudes over all magnetic local times (MLTs) to characterize both the instantaneous spatial extent of chorus and hiss active regions and their wave amplitude distribution in the vicinity of their respective generation regions, making use of the time domain correlation technique. The correlation of lower band chorus wave power dynamics from two spacecraft measurements remains significant up to 250–800 km transverse to the background magnetic field, in agreement with the typical scale of a chorus element, with a shorter correlation length for higher peak wave power. Additionally, a coordinated analysis of average chorus amplitudes at separate locations shows that the radial extent of the chorus active region varies from 0.2 RE on the nightside to 1 RE on the dayside, with an azimuthal width of 1 MLT. The wave power correlation scale of hiss has no fine structure and is generally larger (1,500–3,000 km); its correlation remains nonnegligible up to 1.5 RE. Such observations are consistent with chorus generation by localized electron injections and subsequent hiss amplification at lower L shells from seed chorus waves having propagated and spread over a wider region inside the plasmasphere. The connection between hiss and chorus is further explored statistically through the correlation between their respective wave power variations, suggesting a significant link between them.
Wave Generation, Dissipation, and Disequilibrium in an Embayment With Complex Bathymetry
Authors: Chen Jia‐Lin , Ralston David K. , Geyer W. Rockwell , Sommerfield Christopher K. , Chant Robert J.
Published: October 2018

Heterogeneous, sharply varying bathymetry is common in estuaries and embayments, and complex interactions between the bathymetry and wave processes fundamentally alter the distribution of wave energy. The mechanisms that control the generation and dissipation of wind waves in an embayment with heterogeneous, sharply varying bathymetry are evaluated with an observational and numerical study of the Delaware Estuary. Waves in the lower bay depend on both local wind forcing and remote wave forcing from offshore, but elsewhere in the estuary waves are controlled by the local winds and the response of the wavefield to bathymetric variability. Differences in the wavefield with wind direction highlight the impacts of heterogeneous bathymetry and limited fetch. Under the typical winter northwest wind conditions waves are fetch‐limited in the middle estuary and reach equilibrium with local water depth only in the lower bay. During southerly wind conditions typical of storms, wave energy is near equilibrium in the lower bay, and midestuary waves are attenuated by the combination of whitecapping and bottom friction, particularly over the steep, longitudinal shoals. Although the energy dissipation due to bottom friction is generally small relative to whitecapping, it becomes significant where the waves shoal abruptly due to steep bottom topography. In contrast, directional spreading keeps wave heights in the main channel significantly less than local equilibrium. The wave disequilibrium in the deep navigational channel explains why the marked increase in depth by dredging of the modern channel has had little impact on wave conditions.
Anthropogenic Aerosol Indirect Effects in Cirrus Clouds
Authors: Penner Joyce E. , Zhou Cheng , Garnier Anne , Mitchell David L.
Published: October 2018

We have implemented a parameterization for forming ice in large‐scale cirrus clouds that accounts for the changes in updrafts associated with a spectrum of waves acting within each time step in the model. This allows us to account for the frequency of homogeneous and heterogeneous freezing events that occur within each time step of the model and helps to determine more realistic ice number concentrations as well as changes to ice number concentrations. The model is able to fit observations of ice number at the lowest temperatures in the tropical tropopause but is still somewhat high in tropical latitudes with temperatures between 195°K and 215°K. The climate forcings associated with different representations of heterogeneous ice nuclei (IN or INPs) are primarily negative unless large additions of IN are made, such as when we assumed that all aircraft soot acts as an IN. However, they can be close to zero if it is assumed that all background dust can act as an INP irrespective of how much sulfate is deposited on these particles. Our best estimate for the forcing of anthropogenic aircraft soot in this model is −0.2 ± 0.06 W/m2, while that from anthropogenic fossil/biofuel soot is −0.093 ± 0.033 W/m2. Natural and anthropogenic open biomass burning leads to a net forcing of −0.057 ± 0.05 W/m2.
Glucose homeostasis dependency on acini–islet–acinar (AIA) axis communication: a new possible pathophysiological hypothesis regarding diabetes mellitus
Authors: Pierzynowski Stefan G. , Gregory Peter C. , Filip Rafał , Woliński Jarosław , Pierzynowska Kateryna Goncharova
Published: October 2018

Studies have highlighted the existence of two intra-pancreatic axes of communication: one involved in the regulation of enzyme production by insulin—the insular–acinar axis; and another involved in the regulation of insulin release by pancreatic enzymes—the acini–insular axis. Previous studies by our laboratory show that pancreatic enzymes can affect blood glucose homeostasis and insulin secretion independently of their digestive functions, both from the gut lumen and probably from the blood. As a result we would like to introduce here the concept of acini–islet–acinar (AIA) axis communication (feedback), which could play an important role in the development of obesity and diabetes type 2. The AIA feedback links the endocrine and exocrine parts of the pancreas and emphasizes the essential role that the pancreas plays, as a single organ, in the regulation of glucose homeostasis by amylase most probably in gut epithelium and by insulin and glucagon in peripheral blood.
Gut dysbiosis is associated with the reduced exercise capacity of elderly patients with hypertension
Authors: Yu Yanbo , Mao Genxiang , Wang Jirong , Zhu Liyue , Lv Xiaoling , Tong Qian , Fang Yefei , Lv Yinxiang , Wang Guofu
Published: October 2018

Hypertension is a global health issue, and a reduced exercise capacity is unavoidable for older people. According to recent clinical studies, the intestinal microbiota play a crucial role in the pathogenesis of many human diseases. We investigated whether specific alterations in the gut microbiota contribute to the reduced exercise capacity of elderly patients with hypertension. This study enrolled 56 subjects, and all patients performed a cardiopulmonary exercise test and underwent fecal bacteria sequencing (16 s ribosomal RNA V4 region). According to peak oxygen uptake values, patients were divided into three groups (Weber A = 19, Weber B = 20, and Weber C = 17). The alpha diversity was not significantly different among the three groups. Regarding the beta diversity, Weber A samples were separate from the other two groups in the nonmetric multidimensional scaling ordination plot (ANOSIM pairwise comparisons generated an R > 0.5; p < 0.05). The abundance of Betaproteobacteria, Burkholderiales, Alcaligenaceae, Faecalibacterium and Ruminococcaceae was diminished in subjects with a reduced exercise capacity (LDA score > 4.0). Escherichia coli are a primary producer of trimethylamine and inflammation in the human gut, and the abundance of this bacteria was increased in patients with a reduced exercise capacity (LDA score > 4.0). On the other hand, Lachnospiraceae-Eubacterium_hallii_group, Lachnospiraceae-Lachnoclostridium, Lachnospiraceae-Blautia-Ruminococcus_sp__5_1_39BFAA, and Ruminococcaceae-Faecalibacterium belong to the order Clostridiales that are likely to produce short-chain fatty acids (LDA score > 4.0), and some of these species were enriched in the Weber B or Weber C group in multiple comparisons. Our data pointed to an altered gut microbiota as a potential contributor to the pathogenesis and progression of the reduced exercise capacity of elderly patients with hypertension.
A cysteine-based molecular code informs collagen C-propeptide assembly
Authors: DiChiara Andrew S. , Li Rasia C. , Suen Patreece H. , Hosseini Azade S. , Taylor Rebecca J. , Weickhardt Alexander F. , Malhotra Diya , McCaslin Darrell R. , Shoulders Matthew D.
Published: October 2018

Fundamental questions regarding collagen biosynthesis, especially with respect to the molecular origins of homotrimeric versus heterotrimeric assembly, remain unanswered. Here, we demonstrate that the presence or absence of a single cysteine in type-I collagen’s C-propeptide domain is a key factor governing the ability of a given collagen polypeptide to stably homotrimerize. We also identify a critical role for Ca2+ in non-covalent collagen C-propeptide trimerization, thereby priming the protein for disulfide-mediated covalent immortalization. The resulting cysteine-based code for stable assembly provides a molecular model that can be used to predict, a priori, the identity of not just collagen homotrimers, but also naturally occurring 2:1 and 1:1:1 heterotrimers. Moreover, the code applies across all of the sequence-diverse fibrillar collagens. These results provide new insight into how evolution leverages disulfide networks to fine-tune protein assembly, and will inform the ongoing development of designer proteins that assemble into specific oligomeric forms.
Generation of orthotopically functional salivary gland from embryonic stem cells
Authors: Tanaka Junichi , Ogawa Miho , Hojo Hironori , Kawashima Yusuke , Mabuchi Yo , Hata Kenji , Nakamura Shiro , Yasuhara Rika , Takamatsu Koki , Irié Tarou , Fukada Toshiyuki , Sakai Takayoshi , Inoue Tomio , Nishimura Riko , Ohara Osamu , Saito Ichiro , Ohba Shinsuke , Tsuji Takashi , Mishima Kenji
Published: October 2018

Organoids generated from pluripotent stem cells are used in the development of organ replacement regenerative therapy by recapitulating the process of organogenesis. These processes are strictly regulated by morphogen signalling and transcriptional networks. However, the precise transcription factors involved in the organogenesis of exocrine glands, including salivary glands, remain unknown. Here, we identify a specific combination of two transcription factors (Sox9 and Foxc1) responsible for the differentiation of mouse embryonic stem cell-derived oral ectoderm into the salivary gland rudiment in an organoid culture system. Following orthotopic transplantation into mice whose salivary glands had been removed, the induced salivary gland rudiment not only showed a similar morphology and gene expression profile to those of the embryonic salivary gland rudiment of normal mice but also exhibited characteristics of mature salivary glands, including saliva secretion. This study suggests that exocrine glands can be induced from pluripotent stem cells for organ replacement regenerative therapy.
Patient-derived frontotemporal lobar degeneration brain extracts induce formation and spreading of TDP-43 pathology in vivo
Authors: Porta Sílvia , Xu Yan , Restrepo Clark R. , Kwong Linda K. , Zhang Bin , Brown Hannah J. , Lee Edward B. , Trojanowski John Q. , Lee Virginia M.-Y.
Published: October 2018

The stereotypical distribution of TAR DNA-binding 43 protein (TDP-43) aggregates in frontotemporal lobar degeneration (FTLD-TDP) suggests that pathological TDP-43 spreads throughout the brain via cell-to-cell transmission and correlates with disease progression, but no in vivo experimental data support this hypothesis. We first develop a doxycycline-inducible cell line expressing GFP-tagged cytoplasmic TDP-43 protein (iGFP-NLSm) as a cell-based system to screen and identify seeding activity of human brain-derived pathological TDP-43 isolated from sporadic FTLD-TDP and familial cases with Granulin (FTLD-TDP-GRN) or C9orf72 repeat expansion mutations (FTLD-TDP-C9+). We demonstrate that intracerebral injections of biologically active pathogenic FTLD-TDP seeds into transgenic mice expressing cytoplasmic human TDP-43 (lines CamKIIa-hTDP-43NLSm, rNLS8, and CamKIIa-208) and non-transgenic mice led to the induction of de-novo TDP-43 pathology. Moreover, TDP-43 pathology progressively spreads throughout the brain in a time-dependent manner via the neuroanatomic connectome. Our study suggests that the progression of FTLD-TDP reflects the templated cell-to-cell transneuronal spread of pathological TDP-43.
Indoleacetate decarboxylase is a glycyl radical enzyme catalysing the formation of malodorant skatole
Authors: Liu Dazhi , Wei Yifeng , Liu Xuyang , Zhou Yan , Jiang Li , Yin Jinyu , Wang Feifei , Hu Yiling , Nanjaraj Urs Ankanahalli N. , Liu Yanhong , Ang Ee Lui , Zhao Suwen , Zhao Huimin , Zhang Yan
Published: October 2018

Skatole is a malodorous compound that contributes to the characteristic smell of animal faeces. Although skatole has long been known to originate from bacterial tryptophan fermentation, the enzyme catalysing its formation has so far remained elusive. Here we report the use of comparative genomics for the discovery of indoleacetate decarboxylase, an O2-sensitive glycyl radical enzyme catalysing the decarboxylation of indoleacetate to form skatole as the terminal step of tryptophan fermentation in certain anaerobic bacteria. We describe its biochemical characterization and compare it to other glycyl radical decarboxylases. Indoleacetate decarboxylase may serve as a genetic marker for the identification of skatole-producing environmental and human-associated bacteria, with impacts on human health and the livestock industry.
Immune-suppression by OsHV-1 viral infection causes fatal bacteraemia in Pacific oysters
Authors: de Lorgeril Julien , Lucasson Aude , Petton Bruno , Toulza Eve , Montagnani Caroline , Clerissi Camille , Vidal-Dupiol Jeremie , Chaparro Cristian , Galinier Richard , Escoubas Jean-Michel , Haffner Philippe , Dégremont Lionel , Charrière Guillaume M. , Lafont Maxime , Delort Abigaïl , Vergnes Agnès , Chiarello Marlène , Faury Nicole , Rubio Tristan , Leroy Marc A. , Pérignon Adeline , Régler Denis , Morga Benjamin , Alunno-Bruscia Marianne , Boudry Pierre , Le Roux Frédérique , Destoumieux-Garzόn Delphine , Gueguen Yannick , Mitta Guillaume
Published: October 2018

Infectious diseases are mostly explored using reductionist approaches despite repeated evidence showing them to be strongly influenced by numerous interacting host and environmental factors. Many diseases with a complex aetiology therefore remain misunderstood. By developing a holistic approach to tackle the complexity of interactions, we decipher the complex intra-host interactions underlying Pacific oyster mortality syndrome affecting juveniles of Crassostrea gigas, the main oyster species exploited worldwide. Using experimental infections reproducing the natural route of infection and combining thorough molecular analyses of oyster families with contrasted susceptibilities, we demonstrate that the disease is caused by multiple infection with an initial and necessary step of infection of oyster haemocytes by the Ostreid herpesvirus OsHV-1 µVar. Viral replication leads to the host entering an immune-compromised state, evolving towards subsequent bacteraemia by opportunistic bacteria. We propose the application of our integrative approach to decipher other multifactorial diseases that affect non-model species worldwide.
Predicting CTCF-mediated chromatin interactions by integrating genomic and epigenomic features
Authors: Kai Yan , Andricovich Jaclyn , Zeng Zhouhao , Zhu Jun , Tzatsos Alexandros , Peng Weiqun
Published: October 2018

The CCCTC-binding zinc-finger protein (CTCF)-mediated network of long-range chromatin interactions is important for genome organization and function. Although this network has been considered largely invariant, we find that it exhibits extensive cell-type-specific interactions that contribute to cell identity. Here, we present Lollipop, a machine-learning framework, which predicts CTCF-mediated long-range interactions using genomic and epigenomic features. Using ChIA-PET data as benchmark, we demonstrate that Lollipop accurately predicts CTCF-mediated chromatin interactions both within and across cell types, and outperforms other methods based only on CTCF motif orientation. Predictions are confirmed computationally and experimentally by Chromatin Conformation Capture (3C). Moreover, our approach identifies other determinants of CTCF-mediated chromatin wiring, such as gene expression within the loops. Our study contributes to a better understanding about the underlying principles of CTCF-mediated chromatin interactions and their impact on gene expression.
Unbiased biocatalytic solar-to-chemical conversion by FeOOH/BiVO4/perovskite tandem structure
Authors: Lee Yang Woo , Boonmongkolras Passarut , Son Eun Jin , Kim Jinhyun , Lee Sahng Ha , Kuk Su Keun , Ko Jong Wan , Shin Byungha , Park Chan Beum
Published: October 2018

Redox enzymes catalyze fascinating chemical reactions with excellent regio- and stereo-specificity. Nicotinamide adenine dinucleotide cofactor is essential in numerous redox biocatalytic reactions and needs to be regenerated because it is consumed as an equivalent during the enzymatic turnover. Here we report on unbiased photoelectrochemical tandem assembly of a photoanode (FeOOH/BiVO4) and a perovskite photovoltaic to provide sufficient potential for cofactor-dependent biocatalytic reactions. We obtain a high faradaic efficiency of 96.2% and an initial conversion rate of 2.4 mM h−1 without an external applied bias for the photoelectrochemical enzymatic conversion of α-ketoglutarate to l-glutamate via l-glutamate dehydrogenase. In addition, we achieve a total turnover number and a turnover frequency of the enzyme of 108,800 and 6200 h−1, respectively, demonstrating that the tandem configuration facilitates redox biocatalysis using light as the only energy source.
Space- and time-resolved small angle X-ray scattering to probe assembly of silver nanocrystal superlattices
Authors: Yu Yixuan , Yu Dian , Sadigh Babak , Orme Christine A.
Published: October 2018

The structure of nanocrystal superlattices has been extensively studied and well documented, however, their assembly process is poorly understood. In this work, we demonstrate an in situ space- and time-resolved small angle X-ray scattering measurement that we use to probe the assembly of silver nanocrystal superlattices driven by electric fields. The electric field creates a nanocrystal flux to the surface, providing a systematic means to vary the nanocrystal concentration near the electrode and thereby to initiate nucleation and growth of superlattices in several minutes. Using this approach, we measure the space- and time-resolved concentration and polydispersity gradients during deposition and show how they affect the superlattice constant and degree of order. We find that the field induces a size-selection effect that can reduce the polydispersity near the substrate by 21% leading to better quality crystals and resulting in field strength-dependent superlattice lattice constants.
Mechanochemical feedback control of dynamin independent endocytosis modulates membrane tension in adherent cells
Authors: Thottacherry Joseph Jose , Kosmalska Anita Joanna , Kumar Amit , Vishen Amit Singh , Elosegui-Artola Alberto , Pradhan Susav , Sharma Sumit , Singh Parvinder P. , Guadamillas Marta C. , Chaudhary Natasha , Vishwakarma Ram , Trepat Xavier , del Pozo Miguel A. , Parton Robert G. , Rao Madan , Pullarkat Pramod , Roca-Cusachs Pere , Mayor Satyajit
Published: October 2018

Plasma membrane tension regulates many key cellular processes. It is modulated by, and can modulate, membrane trafficking. However, the cellular pathway(s) involved in this interplay is poorly understood. Here we find that, among a number of endocytic processes operating simultaneously at the cell surface, a dynamin independent pathway, the CLIC/GEEC (CG) pathway, is rapidly and specifically upregulated upon a sudden reduction of tension. Moreover, inhibition (activation) of the CG pathway results in lower (higher) membrane tension. However, alteration in membrane tension does not directly modulate CG endocytosis. This requires vinculin, a mechano-transducer recruited to focal adhesion in adherent cells. Vinculin acts by controlling the levels of a key regulator of the CG pathway, GBF1, at the plasma membrane. Thus, the CG pathway directly regulates membrane tension and is in turn controlled via a mechano-chemical feedback inhibition, potentially leading to homeostatic regulation of membrane tension in adherent cells.
Non-neutralizing antibodies elicited by recombinant Lassa–Rabies vaccine are critical for protection against Lassa fever
Authors: Abreu-Mota Tiago , Hagen Katie R. , Cooper Kurt , Jahrling Peter B. , Tan Gene , Wirblich Christoph , Johnson Reed F. , Schnell Matthias J.
Published: October 2018

Lassa fever (LF), caused by Lassa virus (LASV), is a viral hemorrhagic fever for which no approved vaccine or potent antiviral treatment is available. LF is a WHO priority disease and, together with rabies, a major health burden in West Africa. Here we present the development and characterization of an inactivated recombinant LASV and rabies vaccine candidate (LASSARAB) that expresses a codon-optimized LASV glycoprotein (coGPC) and is adjuvanted by a TLR-4 agonist (GLA-SE). LASSARAB elicits lasting humoral response against LASV and RABV in both mouse and guinea pig models, and it protects both guinea pigs and mice against LF. We also demonstrate a previously unexplored role for non-neutralizing LASV GPC-specific antibodies as a major mechanism of protection by LASSARAB against LF through antibody-dependent cellular functions. Overall, these findings demonstrate an effective inactivated LF vaccine and elucidate a novel humoral correlate of protection for LF.
Extremely low genetic diversity in a circumpolar dragonfly species, Somatochlora sahlbergi (Insecta: Odonata: Anisoptera)
Authors: Kohli Manpreet K. , Sahlén Göran , Kuhn William R. , Ware Jessica L.
Published: October 2018

We present the first empirical treatment of the northernmost breeding dragonfly, Somatochlora sahlbergi. We sequenced populations from United States, Canada, Finland, Sweden and Norway for cytochrome oxidase I (COI) and D2 region of 28s. We found that, despite geographic barriers across its vast arctic range, S. sahlbergi is a single species. Not only does it appear to interbreed across its entire range, there also seems to be almost no variation among European and North American populations in their COI gene fragment (the barcode gene), which is usually extremely variable. We further found that characters thought to be diagnostic for the larvae of S. sahlbergi were absent in our European samples. We review and re-describe the habitat of this species based on new findings from recent field observations. Finally, we report for the first time the likely presence of this species in Japan. We hope our findings will encourage further study of this species and other under-studied insect taxa that inhabit the remote Arctic.
No Reliable Evidence for a Neanderthal-Châtelperronian Association at La Roche-à-Pierrot, Saint-Césaire
Authors: Gravina Brad , Bachellerie François , Caux Solène , Discamps Emmanuel , Faivre Jean-Philippe , Galland Aline , Michel Alexandre , Teyssandier Nicolas , Bordes Jean-Guillaume
Published: October 2018

The demise of Neanderthals and their interaction with dispersing anatomically modern human populations remain some of the most contentious issues in palaeoanthropology. The Châtelperronian, now generally recognized as the first genuine Upper Palaeolithic industry in Western Europe and commonly attributed to the Neanderthals, plays a pivotal role in these debates. The Neanderthal authorship of this techno-complex is based on reported associations of Neanderthal skeletal material with Châtelperronian assemblages at only two sites, La Roche-à-Pierrot (Saint-Césaire) and the Grotte du Renne (Arcy-sur-Cure). The reliability of such an association has, however, been the subject of heated controversy. Here we present a detailed taphonomic, spatial and typo-technological reassessment of the level (EJOP sup) containing the Neanderthal skeletal material at Saint-Césaire. Our assessment of a new larger sample of lithic artifacts, combined with a systematic refitting program and spatial projections of diagnostic artifacts, produced no reliable evidence for a Neanderthal-Châtelperronian association at the site. These results significantly impact current models concerning the Middle-to-Upper Palaeolithic transition in Western Europe and force a critical reappraisal of who exactly were the makers of the Châtelperronian.
Propensity-score-matched evaluation of under-recognition of acute kidney injury and short-term outcomes
Authors: Wu Buyun , Li Li , Cheng Xiaoyan , Yan Wenyan , Liu Yun , Xing Changying , Mao Huijuan
Published: October 2018

Acute kidney injury (AKI) is a common disease, but diagnosis is usually delayed or missed in hospitalized patients. The aim of this study was to investigate the impact of under-recognition of AKI (beyond 3 days after AKI onset) on short-time prognosis. Of 785 patients with under-recognition of AKI and 616 patients with timely-recognition of AKI were propensity matched in a 1:1 ratio. The two groups, with a total of 482 matched patients (241:241), were comparable in baseline covariates. Under-recognition of AKI was not associated with 30-day all-cause mortality in the logistic regression model with covariate adjustment (OR = 1.01, 95% CI = 0.62–1.64, p = 0.967). Sensitivity analyses and subgroup analyses also proved the association. There were also no significant differences in causes of 30-day mortality, in-hospital mortality, recovery of renal function at discharge, length of hospital stay, length of intensive care unit stay or hospitalization costs between the two groups, although timely-recognition group had more chance of renal consult and a little more interventions for AKI. In conclusion, under-recognition of AKI may not be associated with poor short-term outcomes of adult hospitalized patients via these propensity-score-matched analyses.
High fidelity CRISPR/Cas9 increases precise monoallelic and biallelic editing events in primordial germ cells
Authors: Idoko-Akoh Alewo , Taylor Lorna , Sang Helen M. , McGrew Michael J.
Published: October 2018

Primordial germ cells (PGCs), the embryonic precursors of the sperm and egg, are used for the introduction of genetic modifications into avian genome. Introduction of small defined sequences using genome editing has not been demonstrated in bird species. Here, we compared oligonucleotide-mediated HDR using wild type SpCas9 (SpCas9-WT) and high fidelity SpCas9-HF1 in PGCs and show that many loci in chicken PGCs can be precise edited using donors containing CRISPR/Cas9-blocking mutations positioned in the protospacer adjacent motif (PAM). However, targeting was more efficient using SpCas9-HF1 when mutations were introduced only into the gRNA target sequence. We subsequently employed an eGFP-to-BFP conversion assay, to directly compare HDR mediated by SpCas9-WT and SpCas9-HF1 and discovered that SpCas9-HF1 increases HDR while reducing INDEL formation. Furthermore, SpCas9-HF1 increases the frequency of single allele editing in comparison to SpCas9-WT. We used SpCas9-HF1 to demonstrate the introduction of monoallelic and biallelic point mutations into the FGF20 gene and generate clonal populations of edited PGCs with defined homozygous and heterozygous genotypes. Our results demonstrate the use of oligonucleotide donors and high fidelity CRISPR/Cas9 variants to perform precise genome editing with high efficiency in PGCs.
Alterations in the connection topology of brain structural networks in Internet gaming addiction
Authors: Park Chang-hyun , Chun Ji-Won , Cho Hyun , Kim Dai-Jin
Published: October 2018

Internet gaming addiction (IGA), as the most popular subtype of Internet addiction, is becoming a common and widespread mental health concern, but there are still debates on whether IGA constitutes a psychiatric disorder. The view on the brain as a complex network has developed network analysis of neuroimaging data, revealing that abnormalities of brain functional and structural systems are related to alterations in brain network configuration, such as small-world topology, in neuropsychiatric disorders. Here we applied network analysis to diffusion-weighted MRI data of 102 gaming individuals and 41 non-gaming healthy individuals to seek changes in the small-world topology of brain structural networks in IGA. The connection topology of brain structural networks shifted to the direction of random topology in the gaming individuals, irrespective of whether they were diagnosed with Internet gaming disorder. Furthermore, when we simulated targeted or untargeted attacks on nodes, the connection topology of the gaming individuals’ brain structural networks under no attacks was comparable to that of the non-gaming healthy individuals’ brain structural networks under targeted attacks. Alterations in connection topology provide a clue that Internet gaming addicted brains could be as abnormal as brains suffering from targeted damage.
Effects of aspirin-loaded graphene oxide coating of a titanium surface on proliferation and osteogenic differentiation of MC3T3-E1 cells
Authors: Ren Liping , Pan Shuang , Li Haiqing , Li Yanping , He Lina , Zhang Shuang , Che Jingyi , Niu Yumei
Published: October 2018

Graphene oxide (GO) has attracted considerable attention for biomedical applications such as drug delivery because of its two-dimensional structure, which provides a large surface area on both sides of the nanosheet. Here, a new method for titanium (Ti) surface modification involving a GO coating and aspirin (A) loading (A/Ti-GO) was developed, and the bioactive effects on mouse osteoblastic MC3T3-E1 cells were preliminarily studied. The X-ray photoelectron spectrometry indicated new C-O-N, C-Si-O-C, and C-N=C bond formation upon GO coating. Remarkably, the torsion test results showed stable bonding between the GO coating and Ti under a torsional shear force found in clinical settings, in that, there was no tearing or falling off of GO coating from the sample surface. More importantly, through π-π stacking interactions, the release of aspirin loaded on the surface of Ti-GO could sustain for 3 days. Furthermore, the A/Ti-GO surface displayed a significantly higher proliferation rate and differentiation of MC3T3-E1 cells into osteoblasts, which was confirmed by a water-soluble tetrazolium salt-8 (WST-8) assay and alkaline phosphatase activity test. Consequently, Ti surface modification involving GO coating and aspirin loading might be a useful contribution to improve the success rate of Ti implants in patients, especially in bone conditions.
The interplay between adipose-derived stem cells and bladder cancer cells
Authors: Maj Malgorzata , Kokocha Anna , Bajek Anna , Drewa Tomasz
Published: October 2018

Tissue engineering approaches offer alternative strategies for urinary diversion after radical cystectomy. Possible triggering of cancer recurrence remains, however, a significant concern in the application of stem-cell based therapies for oncological patients. Soluble mediators secreted by stem cells induce tissue remodelling effects, but may also promote cancer cells growth and metastasis. We observed a substantial increase in the concentration of IL-6 and IL-8 in the secretome of adipose-derived stem cells (ASCs) co-cultured with bladder cancer cells. Concentrations of GM-CSF, MCP-1 and RANTES were also elevated. Bioactive molecules produced by ASCs increased the viability of 5637 and HT-1376 cells by respectively 15.4% and 10.4% (p < 0.0001). A trend in reduction of adhesion to ECM components was also noted, even though no differences in β-catenin expression were detected. When HT-1376 cells were co-cultured with ASCs their migration and invasion increased by 24.5% (p < 0.0002) and 18.2% (p < 0.002). Expression of p-ERK1/2 increased in 5637 cells (2.2-fold; p < 0.001) and p-AKT in HB-CLS-1 cells (2.0-fold; p < 0.001). Our results confirm that ASCs crosstalk with bladder cancer cells in vitro what influences their proliferation and invasive properties. Since ASCs tropism to tumour microenvironment is well documented their application towards post-oncologic reconstruction should be approached with caution.
Assessing the regional carbon sink with its forming processes- a case study of Liaoning province, China
Authors: Zhu Xian-Jin , Zhang Han-Qi , Gao Yan-Ni , Yin Hong , Chen Zhi , Zhao Tian-Hong
Published: October 2018

Assessing the regional carbon sink sets the basis of regional carbon management, which involves many measures but has large uncertainties. Carbon sink assessment scheme based on its forming processes (CSF) is a recently proposed measure but repeatly calculates emission from water erosion and ignored human inducing carbon inputs. Therefore, we revised the CSF by calculating the direct outputs from land surface and adding human returned carbon (HC) to the input. The revised CSF thus involved gross primary productivity (GPP), ecosystem respiration (ER), carbon removal from cropland (CRC), emission from reactive carbon (ERC), emission from water erosion (Ewat), and HC, which can be obtained from public data sources. Then the revised CSF was applied to the Liaoning province of China. The estimated carbon input of Liaoning province during 2000–2014 was 114.77 ± 8.41 TgC yr−1, while the carbon output was 110.48 ± 8.38 TgC yr−1. The difference between input and output induced a carbon sink of 4.30 ± 2.20 TgC yr−1, accounting for 3.75% of total carbon input. The carbon sink spatially decreased from northeast to southwest, which was highly correlated with that of GPP. However, though its forming fluxes significantly increased from 2000 to 2014, the carbon sink showed a decreasing trend. In addition, the revised scheme only needed published and public data, which made it serve as an alternative approach for regional carbon budget assessment.
Growth and superconductivity of niobium titanium alloy thin films on strontium titanate (001) single-crystal substrates for superconducting joints
Authors: Shimizu Yuhei , Tonooka Kazuhiko , Yoshida Yoshiyuki , Furuse Mitsuho , Takashima Hiroshi
Published: October 2018

Aiming to introduce NbTi alloy superconducting joints for REBa2Cu3O7−δ (REBCO, RE: rare-earth element) superconducting wires, NbTi alloy thin films were deposited at room temperature on SrTiO3 (STO) (001) single-crystal substrates, which have a high lattice matching with REBCO (001). The strain, crystallinity, surface morphology, and superconducting property of the films with various thicknesses were investigated. The NbTi films grew in the orientation with (110)NbTi//(001)STO:[001]NbTi and [11–0] NbTi//[100]STO; that is, the NbTi lattices had two directions in the (110) of NbTi. The strain decreased and the crystallinity improved as the film thickness increased. The films were found to crystallize immediately at the interface between the films and substrates by cross-sectional scanning transmission electron microscopy. The flat surfaces of the films have mesh-like morphologies due to the growth of elongated NbTi grains along the [100] and [010] of the STO, reflecting the in-plane two directions of the NbTi lattices. The superconducting transition temperature of the films increased with improvement in the crystallinity of the films. The preparation of superconducting NbTi alloy thin films with sufficient crystallinity at room temperature suggested the possibility of forming the films on REBCO and the applicability of the films as superconducting joints.
Multi-compartment scaffold fabricated via 3D-printing as in vitro co-culture osteogenic model
Authors: De Giglio Elvira , Bonifacio Maria A. , Ferreira Ana M. , Cometa Stefania , Ti Zhi Yuan , Stanzione Antonella , Dalgarno Kenny , Gentile Piergiorgio
Published: October 2018

The development ofin vitro3D models to get insights into the mechanisms of bone regeneration could accelerate the translation of experimental findings to the clinic, reducing costs and duration of experiments. This work explores the design and manufacturing of multi-compartments structures in poly(ε-caprolactone) (PCL) 3D-printed by Fused Filament Fabrication technique. The construct was designed with interconnected stalls to host stem cells and endothelial cells. Cells were encapsulated within an optimised gellan gum (GG)-based hydrogel matrix, crosslinked using strontium (Sr2+) ions to exploit its bioactivity and finally, assembled within compartments with different sizes. Calcium (Ca2+)-crosslinked gels were also used as control for comparison of Sr2+osteogenic effect. The results obtained demonstrated that Sr2+ions were successfully diffused within the hydrogel matrix and increased the hydrogel matrix strength properties under compressive load. Thein vitroco-culture of human-TERT mesenchymal stem cells (TERT- hMSCs) and human umbilical vein endothelial cells (HUVECs), encapsulated within Sr2+ions containing GG-hydrogels and inter-connected by compartmentalised scaffolds under osteogenic conditions, enhanced cell viability and supported osteogenesis, with a significant increase of alkaline phosphatase activity, osteopontin and osteocalcin respect with the Ca2+-crosslinked GG-PCL scaffolds. These outcomes demonstrate that the design and manufacturing of compartmentalised co-culture of TERT-hMSCs and HUVEC populations enables an effective system to study and promote osteogenesis.
Gravure Printing of Water-based Silver Nanowire ink on Plastic Substrate for Flexible Electronics
Authors: Huang Qijin , Zhu Yong
Published: October 2018

Gravure printing is a promising technique for large-scale printed electronics. However, gravure printing of silver nanowires (AgNWs) so far has been limited in terms of resolution and electrical conductivity. In this study, gravure printing of water-based AgNW ink on a flexible substrate is demonstrated. By tailoring the ink properties, printing conditions and post-printing treatment, gravure printing enables printing of high-resolution, highly conductive AgNW patterns in large areas, with resolution as fine as 50 µm and conductivity as high as 5.34 × 104 S cm−1. The printed AgNW patterns on the flexible substrate show excellent flexibility under repeated bending. All these characteristics demonstrate the excellent potential of gravure printing of AgNWs for developing large-area flexible electronics.
Transcriptome analysis of the genes regulating phytohormone and cellular patterning in Lagerstroemia plant architecture
Authors: Ju Yiqian , Feng Lu , Wu Jiyang , Ye Yuanjun , Zheng Tangchun , Cai Ming , Cheng Tangren , Wang Jia , Zhang Qixiang , Pan Huitang
Published: October 2018

Plant architecture is a popular research topic because plants with different growth habits that may generate economic or ornamental value are in great demand by orchards and nurseries. However, the molecular basis of the architecture of woody perennial plants is poorly understood due to the complexity of the phenotypic and regulatory relationships. Here, transcriptional profiling of dwarf and non-dwarf crapemyrtles was performed, and potential target genes were identified based on the phenotype, histology and phytohormone metabolite levels. An integrated analysis demonstrated that the internode length was explained mainly by cell number and secondarily by cell length and revealed important hormones in regulatory pathway of Lagerstroemia architecture. Differentially expressed genes (DEGs) involved in phytohormone pathways and cellular patterning regulation were analysed, and the regulatory relationships between these parameters were evaluated at the transcriptional level. Exogenous indole-3-acetic acid (IAA) and gibberellin A4 (GA4) treatments further indicated the pivotal role of auxin in cell division within the shoot apical meristem (SAM) and suggested an interaction between auxin and GA4 in regulating the internode length of Lagerstroemia. These results provide insights for further functional genomic studies on the regulatory mechanisms underlying Lagerstroemia plant architecture and may improve the efficiency of woody plant molecular breeding.
Minimally invasive surgery for colorectal cancer remains underutilized in Germany despite its nationwide application over the last decade
Authors: Ghadban Tarik , Reeh Matthias , Bockhorn Maximilian , Heumann Asmus , Grotelueschen Rainer , Bachmann Kai , Izbicki Jakob R. , Perez Daniel R.
Published: October 2018

Minimally invasive surgery (MIS) has superior short-term outcomes than open surgery (OS) for colorectal cancer (CRC). However, a nationwide dataset has not been analysed to confirm these findings. We evaluated the distribution and outcomes of MIS for CRC from 2005 to 2015; all in-patients with CRC surgery procedure codes were identified from hospital data, which are entered into the nationwide diagnosis-related group database and forwarded anonymised to the Federal Bureau of Statistics. We determined absolute MIS, morbidity, and mortality rates for specific sub-categories, including procedure type. We identified 345,913 in-patient files. The MIS rate increased from 6.4% (n = 2366; 2005) to 28.5% (n = 8363; 2015), with the highest rates for sigmoid colon (38%) and rectal (39%) resections. The overall conversion rate was 14.4%, without noticeable improvement over time. International Classification of Disease codes related to postoperative complications were documented more frequently after OS than after MIS. OS was associated with a higher mortality rate (4.7%) than MIS (1.8%) (P < 0.001), even after stratifying patients according to the resection site. Use of MIS remains low in Germany compared with that in other European countries. Underutilization of MIS has to be addressed in the future by promoting structured training programs and standardization of laparoscopic surgery.
Sodium tanshinone IIA sulfonate protects ARPE-19 cells against oxidative stress by inhibiting autophagy and apoptosis
Authors: Han Dongmei , Wu Xingwei , Liu Libin , Shu Wanting , Huang Zhenping
Published: October 2018

Oxidative stress in retinal pigment epithelium (RPE) is considered to be a major contributor to the development and progression of age-related macular degeneration (AMD). Previous investigations have shown that sodium tanshinone IIA sulfonate (STS) can alleviate oxidative stress in haemorrhagic shock-induced organ damage and cigarette smoke-induced chronic obstructive pulmonary disease in mice. However, whether STS has a protective effect in ARPE-19 cells under oxidative stress and its exact mechanisms have not yet been fully elucidated. In the present study, we utilized H2O2 to establish an oxidative stress environment. Our findings show that STS activated the PI3K/AKT/mTOR pathway to inhibit autophagy and diminished the expression of the autophagic proteins Beclin 1, ATG3, ATG7 and ATG9 in ARPE-19 cells under oxidative stress. Detection of the intrinsic apoptosis-related factors BAX, mitochondrial membrane potential (MMP), caspase-9, caspase-3 and BCL-2, as well as the extrinsic apoptosis-related factors c-FLIP, v-FLIP and caspase-8, confirmed that STS inhibited the intrinsic and extrinsic apoptotic pathways, and attenuated apoptosis in ARPE-19 cells under oxidative stress conditions. These findings shed new light on the protective effects of STS in ARPE-19 cells and its mechanisms under oxidative stress to provide novel and promising therapeutic strategies for AMD.
Magnetization switching of multi-state magnetic structures with current-induced torques
Authors: Das Shubhankar , Avraham Liran , Telepinsky Yevgeniy , Mor Vladislav , Schultz Moty , Klein Lior
Published: October 2018

Spintronic devices often require the ability to locally change the magnetic configuration of ferromagnetic structures on a sub-micron scale. A promising route for achieving this goal is the use of heavy metal/ferromagnetic heterostructures where current flowing through the heavy metal layer generates field-like and anti-damping like torques on the magnetic layer. Commonly, such torques are used to switch magnets with a uniaxial anisotropy between two uniformly magnetized states. Here, we use such torques to switch magnetization in Ta/Ni0.80Fe0.20 heterostructures with uniaxial and biaxial anisotropy, where in the latter the magnetization is non-uniform. The anisotropies are induced by shape and the magnetic state is monitored using the planar Hall effect. As structures with several easy axes induced by shape can be part of a magnetic memory element, the results pave the way for multi-level magnetic memory with spin-orbit torque switching.
Induction of the viable but non-culturable state in bacterial pathogens by household cleaners and inorganic salts
Authors: Robben Christian , Fister Susanne , Witte Anna Kristina , Schoder Dagmar , Rossmanith Peter , Mester Patrick
Published: October 2018

Effective monitoring of microbial pathogens is essential for a successful preventive food safety and hygiene strategy. However, as most monitoring strategies are growth-based, these tests fail to detect pathogenic bacteria that have entered the viable but non-culturable (VBNC) state. The present study reports the induction of the VBNC state in five human pathogens by commercially available household cleaners in combination with inorganic salts. We determined that non-ionic surfactants, a common ingredient in household cleaners, can induce the VBNC state, when combined with salts. A screening study with 630 surfactant/salt combinations indicates a correlation between the hydrophobicity of the surfactant and VBNC induction in L. monocytogenes, E. coli, S. enterica serovar Typhimurium, S. aureus and toxin-producing enteropathogenic E. coli. Cells that were exposed to combinations of surfactants and salts for 5 min and up to 1 h lost their culturability on standard growth media while retaining their ATP production, fermentation of sugars and membrane integrity, which suggests intact and active metabolism. Screening also revealed major differences between Gram-negative and Gram-positive bacteria; the latter being more susceptible to VBNC induction. Combinations of such detergents and salts are found in many different environments and reflect realistic conditions in industrial and domestic surroundings. VBNC cells present in industrial environments, food-processing plants and even our daily routine represent a serious health risk due to possible resuscitation, unknown spreading, production of toxins and especially their invisibility to routine detection methods, which rely on culturability of cells and fail to detect VBNC pathogens.