bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of UPR effector proteins ATF6 and XBP1 reduce colorectal cancer cell proliferation and stemness by activating PERK signaling
Authors: Spaan Claudia N. , Smit Wouter L. , van Lidth de Jeude Jooske F. , Meijer Bartolomeus J. , Muncan Vanesa , van den Brink Gijs R. , Heijmans Jarom
Published: June 2019

The unfolded protein response (UPR) acts through its downstream branches, PERK-eIF2α signaling, IRE1α-XBP1 signaling and ATF6 signaling. In the intestine, activation of the UPR through the kinase PERK results in differentiation of intestinal epithelial stem cells and colon cancer stem cells, whereas deletion of XBP1 results in increased stemness and adenomagenesis. How downstream activation of XBP1 and ATF6 influences intestinal stemness and proliferation remains largely unknown. We generated colorectal cancer cells (LS174T) that harbor doxycycline inducible expression of the active forms of either XBP1(s) or ATF61-373. Activation of either XBP1 or ATF6 resulted in reduced cellular proliferation and reduced expression of markers of intestinal epithelial stemness. Moreover, XBP1 and ATF6 activation reduced global protein synthesis and lowered the threshold for UPR activation. XBP1-mediated loss of stemness and proliferation resulted from crossactivation of PERK-eIF2α signaling and could be rescued by constitutive expression of eIF2α phosphatase GADD34. We thus find that enforced activation of XBP1 and ATF6 results in reduction of stemness and proliferation. We expose a novel interaction between XBP1 and PERK-eIF2α signaling.
Site-selectively generated photon emitters in monolayer MoS2 via local helium ion irradiation
Authors: Klein J. , Lorke M. , Florian M. , Sigger F. , Sigl L. , Rey S. , Wierzbowski J. , Cerne J. , Müller K. , Mitterreiter E. , Zimmermann P. , Taniguchi T. , Watanabe K. , Wurstbauer U. , Kaniber M. , Knap M. , Schmidt R. , Finley J. J. , Holleitner A. W.
Published: June 2019

Quantum light sources in solid-state systems are of major interest as a basic ingredient for integrated quantum photonic technologies. The ability to tailor quantum emitters via site-selective defect engineering is essential for realizing scalable architectures. However, a major difficulty is that defects need to be controllably positioned within the material. Here, we overcome this challenge by controllably irradiating monolayer MoS2 using a sub-nm focused helium ion beam to deterministically create defects. Subsequent encapsulation of the ion exposed MoS2 flake with high-quality hBN reveals spectrally narrow emission lines that produce photons in the visible spectral range. Based on ab-initio calculations we interpret these emission lines as stemming from the recombination of highly localized electron–hole complexes at defect states generated by the local helium ion exposure. Our approach to deterministically write optically active defect states in a single transition metal dichalcogenide layer provides a platform for realizing exotic many-body systems, including coupled single-photon sources and interacting exciton lattices that may allow the exploration of Hubbard physics.
Topologically-guided continuous protein crystallization controls bacterial surface layer self-assembly
Authors: Comerci Colin J. , Herrmann Jonathan , Yoon Joshua , Jabbarpour Fatemeh , Zhou Xiaofeng , Nomellini John F. , Smit John , Shapiro Lucy , Wakatsuki Soichi , Moerner W. E.
Published: June 2019

Many bacteria and most archaea possess a crystalline protein surface layer (S-layer), which surrounds their growing and topologically complicated outer surface. Constructing a macromolecular structure of this scale generally requires localized enzymatic machinery, but a regulatory framework for S-layer assembly has not been identified. By labeling, superresolution imaging, and tracking the S-layer protein (SLP) from C. crescentus, we show that 2D protein self-assembly is sufficient to build and maintain the S-layer in living cells by efficient protein crystal nucleation and growth. We propose a model supported by single-molecule tracking whereby randomly secreted SLP monomers diffuse on the lipopolysaccharide (LPS) outer membrane until incorporated at the edges of growing 2D S-layer crystals. Surface topology creates crystal defects and boundaries, thereby guiding S-layer assembly. Unsupervised assembly poses challenges for therapeutics targeting S-layers. However, protein crystallization as an evolutionary driver rationalizes S-layer diversity and raises the potential for biologically inspired self-assembling macromolecular nanomaterials.
Minimal exposure of lipid II cycle intermediates triggers cell wall antibiotic resistance
Authors: Piepenbreier Hannah , Diehl Angelika , Fritz Georg
Published: June 2019

Cell wall antibiotics are crucial for combatting the emerging wave of resistant bacteria. Yet, our understanding of antibiotic action is limited, as many strains devoid of all resistance determinants display far higher antibiotic tolerance in vivo than suggested by the antibiotic-target binding affinity in vitro. To resolve this conflict, here we develop a comprehensive theory for the bacterial cell wall biosynthetic pathway and study its perturbation by antibiotics. We find that the closed-loop architecture of the lipid II cycle of wall biosynthesis features a highly asymmetric distribution of pathway intermediates, and show that antibiotic tolerance scales inversely with the abundance of the targeted pathway intermediate. We formalize this principle of minimal target exposure as intrinsic resistance mechanism and predict how cooperative drug-target interactions can mitigate resistance. The theory accurately predicts the in vivo efficacy for various cell wall antibiotics in different Gram-positive bacteria and contributes to a systems-level understanding of antibiotic action.
Conformational proofreading of distant 40S ribosomal subunit maturation events by a long-range communication mechanism
Authors: Mitterer Valentin , Shayan Ramtin , Ferreira-Cerca Sébastien , Murat Guillaume , Enne Tanja , Rinaldi Dana , Weigl Sarah , Omanic Hajrija , Gleizes Pierre-Emmanuel , Kressler Dieter , Plisson-Chastang Celia , Pertschy Brigitte
Published: June 2019

Eukaryotic ribosomes are synthesized in a hierarchical process driven by a plethora of assembly factors, but how maturation events at physically distant sites on pre-ribosomes are coordinated is poorly understood. Using functional analyses and cryo-EM, we show that ribosomal protein Rps20 orchestrates communication between two multi-step maturation events across the pre-40S subunit. Our study reveals that during pre-40S maturation, formation of essential contacts between Rps20 and Rps3 permits assembly factor Ltv1 to recruit the Hrr25 kinase, thereby promoting Ltv1 phosphorylation. In parallel, a deeply buried Rps20 loop reaches to the opposite pre-40S side, where it stimulates Rio2 ATPase activity. Both cascades converge to the final maturation steps releasing Rio2 and phosphorylated Ltv1. We propose that conformational proofreading exerted via Rps20 constitutes a checkpoint permitting assembly factor release and progression of pre-40S maturation only after completion of all earlier maturation steps.
Convergent genomic signatures of flight loss in birds suggest a switch of main fuel
Authors: Pan Shengkai , Lin Yi , Liu Qiong , Duan Jinzhi , Lin Zhenzhen , Wang Yusong , Wang Xueli , Lam Sin Man , Zou Zhen , Shui Guanghou , Zhang Yu , Zhang Zhengwang , Zhan Xiangjiang
Published: June 2019

Flight loss in birds is as characteristic of the class Aves as flight itself. Although morphological and physiological differences are recognized in flight-degenerate bird species, their contributions to recurrent flight degeneration events across modern birds and underlying genetic mechanisms remain unclear. Here, in an analysis of 295 million nucleotides from 48 bird genomes, we identify two convergent sites causing amino acid changes in ATGLSer321Glyand ACOT7Ala197Valin flight-degenerate birds, which to our knowledge have not previously been implicated in loss of flight. Functional assays suggest that Ser321Gly reduces lipid hydrolytic ability of ATGL, and Ala197Val enhances acyl-CoA hydrolytic activity of ACOT7. Modeling simulations suggest a switch of main energy sources from lipids to carbohydrates in flight-degenerate birds. Our results thus suggest that physiological convergence plays an important role in flight degeneration, and anatomical convergence often invoked may not.
Identification of HIV transmitting CD11c+ human epidermal dendritic cells
Authors: Bertram Kirstie M. , Botting Rachel A. , Baharlou Heeva , Rhodes Jake W. , Rana Hafsa , Graham J. Dinny , Patrick Ellis , Fletcher James , Plasto Toby M. , Truong Naomi R. , Royle Caroline , Doyle Chloe M. , Tong Orion , Nasr Najla , Barnouti Laith , Kohout Mark P. , Brooks Andrew J. , Wines Michael P. , Haertsch Peter , Lim Jake , Gosselink Martijn P. , Ctercteko Grahame , Estes Jacob D. , Churchill Melissa J. , Cameron Paul U. , Hunter Eric , Haniffa Muzlifah A. , Cunningham Anthony L. , Harman Andrew N.
Published: June 2019

Langerhans cells (LC) are thought to be the only mononuclear phagocyte population in the epidermis where they detect pathogens. Here, we show that CD11c+ dendritic cells (DCs) are also present. These cells are transcriptionally similar to dermal cDC2 but are more efficient antigen-presenting cells. Compared to LCs, epidermal CD11c+ DCs are enriched in anogenital tissues where they preferentially interact with HIV, express the higher levels of HIV entry receptor CCR5, support the higher levels of HIV uptake and replication and are more efficient at transmitting the virus to CD4 T cells. Importantly, these findings are observed using both a lab-adapted and transmitted/founder strain of HIV. We also describe a CD33low cell population, which is transcriptionally similar to LCs but does not appear to function as antigen-presenting cells or acts as HIV target cells. Our findings reveal that epidermal DCs in anogenital tissues potentially play a key role in sexual transmission of HIV.
Evidence for low density holes in Jupiter’s ionosphere
Authors: Imai Masafumi , Kolmašová Ivana , Kurth William S. , Santolík Ondřej , Hospodarsky George B. , Gurnett Donald A. , Brown Shannon T. , Bolton Scott J. , Connerney John E. P. , Levin Steven M.
Published: June 2019

Intense electromagnetic impulses induced by Jupiter’s lightning have been recognised to produce both low-frequency dispersed whistler emissions and non-dispersed radio pulses. Here we report the discovery of electromagnetic pulses associated with Jovian lightning. Detected by the Juno Waves instrument during its polar perijove passes, the dispersed millisecond pulses called Jupiter dispersed pulses (JDPs) provide evidence of low density holes in Jupiter’s ionosphere. 445 of these JDP emissions have been observed in snapshots of electric field waveforms. Assuming that the maximum delay occurs in the vicinity of the free space ordinary mode cutoff frequency, we estimate the characteristic plasma densities (5.1 to 250 cm−3) and lengths (0.6 km to 1.3 × 105 km) of plasma irregularities along the line of propagation from lightning to Juno. These irregularities show a direct link to low plasma density holes with ≤250 cm−3 in the nightside ionosphere.
Publisher Correction: Plasmodium falciparum sexual differentiation in malaria patients is associated with host factors and GDV1-dependent genes
Authors: Usui Miho , Prajapati Surendra K. , Ayanful-Torgby Ruth , Acquah Festus K. , Cudjoe Elizabeth , Kakaney Courage , Amponsah Jones A. , Obboh Evans K. , Reddy Deepti K. , Barbeau Michelle C. , Simons Lacy M. , Czesny Beata , Raiciulescu Sorana , Olsen Cara , Abuaku Benjamin K. , Amoah Linda E. , Williamson Kim C.
Published: June 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Learning cellular morphology with neural networks
Authors: Schubert Philipp J. , Dorkenwald Sven , Januszewski Michał , Jain Viren , Kornfeld Joergen
Published: June 2019

Reconstruction and annotation of volume electron microscopy data sets of brain tissue is challenging but can reveal invaluable information about neuronal circuits. Significant progress has recently been made in automated neuron reconstruction as well as automated detection of synapses. However, methods for automating the morphological analysis of nanometer-resolution reconstructions are less established, despite the diversity of possible applications. Here, we introduce cellular morphology neural networks (CMNs), based on multi-view projections sampled from automatically reconstructed cellular fragments of arbitrary size and shape. Using unsupervised training, we infer morphology embeddings (Neuron2vec) of neuron reconstructions and train CMNs to identify glia cells in a supervised classification paradigm, which are then used to resolve neuron reconstruction errors. Finally, we demonstrate that CMNs can be used to identify subcellular compartments and the cell types of neuron reconstructions.
Phononic integrated circuitry and spin–orbit interaction of phonons
Authors: Fu Wei , Shen Zhen , Xu Yuntao , Zou Chang-Ling , Cheng Risheng , Han Xu , Tang Hong X.
Published: June 2019

High-index-contrast optical waveguides are crucial for the development of photonic integrated circuits with complex functionalities. Despite many similarities between optical and acoustic waves, high-acoustic-index-contrast phononic waveguides remain elusive, preventing intricate manipulation of phonons on par with its photonic counterpart. Here, we present the realization of such phononic waveguides and the formation of phononic integrated circuits through exploiting a gallium-nitride-on-sapphire platform, which provides strong confinement and control of phonons. By demonstrating key building blocks analogous to photonic circuit components, we establish the functionality and scalability of the phononic circuits. Moreover, the unidirectional excitation of propagating phononic modes allows the exploration of unconventional spin–orbit interaction of phonons in this circuit platform, which opens up the possibility of novel applications such as acoustic gyroscopic and non-reciprocal devices. Such phononic integrated circuits could provide an invaluable resource for both classical and quantum information processing.
Publisher Correction: Proton mediated spin state transition of cobalt heme analogs
Authors: Zhao Jianping , Peng Qian , Wang Zijian , Xu Wei , Xiao Hongyan , Wu Qi , Sun Hao-Ling , Ma Fang , Zhao Jiyong , Sun Cheng-Jun , Zhao Jianzhang , Li Jianfeng
Published: June 2019

In the original version of this Article, the four structural depictions of orbital distributions were inadvertently omitted from Figure 5. This has now been corrected in both the HTML and PDF versions of the Article.
Reliable electrochemical phase diagrams of magnetic transition metals and related compounds from high-throughput ab initio calculations
Authors: Huang Liang-Feng , Rondinelli James M.
Published: June 2019

Magnetic transition metals (mTM = Cr, Mn, Fe, Co, and Ni) and their complex compounds (oxides, hydroxides, and oxyhydroxides) are highly important material platforms for diverse technologies, where electrochemical phase diagrams with respect to electrode potential and solution pH can be used to effectively understand their corrosion and oxidation behaviors in relevant aqueous environments. Many previous decades-old mTM–Pourbaix diagrams are inconsistent with various direct electrochemical observations, because experimental complexities associated with extracting reliable free energies of formation (ΔfG) lead to inaccuracies in the data used for modeling. Here, we develop a high-throughput simulation approach based on density-functional theory (DFT), which quickly screens structures and compounds using efficient DFT methods and calculates accurate ΔfGvalues, using high-level exchange-correlation functions to obtain ab initio Pourbaix diagrams in comprehensive and close agreement with various important electrochemical, geological, and biomagnetic observations reported over the last few decades. We also analyze the microscopic mechanisms governing the chemical trends among the ΔfGvalues and Pourbaix diagrams to further understand the electrochemical behaviors of mTM-based materials. Last, we provide probability profiles at variable electrode potential and solution pH to show quantitatively the likely coexistence of multiple-phase areas and diffuse phase boundaries.
Robust dynamical invariants in sequential neural activity
Authors: Elices Irene , Levi Rafael , Arroyo David , Rodriguez Francisco B. , Varona Pablo
Published: June 2019

By studying different sources of temporal variability in central pattern generator (CPG) circuits, we unveil fundamental aspects of the instantaneous balance between flexibility and robustness in sequential dynamics -a property that characterizes many systems that display neural rhythms. Our analysis of the triphasic rhythm of the pyloric CPG (Carcinus maenas) shows strong robustness of transient dynamics in keeping not only the activation sequences but also specific cycle-by-cycle temporal relationships in the form of strong linear correlations between pivotal time intervals, i.e. dynamical invariants. The level of variability and coordination was characterized using intrinsic time references and intervals in long recordings of both regular and irregular rhythms. Out of the many possible combinations of time intervals studied, only two cycle-by-cycle dynamical invariants were identified, existing even outside steady states. While executing a neural sequence, dynamical invariants reflect constraints to optimize functionality by shaping the actual intervals in which activity emerges to build the sequence. Our results indicate that such boundaries to the adaptability arise from the interaction between the rich dynamics of neurons and connections. We suggest that invariant temporal sequence relationships could be present in other networks, including those shaping sequences of functional brain rhythms, and underlie rhythm programming and functionality.
Analysis of enriched rare variants in JPH2-encoded junctophilin-2 among Greater Middle Eastern individuals reveals a novel homozygous variant associated with neonatal dilated cardiomyopathy
Authors: Jones Edward G. , Mazaheri Neda , Maroofian Reza , Zamani Mina , Seifi Tahereh , Sedaghat Alireza , Shariati Gholamreza , Jamshidi Yalda , Allen Hugh D. , Wehrens Xander H. T. , Galehdari Hamid , Landstrom Andrew P.
Published: June 2019

Junctophilin-2 (JPH2) is a part of the junctional membrane complex that facilitates calcium-handling in the cardiomyocyte. Previously, missense variants in JPH2 have been linked to hypertrophic cardiomyopathy; however, pathogenic “loss of function” (LOF) variants have not been described. Family-based genetic analysis of GME individuals with cardiomyopathic disease identified an Iranian patient with dilated cardiomyopathy (DCM) as a carrier of a novel, homozygous single nucleotide insertion in JPH2 resulting in a stop codon (JPH2-p.E641*). A second Iranian family with consanguineous parents hosting an identical heterozygous variant had 2 children die in childhood from cardiac failure. To characterize ethnicity-dependent genetic variability in JPH2 and to identify homozygous JPH2 variants associated with cardiac disease, we identified variants in JPH2 in a worldwide control cohort (gnomAD) and 2 similar cohorts from the Greater Middle East (GME Variome, Iranome). These were compared against ethnicity-matched clinical whole exome sequencing (WES) referral tests and a case cohort of individuals with hypertrophic cardiomyopathy (HCM) based on comprehensive review of the literature. Worldwide, 1.45% of healthy individuals hosted a rare JPH2 variant with a significantly higher proportion among GME individuals (4.45%); LOF variants were rare overall (0.04%) yet were most prevalent in GME (0.21%). The increased prevalence of LOF variants in GME individuals was corroborated among region-specific, clinical WES cohorts. In conclusion, we report ethnic-specific differences in JPH2 rare variants, with GME individuals being at higher risk of hosting homozygous LOF variants. This conclusion is supported by the identification of a novel JPH2 LOF variant confirmed by segregation analysis resulting in autosomal recessive pediatric DCM due to presumptive JPH2 truncation.
Optical Coherence Tomography Angiography for Diagnosis of Choroidal Neovascularization in Chronic Central Serous Chorioretinopathy after Photodynamic Therapy
Authors: Wu Jian-Sheng , Chen San-Ni
Published: June 2019

The authors evaluated the proportion of choroidal neovascularization (CNV) detected by spectral-domain optical coherence tomography angiography (OCTA) in eyes with chronic central serous chorioretinopathy (CSC) (more than 3 months) with previous treatment via half-dose photodynamic therapy (PDT). All patients were followed up with at least twelve months. Macular angiograms were obtained using spectral-domain OCT (SD-OCT, RTVue XR; Optovue). CNV was defined as flow in the outer retinal slab between the outer plexiform layer and Bruch’s membrane. Clinical characteristics were compared between CNV and non-CNV groups. Seventy eyes of 61 patients (51 male and 10 female) were included. The average age was 46.2 years old. The average duration of symptom was 32.9 months. All patients were treated with half-dose PDT initially. Eleven eyes (15.7%) received more than one session of PDT. CNV was diagnosed in 32 of 70 eyes (45.7%) based on OCTA. Only 6 of the 32 eyes (18.8%) needed intravitreal anti- vascular endothelial growth factor (VEGF) therapy for the exudative activity of CNV. Older age (p = 0.059), larger PDT spot size (p = 0.024), and thinner subfoveal choroidal thickness (p = 0.008) were noted in CNV group. The authors conclude that OCTA reveals high rates of CNV associated with chronic CSC after PDT. Patients in the CNV group had older age, larger PDT spot size, and thinner subfoveal choroidal thickness. OCTA may be considered as a first step in identifying CNV in chronic CSC following PDT.
Drug repurposing in alternative medicine: herbal digestive Sochehwan exerts multifaceted effects against metabolic syndrome
Authors: Lim Dong-Woo , Kim Hyuck , Kim Young-Mi , Chin Young-Won , Park Won-Hwan , Kim Jai-Eun
Published: June 2019

New drug development is a challenging process that requires high-risk, huge costs and long lead times. Therefore, drug repurposing is considered a strategic and economic way towards successful drug development. Sochehwan (SCH) is a herbal formula well known as a digestive aid in traditional oriental medicine, is referred to in classic medical texts, and is available as an over-the-counter drug for indications of digestive ailments. Interestingly, another medical text written in earlier age describes different indication of SCH yet to be examined. We conducted a series of investigations using maturated adipocytes, free fatty acid (FFA) induced hepatic steatosis model in vitro and high-fat diet (HFD) mice model in vivo. Exposure to SCH regulated expression of adipogenic genes and proteins, significantly inhibiting formation of lipid droplets in 3T3-L1 cells. Similarly, SCH treatment modulated proteins related with energy metabolism decreasing lipid accumulation in FFA induced HepG2 cells. Furthermore, HFD-fed c57BL/6 J mice supplemented with SCH exhibited significant changes in serum glucose and lipid profiles. Histologic analysis of mice liver and adipose tissue showed that SCH administration attenuated hepatic steatosis and hypertrophy of adipose tissue. In overall, the results show that SCH can potentially be used to treat metabolic syndrome (MetS) by enhancing glucose metabolism and inhibiting lipogenesis through activating AMP-activated protein kinase (AMPK) and its downstream signaling. Furthermore, it seems to be a feasible drug repurposing strategy for drugs originating from alternative medicine to revise the value for buried indications of some herbal prescription in old traditional Chinese Medicine (TCM) classics.
Polymorphisms of the cryptochrome 2 and mitoguardin 2 genes are associated with the variation of lipid-related traits in Duroc pigs
Authors: Mármol-Sánchez Emilio , Quintanilla Raquel , Cardoso Taina F. , Jordana Vidal Jordi , Amills Marcel
Published: June 2019

The genetic factors determining the phenotypic variation of porcine fatness phenotypes are still largely unknown. We investigated whether the polymorphism of eight genes (MIGA2, CRY2, NPAS2, CIART, ARNTL2, PER1, PER2 and PCK1), which display differential expression in the skeletal muscle of fasted and fed sows, is associated with the variation of lipid and mRNA expression phenotypes in Duroc pigs. The performance of an association analysis with the GEMMA software demonstrated that the rs330779504 SNP in the MIGA2 gene is associated with LDL concentration at 190 days (LDL2, corrected P-value = 0.057). Moreover, the rs320439526 SNP of the CRY2 gene displayed a significant association with stearic acid content in the longissimus dorsi muscle (LD C18:0, corrected P-value = 0.015). Both SNPs were also associated with the mRNA levels of the corresponding genes in the gluteus medius skeletal muscle. From a biological perspective these results are meaningful because MIGA2 protein plays an essential role in mitochondrial fusion, a process tightly connected with the energy status of the cell, while CRY2 is a fundamental component of the circadian clock. However, inclusion of these two SNPs in chromosome-wide association analyses demonstrated that they are not located at the peaks of significance for the two traits under study (LDL2 for rs330779504 and LD C18:0 for rs320439526), thus implying that these two SNPs do not have causal effects.
In-plane Aligned Colloidal 2D WS2 Nanoflakes for Solution-Processable Thin Films with High Planar Conductivity
Authors: Mastria Rosanna , Scarfiello Riccardo , Altamura Davide , Giannini Cinzia , Liscio Andrea , Kovtun Alessandro , Bianco Giuseppe Valerio , Bruno Giovanni , Grillo Vincenzo , Tavabi Amir H. , Dunin-Borkowski Rafal E. , Nobile Concetta , Cola Adriano , Cozzoli P. Davide , Gambino Salvatore , Rizzo Aurora
Published: June 2019

Two-dimensional transition-metal dichalcolgenides (2D-TMDs) are among the most intriguing materials for next-generation electronic and optoelectronic devices. Albeit still at the embryonic stage, building thin films by manipulating and stacking preformed 2D nanosheets is now emerging as a practical and cost-effective bottom-up paradigm to obtain excellent electrical properties over large areas. Herein, we exploit the ultrathin morphology and outstanding solution stability of 2D WS2colloidal nanocrystals to make thin films of TMDs assembled on a millimetre scale by a layer-by-layer deposition approach. We found that a room-temperature surface treatment with a superacid, performed with the precise scope of removing the native insulating surfactants, promotes in-plane assembly of the colloidal WS2nanoflakes into stacks parallel to the substrate, along with healing of sulphur vacancies in the lattice that are detrimental to electrical conductivity. The as-obtained 2D WS2thin films, characterized by a smooth and compact morphology, feature a high planar conductivity of up to 1 μS, comparable to the values reported for epitaxially grown WS2monolayers, and enable photocurrent generation upon light irradiation over a wide range of visible to near-infrared frequencies.
A Simple Procedure for Creating Scalable Phenotypic Screening Assays in Human Neurons
Authors: Sridharan BanuPriya , Hubbs Christopher , Llamosas Nerea , Kilinc Murat , Singhera Fakhar U. , Willems Erik , Piper David R. , Scampavia Louis , Rumbaugh Gavin , Spicer Timothy P.
Published: June 2019

Neurons created from human induced pluripotent stem cells (hiPSCs) provide the capability of identifying biological mechanisms that underlie brain disorders. IPSC-derived human neurons, or iNs, hold promise for advancing precision medicine through drug screening, though it remains unclear to what extent iNs can support early-stage drug discovery efforts in industrial-scale screening centers. Despite several reported approaches to generate iNs from iPSCs, each suffer from technological limitations that challenge their scalability and reproducibility, both requirements for successful screening assays. We addressed these challenges by initially removing the roadblocks related to scaling of iNs for high throughput screening (HTS)-ready assays. We accomplished this by simplifying the production and plating of iNs and adapting them to a freezer-ready format. We then tested the performance of freezer-ready iNs in an HTS-amenable phenotypic assay that measured neurite outgrowth. This assay successfully identified small molecule inhibitors of neurite outgrowth. Importantly, we provide evidence that this scalable iN-based assay was both robust and highly reproducible across different laboratories. These streamlined approaches are compatible with any iPSC line that can produce iNs. Thus, our findings indicate that current methods for producing iPSCs are appropriate for large-scale drug-discovery campaigns (i.e. >10e5compounds) that read out simple neuronal phenotypes. However, due to the inherent limitations of currently available iN differentiation protocols, technological advances are required to achieve similar scalability for screens that require more complex phenotypes related to neuronal function.
Effects of ten years organic and conventional farming on early seedling traits of evolving winter wheat composite cross populations
Authors: A.V. Vijaya Bhaskar , Baresel Jörg Peter , Weedon Odette , Finckh Maria R.
Published: June 2019

Early vigour traits of wheat composite cross populations (CCPs) based on high yielding (Y) or high quality (Q) or Y*Q varietal intercross evolving under organic or conventional conditions in parallel populations were studied hydroponically. To eliminate storage and year effects, frozen F6, F10, F11and F15seeds were multiplied in one field, resulting in the respective Fx.1generations. This eliminated generation and growing system effects on seed size for the F6.1F10.1and F15.1.Due to a severe winter kill affecting the F11, the generation effect persisted, leading to larger seeds and markedly different seedling traits in the F11.1compared to the F10.1and F15.1. Seedling traits were similar among parallel populations. Shoot length and weight increased in both systems until the F11.1across farming systems and remained constant thereafter. Over time,seminal root length and root weight of organic CCPs increased and total- and specific- root length decreased significantly compared to the conventional CCPs. Rooting patterns under organic conditions suggests better ability to reach deeper soil nutrients. In both systems, Q and YQ CCPs were more vigorous than Y CCPs, confirming genetic differences among populations. Overall, heterogeneous populations appear very plastic and selection pressure was stronger in organic systems.
Sources, distribution and fate of microfibres on the Great Barrier Reef, Australia
Authors: Jensen Lene H. , Motti Cherie A. , Garm Anders L. , Tonin Hemerson , Kroon Frederieke J.
Published: June 2019

Marine microdebris, in particular microplastics (plastics <5 mm), has become an issue of international concern due to its prevalence, persistence and potential adverse impacts on marine ecosystems. Informing source reduction based on ecological effects requires an understanding of the origin, distribution and characteristics of microdebris and the interactions with marine organisms. Here we show widespread contamination of the central Great Barrier Reef environment with microdebris, with microfibres comprising 86% of all items detected. Microdebris intake by coral reef fish was non-random, with chemical composition, shape and colour differing significantly from that detected in surface waters. Furthermore, the origin of microdebris contamination in surface waters is non-random with riverine discharge a likely source for microdebris detected at inshore, but not at offshore reef locations. Our findings demonstrate the complexities associated with determining marine microdebris exposure and fate, and assist in improving future ecological assessments and prioritizing source reduction.
Reactivation of Cytomegalovirus Increases Nitric Oxide and IL-10 Levels in Sepsis and is Associated with Changes in Renal Parameters and Worse Clinical Outcome
Authors: Silva Taylon Felipe , Concato Virgínia Márcia , Tomiotto-Pellissier Fernanda , Gonçalves Manoela Daiele , Bortoleti Bruna Taciane da Silva , Tavares Eliandro Reis , Yamauchi Lucy Megumi , Grion Cintia Magalhães Carvalho , Simão Andréa Name Colado , Miranda-Sapla Milena Menegazzo , Costa Idessania Nazareth , Pavanelli Wander Rogério , Conchon-Costa Ivete
Published: June 2019

CMV reactivation has been widely associated with bacterial sepsis and occurs in approximately 30% of these individuals, is associated with a longer ICU stay, prolongation of the need for mechanical ventilation, and over 80% increase in the mortality rate, being directly associated with severe organ dysfunction and hemodynamic imbalance. Thus, the aim of this study was to evaluate the role of CMV reactivation in sepsis progression. The overall occurrence of cytomegalovirus reactivation in the cohort was 17.58%. Was observed an increase in plasma levels of NO, reduction of percentage of free days of mechanical ventilation and arterial pH, as well as changes in coagulation parameters in the reactivated group. There was also a significant increase in IL-10, creatinine, urea levels and reduction of 24-hour urine output. These variables still correlated with viral load, demonstrating an association between the reactivation process and kidney failure present in sepsis. The reactivated group still had 2.1 times the risk of developing septic shock and an increase in the mortality rates. CMV is reactivated in sepsis and these patients presented a higher risk of developing septic shock and higher mortality rates and our data suggest that IL-10 and NO may be involved in this process.
Estimating Y-Str Mutation Rates and Tmrca Through Deep-Rooting Italian Pedigrees
Authors: Boattini Alessio , Sarno Stefania , Mazzarisi Alessandra M. , Viroli Cinzia , De Fanti Sara , Bini Carla , Larmuseau Maarten H. D. , Pelotti Susi , Luiselli Donata
Published: June 2019

In the population genomics era, the study of Y-chromosome variability is still of the greatest interest for several fields ranging from molecular anthropology to forensics and genetic genealogy. In particular, mutation rates of Y-chromosomal Short Tandem Repeats markers (Y-STRs) are key parameters for different interdisciplinary applications. Among them, testing the patrilineal relatedness between individuals and calculating their Time of Most Recent Common Ancestors (TMRCAs) are of the utmost importance. To provide new valuable estimates and to address these issues, we typed 47 Y-STRs (comprising Yfiler, PowerPlex23 and YfilerPlus loci, the recently defined Rapidly Mutating [RM] panel and 11 additional markers often used in genetic genealogical applications) in 135 individuals belonging to 66 deep-rooting paternal genealogies from Northern Italy. Our results confirmed that the genealogy approach is an effective way to obtain reliable Y-STR mutation rate estimates even with a limited number of samples. Moreover, they showed that the impact of multi-step mutations and backmutations is negligible within the temporal scale usually adopted by forensic and genetic genealogy analyses. We then detected a significant association between the number of mutations within genealogies and observed TMRCAs. Therefore, we compared observed and expected TMRCAs by implementing a Bayesian procedure originally designed by Walsh (2001) and showed that the method yields a good performance (up to 96.72%), especially when using the Infinite Alleles Model (IAM).
Label-free detection of nanoparticles using depth scanning correlation interferometric microscopy
Authors: Aygun Ugur , Urey Hakan , Yalcin Ozkumur Ayca
Published: June 2019

Single particle level visualization of biological nanoparticles such as viruses and exosomes is challenging due to their small size and low dielectric contrast. Fluorescence based methods are highly preferred, however they require labelling which may perturb the functionality of the particle of interest. On the other hand, wide-field interferometric microscopy can be used to detect sub-diffraction limited nanoparticles without using any labels. Here we demonstrate that utilization of defocused images enhances the visibility of nanoparticles in interferometric microscopy and thus improves the detectable size limit. With the proposed method termed as Depth Scanning Correlation (DSC) Interferometric Microscopy, we experimentally demonstrate the detection of sub-35nm dielectric particles without using any labels. Furthermore, we demonstrate direct detection of single exosomes. This label-free and high throughput nanoparticle detection technique can be used to sense and characterize biological particles over a range between a few tens to a few hundred nanometers, where conventional methods are insufficient.
Automated monitoring of behaviour in zebrafish after invasive procedures
Authors: Deakin Anthony G. , Buckley Jonathan , AlZu’bi Hamzah S. , Cossins Andrew R. , Spencer Joseph W. , Al’Nuaimy Waleed , Young Iain S. , Thomson Jack S. , Sneddon Lynne U.
Published: June 2019

Fish are used in a variety of experimental contexts often in high numbers. To maintain their welfare and ensure valid results during invasive procedures it is vital that we can detect subtle changes in behaviour that may allow us to intervene to provide pain-relief. Therefore, an automated method, the Fish Behaviour Index (FBI), was devised and used for testing the impact of laboratory procedures and efficacy of analgesic drugs in the model species, the zebrafish. Cameras with tracking software were used to visually track and quantify female zebrafish behaviour in real time after a number of laboratory procedures including fin clipping, PIT tagging, and nociceptor excitation via injection of acetic acid subcutaneously. The FBI was derived from activity and distance swum measured before and after these procedures compared with control and sham groups. Further, the efficacy of a range of drugs with analgesic properties to identify efficacy of these agents was explored. Lidocaine (5 mg/L), flunixin (8 mg/L) and morphine (48 mg/L) prevented the associated reduction in activity and distance swum after fin clipping. From an ethical perspective, the FBI represents a significant refinement in the use of zebrafish and could be adopted across a wide range of biological disciplines.
Seasonal development of a coastal microbial mat
Authors: Cardoso Daniela Clara , Cretoiu Mariana Silvia , Stal Lucas J. , Bolhuis Henk
Published: June 2019

Growth and activity of coastal microbial mats is strongly seasonal. The development of these mats starts in early spring and fully maturate during late summer, where after growth ceases and subsequently the mat deteriorates by erosion and decomposition in winter. Here, the composition of the microbial community of three different mats developing along the tidal gradient of the North Sea beach of the Dutch barrier island Schiermonnikoog was analysed. The 16S ribosomal RNA molecules and the associated gene were sequenced in order to obtain the active (RNA) and resident (DNA) community members, respectively. Proteobacteria, Cyanobacteria, and Bacteroidetes dominated the mats during the whole year but considerable differences among these groups were found along the tidal gradient and seasonally when observed at a finer taxonomic resolution. Richness and diversity increased during the year starting from a pioneering community that is gradually succeeded by a more diverse climax community. The initial pioneers consisted of the cold-adapted photoautotrophic cyanobacterium Nodularia sp. and potential cold adapted members of the alphaproteobacterial Loktanella genus. These pioneers were succeeded by, amongst others, cyanobacteria belonging to the genera Leptolyngbya, Lyngbya, and Phormidium. At the upper littoral (Dune site), which was characterized by an extensive salt marsh vegetation, the mats contained a distinct bacterial community that potentially contribute to or benefit from plant decay. This study reports in detail on the seasonal changes and succession of these coastal microbial mat communities and discusses the potential forces that drive these changes.
Broadband and Tunable RCS Reduction using High-order Reflections and Salisbury-type Absorption Mechanisms
Authors: Song Jiakun , Wu Xiaoyu , Huang Cheng , Yang Jianing , Ji Chen , Zhang Changlei , Luo Xiangang
Published: June 2019

In this paper, a broadband and tunable radar cross section (RCS) reduction structure is proposed by using the hybrid physical mechanism that is based on high-order reflections and Salisbury-type absorption. Our design combines the high-index grating structure with a traditional Salisbury screen in which the lossy sheet is made of a graphene structure. When it is illuminated by a plane wave with normal incidence, the Salisbury screen can absorb the incoming wave, and the introducing high-index grating structure could further reduce the backward scattering wave by generating high-order reflection beams, which broadens the RCS reduction bandwidth. In addition, the RCS reduction level can be dynamically controlled by tuning the surface resistance of the graphene layer. Simulated results show that the proposed structure can realize tunable RCS reduction between 4.1 and 18 GHz under normal incidence with different graphene resistances. Experimental results are in accordance with those of the simulation results. In addition, the scattering field distributions and the plots of surface power loss density have been illustrated to analyze the RCS-reduction mechanism of our structure.
An in vitro pressure model towards studying the response of primary retinal ganglion cells to elevated hydrostatic pressures
Authors: Wu Jing , Mak Heather Kayew , Chan Yau Kei , Lin Chen , Kong Cihang , Leung Christopher Kai Shun , Shum Ho Cheung
Published: June 2019

Glaucoma is a leading cause of blindness characterized by progressive degeneration of retinal ganglion cells (RGCs). A well-established risk factor for the development and progression of glaucoma is elevation of intraocular pressure (IOP). However, how elevated IOP leads to RGC degeneration remains poorly understood. Here, we fabricate a facile, tunable hydrostatic pressure platform to study the effect of increased hydrostatic pressure on RGC axon and total neurite length, cell body area, dendritic branching, and cell survival. The hydrostatic pressure can be adjusted by varying the height of a liquid reservoir attached to a three-dimensional (3D)-printed adapter. The proposed platform enables long-term monitoring of primary RGCs in response to various pressure levels. Our results showed pressure-dependent changes in the axon length, and the total neurite length. The proportion of RGCs with neurite extensions significantly decreased by an average of 38 ± 2% (mean ± SEM) at pressures 30 mmHg and above (p < 0.05). The axon length and total neurite length decreased at a rate of 1.65 ± 0.18 μm and 4.07 ± 0.34 μm, respectively (p < 0.001), for each mmHg increase in pressure after 72 hours pressure treatment. Dendritic branching increased by 0.20 ± 0.05 intersections/day at pressures below 25 mmHg, and decreased by 0.07 ± 0.01 intersections/day at pressures above 25 mmHg (p < 0.001). There were no significant changes in cell body area under different levels of hydrostatic pressure (p ≥ 0.05). Application of this model will facilitate studies on the biophysical mechanisms that contribute to the pathophysiology of glaucoma and provide a channel for the screening of potential pharmacological agents for neuroprotection.
Core regulon of the global anaerobic regulator Anr targets central metabolism functions in Pseudomonas species
Authors: Tribelli Paula M. , Lujan Adela M. , Pardo Agustín , Ibarra José G. , Fernández Do Porto Darío , Smania Andrea , López Nancy I.
Published: June 2019

A comparative genome analysis of the global anaerobic regulator Anr regulon in five species of Pseudomonas with different life style was performed. Expression of this regulator was detected in all analyzed Pseudomonas. The predicted Anr regulon (pan-regulon) consisted of 253 genes. However, only 11 Anr-boxes located upstream of qor/hemF, hemN, cioA/PA3931, azu, rpsL, gltP, orthologous to PA2867, cspD, tyrZ, slyD and oprG, were common to all species. Whole genome in silico prediction of metabolic pathways identified genes belonging to heme biosynthesis, cytochromes and Entner-Doudoroff pathway as members of Anr regulon in all strains. Extending genome analysis to 28 Pseudomonas spp. spanning all phylogenetic groups showed Anr-boxes conservation in genes related to these functions. When present, genes related to anaerobic metabolism were predicted to hold Anr-boxes. Focused on the genomes of eight P. aeruginosa isolates of diverse origins, we observed a conserved regulon, sharing nearly 80% of the genes, indicating its key role in this opportunistic pathogen. The results suggest that the core Anr regulon comprises genes involved in central metabolism and aerobic electron transport chain, whereas those genes related to anaerobic metabolism and other functions constitute the accessory Anr-regulon, thereby differentially contributing to the ecological fitness of each Pseudomonas species.
Geometrically designed domain wall trap in tri-segmented nickel magnetic nanowires for spintronics devices
Authors: Nasirpouri Farzad , Peighambari-Sattari Seyed-Majid , Bran Cristina , Palmero Ester M. , Berganza Eguiarte Eider , Vazquez Manuel , Patsopoulos Aristotelis , Kechrakos Dimitris
Published: June 2019

“Domain wall traps” have been engineered and well-exploited in nanostrips by creating a geometrical trapping site, e.g. a single notch along a stripe, compared to diameter-modulated (DM) cylindrical magnetic nanowires (NWs) where multi-segmented DM-NWs have been generally studied. Here, we report our systematic study on the magnetization behavior, domain wall structure and its nucleation/propagation in tri-segmented diameter-modulated Ni nanowires, a simple system to investigate the magnetization reversal as function of segment geometry and lay-out order. We find out that the magnetization behavior of single Ni DM-NWs exhibits the significance of positional ordering of thick and thin segments, distinguished by two distinct geometries including: dumbbell-type (type I) and rolling pin-type (type II). Based on experimental and theoretical simulations, it was evidenced that the wide-narrow junctions create trap sites for domain walls where the narrow segment restricts their motion. This type of geometrically engineered nanowires exhibit potential efficiency for future novel spintronic devices in particular when assembled in arrays of DM-NWs as a practical three-dimensional memory device.
Rapid population transfer of a two-level system by a polychromatic driving field
Authors: Li D. X. , Shao X. Q.
Published: June 2019

We propose a simple exact analytical solution for a model consisting of a two-level system and a polychromatic driving field. It helps us to realize a rapid complete population transfer from the ground state to the excited state, and the system can be stable at the excited state for an extremely long time. A combination of the mechanism and the Rydberg atoms successfully prepares the Bell state and multipartite W state, and the experimental feasibility is discussed via the current experimental parameters. Finally, the simple exact analytical solution is generalized into a three-level system, which leads to a significant enhancement of the robustness against dissipation.