bluuebunny/crossref_metadata_2025 huggingface dataset:
Bioactuators based on stimulus-responsive hydrogels and their emerging biomedical applications
Authors: Shi Qiang , Liu Hao , Tang Deding , Li Yuhui , Li XiuJun , Xu Feng
Published: November 2019

The increasingly intimate bond connecting soft actuation devices and emerging biomedical applications is triggering the development of novel materials with superb biocompatibility and a sensitive actuation capability that can reliably function as bio-use-oriented actuators in a human-friendly manner. Stimulus-responsive hydrogels are biocompatible with human tissues/organs, have sufficient water content, are similar to extracellular matrices in structure and chemophysical properties, and are responsive to external environmental stimuli, and these materials have recently attracted massive research interest for fabricating bioactuators. The great potential of employing such hydrogels that respond to various stimuli (e.g., pH, temperature, light, electricity, and magnetic fields) for actuation purposes has been revealed by their performances in real-time biosensing systems, targeted drug delivery, artificial muscle reconstruction, and cell microenvironment engineering. In this review, the material selection of hydrogels with multiple stimulus-responsive mechanisms for actuator fabrication is first introduced, followed by a detailed introduction to and discussion of the most recent progress in emerging biomedical applications of hydrogel-based bioactuators. Final conclusions, existing challenges, and upcoming development prospects are noted in light of the status quo of bioactuators based on stimulus-responsive hydrogels.
Low temperature upregulates cwp expression and modifies alternative splicing patterns, increasing the severity of cwp-induced tomato fruit cuticular microfissures
Authors: Chechanovsky Noam , Hovav Ran , Frenkel Rina , Faigenboim Adi , Eselson Yelena , Petreikov Marina , Moy Michal , Shen Shmuel , Schaffer Arthur A.
Published: November 2019

The cwp (cuticular water permeability) gene controls the development of cuticular microfissuring and subsequent fruit dehydration in tomato. The gene underwent silencing in the evolution of the fleshy cultivated tomato but is expressed in the primitive wild tomato relatives. The introgression of the expressed allele from the wild S. habrochaites (cwph) into the cultivated tomato (Solanum lycopersicum) leads to the phenotype of fruit water loss during and following ripening. In this report, we show that low temperature impacts on the severity of the cuticular microfissure phenotype via a combination of effects on both expression and alternative splicing of cwph. The cwp gene, comprising four exons and three introns, undergoes post-transcriptional alternative splicing processes, leading to seven alternative transcripts that differ in reading-frame lengths. Transgenic plants expressing each of the alternative transcripts identified the longest reading frame (VAR1) as the functional splice variant. Low temperature led to a strong upregulation of cwph expression, compounded by an increase in the relative proportion of the functional VAR1 transcript, leading to increased severity of microfissuring of the cuticle. In summary, we demonstrate the molecular mechanism behind the horticultural phenomenon of the low-temperature effect on cuticular microfissures in the dehydrating tomato.
Effective genome editing and identification of a regiospecific gallic acid 4-O-glycosyltransferase in pomegranate (Punica granatum L.)
Authors: Chang Lijing , Wu Sheng , Tian Li
Published: November 2019

Pomegranate (Punica granatum L.) trees are woody perennials that bear colorful and nutritious fruits rich in phenolic metabolites, e.g., hydrolyzable tannins (HTs) and flavonoids. We here report genome editing and gene discovery in pomegranate hairy roots using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) (CRISPR/Cas9), coupled with transcriptome and biochemical analyses. Single guide RNAs (sgRNAs) were designed to target two UDP-dependent glycosyltransferases (UGTs), PgUGT84A23 and PgUGT84A24, which possess overlapping activities in β-glucogallin (a galloylglucose ester; biosynthetic precursor of HTs) biosynthesis. A unique accumulation of gallic acid 3-O- and 4-O-glucosides (galloylglucose ethers) was observed in the PgUGT84A23 and PgUGT84A24 dual CRISPR/Cas9-edited lines (i.e., ugt84a23 ugt84a24) but not the control (empty vector) or PgUGT84A23/PgUGT84A24 single edited lines (ugt84a23 or ugt84a24). Transcriptome and real-time qPCR analyses identified 11 UGTs with increased expression in the ugt84a23 ugt84a24 hairy roots compared to the controls. Of the 11 candidate UGTs, only PgUGT72BD1 used gallic acid as substrate and produced a regiospecific product gallic acid 4-O-glucoside. This work demonstrates that the CRISPR/Cas9 method can facilitate functional genomics studies in pomegranate and shows promise for capitalizing on the metabolic potential of pomegranate for germplasm improvement.
Early anthropoid femora reveal divergent adaptive trajectories in catarrhine hind-limb evolution
Authors: Almécija Sergio , Tallman Melissa , Sallam Hesham M. , Fleagle John G. , Hammond Ashley S. , Seiffert Erik R.
Published: November 2019

The divergence of crown catarrhines—i.e., the split of cercopithecoids (Old World monkeys) from hominoids (apes and humans)—is a poorly understood phase in our shared evolutionary history with other primates. The two groups differ in the anatomy of the hip joint, a pattern that has been linked to their locomotor strategies: relatively restricted motion in cercopithecoids vs. more eclectic movements in hominoids. Here we take advantage of the first well-preserved proximal femur of the early Oligocene stem catarrhine Aegyptopithecus to investigate the evolution of this anatomical region using 3D morphometric and phylogenetically-informed evolutionary analyses. Our analyses reveal that cercopithecoids and hominoids have undergone divergent evolutionary transformations of the proximal femur from a similar ancestral morphology that is not seen in any living anthropoid, but is preserved in Aegyptopithecus, stem platyrrhines, and stem cercopithecoids. These results highlight the relevance of fossil evidence for illuminating key adaptive shifts in primate evolution.
Expanding the limits of the second genetic code with ribozymes
Authors: Lee Joongoo , Schwieter Kenneth E. , Watkins Andrew M. , Kim Do Soon , Yu Hao , Schwarz Kevin J. , Lim Jongdoo , Coronado Jaime , Byrom Michelle , Anslyn Eric V. , Ellington Andrew D. , Moore Jeffrey S. , Jewett Michael C.
Published: November 2019

The site-specific incorporation of noncanonical monomers into polypeptides through genetic code reprogramming permits synthesis of bio-based products that extend beyond natural limits. To better enable such efforts, flexizymes (transfer RNA (tRNA) synthetase-like ribozymes that recognize synthetic leaving groups) have been used to expand the scope of chemical substrates for ribosome-directed polymerization. The development of design rules for flexizyme-catalyzed acylation should allow scalable and rational expansion of genetic code reprogramming. Here we report the systematic synthesis of 37 substrates based on 4 chemically diverse scaffolds (phenylalanine, benzoic acid, heteroaromatic, and aliphatic monomers) with different electronic and steric factors. Of these substrates, 32 were acylated onto tRNA and incorporated into peptides by in vitro translation. Based on the design rules derived from this expanded alphabet, we successfully predicted the acylation of 6 additional monomers that could uniquely be incorporated into peptides and direct N-terminal incorporation of an aldehyde group for orthogonal bioconjugation reactions.
Universal scaling relations for the rational design of molecular water oxidation catalysts with near-zero overpotential
Authors: Craig Michael John , Coulter Gabriel , Dolan Eoin , Soriano-López Joaquín , Mates-Torres Eric , Schmitt Wolfgang , García-Melchor Max
Published: November 2019

A major roadblock in realizing large-scale production of hydrogen via electrochemical water splitting is the cost and inefficiency of current catalysts for the oxygen evolution reaction (OER). Computational research has driven important developments in understanding and designing heterogeneous OER catalysts using linear scaling relationships derived from computed binding energies. Herein, we interrogate 17 of the most active molecular OER catalysts, based on different transition metals (Ru, Mn, Fe, Co, Ni, and Cu), and show they obey similar scaling relations to those established for heterogeneous systems. However, we find that the conventional OER descriptor underestimates the activity for very active OER complexes as the standard approach neglects a crucial one-electron oxidation that many molecular catalysts undergo prior to O–O bond formation. Importantly, this additional step allows certain molecular catalysts to circumvent the “overpotential wall”, leading to enhanced performance. With this knowledge, we establish fundamental principles for the design of ideal molecular OER catalysts.
Evolutionary games on isothermal graphs
Authors: Allen Benjamin , Lippner Gabor , Nowak Martin A.
Published: November 2019

Population structure affects the outcome of natural selection. These effects can be modeled using evolutionary games on graphs. Recently, conditions were derived for a trait to be favored under weak selection, on any weighted graph, in terms of coalescence times of random walks. Here we consider isothermal graphs, which have the same total edge weight at each node. The conditions for success on isothermal graphs take a simple form, in which the effects of graph structure are captured in the ‘effective degree’—a measure of the effective number of neighbors per individual. For two update rules (death-Birth and birth-Death), cooperative behavior is favored on a large isothermal graph if the benefit-to-cost ratio exceeds the effective degree. For two other update rules (Birth-death and Death-birth), cooperation is never favored. We relate the effective degree of a graph to its spectral gap, thereby linking evolutionary dynamics to the theory of expander graphs. Surprisingly, we find graphs of infinite average degree that nonetheless provide strong support for cooperation.
Programming emergent symmetries with saddle-splay elasticity
Authors: Xia Yu , DeBenedictis Andrew A. , Kim Dae Seok , Chen Shenglan , Kim Se-Um , Cleaver Douglas J. , Atherton Timothy J. , Yang Shu
Published: November 2019

The director field adopted by a confined liquid crystal is controlled by a balance between the externally imposed interactions and the liquid’s internal orientational elasticity. While the latter is usually considered to resist all deformations, liquid crystals actually have an intrinsic propensity to adopt saddle-splay arrangements, characterised by the elastic constant $${K}_{24}$$

K

24

. In most realisations, dominant surface anchoring treatments suppress such deformations, rendering $${K}_{24}$$

K

24

immeasurable. Here we identify regimes where more subtle, patterned surfaces enable saddle-splay effects to be both observed and exploited. Utilising theory and continuum calculations, we determine experimental regimes where generic, achiral liquid crystals exhibit spontaneously broken surface symmetries. These provide a new route to measuring $${K}_{24}$$

K

24

. We further demonstrate a multistable device in which weak, but directional, fields switch between saddle-splay-motivated, spontaneously-polar surface states. Generalising beyond simple confinement, our highly scalable approach offers exciting opportunities for low-field, fast-switching optoelectronic devices which go beyond current technologies.
Super-geometric electron focusing on the hexagonal Fermi surface of PdCoO2
Authors: Bachmann Maja D. , Sharpe Aaron L. , Barnard Arthur W. , Putzke Carsten , König Markus , Khim Seunghyun , Goldhaber-Gordon David , Mackenzie Andrew P. , Moll Philip J. W.
Published: November 2019

Geometric electron optics may be implemented in solids when electron transport is ballistic on the length scale of a device. Currently, this is realized mainly in 2D materials characterized by circular Fermi surfaces. Here we demonstrate that the nearly perfectly hexagonal Fermi surface of PdCoO2 gives rise to highly directional ballistic transport. We probe this directional ballistic regime in a single crystal of PdCoO2 by use of focused ion beam (FIB) micro-machining, defining crystalline ballistic circuits with features as small as 250 nm. The peculiar hexagonal Fermi surface naturally leads to enhanced electron self-focusing effects in a magnetic field compared to circular Fermi surfaces. This super-geometric focusing can be quantitatively predicted for arbitrary device geometry, based on the hexagonal cyclotron orbits appearing in this material. These results suggest a novel class of ballistic electronic devices exploiting the unique transport characteristics of strongly faceted Fermi surfaces.
Active DNA unwinding and transport by a membrane-adapted helicase nanopore
Authors: Sun Ke , Zhao Changjian , Zeng Xiaojun , Chen Yuejia , Jiang Xin , Ding Xianting , Gou Lu , Xie Haiyang , Li Xinqiong , Zhang Xialin , Lin Sheng , Dou Linqin , Wei Long , Niu Haofu , Zhang Ming , Tian Ruocen , Sawyer Erica , Yuan Qingyue , Huang Yuqin , Chen Piaopiao , Zhao Chengjian , Zhou Cuisong , Ying Binwu , Shi Bingyang , Wei Xiawei , Jiang Ruotian , Zhang Lei , Lu Guangwen , Geng Jia
Published: November 2019

Nanoscale transport through nanopores and live-cell membranes plays a vital role in both key biological processes as well as biosensing and DNA sequencing. Active translocation of DNA through these nanopores usually needs enzyme assistance. Here we present a nanopore derived from truncated helicase E1 of bovine papillomavirus (BPV) with a lumen diameter of c.a. 1.3 nm. Cryogenic electron microscopy (cryo-EM) imaging and single channel recording confirm its insertion into planar lipid bilayer (BLM). The helicase nanopore in BLM allows the passive single-stranded DNA (ssDNA) transport and retains the helicase activity in vitro. Furthermore, we incorporate this helicase nanopore into the live cell membrane of HEK293T cells, and monitor the ssDNA delivery into the cell real-time at single molecule level. This type of nanopore is expected to provide an interesting tool to study the biophysics of biomotors in vitro, with potential applications in biosensing, drug delivery and real-time single cell analysis.
Single-digit-micrometer thickness wood speaker
Authors: Gan Wentao , Chen Chaoji , Kim Hyun-Tae , Lin Zhiwei , Dai Jiaqi , Dong Zhihua , Zhou Zhan , Ping Weiwei , He Shuaiming , Xiao Shaoliang , Yu Miao , Hu Liangbing
Published: November 2019

Thin films of several microns in thickness are ubiquitously used in packaging, electronics, and acoustic sensors. Here we demonstrate that natural wood can be directly converted into an ultrathin film with a record-small thickness of less than 10 μm through partial delignification followed by densification. Benefiting from this aligned and laminated structure, the ultrathin wood film exhibits excellent mechanical properties with a high tensile strength of 342 MPa and a Young’s modulus of 43.6 GPa, respectively. The material’s ultrathin thickness and exceptional mechanical strength enable excellent acoustic properties with a 1.83-times higher resonance frequency and a 1.25-times greater displacement amplitude than a commercial polypropylene diaphragm found in an audio speaker. As a proof-of-concept, we directly use the ultrathin wood film as a diaphragm in a real speaker that can output music. The ultrathin wood film with excellent mechanical property and acoustic performance is a promising candidate for next-generation acoustic speakers.
Functionalized azetidines via visible light-enabled aza Paternò-Büchi reactions
Authors: Becker Marc R. , Richardson Alistair D. , Schindler Corinna S.
Published: November 2019

Azetidines are four-membered nitrogen-containing heterocycles that hold great promise in current medicinal chemistry due to their desirable pharmacokinetic effects. However, a lack of efficient synthetic methods to access functionalized azetidines has hampered their incorporation into pharmaceutical lead structures. As a [2+2] cycloaddition reaction between imines and alkenes, the aza Paternò-Büchi reaction arguably represents the most direct approach to functionalized azetidines. Hampered by competing reaction paths accessible upon photochemical excitation of the substrates, the current synthetic utility of these transformations is greatly restricted. We herein report the development of a visible light-enabled aza Paternò-Büchi reaction that surmounts existing limitations and represents a mild solution for the direct formation of functionalized azetidines from imine and alkene containing precursors.
A generalized Stark effect electromodulation model for extracting excitonic properties in organic semiconductors
Authors: Liu Taili , Foo Yishu , Zapien Juan Antonio , Li Menglin , Tsang Sai-Wing
Published: November 2019

Electromodulation (EM) spectroscopy, a powerful technique to monitor the changes in polarizabilitypand dipole momentuof materials upon photo-excitation, can bring direct insight into the excitonic properties of materials. However, extracting Δpand Δufrom the electromodulation spectrum relies on fitting with optical absorption of the materials where optical effect in different device geometries might introduce large variation in the extracted values. Here, we demonstrate a systematic electromodulation study with various fitting approaches in both commonly adopted reflection and transmission device architectures. Strikingly, we have found that the previously ascribed continuum state threshold from the deviation between the measured and fitting results is questionable. Such deviation is found to be caused by the overlooked optical interference and electrorefraction effect. A generalized electromodulation model is proposed to incorporate the two effects, and the extracted Δpand Δuhave excellent consistency in both reflection and transmission modes in all organic film thicknesses.
Hierarchical nanostructured aluminum alloy with ultrahigh strength and large plasticity
Authors: Wu Ge , Liu Chang , Sun Ligang , Wang Qing , Sun Baoan , Han Bin , Kai Ji-Jung , Luan Junhua , Liu Chain Tsuan , Cao Ke , Lu Yang , Cheng Lizi , Lu Jian
Published: November 2019

High strength and high ductility are often mutually exclusive properties for structural metallic materials. This is particularly important for aluminum (Al)-based alloys which are widely commercially employed. Here, we introduce a hierarchical nanostructured Al alloy with a structure of Al nanograins surrounded by nano-sized metallic glass (MG) shells. It achieves an ultrahigh yield strength of 1.2 GPa in tension (1.7 GPa in compression) along with 15% plasticity in tension (over 70% in compression). The nano-sized MG phase facilitates such ultrahigh strength by impeding dislocation gliding from one nanograin to another, while continuous generation-movement-annihilation of dislocations in the Al nanograins and the flow behavior of the nano-sized MG phase result in increased plasticity. This plastic deformation mechanism is also an efficient way to decrease grain size to sub-10 nm size for low melting temperature metals like Al, making this structural design one solution to the strength-plasticity trade-off.
Designing yeast as plant-like hyperaccumulators for heavy metals
Authors: Sun George L. , Reynolds Erin. E. , Belcher Angela M.
Published: November 2019

Hyperaccumulators typically refer to plants that absorb and tolerate elevated amounts of heavy metals. Due to their unique metal trafficking abilities, hyperaccumulators are promising candidates for bioremediation applications. However, compared to bacteria-based bioremediation systems, plant life cycle is long and growing conditions are difficult to maintain hindering their adoption. Herein, we combine the robust growth and engineerability of bacteria with the unique waste management mechanisms of plants by using a more tractable platform-the common baker’s yeast-to create plant-like hyperaccumulators. Through overexpression of metal transporters and engineering metal trafficking pathways, engineered yeast strains are able to sequester metals at concentrations 10–100 times more than established hyperaccumulator thresholds for chromium, arsenic, and cadmium. Strains are further engineered to be selective for either cadmium or strontium removal, specifically for radioactive Sr90. Overall, this work presents a systematic approach for transforming yeast into metal hyperaccumulators that are as effective as their plant counterparts.
An inhalable nanoparticulate STING agonist synergizes with radiotherapy to confer long-term control of lung metastases
Authors: Liu Yang , Crowe William N. , Wang Lulu , Lu Yong , Petty W. Jeffrey , Habib Amyn A. , Zhao Dawen
Published: November 2019

Mounting evidence suggests that the tumor microenvironment is profoundly immunosuppressive. Thus, mitigating tumor immunosuppression is crucial for inducing sustained antitumor immunity. Whereas previous studies involved intratumoral injection, we report here an inhalable nanoparticle-immunotherapy system targeting pulmonary antigen presenting cells (APCs) to enhance anticancer immunity against lung metastases. Inhalation of phosphatidylserine coated liposome loaded with STING agonist cyclic guanosine monophosphate–adenosine monophosphate (NP-cGAMP) in mouse models of lung metastases enables rapid distribution of NP-cGAMP to both lungs and subsequent uptake by APCs without causing immunopathology. NP-cGAMP designed for enhanced cytosolic release of cGAMP stimulates STING signaling and type I interferons production in APCs, resulting in the pro-inflammatory tumor microenvironment in multifocal lung metastases. Furthermore, fractionated radiation delivered to one tumor-bearing lung synergizes with inhaled NP-cGAMP, eliciting systemic anticancer immunity, controlling metastases in both lungs, and conferring long-term survival in mice with lung metastases and with repeated tumor challenge.
Memory effects of Eurasian land processes cause enhanced cooling in response to sea ice loss
Authors: Nakamura Tetsu , Yamazaki Koji , Sato Tomonori , Ukita Jinro
Published: November 2019

Amplified Arctic warming and its relevance to mid-latitude cooling in winter have been intensively studied. Observational evidence has shown strong connections between decreasing sea ice and cooling over the Siberian/East Asian regions. However, the robustness of such connections remains a matter of discussion because modeling studies have shown divergent and controversial results. Here, we report a set of general circulation model experiments specifically designed to extract memory effects of land processes that can amplify sea ice–climate impacts. The results show that sea ice–induced cooling anomalies over the Eurasian continent are memorized in the snow amount and soil temperature fields, and they reemerge in the following winters to enhance negative Arctic Oscillation-like anomalies. The contribution from this memory effect is similar in magnitude to the direct effect of sea ice loss. The results emphasize the essential role of land processes in understanding and evaluating the Arctic–mid-latitude climate linkage.
Coordinated program between primary care and sleep unit for the management of obstructive sleep apnea
Authors: Mayos Mercè , Peñacoba Patricia , Pijoan Anna María Pedro , Santiveri Carme , Flor Xavier , Juvanteny Joan , Sampol Gabriel , Lloberes Patricia , Aoiz José Ignacio , Bayó Joan , Grau Núria , Fortuna Ana M. , Plaza Vicente , Llauger M. Antònia
Published: November 2019

The purpose of this study is to develop and validate a work model in the primary health-care setting for identifying patients with obstructive sleep apnea–hypopnea syndrome (OSAHS) based on clinical variables and an ambulatory sleep monitoring study. After screening, patients with mild–moderate OSAHS could be managed by primary care physicians, whereas those identified with severe OSAHS would be referred to specialists from sleep units for starting specific treatment. The proposed model does not move the entire health-care process to a generally overburdened primary care level and favors the coordinated work and the necessary flexibility to adapt the model to challenges and perspectives of OSAHS.
Gender similarities in the brain during mathematics development
Authors: Kersey Alyssa J. , Csumitta Kelsey D. , Cantlon Jessica F.
Published: November 2019

Some scientists and public figures have hypothesized that women and men differ in their pursuit of careers in science, technology, engineering, and mathematics (STEM) owing to biological differences in mathematics aptitude. However, little evidence supports such claims. Some studies of children and adults show gender differences in mathematics performance but in those studies it is impossible to disentangle intrinsic, biological differences from sociocultural influences. To investigate the early biology of mathematics and gender, we tested for gender differences in the neural processes of mathematics in young children. We measured 3–10-year-old children’s neural development with functional magnetic resonance imaging (fMRI) during naturalistic viewing of mathematics education videos. We implemented both frequentist and Bayesian analyses that quantify gender similarities and differences in neural processes. Across all analyses girls and boys showed significant gender similarities in neural functioning, indicating that boys and girls engage the same neural system during mathematics development.
Stress and productivity patterns of interrupted, synergistic, and antagonistic office activities
Authors: Zaman Shaila , Wesley Amanveer , Silva Dennis Rodrigo Da Cunha , Buddharaju Pradeep , Akbar Fatema , Gao Ge , Mark Gloria , Gutierrez-Osuna Ricardo , Pavlidis Ioannis
Published: November 2019

We describe a controlled experiment, aiming to study productivity and stress effects of email interruptions and activity interactions in the modern office. The measurement set includes multimodal data for n = 63 knowledge workers who volunteered for this experiment and were randomly assigned into four groups: (G1/G2) Batch email interruptions with/without exogenous stress. (G3/G4) Continual email interruptions with/without exogenous stress. To provide context, the experiment’s email treatments were surrounded by typical office tasks. The captured variables include physiological indicators of stress, measures of report writing quality and keystroke dynamics, as well as psychometric scores and biographic information detailing participants’ profiles. Investigations powered by this dataset are expected to lead to personalized recommendations for handling email interruptions and a deeper understanding of synergistic and antagonistic office activities. Given the centrality of email in the modern office, and the importance of office work to people’s lives and the economy, the present data have a valuable role to play.
Complete Human Penile Scaffold for Composite Tissue Engineering: Organ Decellularization and Characterization
Authors: Tan Yu , Landford Wilmina N. , Garza Matthew , Suarez Allister , Zhou Zhengbing , Coon Devin
Published: November 2019

Reconstruction for total penile defects presents unique challenges due to its anatomical and functional complexity. Standard methods suffer from high complication rates and poor functional outcomes. In this work we have developed the first protocol for decellularizing whole-organ human penile specimens for total penile tissue engineering. The use of a hybrid decellularization scheme combining micro-arterial perfusion, urethral catheter perfusion and external diffusion enabled the creation of a full-size scaffold with removal of immunogenic components. Decellularization was complete as assessed by H&E and immunohistochemistry, while quantification of residual DNA showed acceptably low levels (<50 ng/mg). An intact ECM was maintained with histologic architecture preservation on H&E and SEM as well as preservation of key proteins such as collagen-1, laminin and fibronectin and retention of growth factors VEGF (45%), EGF (57%) and TGF-beta1 (42%) on ELISA. Post-decellularization patency of the cavernosal arteries for future use in reseeding was demonstrated. Scaffold biocompatibility was evaluated using human adipose-derived stromal vascular cells. Live/Dead stains showed the scaffold successfully supported cell survival and expansion. Influence on cellular behavior was seen with significantly higher expression of VWF, COL1, SM22 and Desmin as compared to cell monolayer. Preliminary evidence for regional tropism was also seen, with formation of microtubules and increased endothelial marker expression in the cavernosa. This report of successful decellularization of the complete human phallus is an initial step towards developing a tissue engineered human penile scaffold with potential for more successfully restoring cosmetic, urinary and sexual function after complete penile loss.
Neural oscillations during cognitive processes in an App knock-in mouse model of Alzheimer’s disease pathology
Authors: Jacob Sofia , Davies Gethin , De Bock Marijke , Hermans Bart , Wintmolders Cindy , Bottelbergs Astrid , Borgers Marianne , Theunis Clara , Van Broeck Bianca , Manyakov Nikolay V. , Balschun Detlef , Drinkenburg Wilhelmus H.I.M.
Published: November 2019

Multiple animal models have been created to gain insight into Alzheimer’s disease (AD) pathology. Among the most commonly used models are transgenic mice overexpressing human amyloid precursor protein (APP) with mutations linked to familial AD, resulting in the formation of amyloid β plaques, one of the pathological hallmarks observed in AD patients. However, recent evidence suggests that the overexpression of APP by itself can confound some of the reported observations. Therefore, we investigated in the present study the AppNL-G-Fmodel, an App knock-in (App-KI) mouse model that develops amyloidosis in the absence of APP-overexpression. Our findings at the behavioral, electrophysiological, and histopathological level confirmed an age-dependent increase in Aβ1–42 levels and plaque deposition in these mice in accordance with previous reports. This had apparently no consequences on cognitive performance in a visual discrimination (VD) task, which was largely unaffected in AppNL-G-F mice at the ages tested. Additionally, we investigated neurophysiological functioning of several brain areas by phase-amplitude coupling (PAC) analysis, a measure associated with adequate cognitive functioning, during the VD task (starting at 4.5 months) and the exploration of home environment (at 5 and 8 months of age). While we did not detect age-dependent changes in PAC during home environment exploration for both the wild-type and the AppNL-G-F mice, we did observe subtle changes in PAC in the wild-type mice that were not present in the AppNL-G-F mice.
Microarray Embedding/Sectioning for Parallel Analysis of 3D Cell Spheroids
Authors: Gabriel Jonathan , Brennan David , Elisseeff Jennifer H. , Beachley Vince
Published: November 2019

Three-dimensional cell spheroid models can be used to predict the effect of drugs and therapeutics and to model tissue development and regeneration. The utility of these models is enhanced by high throughput 3D spheroid culture technologies allowing researchers to efficiently culture numerous spheroids under varied experimental conditions. Detailed analysis of high throughput spheroid culture is much less efficient and generally limited to narrow outputs, such as metabolic viability. We describe a microarray approach that makes traditional histological embedding/sectioning/staining feasible for large 3D cell spheroid sample sets. Detailed methodology to apply this technology is provided. Analysis of the technique validates the potential for efficient histological analysis of up to 96 spheroids in parallel. By integrating high throughput 3D spheroid culture technologies with advanced immunohistochemical techniques, this approach will allow researchers to efficiently probe expression of multiple biomarkers with spatial localization within 3D structures. Quantitative comparison of staining will have improved inter- and intra-experimental reproducibility as multiple samples are collectively processed, stained, and imaged on a single slide.
Stochastic and Heterogeneous Cancer Cell Migration: Experiment and Theory
Authors: Kwon Taejin , Kwon Ok-Seon , Cha Hyuk-Jin , Sung Bong June
Published: November 2019

Cell migration, an essential process for normal cell development and cancer metastasis, differs from a simple random walk: the mean-square displacement (〈(Δr)2(t)〉) of cells sometimes shows non-Fickian behavior, and the spatiotemporal correlation function (G(r, t)) of cells is often non-Gaussian. We find that this intriguing cell migration should be attributed to heterogeneity in a cell population, even one with a homogeneous genetic background. There are two limiting types of heterogeneity in a cell population: cellular heterogeneity and temporal heterogeneity. Cellular heterogeneity accounts for the cell-to-cell variation in migration capacity, while temporal heterogeneity arises from the temporal noise in the migration capacity of single cells. We illustrate that both cellular and temporal heterogeneity need to be taken into account simultaneously to elucidate cell migration. We investigate the two-dimensional migration of A549 lung cancer cells using time-lapse microscopy and find that the migration of A549 cells is Fickian but has a non-Gaussian spatiotemporal correlation. We find that when a theoretical model considers both cellular and temporal heterogeneity, the model reproduces all of the anomalous behaviors of cancer cell migration.
RNF34 overexpression exacerbates neurological deficits and brain injury in a mouse model of intracerebral hemorrhage by potentiating mitochondrial dysfunction-mediated oxidative stress
Authors: Qu Xin , Wang Ning , Chen Wenjin , Qi Meng , Xue Yueqiao , Cheng Weitao
Published: November 2019

Intracerebral hemorrhage (ICH) is a common neurological condition associated with high disability and mortality. Alterations in protein ubiquitination have emerged as a key mechanism in the pathogenesis of neurological diseases. Here, we investigated the effects of the E3 ubiquitin ligase ring finger protein 34 (RNF34) on neurological deficits and brain injury in ICH mice. An ICH model was established via intracerebral injection of autologous blood into wild-type and RNF34 transgenic mice. Brain injury, neurological function, neuronal activity, and oxidative stress levels were measured, respectively. The underlying mechanisms were explored by molecular and cellular approaches. Our results showed that RNF34 overexpression in mice significantly aggravated the ICH-induced memory impairment, brain edema, infarction, hematoma volume, and loss of neuronal activity. RNF34 and oxidative stress levels gradually increased from 6 to 48 h after the ICH challenge and were positively correlated. The ICH-induced increase in intracellular ROS, superoxide anion, and mROS generation and the decrease in adenosine triphosphate production were exacerbated in RNF34 transgenic mice, but NADPH oxidase activity was unaffected. Moreover, RNF34 upregulation potentiated the ICH-induced decrease in PGC-1α, UCP2, and MnSOD expressions. RNF34 interacted with PGC-1α and targeted it for ubiquitin-dependent degradation. This study reveals that RNF34 exacerbates neurological deficits and brain injury by facilitating PGC-1α protein degradation and promoting mitochondrial dysfunction-mediated oxidative stress.
Identifying inaccuracies in gene expression estimates from unstranded RNA-seq data
Authors: Pomaznoy Mikhail , Sethi Ashu , Greenbaum Jason , Peters Bjoern
Published: November 2019

RNA-seq methods are widely utilized for transcriptomic profiling of biological samples. However, there are known caveats of this technology which can skew the gene expression estimates. Specifically, if the library preparation protocol does not retain RNA strand information then some genes can be erroneously quantitated. Although strand-specific protocols have been established, a significant portion of RNA-seq data is generated in non-strand-specific manner. We used a comprehensive stranded RNA-seq dataset of 15 blood cell types to identify genes for which expression would be erroneously estimated if strand information was not available. We found that about 10% of all genes and 2.5% of protein coding genes have a two-fold or higher difference in estimated expression when strand information of the reads was ignored. We used parameters of read alignments of these genes to construct a machine learning model that can identify which genes in an unstranded dataset might have incorrect expression estimates and which ones do not. We also show that differential expression analysis of genes with biased expression estimates in unstranded read data can be recovered by limiting the reads considered to those which span exonic boundaries. The resulting approach is implemented as a package available at https://github.com/mikpom/uslcount.
Novel Gd3+-doped silica-based optical fiber material for dosimetry in proton therapy
Authors: Hoehr C. , Morana A. , Duhamel O. , Capoen B. , Trinczek M. , Paillet P. , Duzenli C. , Bouazaoui M. , Bouwmans G. , Cassez A. , Ouerdane Y. , Boukenter A. , El Hamzaoui H. , Girard S.
Published: November 2019

Optical fibers hold promise for accurate dosimetry in small field proton therapy due to their superior spatial resolution and the lack of significant Cerenkov contamination in proton beams. One known drawback for most scintillation detectors is signal quenching in areas of high linear energy transfer, as is the case in the Bragg peak region of a proton beam. In this study, we investigated the potential of innovative optical fiber bulk materials using the sol-gel technique for dosimetry in proton therapy. This type of glass is made of amorphous silica (SiO$${}_{2}$$

2

) and is doped with Gd$${}^{3+}$$

3
+

ions and possesses very interesting light emission properties with a luminescence band around 314 nm when exposed to protons. The fibers were manufactured at the University of Lille and tested at the TRIUMF Proton Therapy facility with 8.2–62.9 MeV protons and 2–6 nA of extracted beam current. Dose-rate dependence and quenching were measured and compared to other silica-based fibers also made by sol-gel techniques and doped with Ce$${}^{3+}$$

3
+

and Cu$${}^{+}$$

+

. The three fibers present strong luminescence in the UV (Gd) or visible (Cu,Ce) under irradiation, with the emission intensities related directly to the proton flux. In addition, the 0.5 mm diameter Gd$${}^{3+}$$

3
+

-doped fiber shows superior resolution of the Bragg peak, indicating significantly reduced quenching in comparison to the Ce$${}^{3+}$$

3
+

and Cu$${}^{+}$$

+

fibers with a Birks’ constant, k$${}_{B}$$

B

, of (0.0162 $$\pm $$
±
0.0003) cm/MeV in comparison to (0.0333 $$\pm $$
±
0.0006) cm/MeV and (0.0352 $$\pm $$
±
0.0003) cm/MeV, respectively. To our knowledge, this is the first report of such an interesting k$${}_{B}$$

B

for a silica-based optical fiber material, showing clearly that this fiber presents lower quenching than common plastic scintillators. This result demonstrates the high potential of this inorganic fiber material for proton therapy dosimetry.
Blood Pressure Estimation Using On-body Continuous Wave Radar and Photoplethysmogram in Various Posture and Exercise Conditions
Authors: Pour Ebrahim Malikeh , Heydari Fatemeh , Wu Taiyang , Walker Katherine , Joe Keith , Redoute Jean-Michel , Yuce Mehmet Rasit
Published: November 2019

The pulse arrival time (PAT), pre-ejection period (PEP) and pulse transit time (PTT) are calculated using on-body continuous wave radar (CWR), Photoplethysmogram (PPG) and Electrocardiogram (ECG) sensors for wearable continuous systolic blood pressure (SBP) measurements. The CWR and PPG sensors are placed on the sternum and left earlobe respectively. This paper presents a signal processing method based on wavelet transform and adaptive filtering to remove noise from CWR signals. Experimental data are collected from 43 subjects in various static postures and 26 subjects doing 6 different exercise tasks. Two mathematical models are used to calculate SBPs from PTTs/PATs. For 38 subjects participating in posture tasks, the best cumulative error percentage (CEP) is 92.28% and for 21 subjects participating in exercise tasks, the best CEP is 82.61%. The results show the proposed method is promising in estimating SBP using PTT. Additionally, removing PEP from PAT leads to improving results by around 9%. The CWR sensors present a low-power, continuous and potentially wearable system with minimal body contact to monitor aortic valve mechanical activities directly. Results of this study, of wearable radar sensors, demonstrate the potential superiority of CWR-based PEP extraction for various medical monitoring applications, including BP measurement.
Reduced RhoA expression enhances breast cancer metastasis with a concomitant increase in CCR5 and CXCR4 chemokines signaling
Authors: Kalpana Gardiyawasam , Figy Christopher , Yeung Miranda , Yeung Kam C.
Published: November 2019

The role of RhoA GTPases in breast cancer tumorigenesis and metastasis is unclear. Early studies within which mutations in RhoA were designed based on cancer-associated mutations in Ras supported an oncogene role for RhoA. However, recent whole-genome sequencing studies of cancers raised the possibility that RhoA may have a tumor suppression function. Here, using a syngeneic triple negative breast cancer murine model we investigated the physiological effects of reduced RhoA expression on breast cancer tumorigenesis and metastasis. RhoA knockdown had no effect on primary tumor formation and tumor proliferation, concurring with our in vitro findings where reduced RhoA had no effect on breast cancer cell proliferation and clonogenic growth. In contrast, primary tumors with RhoA knockdown efficiently invaded sentinel lymph nodes and significantly metastasized to lungs compared to control tumors. Mechanistically, the current study demonstrated that this is achieved by promoting a pro-tumor microenvironment, with increased cancer-associated fibroblasts and macrophage infiltration, and by modulating the CCL5-CCR5 and CXCL12-CXCR4 chemokine axes in the primary tumor. To our knowledge, this is the first such mechanistic study in breast cancer showing the ability of RhoA to suppress chemokine receptor expression in breast tumor cells. Our work suggests a physiological lung and lymph node metastasis suppressor role for RhoA GTPase in breast cancer.
Temperature elevation and Vibrio cyclitrophicus infection reduce the diversity of haemolymph microbiome of the mussel Mytilus coruscus
Authors: Li Yi-Feng , Chen Yan-Wen , Xu Jia-Kang , Ding Wen-Yang , Shao An-Qi , Zhu You-Ting , Wang Chong , Liang Xiao , Yang Jin-Long
Published: November 2019

Haemolymph microbiome was considered to be unique to healthy invertebrates and beneficial to the host against external pathogens, including disease resistance and maintenance of homeostasis. Here, we investigated the effects of elevated water temperature on infection of haemolymph microbiome of the hard-shelled mussel (Mytilus coruscus). Exposure toVibrio.cyclitrophicusresulted in high mortality of mussels on day nine at 27 °C. The haemolymph was collected to determine the microbiota by 16 S rRNA gene sequencing. Exposure to waterborneV.cyclitrophicusincreased the mortality of mussels that was associated with a reduction in the diversity of their microbial community. Principal coordinate analysis (PCoA) revealed that temperature was an essential factor in shaping microbial communities in mussel haemolymph.Vibrioexposure promoted the proliferation of opportunistic pathogens (e.g.,ArcobacterandFrancisella) at a lower temperature. A high abundance ofVibriopresent in live and dead mussels, at 27 °C might contribute greatly to mortality, as indicated by linear discriminant analysis effect size (LEfSe). These data suggested that the dynamics of microbial community have unique biomarker species in mussel haemolymph that could be used as health indicators. An elevated temperature may reduce the ability of bacterial elimination function against infection in mussel haemolymph.
Risk of harm from alcohol use and heavy alcohol consumption: Its association with other NCD risk factors in Thailand
Authors: Jakkaew Nalinee , Pinyopornpanish Kanokporn , Jiraporncharoen Wichuda , Wisetborisut Anawat , Jiraniramai Surin , Hashmi Ahmar , Angkurawaranon Chaisiri
Published: November 2019

While there is an abundance of literature examining the relation between quantity of alcohol consumption and risk factors for non-communicable diseases (NCD), there is less evidence on whether the risk of harm from alcohol use would have a similar relationship with NCD risk factors. The study aims to determine the association between level of harm from alcohol use and NCD risk factors. A cross-sectional survey was conducted among health care workers in Thailand in 2013. The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) was used to assessed risk of harm from alcohol use. The results suggest that higher risk of harm from alcohol use was associated with two of the eight NCD risk factors among women (higher blood pressure and higher triglyceride level) and five of the eight NCD risk factors among men (smoking, physical inactivity, higher blood pressure, higher blood glucose and higher triglyceride level). For men, assessing risk of harm could be incorporated as part of NCD programs as practitioners do not have to worry about the accuracy of the alcohol quantification and conversion to standard drinks. However, among women, quantifying volume may still be needed.
Simvastatin mediates inhibition of exosome synthesis, localization and secretion via multicomponent interventions
Authors: Kulshreshtha Ankur , Singh Swati , Ahmad Mohd , Khanna Kritika , Ahmad Tanveer , Agrawal Anurag , Ghosh Balaram
Published: November 2019

Discovery of exosomes as modulator of cellular communication has added a new dimension to our understanding of biological processes. Exosomes influence the biological systems by mediating trans-communication across tissues and cells, which has important implication for health and disease. In absence of well-characterized modulators of exosome biogenesis, an alternative option is to target pathways generating important exosomal components. Cholesterol represents one such essential component required for exosomal biogenesis. We initiated this study to test the hypothesis that owing to its cholesterol lowering effect, simvastatin, a HMG CoA inhibitor, might be able to alter exosome formation and secretion. Simvastatin was tested for its effect on exosome secretion under various in-vitro and in-vivo settings and was found to reduce the secretion of exosome from various cell-types. It was also found to alter the levels of various proteins important for exosome production. Murine model of Acute Airway Inflammation was used for further validation of our findings. We believe that the knowledge acquired in this study holds potential for extension to other exosome dominated pathologies and model systems.