bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing Spatio‐Temporal Variability of Free Gas in Surficial Cohesive Sediments Using Tidal Pressure Fluctuations
Authors: Garziglia Sebastien , Sultan Nabil , Thomas Yannick , Ker Stephan , Marsset Bruno , Bompais Xavier , Woerther Patrice , Witt Christoph , Kopf Achim , Apprioual Ronan
Published: October 2021

From a geohazard assessment perspective, the distribution, content, and dynamics of free gas in surficial sediment were addressed by imaging and monitoring the upper 15 m beneath the shelf offshore Nice, France. Based on high‐resolution seismic data covering three sites where pore pressure was recorded over three and a half years, the presence of free gas was determined in the upper 2.75–14.75 m of cohesive, silty clay. Seismic velocity changes delineate two layers with gas volume fractions ranging from 0.12% to 1.89%. By considering the tidal response recorded by eight pore pressure sensors, estimates of gas volume fractions vary from 0.26% to more than 9.4% on a spatio‐temporal scale which cannot be achieved with seismic data. To depict spatio‐temporal patterns three types of free gas occurrence (FGO) were distinguished. Type 3 FGO uniquely showed sawtooth fluctuations in overpressure of 27%–45% of the hydrostatic effective stress as evidence of bubble growth and rise. The other two types showed long‐term overpressure trends indicative of a situation whereby bubble growth has ceased. Type 1 FGOs are distinguished from type 2 by their gas volume fraction lower than 9.4% and ratios of overpressure to hydrostatic effective stress lower than 0.3. Values higher than this threshold are considered sufficient for shear failure to initiate from the steep shelf edge (>20°). Beyond site‐specific insights, the distinction of FGO from their overpressure levels yields testable implications for the dynamics of methane in sediments.
Multisystem Synthesis of Radar Sounding Observations of the Amundsen Sea Sector From the 2004–2005 Field Season
Authors: Chu Winnie , Hilger Andrew M. , Culberg Riley , Schroeder Dustin M. , Jordan Thomas M. , Seroussi Helene , Young Duncan A. , Blankenship Donald D. , Vaughan David G.
Published: October 2021

The Amundsen Sea Embayment of the West Antarctic Ice Sheet contains Thwaites and Pine Island Glaciers, two of the most rapidly changing glaciers in Antarctica. To date, Pine Island and Thwaites Glaciers have only been observed by independent airborne radar sounding surveys, but a combined cross‐basin analysis that investigates the basal conditions across the Pine Island‐Thwaites Glaciers boundary has not been performed. Here, we combine two radar surveys and correct for their differences in system parameters to produce unified englacial attenuation and basal relative reflectivity maps spanning both Pine Island and Thwaites Glaciers. Relative reflectivities range from −24.8 to +37.4 dB with the highest values beneath fast‐flowing ice at the ice sheet margin. By comparing our reflectivity results with previously derived radar specularity and trailing bed echoes at Thwaites Glacier, we find a highly diverse subglacial landscape and hydrologic conditions that evolve along‐flow. Together, these findings highlight the potential for joint airborne radar analysis with ground‐based seismic and geomorphological observations to understand variations in the bed properties and cross‐catchment interactions of ice streams and outlet glaciers.
Sequential measurement of the neurosensory retina in hypertensive disorders of pregnancy: a model of microvascular injury in hypertensive emergency
Authors: Herman Robert J. , Ambasta Anshula , Williams R. Geoff , Zarnke Kelly B. , Costello Fiona E. , Peng Mingkai , Hawkins T. Lee-Ann
Published: October 2021

Optical coherence tomography of the eye suggests the retina thins in normal pregnancy. Our objectives were to confirm and extend these observations to women with hypertensive disorders of pregnancy (HDP). Maternal demographics, clinical/laboratory findings and measurements of macular thickness were repeatedly collected at gestational ages <20 weeks, 20-weeks to delivery, at delivery and postpartum. The primary outcome was the change in macular thickness from non-pregnant dimensions in women with incident HDP compared to non-hypertensive pregnant controls. Secondary outcomes were the relationship(s) between mean arterial pressure (MAP) and macular response. Data show macular thicknesses diminished at <20 weeks gestation in each of 27 pregnancies ending in HDP (mean 3.94 µm; 95% CI 4.66, 3.21) and 11 controls (mean 3.92 µm; 5.05, 2.79; P < 0.001 versus non-pregnant dimensions in both; P = 0.983 HDP versus controls). This thinning response continued to delivery in all controls and in 7 women with HDP superimposed on chronic hypertension. Macular thinning was lost after 20 weeks gestation in the other 20 women with HDP. MAP at loss of macular thinning in women without prior hypertension (n = 12) was identical to MAP at enrollment. However, mean MAP subsequently rose 19 mmHg (15, 22) leading to de novo HDP in all 12 women. Loss of thinning leading to a rise in MAP was also observed in 8 of 15 women with HDP superimposed on chronic hypertension. We conclude the macula thins in most women in early pregnancy. Those who lose this early macular thinning response often develop blood pressure elevations leading to HDP.
Exercise as a model to identify microRNAs linked to human cognition: a role for microRNA-409 and microRNA-501
Authors: Goldberg Maria , Islam Md Rezaul , Kerimoglu Cemil , Lancelin Camille , Gisa Verena , Burkhardt Susanne , Krüger Dennis M. , Marquardt Till , Malchow Berend , Schmitt Andrea , Falkai Peter , Sananbenesi Farahnaz , Fischer Andre
Published: October 2021

MicroRNAs have been linked to synaptic plasticity and memory function and are emerging as potential biomarkers and therapeutic targets for cognitive diseases. Most of these data stem from the analysis of model systems or postmortem tissue from patients which mainly represents an advanced stage of pathology. Due to the in-accessibility of human brain tissue upon experimental manipulation, it is still challenging to identify microRNAs relevant to human cognition, which is however a key step for future translational studies. Here, we employ exercise as an experimental model for memory enhancement in healthy humans with the aim to identify microRNAs linked to memory function. By analyzing the circulating smallRNAome we find a cluster of 18 microRNAs that are highly correlated to cognition. MicroRNA-409-5p and microRNA-501-3p were the most significantly regulated candidates. Functional analysis revealed that the two microRNAs are important for neuronal integrity, synaptic plasticity, and morphology. In conclusion, we provide a novel approach to identify microRNAs linked to human memory function.
Alpelisib combination treatment as novel targeted therapy against hepatocellular carcinoma
Authors: Xu Hongwei , Chen Kefei , Shang Runze , Chen Xinyan , Zhang Yi , Song Xinhua , Evert Matthias , Zhong Sheng , Li Bo , Calvisi Diego F. , Chen Xin
Published: October 2021

Hepatocellular carcinoma (HCC) is the sixth most common primary cancer with an unsatisfactory long-term survival. Gain of function mutations of PIK3CA occur in a subset of human HCC. Alpelisib, a selective PIK3CA inhibitor, has been approved by the FDA to treat PIK3CA mutant breast cancers. In this manuscript, we evaluated the therapeutic efficacy of alpelisib, either alone or in combination, for the treatment of HCC. We tested alpelisib in mouse HCC induced by hydrodynamic injection of c-Met/PIK3CA(H1047R) (c-Met/H1047R), c-Met/PIK3CA(E545K) (c-Met/E545K), and c-Met/sgPten gene combinations. Alpelisib slowed down the growth of c-Met/H1047R and c-Met/E545K HCC but was ineffective in c-Met/sgPten HCC. Mechanistically, alpelisib inhibited p-ERK and p-AKT in c-Met/H1047R and c-Met/E545K HCC progression but did not affect the mTOR pathway or genes involved in cell proliferation. In human HCC cell lines transfected with PIK3CA(H1047R), alpelisib synergized with the mTOR inhibitor MLN0128 or the CDK4/6 inhibitor palbociclib to suppress HCC cell growth. In c-Met/H1047R mice, alpelisib/MLN0128 or alpelisib/palbociclib combination therapy caused tumor regression. Our study demonstrates that alpelisib is effective for treating PIK3CA-mutated HCC by inhibiting MAPK and AKT cascades. Furthermore, combining alpelisib with mTOR or CDK4/6 inhibitors has a synergistic efficacy against PIK3CA-mutated HCC, providing novel opportunities for precision medicine against HCC.
OTULIN maintains skin homeostasis by controlling keratinocyte death and stem cell identity
Authors: Hoste Esther , Lecomte Kim , Annusver Karl , Vandamme Niels , Roels Jana , Maschalidi Sophia , Verboom Lien , Vikkula Hanna-Kaisa , Sze Mozes , Van Hove Lisette , Verstaen Kevin , Martens Arne , Hochepied Tino , Saeys Yvan , Ravichandran Kodi , Kasper Maria , van Loo Geert
Published: October 2021

OTULIN is a deubiquitinase that specifically cleaves linear ubiquitin chains. Here we demonstrate that the ablation ofOtulinselectively in keratinocytes causes inflammatory skin lesions that develop into verrucous carcinomas. Genetic deletion ofTnfr1, knockin expression of kinase-inactiveRipk1or keratinocyte-specific deletion ofFaddandMlklcompletely rescues mice with OTULIN deficiency from dermatitis and tumorigenesis, thereby identifying keratinocyte cell death as the driving force for inflammation. Single-cell RNA-sequencing comparing non-lesional and lesional skin reveals changes in epidermal stem cell identity in OTULIN-deficient keratinocytes prior to substantial immune cell infiltration. Keratinocytes lacking OTULIN display a type-1 interferon and IL-1β response signature, and genetic or pharmacologic inhibition of these cytokines partially inhibits skin inflammation. Finally, expression of a hypomorphic mutantOtulinallele, previously shown to cause OTULIN-related autoinflammatory syndrome in humans, induces a similar inflammatory phenotype, thus supporting the importance of OTULIN for restraining skin inflammation and maintaining immune homeostasis.
Stage-resolved Hi-C analyses reveal meiotic chromosome organizational features influencing homolog alignment
Authors: Zuo Wu , Chen Guangming , Gao Zhimei , Li Shuai , Chen Yanyan , Huang Chenhui , Chen Juan , Chen Zhengjun , Lei Ming , Bian Qian
Published: October 2021

During meiosis, chromosomes exhibit dramatic changes in morphology and intranuclear positioning. How these changes influence homolog pairing, alignment, and recombination remain elusive. Using Hi-C, we systematically mapped 3D genome architecture throughout all meiotic prophase substages during mouse spermatogenesis. Our data uncover two major chromosome organizational features varying along the chromosome axis during early meiotic prophase, when homolog alignment occurs. First, transcriptionally active and inactive genomic regions form alternating domains consisting of shorter and longer chromatin loops, respectively. Second, the force-transmitting LINC complex promotes the alignment of ends of different chromosomes over a range of up to 20% of chromosome length. Both features correlate with the pattern of homolog interactions and the distribution of recombination events. Collectively, our data reveal the influences of transcription and force on meiotic chromosome structure and suggest chromosome organization may provide an infrastructure for the modulation of meiotic recombination in higher eukaryotes.
ClusterMap for multi-scale clustering analysis of spatial gene expression
Authors: He Yichun , Tang Xin , Huang Jiahao , Ren Jingyi , Zhou Haowen , Chen Kevin , Liu Albert , Shi Hailing , Lin Zuwan , Li Qiang , Aditham Abhishek , Ounadjela Johain , Grody Emanuelle I. , Shu Jian , Liu Jia , Wang Xiao
Published: October 2021

Quantifying RNAs in their spatial context is crucial to understanding gene expression and regulation in complex tissues. In situ transcriptomic methods generate spatially resolved RNA profiles in intact tissues. However, there is a lack of a unified computational framework for integrative analysis of in situ transcriptomic data. Here, we introduce an unsupervised and annotation-free framework, termed ClusterMap, which incorporates the physical location and gene identity of RNAs, formulates the task as a point pattern analysis problem, and identifies biologically meaningful structures by density peak clustering (DPC). Specifically, ClusterMap precisely clusters RNAs into subcellular structures, cell bodies, and tissue regions in both two- and three-dimensional space, and performs consistently on diverse tissue types, including mouse brain, placenta, gut, and human cardiac organoids. We demonstrate ClusterMap to be broadly applicable to various in situ transcriptomic measurements to uncover gene expression patterns, cell niche, and tissue organization principles from images with high-dimensional transcriptomic profiles.
Modeling alpha-synuclein pathology in a human brain-chip to assess blood-brain barrier disruption
Authors: Pediaditakis Iosif , Kodella Konstantia R. , Manatakis Dimitris V. , Le Christopher Y. , Hinojosa Chris D. , Tien-Street William , Manolakos Elias S. , Vekrellis Kostas , Hamilton Geraldine A. , Ewart Lorna , Rubin Lee L. , Karalis Katia
Published: October 2021

Parkinson’s disease and related synucleinopathies are characterized by the abnormal accumulation of alpha-synuclein aggregates, loss of dopaminergic neurons, and gliosis of the substantia nigra. Although clinical evidence and in vitro studies indicate disruption of the Blood-Brain Barrier in Parkinson’s disease, the mechanisms mediating the endothelial dysfunction is not well understood. Here we leveraged the Organs-on-Chips technology to develop a human Brain-Chip representative of the substantia nigra area of the brain containing dopaminergic neurons, astrocytes, microglia, pericytes, and microvascular brain endothelial cells, cultured under fluid flow. Our αSyn fibril-induced model was capable of reproducing several key aspects of Parkinson’s disease, including accumulation of phosphorylated αSyn (pSer129-αSyn), mitochondrial impairment, neuroinflammation, and compromised barrier function. This model may enable research into the dynamics of cell-cell interactions in human synucleinopathies and serve as a testing platform for target identification and validation of novel therapeutics.
Selectivity descriptors for the direct hydrogenation of CO2 to hydrocarbons during zeolite-mediated bifunctional catalysis
Authors: Ramirez Adrian , Gong Xuan , Caglayan Mustafa , Nastase Stefan-Adrian F. , Abou-Hamad Edy , Gevers Lieven , Cavallo Luigi , Dutta Chowdhury Abhishek , Gascon Jorge
Published: October 2021

Cascade processes are gaining momentum in heterogeneous catalysis. The combination of several catalytic solids within one reactor has shown great promise for the one-step valorization of C1-feedstocks. The combination of metal-based catalysts and zeolites in the gas phase hydrogenation of CO2 leads to a large degree of product selectivity control, defined mainly by zeolites. However, a great deal of mechanistic understanding remains unclear: metal-based catalysts usually lead to complex product compositions that may result in unexpected zeolite reactivity. Here we present an in-depth multivariate analysis of the chemistry involved in eight different zeolite topologies when combined with a highly active Fe-based catalyst in the hydrogenation of CO2 to olefins, aromatics, and paraffins. Solid-state NMR spectroscopy and computational analysis demonstrate that the hybrid nature of the active zeolite catalyst and its preferred CO2-derived reaction intermediates (CO/ester/ketone/hydrocarbons, i.e., inorganic-organic supramolecular reactive centers), along with 10 MR-zeolite topology, act as descriptors governing the ultimate product selectivity.
Seismological expression of the iron spin crossover in ferropericlase in the Earth’s lower mantle
Authors: Shephard Grace E. , Houser Christine , Hernlund John W. , Valencia-Cardona Juan J. , Trønnes Reidar G. , Wentzcovitch Renata M.
Published: October 2021

The two most abundant minerals in the Earth’s lower mantle are bridgmanite and ferropericlase. The bulk modulus of ferropericlase (Fp) softens as iron d-electrons transition from a high-spin to low-spin state, affecting the seismic compressional velocity but not the shear velocity. Here, we identify a seismological expression of the iron spin crossover in fast regions associated with cold Fp-rich subducted oceanic lithosphere: the relative abundance of fast velocities in P- and S-wave tomography models diverges in the ~1,400-2,000 km depth range. This is consistent with a reduced temperature sensitivity of P-waves throughout the iron spin crossover. A similar signal is also found in seismically slow regions below ~1,800 km, consistent with broadening and deepening of the crossover at higher temperatures. The corresponding inflection in P-wave velocity is not yet observed in 1-D seismic profiles, suggesting that the lower mantle is composed of non-uniformly distributed thermochemical heterogeneities which dampen the global signature of the Fp spin crossover.
The regulatory landscape of the human HPF1- and ARH3-dependent ADP-ribosylome
Authors: Hendriks Ivo A. , Buch-Larsen Sara C. , Prokhorova Evgeniia , Elsborg Jonas D. , Rebak Alexandra K.L.F.S. , Zhu Kang , Ahel Dragana , Lukas Claudia , Ahel Ivan , Nielsen Michael L.
Published: October 2021

Despite the involvement of Poly(ADP-ribose) polymerase-1 (PARP1) in many important biological pathways, the target residues of PARP1-mediated ADP-ribosylation remain ambiguous. To explicate the ADP-ribosylation regulome, we analyze human cells depleted for key regulators of PARP1 activity, histone PARylation factor 1 (HPF1) and ADP-ribosylhydrolase 3 (ARH3). Using quantitative proteomics, we characterize 1,596 ADP-ribosylation sites, displaying up to 1000-fold regulation across the investigated knockout cells. We find that HPF1 and ARH3 inversely and homogenously regulate the serine ADP-ribosylome on a proteome-wide scale with consistent adherence to lysine-serine-motifs, suggesting that targeting is independent of HPF1 and ARH3. Notably, we do not detect an HPF1-dependent target residue switch from serine to glutamate/aspartate under the investigated conditions. Our data support the notion that serine ADP-ribosylation mainly exists as mono-ADP-ribosylation in cells, and reveal a remarkable degree of histone co-modification with serine ADP-ribosylation and other post-translational modifications.
Enhanced bulk photovoltaic effect in two-dimensional ferroelectric CuInP2S6
Authors: Li Yue , Fu Jun , Mao Xiaoyu , Chen Chen , Liu Heng , Gong Ming , Zeng Hualing
Published: October 2021

The photocurrent generation in photovoltaics relies essentially on the interface of p-n junction or Schottky barrier with the photoelectric efficiency constrained by the Shockley-Queisser limit. The recent progress has shown a promising route to surpass this limit via the bulk photovoltaic effect for crystals without inversion symmetry. Here we report the bulk photovoltaic effect in two-dimensional ferroelectric CuInP2S6 with enhanced photocurrent density by two orders of magnitude higher than conventional bulk ferroelectric perovskite oxides. The bulk photovoltaic effect is inherently associated to the room-temperature polar ordering in two-dimensional CuInP2S6. We also demonstrate a crossover from two-dimensional to three-dimensional bulk photovoltaic effect with the observation of a dramatic decrease in photocurrent density when the thickness of the two-dimensional material exceeds the free path length at around 40 nm. This work spotlights the potential application of ultrathin two-dimensional ferroelectric materials for the third-generation photovoltaic cells.
In situ and transcriptomic identification of microglia in synapse-rich regions of the developing zebrafish brain
Authors: Silva Nicholas J. , Dorman Leah C. , Vainchtein Ilia D. , Horneck Nadine C. , Molofsky Anna V.
Published: October 2021

Microglia are brain resident macrophages that play vital roles in central nervous system (CNS) development, homeostasis, and pathology. Microglia both remodel synapses and engulf apoptotic cell corpses during development, but whether unique molecular programs regulate these distinct phagocytic functions is unknown. Here we identify a molecularly distinct microglial subset in the synapse rich regions of the zebrafish (Danio rerio) brain. We found that ramified microglia increased in synaptic regions of the midbrain and hindbrain between 7 and 28 days post fertilization. In contrast, microglia in the optic tectum were ameboid and clustered around neurogenic zones. Using single-cell mRNA sequencing combined with metadata from regional bulk sequencing, we identified synaptic-region associated microglia (SAMs) that were highly enriched in the hindbrain and expressed multiple candidate synapse modulating genes, including genes in the complement pathway. In contrast, neurogenic associated microglia (NAMs) were enriched in the optic tectum, had active cathepsin activity, and preferentially engulfed neuronal corpses. These data reveal that molecularly distinct phagocytic programs mediate synaptic remodeling and cell engulfment, and establish the zebrafish hindbrain as a model for investigating microglial-synapse interactions.
Characterisation of tumour microenvironment remodelling following oncogene inhibition in preclinical studies with imaging mass cytometry
Authors: van Maldegem Febe , Valand Karishma , Cole Megan , Patel Harshil , Angelova Mihaela , Rana Sareena , Colliver Emma , Enfield Katey , Bah Nourdine , Kelly Gavin , Tsang Victoria Siu Kwan , Mugarza Edurne , Moore Christopher , Hobson Philip , Levi Dina , Molina-Arcas Miriam , Swanton Charles , Downward Julian
Published: October 2021

Mouse models are critical in pre-clinical studies of cancer therapy, allowing dissection of mechanisms through chemical and genetic manipulations that are not feasible in the clinical setting. In studies of the tumour microenvironment (TME), multiplexed imaging methods can provide a rich source of information. However, the application of such technologies in mouse tissues is still in its infancy. Here we present a workflow for studying the TME using imaging mass cytometry with a panel of 27 antibodies on frozen mouse tissues. We optimise and validate image segmentation strategies and automate the process in a Nextflow-based pipeline (imcyto) that is scalable and portable, allowing for parallelised segmentation of large multi-image datasets. With these methods we interrogate the remodelling of the TME induced by a KRAS G12C inhibitor in an immune competent mouse orthotopic lung cancer model, highlighting the infiltration and activation of antigen presenting cells and effector cells.
Tunable seesaw-like 3D capacitive sensor for force and acceleration sensing
Authors: Ye Jilong , Zhang Fan , Shen Zhangming , Cao Shunze , Jin Tianqi , Guo Xiaogang , Li Zhihong , Lin Li , Zhang Yihui
Published: October 2021

To address the resource-competing issue between high sensitivity and wide working range for a stand-alone sensor, development of capacitive sensors with an adjustable gap between two electrodes has been of growing interest. While several approaches have been developed to fabricate tunable capacitive sensors, it remains challenging to achieve, simultaneously, a broad range of tunable sensitivity and working range in a single device. In this work, a 3D capacitive sensor with a seesaw-like shape is designed and fabricated by the controlled compressive buckling assembly, which leverages the mechanically tunable configuration to achieve high-precision force sensing (resolution ~5.22 nN) and unprecedented adjustment range (by ~33 times) of sensitivity. The mechanical tests under different loading conditions demonstrate the stability and reliability of capacitive sensors. Incorporation of an asymmetric seesaw-like structure design in the capacitive sensor allows the acceleration measurement with a tunable sensitivity. These results suggest simple and low-cost routes to high-performance, tunable 3D capacitive sensors, with diverse potential applications in wearable electronics and biomedical devices.
An updated genome-scale metabolic network reconstruction of Pseudomonas aeruginosa PA14 to characterize mucin-driven shifts in bacterial metabolism
Authors: Payne Dawson D. , Renz Alina , Dunphy Laura J. , Lewis Taylor , Dräger Andreas , Papin Jason A.
Published: October 2021

Mucins are present in mucosal membranes throughout the body and play a key role in the microbe clearance and infection prevention. Understanding the metabolic responses of pathogens to mucins will further enable the development of protective approaches against infections. We update the genome-scale metabolic network reconstruction (GENRE) of one such pathogen, Pseudomonas aeruginosa PA14, through metabolic coverage expansion, format update, extensive annotation addition, and literature-based curation to produce iPau21. We then validate iPau21 through MEMOTE, growth rate, carbon source utilization, and gene essentiality testing to demonstrate its improved quality and predictive capabilities. We then integrate the GENRE with transcriptomic data in order to generate context-specific models of P. aeruginosa metabolism. The contextualized models recapitulated known phenotypes of unaltered growth and a differential utilization of fumarate metabolism, while also revealing an increased utilization of propionate metabolism upon MUC5B exposure. This work serves to validate iPau21 and demonstrate its utility for providing biological insights.
Assessing the effects of a novel biostimulant to enhance leafminer resistance and plant growth on common bean
Authors: Mostafa Amr A. , El-Rahman Soheir N. Abd , Shehata Said , Abdallah Naglaa A. , Omar Hanaa S.
Published: October 2021

The leafminer Liriomyza trifolii is one of the major insects that affect Phaseolus vulgaris production worldwide. Novel and safe biobased stimulator compound (BSTC) with micronutrient-amino acid chelated compounds was developed from natural compounds and was used for foliar spray of P. vulgaris. Treated plants showed significantly increased in quality and productivity as well as significant reduction in leafminer infestation by close the tunnel end resulting in larvae suffocation and death. BSTC contains chemical composition that has important function in inducing immunity and resistance against insects, enhance plant growth and production. Also, HPLC showed that the assembled BSTC is rich in nucleobases than yeast extract (> 56 fold). Aminochelation zinc enhanced the rate of absorption of nutrient compounds and could participate in safe biofortification strategy. The expression of plant defense related genes under BSTC treatment revealed strong correlations between the transcription rates of defense related genes. Based on binding energies and interacting residues of six vital insect proteins, the best-docked complexes was obtained with disodium 5′-inosinate, delphinidin 3-glucoside and hyperoside. Obtained findings indicate that the foliar application of BSTC can enhance plant growth and productivity, uptake of important elements, expression of defense related genes and inhibit insect essential genes.
Label-free functional and structural imaging of liver microvascular complex in mice by Jones matrix optical coherence tomography
Authors: Mukherjee Pradipta , Miyazawa Arata , Fukuda Shinichi , Yamashita Toshiharu , Lukmanto Donny , Okada Kosuke , El-Sadek Ibrahim Abd , Zhu Lida , Makita Shuichi , Oshika Tetsuro , Yasuno Yoshiaki
Published: October 2021

We demonstrate label-free imaging of the functional and structural properties of microvascular complex in mice liver. The imaging was performed by a custom-built Jones-matrix based polarization sensitive optical coherence tomography (JM-OCT), which is capable of measuring tissue’s attenuation coefficient, birefringence, and tiny tissue dynamics. Two longitudinal studies comprising a healthy liver and an early fibrotic liver model were performed. In the healthy liver, we observed distinctive high dynamics beneath the vessel at the initial time point (0 h) and reappearance of high dynamics at 32-h time point. In the early fibrotic liver model, we observed high dynamics signal that reveals a clear network vascular structure by volume rendering. Longitudinal time-course imaging showed that these high dynamics signals faded and decreased over time.
A modeling study on utilizing low temperature sprayed In2S3 as the buffer layer of CuBaSn(S, Se) solar cells
Authors: Hashemi Maryam , Minbashi Mehran , Ghorashi Seyed Mohammad Bagher , Ghobadi Arash
Published: October 2021

This study represents the investigation of In2S3 thin films as an electron transport layer in the CuBaSn(S, Se)-CBT(S, Se) solar cells, which have been deposited using the Chemical Spray Pyrolysis method. For studying the electrical properties of films such as conduction and valence band, carrier densities, Fermi level, flat band potential, and semiconductor type, the Mott–Schottky analysis has been used. UV–VIS, XRD, and FESEM have been applied to investigate the optical properties of the layers and the layer’s morphologies. The experimental CBT(S, Se) solar cell has been simulated and validated as the next step. After that, the In2S3 layer has been used as the electron transport layer. The results represent that the In2S3 layer is a suitable substitution for toxic CdS. Finally, the In2S3 properties are varied in reasonable ranges, which means different electron transport layers are screened.
The association between serum activin A levels and albuminuria among community-dwelling middle-aged and older adults in Taiwan
Authors: Chang Shih-Chen , Hsu Chien-Yi , Liu Li-Kuo , Lu Ya-Wen , Tsai Yi-Lin , Chou Ruey-Hsing , Huang Po-Hsun , Chen Liang-Kung , Lin Shing-Jong
Published: October 2021

Activin A, a cytokine belonging to the transforming growth factor-β family, has been shown to play pivotal roles in tissue remodeling after renal injury and is present in elevated levels in diabetic patients. However, the association between activin A and albuminuria remains unclear. We aimed to evaluate their association by using cross-sectional data from community-dwelling middle-aged and older adults in Taiwan. We assessed 466 participants (67% male; mean age 71 ± 13 years) from the I-Lan Longitudinal Aging study for whom data pertaining to serum activin A level and urine albumin-to-creatinine ratio (UACR) were available. Of these, 323 (69%) had normal albuminuria, 123 (26%) had microalbuminuria, and 20 (4%) had overt albuminuria. Patients with overt albuminuria and microalbuminuria had significantly higher activin A concentrations than those in the normal albuminuria group (p < 0.001). Circulating activin A was significantly correlated with multiple risk factors, including higher systolic blood pressure and higher UACR. Univariate and multivariate results indicated that activin A level was an independent variable for albuminuria. The cutoff value of 602 pg/mL of activin A demonstrated a sensitivity of 70.6% and specificity of 75.7% (AUC 0.774) in diagnosing overt albuminuria. In conclusion, middle-aged and older adults with elevated activin A levels were associated with a higher incidence of albuminuria.
Characterization of autofluorescence and quantitative protoporphyrin IX biomarkers for optical spectroscopy-guided glioma surgery
Authors: Black David , Kaneko Sadahiro , Walke Anna , König Simone , Stummer Walter , Suero Molina Eric
Published: October 2021

5-Aminolevulinic acid (5-ALA)-mediated fluorescence does not effectively depict low grade gliomas (LGG) or the infiltrative tumor portion of high-grade gliomas (HGG). While spectroscopy improves sensitivity and precision, this is currently limited by autofluorescence and a second protoporphyrin IX (PpIX) fluorescence state at 620 nm. We investigated the autofluorescence to better characterize the present spectra and thus increase PpIX quantification precision and sensitivity. This study included 128 patients undergoing surgery for malignant glioma. 5-ALA (Gliolan) was administered before anesthesia, and fluorescence was measured using a hyperspectral device. It was found that all 2692 measured spectra consisted of contributions from 620 to 634 nm PpIX, NADH, lipofuscin, and flavins. The basis spectra were characterized and their use in spectral unmixing led to 82.4% lower fitting error for weakly fluorescing areas (p < 0.001), and 92.3% fewer false positive tumor identifications in control measurements (p = 0.0065) compared to previous works. They also decreased the PpIX620 contribution, thus halving the mean Ratio620/634 (p < 0.001). The ratio was approximately 0 for HGGs and increasing for LGGs, as demonstrated previously. Additionally, the Ratio620/634, the MIB-1/Ki-67 proliferation index, and the PpIX peak blue-shift were found to be significantly related to WHO grade, fluorescence visibility, and PpIX contribution (p < 0.001), and the value of these three as quantitative biomarkers is discussed.
Development of Nanobodies against Mal de Río Cuarto virus major viroplasm protein P9-1 for diagnostic sandwich ELISA and immunodetection
Authors: Llauger Gabriela , Monti Demián , Adúriz Matías , Romão Ema , Dumón Analía Delina , Mattio María Fernanda , Wigdorovitz Andrés , Muyldermans Serge , Vincke Cécile , Parreño Viviana , del Vas Mariana
Published: October 2021

Mal de Río Cuarto virus (MRCV) is a member of the genus Fijivirus of the family Reoviridae that causes a devastating disease in maize and is persistently and propagatively transmitted by planthopper vectors. Virus replication and assembly occur within viroplasms formed by viral and host proteins. This work describes the isolation and characterization of llama-derived Nanobodies (Nbs) recognizing the major viral viroplasm component, P9-1. Specific Nbs were selected against recombinant P9-1, with affinities in the nanomolar range as measured by surface plasmon resonance. Three selected Nbs were fused to alkaline phosphatase and eGFP to develop a sandwich ELISA test which showed a high diagnostic sensitivity (99.12%, 95% CI 95.21–99.98) and specificity (100%, 95% CI 96.31–100) and a detection limit of 0.236 ng/ml. Interestingly, these Nanobodies recognized different P9-1 conformations and were successfully employed to detect P9-1 in pull-down assays of infected maize extracts. Finally, we demonstrated that fusions of the Nbs to eGFP and RFP allowed the immunodetection of virus present in phloem cells of leaf thin sections. The Nbs developed in this work will aid the study of MRCV epidemiology, assist maize breeding programs, and be valuable tools to boost fundamental research on viroplasm structure and maturation.
Urohidrosis as an overlooked cooling mechanism in long-legged birds
Authors: Cabello-Vergel Julián , Soriano-Redondo Andrea , Villegas Auxiliadora , Masero José A. , Guzmán Juan M. Sánchez , Gutiérrez Jorge S.
Published: October 2021

Behavioural thermoregulation could buffer the impacts of climate warming on vertebrates. Specifically, the wetting of body surfaces and the resulting evaporation of body fluids serves as a cooling mechanism in a number of vertebrates coping with heat. Storks (Ciconiidae) frequently excrete onto their legs to prevent overheating, a phenomenon known as urohidrosis. Despite the increasingly recognised role of bare and highly vascularised body parts in heat exchange, the ecological and evolutionary determinants of urohidrosis have been largely ignored. We combine urohidrosis data from a scientifically curated media repository with microclimate and ecological data to investigate the determinants of urohidrosis in all extant stork species. Our phylogenetic generalised linear mixed models show that high temperature, humidity and solar radiation, and low wind speed, promote the use of urohidrosis across species. Moreover, species that typically forage in open landscapes exhibit a more pronounced use of urohidrosis than those mainly foraging in waterbodies. Substantial interspecific variation in temperature thresholds for urohidrosis prevalence points to different species vulnerabilities to high temperatures. This integrated approach that uses online data sources and methods to model microclimates should provide insight into animal thermoregulation and improve our capacity to make accurate predictions of climate change’s impact on biodiversity.
SHP-2 deletion in CD4Cre expressing chondrocyte precursors leads to tumor development with wrist tropism
Authors: McNamara Jeffrey T. , Huntington Kelsey E. , Borys Samantha , Jayasuriya Chathuraka T. , Brossay Laurent
Published: October 2021

Due to redundancy with other tyrosine phosphatases, the ubiquitously expressed tyrosine phosphatase SHP-2 (encoded by Ptpn11) is not required for T cell development. However, Ptpn11 gene deletion driven by CD4 Cre recombinase leads to cartilage tumors in the wrist. Using a fate mapping system, we demonstrate that wrist tumor development correlates with increased frequency and numbers of non-hematopoietic lineage negative CD45 negative cells with a bone chondrocyte stromal cell precursor cell (BCSP) phenotype. Importantly, the BCSP subset has a history of CD4 expression and a marked wrist location tropism, explaining why the wrist is the main site of tumor development. Mechanistically, we found that in SHP-2 absence, SOX-9 is no longer regulated, leading to an uncontrolled proliferation of the BCSP subset. Altogether, these results identify a unique subset of chondrocyte precursors tightly regulated by SHP-2. These findings underscore the need for the development of methods to therapeutically target this subset of cells, which could potentially have an impact on treatment of SHP-2 dysfunction linked debilitating diseases.
SNP markers reveal relationships between fruit paternity, fruit quality and distance from a cross-pollen source in avocado orchards
Authors: Kämper Wiebke , Ogbourne Steven M. , Hawkes David , Trueman Stephen J.
Published: October 2021

Cross-pollination can improve fruit yield, fruit size and nutritional quality of many food crops. However, we rarely understand what proportions of the crop result from self- or cross-pollination, how cross-pollination affects crop quality, and how far pollen is transported by pollinators. Management strategies to improve pollination services are consequently not optimal for many crops. We utilised a series of SNP markers, unique for each cultivar of avocado, to quantify proportions of self- and cross-paternity in fruit of Hass avocado at increasing distances from cross-pollen sources. We assessed whether distance from a cross-pollen source determined the proportions of self-pollinated and cross-pollinated fruit, and evaluated how self- and cross-paternity affected fruit size and nutritional quality. Avocado fruit production resulted from both self- and cross-pollination in cultivar Hass in Queensland, Australia. Cross-pollination levels decreased with increasing distance from a cross-pollen source, from 63% in the row adjacent to another cultivar to 25% in the middle of a single-cultivar block, suggesting that pollen transport was limited across orchard rows. Limited pollen transport did not affect fruit size or quality in Hass avocados as xenia effects of a Shepard polliniser on size and nutritional quality were minor.
SARS-CoV-2 inhibition using a mucoadhesive, amphiphilic chitosan that may serve as an anti-viral nasal spray
Authors: Pyrć Krzysztof , Milewska Aleksandra , Duran Emilia Barreto , Botwina Paweł , Dabrowska Agnieszka , Jedrysik Malwina , Benedyk Malgorzata , Lopes Rui , Arenas-Pinto Alejandro , Badr Moutaz , Mellor Ryan , Kalber Tammy L. , Fernandez-Reyes Delmiro , Schätzlein Andreas G. , Uchegbu Ijeoma F.
Published: October 2021

There are currently no cures for coronavirus infections, making the prevention of infections the only course open at the present time. The COVID-19 pandemic has been difficult to prevent, as the infection is spread by respiratory droplets and thus effective, scalable and safe preventive interventions are urgently needed. We hypothesise that preventing viral entry into mammalian nasal epithelial cells may be one way to limit the spread of COVID-19. Here we show that N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan (GCPQ), a positively charged polymer that has been through an extensive Good Laboratory Practice toxicology screen, is able to reduce the infectivity of SARS-COV-2 in A549ACE2+ and Vero E6 cells with a log removal value of − 3 to − 4 at a concentration of 10–100 μg/ mL (p < 0.05 compared to untreated controls) and to limit infectivity in human airway epithelial cells at a concentration of 500 μg/ mL (p < 0.05 compared to untreated controls). In vivo studies using transgenic mice expressing the ACE-2 receptor, dosed nasally with SARS-COV-2 (426,000 TCID50/mL) showed a trend for nasal GCPQ (20 mg/kg) to inhibit viral load in the respiratory tract and brain, although the study was not powered to detect statistical significance. GCPQ’s electrostatic binding to the virus, preventing viral entry into the host cells, is the most likely mechanism of viral inhibition. Radiolabelled GCPQ studies in mice show that at a dose of 10 mg/kg, GCPQ has a long residence time in mouse nares, with 13.1% of the injected dose identified from SPECT/CT in the nares, 24 h after nasal dosing. With a no observed adverse effect level of 18 mg/kg in rats, following a 28-day repeat dose study, clinical testing of this polymer, as a COVID-19 prophylactic is warranted.
Radiofrequency therapy improves exercise capacity of mice with emphysema
Authors: Tsutsui Mai , Cheung Chung Yan , Wada Takeyuki , Jaw Jen-erh , Yang Cheng Wei Tony , Bernatchez Pascal , White Zoe , Yang Chen Xi , Bae Eun Jeong Annie , Choi Lauren H. , Gelbart Dan , Lichtenstein Samuel , Machan Lindsay , Elizur Eran , Wolff Kim , Goodacre Evan , Lipnicki Marek , Wong Denny , Sin Don D.
Published: October 2021

Emphysema is a common phenotype of chronic obstructive pulmonary disease (COPD). Although resection of emphysematous tissue can improve lung mechanics, it is invasive and fraught with adverse effects. Meanwhile, radiofrequency (RF) treatment is an extracorporeal method that leads to tissue destruction and remodeling, resulting in “volume reduction” and overall improvement in lung compliance of emphysematous lungs. Whether these changes lead to improved exercise tolerance is unknown. Here, we investigated the effectiveness of RF treatment to improve the exercise capacity of mice with emphysema. Fifty-two mice (7 weeks of age) were used in this experiment. A bilateral emphysema model was created by intratracheally instilling porcine pancreatic elastase (PPE) (1.5U/100 g body weight). RF treatment (0.5 W/ g body weight) was administered extracorporeally 14 days later and mice were sacrificed after another 21 days. The exercise capacity of mice was measured using a treadmill. Treadmill runs were performed just before PPE instillation (baseline), before RF treatment and before sacrifice. Following sacrifice, lung compliance and mean linear intercept (Lm) were measured and fibrosis was assessed using a modified Ashcroft score. There were 3 experimental groups: controls (instilled with saline, n = 12), emphysema (instilled with porcine pancreatic elastase, PPE, n = 11) and emphysema + treatment (instilled with PPE and given RF, n = 9). At endpoint, the maximum velocity of the emphysema + treatment group was significantly higher than that of the emphysema group, indicating improved exercise tolerance (86.29% of baseline vs 61.69% of baseline, p = 0.01). Histological analysis revealed a significant reduction in emphysema as denoted by Lm between the two groups (median 29.60 µm vs 35.68 µm, p = 0.03). The emphysema + treatment group also demonstrated a higher prevalence of lung fibrosis (≧Grade 3) compared with the emphysema group (11.7% vs 5.4%, p < 0.01). No severe adverse events from RF were observed. RF treatment improved the exercise capacity of mice with emphysema. These data highlight the therapeutic potential of RF treatment in improving the functional status of patients with COPD.
Robust and universal predictive models for frictional pressure drop during two-phase flow in smooth helically coiled tube heat exchangers
Authors: Moradkhani M. A. , Hosseini Seyyed Hossein , Mansouri M. , Ahmadi G. , Song Mengjie
Published: October 2021

There is a lack of well-verified models in the literature for the prediction of the frictional pressure drop (FPD) in the helically coiled tubes at different conditions/orientations. In this study, the robust and universal models for estimating two-phase FPD in smooth coiled tubes with different orientations were developed using several intelligent approaches. For this reason, a databank comprising 1267 experimental data samples was collected from 12 independent studies, which covers a broad range of fluids, tube diameters, coil diameters, coil axis inclinations, mass fluxes, saturation temperatures, and vapor qualities. The earlier models for straight and coiled tubes were examined using the collected database, which showed absolute average relative error (AARE) higher than 21%. The most relevant dimensionless groups were used as models’ inputs, and the neural network approach of multilayer perceptron and radial basis functions (RBF) were developed based on the homogenous equilibrium method. Although both intelligent models exhibited excellent accuracy, the RBF model predicted the best results with AARE 4.73% for the testing process. In addition, an explicit FPD model was developed by the genetic programming (GP), which showed the AARE of 14.97% for all data points. Capabilities of the proposed models under different conditions were described and, the sensitivity analyses were performed.
Monolithic processing of a layered flexible robotic actuator film for kinetic electronics
Authors: Zhang Shiyi , Wang Joseph , Hayashi Kenshi , Sassa Fumihiro
Published: October 2021

Low-invasive soft robotic techniques can potentially be used for developing next-generation body–machine interfaces. Most soft robots require complicated fabrication processes involving 3D printing and bonding/assembling. In this letter, we describe a monolithic soft microrobot fabrication process for the mass production of soft film robots with a complex structure by simple 2D processing of a robotic actuator film. The 45 µg/mm2 lightweight film robot can be driven at a voltage of CMOS compatible 5 V with 0.15 mm−1 large curvature changes; it can generate a force 5.7 times greater than its self-weight. In a durability test, actuation could be carried out over 8000 times without degradation. To further demonstrate this technique, three types of film robots with multiple degrees of freedom and a moving illuminator robot were fabricated. This technique can easily integrate various electrical circuits developed in the past to robotic systems and can be used for developing advanced wearable sensing devices; it can be called “Kinetic electronics”.
Speckle patterns formed by broadband terahertz radiation and their applications for ghost imaging
Authors: Leibov Lev , Ismagilov Azat , Zalipaev Victor , Nasedkin Boris , Grachev Yaroslav , Petrov Nikolay , Tcypkin Anton
Published: October 2021

Speckle patterns can be very promising for many applications due to their unique properties. This paper presents the possibility of numerically and experimentally formation of speckle patterns using broadband THz radiation. Strong dependence of the statistical parameters of speckles, such as size and sharpness on the parameters of the diffuser are demonstrated: the correlation length and the mean square deviation of the phase surface inhomogeneity. As the surface correlation length is increasing, the speckle size also increases and its sharpness goes down. Alternatively, the magnification of the standard deviation of the surface height leads to the speckle size diminishing and growth of the speckle sharpness. The dimensions of the experimentally formed speckles correspond to the results of numerical simulation. The possibility of utilizing formed speckle patterns for the implementation of the ghost imaging technique has been demonstrated by methods of numerical modeling.