bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure of a type IV secretion system core complex encoded by multi-drug resistance F plasmids
Authors: Liu Xiangan , Khara Pratick , Baker Matthew L. , Christie Peter J. , Hu Bo
Published: January 2022

Bacterial type IV secretion systems (T4SSs) are largely responsible for the proliferation of multi-drug resistance. We solved the structure of the outer-membrane core complex (OMCCF) of a T4SS encoded by a conjugative F plasmid at <3.0 Å resolution by cryoelectron microscopy. The OMCCF consists of a 13-fold symmetrical outer ring complex (ORC) built from 26 copies of TraK and TraV C-terminal domains, and a 17-fold symmetrical central cone (CC) composed of 17 copies of TraB β-barrels. Domains of TraV and TraB also bind the CC and ORC substructures, establishing that these proteins undergo an intraprotein symmetry alteration to accommodate the C13:C17 symmetry mismatch. We present evidence that other pED208-encoded factors stabilize the C13:C17 architecture and define the importance of TraK, TraV and TraB domains to T4SSF function. This work identifies OMCCF structural motifs of proposed importance for structural transitions associated with F plasmid dissemination and F pilus biogenesis.
The QChip1 knowledgebase and microarray for precision medicine in Qatar
Authors: Rodriguez-Flores Juan L. , Messai-Badji Radja , Robay Amal , Temanni Ramzi , Syed Najeeb , Markovic Monika , Al-khayat Eiman , Qafoud Fatima , Nawaz Zafar , Badii Ramin , Al-Sarraj Yasser , Mbarek Hamdi , Al-Muftah Wadha , Alvi Muhammad , Rostami Mahboubeh R. , Cruzado Juan Carlos Martinez , Mezey Jason G. , Shakaki Alya Al , Malek Joel A. , Greenblatt Matthew B. , Fakhro Khalid A. , Machaca Khaled , Al-Nabet Ajayeb , Afifi Nahla , Brooks Andrew , Ismail Said I. , Althani Asmaa , Crystal Ronald G.
Published: January 2022

Risk genes for Mendelian (single-gene) disorders (SGDs) are consistent across populations, but pathogenic risk variants that cause SGDs are typically population-private. The goal was to develop “QChip1,” an inexpensive genotyping microarray to comprehensively screen newborns, couples, and patients for SGD risk variants in Qatar, a small nation on the Arabian Peninsula with a high degree of consanguinity. Over 108variants in 8445 Qatari were identified for inclusion in a genotyping array containing 165,695 probes for 83,542 known and potentially pathogenic variants in 3438 SGDs. QChip1 had a concordance with whole-genome sequencing of 99.1%. Testing of QChip1 with 2707 Qatari genomes identified 32,674 risk variants, an average of 134 pathogenic alleles per Qatari genome. The most common pathogenic variants were those causing homocystinuria (1.12% risk allele frequency), and Stargardt disease (2.07%). The majority (85%) of Qatari SGD pathogenic variants were not present in Western populations such as European American, South Asian American, and African American in New York City and European and Afro-Caribbean in Puerto Rico; and only 50% were observed in a broad collection of data across the Greater Middle East including Kuwait, Iran, and United Arab Emirates. This study demonstrates the feasibility of developing accurate screening tools to identify SGD risk variants in understudied populations, and the need for ancestry-specific SGD screening tools.
Chemical crystallography by serial femtosecond X-ray diffraction
Authors: Schriber Elyse A. , Paley Daniel W. , Bolotovsky Robert , Rosenberg Daniel J. , Sierra Raymond G. , Aquila Andrew , Mendez Derek , Poitevin Frédéric , Blaschke Johannes P. , Bhowmick Asmit , Kelly Ryan P. , Hunter Mark , Hayes Brandon , Popple Derek C. , Yeung Matthew , Pareja-Rivera Carina , Lisova Stella , Tono Kensuke , Sugahara Michihiro , Owada Shigeki , Kuykendall Tevye , Yao Kaiyuan , Schuck P. James , Solis-Ibarra Diego , Sauter Nicholas K. , Brewster Aaron S. , Hohman J. Nathan
Published: January 2022

Inorganic–organic hybrid materials represent a large share of newly reported structures, owing to their simple synthetic routes and customizable properties1. This proliferation has led to a characterization bottleneck: many hybrid materials are obligate microcrystals with low symmetry and severe radiation sensitivity, interfering with the standard techniques of single-crystal X-ray diffraction2,3 and electron microdiffraction4–11. Here we demonstrate small-molecule serial femtosecond X-ray crystallography (smSFX) for the determination of material crystal structures from microcrystals. We subjected microcrystalline suspensions to X-ray free-electron laser radiation12,13 and obtained thousands of randomly oriented diffraction patterns. We determined unit cells by aggregating spot-finding results into high-resolution powder diffractograms. After indexing the sparse serial patterns by a graph theory approach14, the resulting datasets can be solved and refined using standard tools for single-crystal diffraction data15–17. We describe the ab initio structure solutions of mithrene (AgSePh)18–20, thiorene (AgSPh) and tethrene (AgTePh), of which the latter two were previously unknown structures. In thiorene, we identify a geometric change in the silver–silver bonding network that is linked to its divergent optoelectronic properties20. We demonstrate that smSFX can be applied as a general technique for structure determination of beam-sensitive microcrystalline materials at near-ambient temperature and pressure.
Global fine-scale changes in ambient NO2 during COVID-19 lockdowns
Authors: Cooper Matthew J. , Martin Randall V. , Hammer Melanie S. , Levelt Pieternel F. , Veefkind Pepijn , Lamsal Lok N. , Krotkov Nickolay A. , Brook Jeffrey R. , McLinden Chris A.
Published: January 2022

Nitrogen dioxide (NO2) is an important contributor to air pollution and can adversely affect human health1–9. A decrease in NO2 concentrations has been reported as a result of lockdown measures to reduce the spread of COVID-1910–20. Questions remain, however, regarding the relationship of satellite-derived atmospheric column NO2 data with health-relevant ambient ground-level concentrations, and the representativeness of limited ground-based monitoring data for global assessment. Here we derive spatially resolved, global ground-level NO2 concentrations from NO2 column densities observed by the TROPOMI satellite instrument at sufficiently fine resolution (approximately one kilometre) to allow assessment of individual cities during COVID-19 lockdowns in 2020 compared to 2019. We apply these estimates to quantify NO2 changes in more than 200 cities, including 65 cities without available ground monitoring, largely in lower-income regions. Mean country-level population-weighted NO2 concentrations are 29% ± 3% lower in countries with strict lockdown conditions than in those without. Relative to long-term trends, NO2 decreases during COVID-19 lockdowns exceed recent Ozone Monitoring Instrument (OMI)-derived year-to-year decreases from emission controls, comparable to 15 ± 4 years of reductions globally. Our case studies indicate that the sensitivity of NO2 to lockdowns varies by country and emissions sector, demonstrating the critical need for spatially resolved observational information provided by these satellite-derived surface concentration estimates.
Quantum logic with spin qubits crossing the surface code threshold
Authors: Xue Xiao , Russ Maximilian , Samkharadze Nodar , Undseth Brennan , Sammak Amir , Scappucci Giordano , Vandersypen Lieven M. K.
Published: January 2022

High-fidelity control of quantum bits is paramount for the reliable execution of quantum algorithms and for achieving fault tolerance—the ability to correct errors faster than they occur1. The central requirement for fault tolerance is expressed in terms of an error threshold. Whereas the actual threshold depends on many details, a common target is the approximately 1% error threshold of the well-known surface code2,3. Reaching two-qubit gate fidelities above 99% has been a long-standing major goal for semiconductor spin qubits. These qubits are promising for scaling, as they can leverage advanced semiconductor technology4. Here we report a spin-based quantum processor in silicon with single-qubit and two-qubit gate fidelities, all of which are above 99.5%, extracted from gate-set tomography. The average single-qubit gate fidelities remain above 99% when including crosstalk and idling errors on the neighbouring qubit. Using this high-fidelity gate set, we execute the demanding task of calculating molecular ground-state energies using a variational quantum eigensolver algorithm5. Having surpassed the 99% barrier for the two-qubit gate fidelity, semiconductor qubits are well positioned on the path to fault tolerance and to possible applications in the era of noisy intermediate-scale quantum devices.
Engineered ACE2 decoy mitigates lung injury and death induced by SARS-CoV-2 variants
Authors: Zhang Lianghui , Dutta Soumajit , Xiong Shiqin , Chan Matthew , Chan Kui K. , Fan Timothy M. , Bailey Keith L. , Lindeblad Matthew , Cooper Laura M. , Rong Lijun , Gugliuzza Anthony F. , Shukla Diwakar , Procko Erik , Rehman Jalees , Malik Asrar B.
Published: January 2022

Vaccine hesitancy and emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) escaping vaccine-induced immune responses highlight the urgency for new COVID-19 therapeutics. Engineered angiotensin-converting enzyme 2 (ACE2) proteins with augmented binding affinities for SARS-CoV-2 spike (S) protein may prove to be especially efficacious against multiple variants. Using molecular dynamics simulations and functional assays, we show that three amino acid substitutions in an engineered soluble ACE2 protein markedly augmented the affinity for the S protein of the SARS-CoV-2 WA-1/2020 isolate and multiple VOCs: B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma) and B.1.617.2 (Delta). In humanized K18-hACE2 mice infected with the SARS-CoV-2 WA-1/2020 or P.1 variant, prophylactic and therapeutic injections of soluble ACE22.v2.4-IgG1 prevented lung vascular injury and edema formation, essential features of CoV-2-induced SARS, and above all improved survival. These studies demonstrate broad efficacy in vivo of an engineered ACE2 decoy against SARS-CoV-2 variants in mice and point to its therapeutic potential.
Effectiveness of COVID-19 booster vaccines against COVID-19-related symptoms, hospitalization and death in England
Authors: Andrews Nick , Stowe Julia , Kirsebom Freja , Toffa Samuel , Sachdeva Ruchira , Gower Charlotte , Ramsay Mary , Lopez Bernal Jamie
Published: January 2022

Booster vaccination with messenger RNA (mRNA) vaccines has been offered to adults in England starting on 14 September 2021. We used a test-negative case–control design to estimate the relative effectiveness of a booster dose of BNT162b2 (Pfizer-BioNTech) compared to only a two-dose primary course (at least 175 days after the second dose) or unvaccinated individuals from 13 September 2021 to 5 December 2021, when Delta variant was dominant in circulation. Outcomes were symptomatic coronavirus disease 2019 (COVID-19) and hospitalization. The relative effectiveness against symptomatic disease 14–34 days after a BNT162b2 or mRNA-1273 (Moderna) booster after a ChAdOx1-S (AstraZeneca) and BNT162b2 as a primary course ranged from around 85% to 95%. Absolute vaccine effectiveness ranged from 94% to 97% and was similar in all age groups. Limited waning was seen 10 or more weeks after the booster. Against hospitalization or death, absolute effectiveness of a BNT162b2 booster ranged from around 97% to 99% in all age groups irrespective of the primary course, with no evidence of waning up to 10 weeks. This study provides real-world evidence of substantially increased protection from the booster vaccine dose against mild and severe disease irrespective of the primary course.
Impact of measurement timing on reproducibility of testing among haemodialysis patients
Authors: Junqué Jiménez Anna , Tomás Bernabeu Ester , Andreu Périz Lola , Segura Ortí Eva
Published: January 2022

Accurate evaluation of physical function in patients undergoing haemodialysis is crucial in the analysis of the impact of exercise programs in this population. The aim of this study was to evaluate the reproducibility of several physical functional tests, depending on the timing of their implementation (before the HD session vs. non-HD days). This is a prospective, non-experimental, descriptive study. Thirty patients in haemodialysis were evaluated twice, 1 week apart. The test session was performed before the haemodialysis session started and a retest was performed in non-dialysis day. The testing battery included the short physical performance battery, sit-to-stand tests, 6 min walk test, one-leg stand test, timed up and go, and handgrip strength with and without forearm support. The intra-rater reproducibility was determined by the intraclass correlation coefficients and the agreement was assessed by Bland–Altman analysis. The intraclass correlation coefficients values ranged from 0.86 to 0.96, so that all tests showed good to very good relative reliability. The mean differences between trials of sit to stand 10 and 60, timed up and go and all the handgrip tests were close to zero, indicating no systematic differences between trials. Large range of values between trials was observed for the 6 min walk test, gait speed, one-leg stand test and short physical performance battery, indicating a systematic bias for these four tests. In conclusion,  the sit to stand 10 and 60, timed up and go and handgrip tests had good to excellent test–retest reliability in measuring physical function in different dialysis days of patients undertaking haemodialysis. The minimal detectable change values are provided for this population. Bias were found for the 6 min walk test, gait speed, Short physical performance battery or one-leg stand test when the testing day changed.
Comprehensive characterization of 11 prognostic alternative splicing events in ovarian cancer interacted with the immune microenvironment
Authors: Yue Congbo , Zhao Tianyi , Zhang Shoucai , Liu Yingjie , Zheng Guixi , Zhang Yi
Published: January 2022

Alternative splicing (AS) events play a crucial role in the tumorigenesis and progression of cancer. Transcriptome data and Percent Spliced In (PSI) values of ovarian cancer patients were downloaded from TCGA database and TCGA SpliceSeq. Totally we identified 1472 AS events that were associated with survival of ovarian serous cystadenocarcinoma (OC) and exon skipping (ES) was the most important type. Univariate and multivariate Cox regression analysis were performed to identify survival-associated AS events and developed the prognostic model based on 11-AS events. The immune cells and different response to cytotoxic T lymphocyte associated antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) blockers in low-risk and high-risk group of OC patients were analyzed. Ten kinds of immune cells were found up-regulated in low-risk group. Activated B cell, natural killer T cell, natural killer cell and regulatory T cell were associated with survival of OC. The patients in low-risk group had good response to CTLA-4 and PD-1 blockers treatment. Moreover, a regulatory network was established according to the correlation between AS events and splicing factors (SFs). The present study provided valuable insights into the underlying mechanisms of OC. AS events that were correlated with the immune system might be potential therapeutic targets.
Creating electronic oscillator-based Ising machines without external injection locking
Authors: Vaidya Jaykumar , Surya Kanthi R. S. , Shukla Nikhil
Published: January 2022

Coupled electronic oscillators have recently been explored as a compact, integrated circuit- and room temperature operation-compatible hardware platform to design Ising machines. However, such implementations presently require the injection of an externally generated second-harmonic signal to impose the phase bipartition among the oscillators. In this work, we experimentally demonstrate a new electronic autaptic oscillator (EAO) that uses engineered feedback to eliminate the need for the generation and injection of the external second harmonic signal to minimize the Ising Hamiltonian. Unlike conventional relaxation oscillators that typically decay with a single time constant, the feedback in the EAO is engineered to generate two decay time constants which effectively helps generate the second harmonic signal internally. Using this oscillator design, we show experimentally, that a system of capacitively coupled EAOs exhibits the desired bipartition in the oscillator phases without the need for any external second harmonic injection, and subsequently, demonstrate its application in solving the computationally hard Maximum Cut (MaxCut) problem. Our work not only establishes a new oscillator design aligned to the needs of the oscillator Ising machine but also advances the efforts to creating application specific analog computing platforms.
The gut microbiota of chickens in a commercial farm treated with a Salmonella phage cocktail
Authors: Clavijo Viviana , Morales Tatiana , Vives-Flores Martha Josefina , Reyes Muñoz Alejandro
Published: January 2022

The microbiota in broiler chicken intestines affects the animals’ health, metabolism, and immunity both positively and negatively. Accordingly, it has a significant impact on animal productivity. Phages, host-specific parasites of bacterial cells, are a promising antimicrobial alternative that selectively target pathogens without disturbing the microbiota. The purpose of this study is to further characterize the commensal microbial community at production scale in broiler chickens treated with a Salmonella phage treatment. We evaluated the cecal microbiota of broilers reared in a commercial farming system where a phage cocktail against Salmonella, SalmoFree was supplied to animals. To do so, two field trials were conducted, incorporating three doses of phages in the broilers’ drinking water. Our results showed that the core microbiome (taxa that were present in more than 50% of samples) contained species that are key to microbiota adaptation in the last stage of the production cycle. Among these, there are some important degraders of complex polysaccharides and producers of short chain fatty acids (SCFA) such as Eisenbergiella and Lachnoclostridium. The phage cocktail did not affect the normal development of the microbiota’s structure. The addition of the phage cocktail resulted in a significant reduction in Campylobacter and an increase in Butyricimonas, Helicobacter and Rikenellaceae, which are common inhabitants in chicken gut with known negative and positive effects on their health and metabolism. Altogether, we consider that these results contribute valuable information to the implementation of large-scale phage therapy technologies.
A model for cascading failures with the probability of failure described as a logistic function
Authors: Kim Minjung , Kim Jun Soo
Published: January 2022

In most cascading failure models in networks, overloaded nodes are assumed to fail and are removed from the network. However, this is not always the case due to network mitigation measures. Considering the effects of these mitigating measures, we propose a new cascading failure model that describes the probability that an overloaded node fails as a logistic function. By performing numerical simulations of cascading failures on Barabási and Albert (BA) scale-free networks and a real airport network, we compare the results of our model and the established model describing the probability of failure as a linear function. The simulation results show that the difference in the robustness of the two models depends on the initial load distribution and the redistribution of load. We further investigate the conditions of our new model under which the network exhibits the strongest robustness in terms of the load distribution and the network topology. We find the optimal value for the parameter of the load distribution and demonstrate that the robustness of the network improves as the average degree increases. The results regarding the optimal load distribution are verified by theoretical analysis. This work can be used to develop effective mitigation measures and design networks that are robust to cascading failure phenomena.
High speed, long range, deep penetration swept source OCT for structural and angiographic imaging of the anterior eye
Authors: Chen Siyu , Potsaid Benjamin , Li Yan , Lin Junhong , Hwang Yunchan , Moult Eric M. , Zhang Jason , Huang David , Fujimoto James G.
Published: January 2022

This study reports the development of prototype swept-source optical coherence tomography (SS-OCT) technology for imaging the anterior eye. Advances in vertical-cavity surface-emitting laser (VCSEL) light sources, signal processing, optics and mechanical designs, enable a unique combination of high speed, long range, and deep penetration that addresses the challenges of anterior eye imaging. We demonstrate SS-OCT with a 325 kHz A-scan rate, 12.2 µm axial resolution (in air), and 15.5 mm depth range (in air) at 1310 nm wavelength. The ultrahigh 325 kHz A-scan rate not only facilitates biometry measurements by minimizing acquisition time and thus reducing motion, but also enables volumetric OCT for comprehensive structural analysis and OCT angiography (OCTA) for visualizing vasculature. The 15.5 mm (~ 11.6 mm in tissue) depth range spans all optical surfaces from the anterior cornea to the posterior lens capsule. The 1310 nm wavelength range enables structural OCT and OCTA deep in the sclera and through the iris. Achieving high speed and long range requires linearizing the VCSEL wavenumber sweep to efficiently utilize analog-to-digital conversion bandwidth. Dual channel recording of the OCT and calibration interferometer fringe signals, as well as sweep to sweep wavenumber compensation, is used to achieve invariant 12.2 µm (~ 9.1 µm in tissue) axial resolution and optimum point spread function throughout the depth range. Dynamic focusing using a tunable liquid lens extends the effective depth of field while preserving the lateral resolution. Improved optical and mechanical design, including parallax “split view” iris cameras and stable, ergonomic patient interface, facilitates accurate instrument positioning, reduces patient motion, and leads to improved imaging data yield and measurement accuracy. We present structural and angiographic OCT images of the anterior eye, demonstrating the unique imaging capabilities using representative scanning protocols which may be relevant to future research and clinical applications.
Phenolic compound profile of probiotic (Lacticaseibacillus rhamnosus LR5) fortified vegetable tablet and probiotic survival in the simulated gastrointestinal tract
Authors: Jafari Saeid , Thongmat Krongkan , Kijpatanasilp Isaya , Kerdsup Paramaporn , Naknaen Phisut , Taweechotipatr Malai , Assatarakul Kitipong
Published: January 2022

The objectives of this research were to study the changes of phenolic compounds in vegetable (yellow VS green) tablets with/without probiotics (Lacticaseibacillus rhamnosus LR5) supplementation by using high performance liquid chromatography and probiotic survivability through the simulated gastrointestinal tract. The green vegetable tablets with/without probiotics had a greater (p ≤ 0.05) phenolic content compared to the yellow ones. There were no significant differences of most phenolic compound contents between probiotic-supplemented vegetable tablets and non-probiotic supplemented ones (p > 0.05). The contents of ferulic acid, epicatechin, tannic acid and rutin for both vegetable tablets tended to decrease through passing the stomach (1 and 2 h) and small intestine (2 and 4 h), however, the content of catechin in the yellow vegetable tablets tended to increase. The results also showed that the survival of Lacticaseibacillus rhamnosus LR5 slightly decreased through the simulated gastrointestinal tract. The vibrations from FTIR appeared in the wave length of 4000–3100, 3000–2800 and 1652–1545 cm−1, which accounted for the change in the N–H bonds of the amine group, changes in the structure of fatty acids and the change of carbonyl groups, respectively. This work highlighted the opportunity of application of probiotics in food products; especially non-dairy foods for consumer with dairy allergy.
Genome and transcriptome profiling of spontaneous preterm birth phenotypes
Authors: Gupta Juhi K. , Care Angharad , Goodfellow Laura , Alfirevic Zarko , Müller-Myhsok Bertram , Alfirevic Ana
Published: January 2022

Preterm birth (PTB) occurs before 37 weeks of gestation. Risk factors include genetics and infection/inflammation. Different mechanisms have been reported for spontaneous preterm birth (SPTB) and preterm birth following preterm premature rupture of membranes (PPROM). This study aimed to identify early pregnancy biomarkers of SPTB and PPROM from the maternal genome and transcriptome. Pregnant women were recruited at the Liverpool Women’s Hospital. Pregnancy outcomes were categorised as SPTB, PPROM (≤ 34 weeks gestation, n = 53), high-risk term (HTERM, ≥ 37 weeks, n = 126) or low-risk (no history of SPTB/PPROM) term (LTERM, ≥ 39 weeks, n = 188). Blood samples were collected at 16 and 20 weeks gestation from which, genome (UK Biobank Axiom array) and transcriptome (Clariom D Human assay) data were acquired. PLINK and R were used to perform genetic association and differential expression analyses and expression quantitative trait loci (eQTL) mapping. Several significant molecular signatures were identified across the analyses in preterm cases. Genome-wide significant SNP rs14675645 (ASTN1) was associated with SPTB whereas microRNA-142 transcript and PPARG1-FOXP3 gene set were associated with PPROM at week 20 of gestation and is related to inflammation and immune response. This study has determined genomic and transcriptomic candidate biomarkers of SPTB and PPROM that require validation in diverse populations.
Construction of SARS-CoV-2 virus-like particles in plant
Authors: Moon Ki-Beom , Jeon Jae-Heung , Choi Hyukjun , Park Ji-Sun , Park Su-Jin , Lee Hyo-Jun , Park Jeong Mee , Cho Hye Sun , Moon Jae Sun , Oh Hyunwoo , Kang Sebyung , Mason Hugh S. , Kwon Suk-Yoon , Kim Hyun-Soon
Published: January 2022

The pandemic of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused a public health emergency, and research on the development of various types of vaccines is rapidly progressing at an unprecedented development speed internationally. Some vaccines have already been approved for emergency use and are being supplied to people around the world, but there are still many ongoing efforts to create new vaccines. Virus-like particles (VLPs) enable the construction of promising platforms in the field of vaccine development. Here, we demonstrate that non-infectious SARS-CoV-2 VLPs can be successfully assembled by co-expressing three important viral proteins membrane (M), envelop (E) and nucleocapsid (N) in plants. Plant-derived VLPs were purified by sedimentation through a sucrose cushion. The shape and size of plant-derived VLPs are similar to native SARS-CoV-2 VLPs without spike. Although the assembled VLPs do not have S protein spikes, they could be developed as formulations that can improve the immunogenicity of vaccines including S antigens, and further could be used as platforms that can carry S antigens of concern for various mutations.
Experimental inoculation trial to determine the effects of temperature and humidity on White-nose Syndrome in hibernating bats
Authors: Frick Winifred F. , Johnson Emily , Cheng Tina L. , Lankton Julia S. , Warne Robin , Dallas Jason , Parise Katy L. , Foster Jeffrey T. , Boyles Justin G. , McGuire Liam P.
Published: January 2022

Disease results from interactions among the host, pathogen, and environment. Inoculation trials can quantify interactions among these players and explain aspects of disease ecology to inform management in variable and dynamic natural environments. White-nose Syndrome, a disease caused by the fungal pathogen, Pseudogymnoascus destructans (Pd), has caused severe population declines of several bat species in North America. We conducted the first experimental infection trial on the tri-colored bat, Perimyotis subflavus, to test the effect of temperature and humidity on disease severity. We also tested the effects of temperature and humidity on fungal growth and persistence on substrates. Unexpectedly, only 37% (35/95) of bats experimentally inoculated with Pd at the start of the experiment showed any infection response or disease symptoms after 83 days of captive hibernation. There was no evidence that temperature or humidity influenced infection response. Temperature had a strong effect on fungal growth on media plates, but the influence of humidity was more variable and uncertain. Designing laboratory studies to maximize research outcomes would be beneficial given the high costs of such efforts and potential for unexpected outcomes. Understanding the influence of microclimates on host–pathogen interactions remains an important consideration for managing wildlife diseases, particularly in variable environments.
Hepatic galectin-3 is associated with lipid droplet area in non-alcoholic steatohepatitis in a new swine model
Authors: Herrera-Marcos Luis V. , Martínez-Beamonte Roberto , Macías-Herranz Manuel , Arnal Carmen , Barranquero Cristina , Puente-Lanzarote Juan J. , Gascón Sonia , Herrero-Continente Tania , Gonzalo-Romeo Gonzalo , Alastrué-Vera Víctor , Gutiérrez-Blázquez Dolores , Lou-Bonafonte José M. , Surra Joaquín C. , Rodríguez-Yoldi María J. , García-Gil Agustín , Güemes Antonio , Osada Jesús
Published: January 2022

Non-alcoholic fatty liver disease (NAFLD) is currently a growing epidemic disease that can lead to cirrhosis and hepatic cancer when it evolves into non-alcoholic steatohepatitis (NASH), a gap not well understood. To characterize this disease, pigs, considered to be one of the most similar to human experimental animal models, were used. To date, all swine-based settings have been carried out using rare predisposed breeds or long-term experiments. Herein, we fully describe a new experimental swine model for initial and reversible NASH using cross-bred animals fed on a high saturated fat, fructose, cholesterol, cholate, choline and methionine-deficient diet. To gain insight into the hepatic transcriptome that undergoes steatosis and steatohepatitis, we used RNA sequencing. This process significantly up-regulated 976 and down-regulated 209 genes mainly involved in cellular processes. Gene expression changes of 22 selected transcripts were verified by RT-qPCR. Lipid droplet area was positively associated with CD68, GPNMB, LGALS3, SLC51B and SPP1, and negatively with SQLE expressions. When these genes were tested in a second experiment of NASH reversion, LGALS3, SLC51B and SPP1 significantly decreased their expression. However, only LGALS3 was associated with lipid droplet areas. Our results suggest a role for LGALS3 in the transition of NAFLD to NASH.
Surface temperature controls the pattern of post-earthquake landslide activity
Authors: Loche Marco , Scaringi Gianvito , Yunus Ali P. , Catani Filippo , Tanyaş Hakan , Frodella William , Fan Xuanmei , Lombardo Luigi
Published: January 2022

The patterns and controls of the transient enhanced landsliding that follows strong earthquakes remain elusive. Geostatistical models can provide clues on the underlying processes by identifying relationships with a number of physical variables. These models do not typically consider thermal information, even though temperature is known to affect the hydro-mechanical behavior of geomaterials, which, in turn, controls slope stability. Here, we develop a slope unit-based multitemporal susceptibility model for the epicentral region of the 2008 Wenchuan earthquake to explore how land surface temperature (LST) relates to landslide patterns over time. We find that LST can explain post-earthquake landsliding while it has no visible effect on the coseismic scene, which is dominated by the strong shaking. Specifically, as the landscape progressively recovers and landslide rates decay to pre-earthquake levels, a positive relationship between LST and landslide persistence emerges. This seems consistent with the action of healing processes, capable of restoring the thermal sensitivity of the slope material after the seismic disturbance. Although analyses in other contexts (not necessarily seismic) are warranted, we advocate for the inclusion of thermal information in geostatistical modeling as it can help form a more physically consistent picture of slope stability controls.
Characterization of 3D-printed PLA parts with different raster orientations and printing speeds
Authors: Khosravani Mohammad Reza , Berto Filippo , Ayatollahi Majid R. , Reinicke Tamara
Published: January 2022

Fabrication based on additive manufacturing (AM) process from a three-dimensional (3D) model has received significant attention in the past few years. Although 3D printing was introduced for production of prototypes, it has been currently used for fabrication of end-use products. Therefore, the mechanical behavior and strength of additively manufactured parts has become of significant importance. 3D printing has been affected by different parameters during preparation, printing, and post-printing processes, which have influence on quality and behavior of the additively manufactured components. This paper discusses the effects of two printing parameters on the mechanical behavior of additively manufactured components. In detail, polylactic acid material was used to print test coupons based on fused deposition modeling process. The specimens with five different raster orientations were printed with different printing speeds. Later, a series of tensile tests was performed under static loading conditions. Based on the results, strength and stiffness of the examined specimens have been determined. Moreover, dependency of the strength and elastic modulus of 3D-printed parts on the raster orientation has been documented. In the current study, fractured specimens were visually investigated by a free-angle observation system. The experimental findings can be used for the development of computational models and next design of structural components.
Mental imagery can generate and regulate acquired differential fear conditioned reactivity
Authors: Greening Steven G. , Lee Tae-Ho , Burleigh Lauryn , Grégoire Laurent , Robinson Tyler , Jiang Xinrui , Mather Mara , Kaplan Jonas
Published: January 2022

Mental imagery is an important tool in the cognitive control of emotion. The present study tests the prediction that visual imagery can generate and regulate differential fear conditioning via the activation and prioritization of stimulus representations in early visual cortices. We combined differential fear conditioning with manipulations of viewing and imagining basic visual stimuli in humans. We discovered that mental imagery of a fear-conditioned stimulus compared to imagery of a safe conditioned stimulus generated a significantly greater conditioned response as measured by self-reported fear, the skin conductance response, and right anterior insula activity (experiment 1). Moreover, mental imagery effectively down- and up-regulated the fear conditioned responses (experiment 2). Multivariate classification using the functional magnetic resonance imaging data from retinotopically defined early visual regions revealed significant decoding of the imagined stimuli in V2 and V3 (experiment 1) but significantly reduced decoding in these regions during imagery-based regulation (experiment 2). Together, the present findings indicate that mental imagery can generate and regulate a differential fear conditioned response via mechanisms of the depictive theory of imagery and the biased-competition theory of attention. These findings also highlight the potential importance of mental imagery in the manifestation and treatment of psychological illnesses.
Identification of putative essential protein domains from high-density transposon insertion sequencing
Authors: Rahman A. S. M. Zisanur , Timmerman Lukas , Gallardo Flyn , Cardona Silvia T.
Published: January 2022

A first clue to gene function can be obtained by examining whether a gene is required for life in certain standard conditions, that is, whether a gene is essential. In bacteria, essential genes are usually identified by high-density transposon mutagenesis followed by sequencing of insertion sites (Tn-seq). These studies assign the term “essential” to whole genes rather than the protein domain sequences that encode the essential functions. However, genes can code for multiple protein domains that evolve their functions independently. Therefore, when essential genes code for more than one protein domain, only one of them could be essential. In this study, we defined this subset of genes as “essential domain-containing” (EDC) genes. Using a Tn-seq data set built-in Burkholderia cenocepacia K56-2, we developed an in silico pipeline to identify EDC genes and the essential protein domains they encode. We found forty candidate EDC genes and demonstrated growth defect phenotypes using CRISPR interference (CRISPRi). This analysis included two knockdowns of genes encoding the protein domains of unknown function DUF2213 and DUF4148. These putative essential domains are conserved in more than two hundred bacterial species, including human and plant pathogens. Together, our study suggests that essentiality should be assigned to individual protein domains rather than genes, contributing to a first functional characterization of protein domains of unknown function.
Upregulated WTAP expression appears to both promote breast cancer growth and inhibit lymph node metastasis
Authors: Wang Chao-Qun , Tang Chih-Hsin , Wang Yan , Huang Bi-Fei , Hu Gui-Nv , Wang Qian , Shao Jun-Kang
Published: January 2022

It is unclear as to whether Wilms’ tumor 1-associated protein (WTAP) promotes or suppresses breast cancer. This immunohistochemistry analysis explored levels of WTAP expression in 347 cases of breast cancer and analyzed the relationship between WTAP expression and the clinicopathological characteristics and prognosis of breast cancer patients. The rate of high WTAP expression was significantly higher in breast cancer tissue than in adjacent normal breast tissue (37.5% vs 0.0%; P < 0.001). WTAP expression was positively associated with tumor size and grade, and negatively associated with axillary lymph node metastasis, estrogen and progesterone receptor status. Rates of high WTAP expression were 66.1% in triple-negative breast cancer (TNBC) tissue and 31.3% in non-TNBC tissue. In multiple logistic regression analysis, independent predictors of WTAP expression in breast cancer included larger tumor size (odds ratio = 1.907; 95% confidence interval: 1.185–3.067; P = 0.008), lymph node metastasis (0.597; 0.373–0.956; P = 0.032) and TNBC status (3.735; 2.056–6.784; P < 0.001). No clear relationship was observed between patient prognosis and WTAP expression. We suggest that WTAP expression is upregulated in breast cancer and appears to both promote tumor growth and inhibit lymph node metastasis.
Excessive laxity of connective tissue in constipated children
Authors: Załęski Andrzej , Gawrońska Agnieszka , Albrecht Piotr , Banasiuk Marcin
Published: January 2022

Excessive laxity of the connective tissue refers to a group of inherited abnormalities manifested by disturbances in the functioning of internal organs, including the gastrointestinal tract. Increased susceptibility to stretching of the distal part of the large intestine and abnormal colonic motor function could explain the predisposition to the development of functional constipation in some children. Our aim was to determine whether patients with functional constipation are more likely to be characterized by congenital laxity of connective tissue compared to the population of healthy children. Children diagnosed with functional constipation according to the Rome III criteria were prospectively enrolled in the study (study group, S) and compared to otherwise healthy children (control group, C). Excessive laxity of the connective tissue was evaluated using the Beighton Score (BS) and expressed as median and interquartile range (IQR). The study included 411 patients (median age 7.8 years, min 3 years, max 18 years; 49% male), comprising 211 patients in the S group and 200 children in the C group. The median BS in the S group was significantly higher than in the C group (median: 5 points [IQR: 1–4.5] vs 2 points [IQR: 3–7], respectively; p = 0.000).Furthermore, increased connective tissue laxity was observed more frequently in females (p < 0.05). Increased connective tissue laxity was more frequent in children with functional constipation, especially in girls. Excessive laxity of the connective tissue may be one of the etiological factors of functional constipation in children.
Polymer indicator displacement assay: electrochemical glucose monitoring based on boronic acid receptors and graphene foam competitively binding with poly-nordihydroguaiaretic acid
Authors: Wikeley Simon M. , Przybylowski Jakub , Lozano-Sanchez Pablo , Caffio Marco , James Tony D. , Bull Steven D. , Fletcher Philip J. , Marken Frank
Published: January 2022

A poly-nordihydroguaiaretic acid film is employed as a voltammetric indicator for bound/unbound boronic acid sites to report on glucose and fructose concentration.
Macrophage membrane coated nanoparticles: a biomimetic approach for enhanced and targeted delivery
Authors: Khatoon Nafeesa , Zhang Zefei , Zhou Chunhui , Chu Maoquan
Published: January 2022

Macrophage membrane coated nanomaterials are used in various therapies, against infections and inflammation in order to combat immune barriers without compromising the efficacy of “cargo” molecules.
Evolution of Cu single atom catalysts to nanoclusters during CO2 reduction to CO
Authors: Yan Liu , Liang Xiao-Du , Sun Yue , Xiao Liang-Ping , Lu Bang-An , Li Guang , Li Yu-Yang , Hong Yu-Hao , Wan Li-Yang , Chen Chi , Yang Jian , Zhou Zhi-You , Tian Na , Sun Shi-Gang
Published: January 2022

Cu single-atom sites can aggregate into more active Cu nanoclusters during electrochemical CO2 reduction.
Encapsulation of closo-dodecaiodododecaborate in 2-hydroxypropyl-γ-cyclodextrin prevents hemolysis
Authors: Hollow Sophia E. , Johnstone Timothy C.
Published: January 2022

Na2B12I12 is a candidate X-ray contrast agent, but produces rapid hemolysis at the concentrations needed for medical imaging. Encapsulation within 2-hydroxypropyl-γ-cyclodextrin effectively protects red blood cells at substoichiometric levels.
Synthesis of polyantimony ligand complexes starting from Cp*4Sb4
Authors: Heinl Veronika , Balázs Gábor , Seidl Michael , Scheer Manfred
Published: January 2022

Cp*4Sb4 as Sb source for the formation of poly-Sb ligand complexes was examined. Whole or partial degradation of the Sb4 unit can be observed as well as a substitution of Cp* by Fe or Mo fragments. As a result, e.g. [{CpRFe(CO)2}4(μ4-Sb4)] (CpR = Cp′′, Cp′′′) are formed.
Bimetallic metal–organic frameworks for tumor inhibition via combined photothermal-immunotherapy
Authors: Li Anning , Wang Ning , Song Yuxuan , Sun Haifeng , Cui Jiwei , Zhang Guiqiang , Yu Qun
Published: January 2022

Nanoparticles for immuno-photothermal therapy were constructed by encapsulating photosensitizers and aluminum ions into zeolitic imidazolate framework-8, which significantly inhibited the growth of primary and rechallenged tumors.
Steric influence on solvate formation – a comparison of resorcylic acid and two brominated derivatives
Authors: Edkins Katharina , Tweedy Jane , Fung Stephanie , Edkins Robert M.
Published: January 2022

Unbalanced steric bulk can lead to increased solvate formation as shown in non-, mono- and dibrominated resorcylic acid.
Realizing overgrowth in the homo-PVT process for 2 inch AlN single crystals
Authors: Zhao Qiyue , Zhu Xingyu , Han Tong , Wang Zeren , Wu Jiejun , Yu Tongjun
Published: January 2022

Large-size AlN crystal homo-PVT process is distinguished by the growth of prismatic grains in a macroscopic 3-dimensional mode, and that overgrowth plays a key role in the merging of grains under a lateral overgrown c-plane surface.
Full-dimensional Schrödinger wavefunction calculations using tensors and quantum computers: the Cartesian component-separated approach
Authors: Poirier Bill , Jerke Jonathan
Published: January 2022

Traditional quantum chemistry is based on separability by particle. Here, we explore a radically different approach, based on separability by Cartesian component.
Probing the solvation of the α-helix with extended amide III bands in Raman optical activity
Authors: Yamamoto Shigeki , Kimura Fumiya
Published: January 2022

Experimental and theoretical studies on the Raman optical activity (ROA) of α-helical peptides and proteins clarify that the ROA intensity ratio of the two extended amide III bands can be a permittivity indicator of the surrounding medium of the α-helix.
Variable dimensionality of the anion framework in four new borophosphates and fluoroborophosphates with short cutoff edges
Authors: Zhang Ruonan , Guo Siru , Wang Xuping , Yang Rong , Chen Zhen , Zhang Wenyao , Zhang Fangfang , Guo Zhiyong , Han Shujuan , Yang Zhihua
Published: January 2022

Four new borophosphates and fluoroborophosphates constructed by using tetrahedral groups, which possess variable dimensionality of the anion framework, have been obtained.
Enhancement in the active site exposure in a porphyrin-based PIL/graphene composite catalyst for the highly efficient conversion of CO2
Authors: Guo Xiao-Xuan , Zhang Feng-Lei , Muhammad Yaseen , Hu Dong-Liang , Cai Zhao-Tian , Xiao Guo-Min
Published: January 2022

This work synthesized a PIL composite catalyst based on anin-situsurface construction strategy. This strategy promoted the stable loading of PIL in a small-size state, ensuring that the catalyst provided sufficient active sites for CO2 conversion.
Atomic Co decorated free-standing graphene electrode assembly for efficient hydrogen peroxide production in acid
Authors: Lin Zeheng , Zhang Qingran , Pan Jian , Tsounis Constantine , Esmailpour Ali Asghar , Xi Shibo , Yang Hui Ying , Han Zhaojun , Yun Jimmy , Amal Rose , Lu Xunyu
Published: January 2022

A novel oxygen reduction reaction (ORR) electrode comprising isolated Co atom decorated vertically aligned graphene nanosheets is designed, which can enable the most energy-efficient, rapid acidic H2O2 production in a flow-cell reactor.
Butyl-fructooligosaccharides modulate gut microbiota in healthy mice and ameliorate ulcerative colitis in a DSS-induced model
Authors: Kang Sini , You Hyun Ju , Ju Ying , Kim Hee Jung , Jeong Yun Ju , Johnston Tony V. , Ji Geun Eog , Ku Seockmo , Park Myeong Soo
Published: January 2022

Butyl-fructooligosaccharides (B-FOSs) are synthetic molecules designed to combine the biofunctionalities of butyrate and fructooligosaccharides (FOSs), which solve the difficulty with oral butyrate delivery.
Large-leaf yellow tea attenuates high glucose-induced vascular endothelial cell injury by up-regulating autophagy and down-regulating oxidative stress
Authors: Wang Pu , Huang Yihai , Ren Jiayue , Rong Yuezhao , Fan Lili , Zhang Peng , Zhang Xueying , Xi Junxiao , Mao Shuying , Su Min , Zhang Baobao , Bao Guanhu , Wu Feihua
Published: January 2022

HLYTBE protects HUVECs against HG-induced injury via AMPK/mTOR-regulated autophagy and inhibiting oxidative stress. Moreover, HLYTBE improves glucose and lipid metabolism, exhibits antioxidant activity and reduces arterial vascular injury in vivo.
Influence of the particle size of encapsulated chia oil on the oil release and bioaccessibility during in vitro gastrointestinal digestion
Authors: Álvarez Rudy , Giménez Begoña , Mackie Alan , Torcello-Gómez Amelia , Quintriqueo Alejandra , Oyarzun-Ampuero Felipe , Robert Paz
Published: January 2022

Among vegetable oils, chia oil has been gaining interest in recent years due to its high linolenic acid content (ALA, 18:3 ω3).