bluuebunny/crossref_metadata_2025 huggingface dataset:
Computational and in vitro experimental analyses of the Anti-COVID-19 potential of Mortaparib and MortaparibPlus
Authors: Kumar Vipul , Sari Anissa Nofita , Meidinna Hazna Noor , Dhanjal Jaspreet Kaur , Subramani Chandru , Basu Brohmomoy , Kaul Sunil C , Vrati Sudhanshu , Sundar Durai , Wadhwa Renu
Published: October 2021

COVID-19 pandemic caused by SARS-CoV-2 virus has become a global health emergency. Although new vaccines have been generated and being implicated, discovery and application of novel preventive and control measures are warranted. We aimed to identify compound/s that may possess the potential to either block the entry of virus to host cells or attenuate its replication upon infection. Using host cell surface receptor expression (Angiotensin-converting enzyme 2 (ACE2) and Transmembrane protease serine 2 (TMPRSS2) analysis as an assay, we earlier screened several synthetic and natural compounds and identified candidates that showed ability to downregulate their expression. Here, we report experimental and computational analyses of two small molecules, Mortaparib and MortaparibPlus that were initially identified as dual novel inhibitors of mortalin and PARP-1, for their activity against SARS-CoV-2. In silico analyses showed that MortaparibPlus, but not Mortaparib, stably binds into the catalytic pocket of TMPRSS2. In vitro analysis of control and treated cells revealed that MortaparibPlus caused downregulation of ACE2 and TMPRSS2; Mortaparib did not show any effect. Furthermore, computational analysis on SARS-CoV-2 main protease (Mpro) that also predicted the inhibitory activity of MortaparibPlus.  However, cell based anti-virus drug screening assay showed 30~60% viral inhibition in cells treated with non-toxic doses of either MortaparibPlus or Mortaparib. The data suggests that these two closely related compounds possess multimodal anti-COVID 19 activities. Whereas MortaparibPlus works through direct interactions/effects on the host cell surface receptors (ACE2 and TMPRSS2) and the virus protein (Mpro), Mortaparib involves independent mechanisms, elucidation of which warrants further studies.
Disentangled and controllable sketch creation based on disentangling the structure and color enhancement
Authors: Gao Nan , Ren Hui , Li Jia , Su ZhiBin
Published: October 2021

Existing sketch‐based image processing methods include sketch recognition, sketch synthesis and sketch‐based image retrieval. For sketch creation, a meaningful task is proposed namely disentangled and controllable sketch creation (DCSC) based on disentangling the structure and color enhancement. Specifically, as the first subtask, sketch structure enhancement (SSE) is used to enhance a non‐professional sketch (NPS) and obtain a professional sketch (PS), which is a process denoted as NPS2PS. A data set named SketchMan is first provided, consisting of NPSs and PSs with various postures in different scenes. SSE is trained as a conditional image‐to‐image translation problem, and there are three models: direct sketch‐to‐sketch (SS), grayscale guided SS and contour guided SS. Multiple IOU metrics are proposed based on Corner Point Map (CPM), Straight Line Map (SLM) and Segmented Area Map (SAM). As the second subtask, sketch color enhancement (SCE) is trained as a two‐stage framework containing a topology enhancement network (TE‐Net) that maps a sketch to the corresponding grayscale domain and a color injection network (CI‐Net) that injects the global color feature to the AdaIN residual blocks to perform adaptive sketch colorization. The TE‐Net and CI‐Net disentangle the topological and color features to perform more controllable and diverse SCE results. Experimental results demonstrate that our proposed methods are effective to address the challenging and meaningful DCSC task compared with other state‐of‐the‐art methods.
A two‐turn loop active magnetic field probe design for high sensitivity near‐field measurement
Authors: Shao Weiheng , Li Jianke , Huang Quan , Shao E , Liu Jiesheng , He Xiao , Yi Zhiqiang , Fang Wenxiao , Zhou Changjian
Published: October 2021

This paper develops an active magnetic near field probe (H‐field probe) by using a four‐layer printed circuit board (PCB) technique. Two‐turn detection structure and a low noise amplifier are used to improve probe's frequency response. The two‐turn detection structure can maximize the use of PCB stack resources, and a 14.5 dB gain amplifier can increase signal output capability. The probe can then be used for electromagnetic compatibility (EMC) test from 150 kHz to 3 GHz. Compared with traditional active shielded‐loop H‐field probe (TAHP) with loop area of 500 m, the frequency response of the proposed probe can improve 20 dB at 0.5 GHz. Different from the method of comparing the sensitivity of the probe only through the frequency response, this paper measures and analyzes the real sensitivity of the probing device composed of the proposed probe. Under the condition of the same receiver parameter setting, the sensitivity at 0.5 GHz is increased by 11.7 dB compared with commercial passive probing device and 20.2 dB at 0.5 GHz compared with the probing device with TAHP device. It reaches −32.4 dB μA. In addition, the proposed probe has acceptable spatial resolution of 1.28 mm at 1 GHz, which is more suitable for printed circuit board level EMI analysis.
Studying the merging cluster Abell 3266 with eROSITA
Authors: Sanders J. S. , Biffi V. , Brüggen M. , Bulbul E. , Dennerl K. , Dolag K. , Erben T. , Freyberg M. , Gatuzz E. , Ghirardini V. , Hoang D. N. , Klein M. , Liu A. , Merloni A. , Pacaud F. , Ramos-Ceja M. E. , Reiprich T. H. , ZuHone J. A.
Published: October 2021

Abell 3266 is one of the X-ray brightest galaxy clusters in the sky and is a well-known merging system. Using the ability of the eROSITA telescope onboard SRG (Spectrum Röntgen Gamma) to observe a wide field with a single pointing, we analysed a new observation of the cluster out to a radius of R200. The X-ray images highlight sub-structures present in the cluster, including the north-east-south-west merger seen in previous ASCA, Chandra, and XMM-Newton data, a merging group towards the north-west, and filamentary structures between the core and one or more groups towards the west. We compute spatially resolved spectroscopic maps of the thermodynamic properties of the cluster, including the metallicity. The merging subclusters are seen as low entropy material within the cluster. The filamentary structures could be the rims of a powerful outburst of an active galactic nucleus, or most likely material stripped from the western group(s) as they passed through the cluster core. Seen in two directions is a pressure jump at a radius of 1.1 Mpc, which is consistent with a shock with a Mach number of ~1.5–1.7. The eROSITA data confirm that the cluster is not a simple merging system, but it is made up of several subclusters which are merging or will shortly merge. We computed a hydrostatic mass from the eROSITA data, finding good agreement with a previous XMM-Newton result. With this pointing we detect several extended sources, where we find secure associations between z = 0.36–1.0 for seven of them, that is background galaxy groups and clusters, highlighting the power of eROSITA to find such systems.
In vitro 3D liver tumor microenvironment models for immune cell therapy optimization
Authors: Lam Maxine , Reales-Calderon Jose Antonio , Ow Jin Rong , Adriani Giulia , Pavesi Andrea
Published: October 2021

Despite diagnostic and therapeutic advances, liver cancer kills more than 18 million people every year worldwide, urging new strategies to model the disease and to improve the current therapeutic options. In vitro tumor models of human cancer continue to evolve, and they represent an important screening tool. However, there is a tremendous need to improve the physiological relevance and reliability of these in vitro models to fulfill today's research requirements for better understanding of cancer progression and treatment options at different stages of the disease. This review describes the hepatocellular carcinoma microenvironmental characteristics and illustrates the current immunotherapy strategy to fight the disease. Moreover, we present a recent collection of 2D and 3D in vitro liver cancer models and address the next generation of in vitro systems recapitulating the tumor microenvironment complexity in more detail.
Polarization-based surface enhanced Raman scattering from single colloidal DNA decorated with 3 nm silicon nanoparticles
Authors: Mantey Kevin , Quagliano Lucia , Rezk Ayman , Palleschi Simonetta , Abuhassan Laila , Nayfeh Ammar , Bahceci Ersin , H. Nayfeh Munir
Published: October 2021

Surface enhanced Raman scattering (SERS), in which sample molecules are placed in the proximity of conducting nanostructures, subjects the molecules to intense electron oscillation (plasmon) field. The intense field, however, may cause heavy distortion and thermal damage to the molecule as well as non-separable and heavy convolution with the metal electronic structure. We utilized 3-nm red luminescent Si nanoparticles decorating the DNA molecules (drawn electrostatically) to enhance Raman scattering in solution at 532 nm. We demonstrated that the nanoparticles enhance the spectral resolution and intensity of vibrations of DNA by two orders of magnitude and reveal vibrations that are otherwise weak or forbidden. Theoretically, we conducted calculations of Mie scattering and three-dimensional finite-difference time-domain scattering and obtained the wavelength dependence of the near-field distribution from single or dimer Si particles. The simulations show moderate intensity enhancement (25–40-fold) and exciton resonances. Moreover, it shows that the near field is highly confined, extending only to 3–5 Å from the Si particle (atomic scale) compared to several nanometers for metal nanoparticles. The observed SERS-type characteristics are understood in terms of polarization-based light scattering, which is possible by the use of Si of highly reduced size for which the polarizability and exciton processes are strong. However, multilayers contribute to metal SERS, and monolayers/single molecules dominate the Si case. Weaker but highly confined, ultra-short range polarization-based scattering provides an alternative to plasmon and Mie scattering, while providing practical, straightforward interpretation of vibration printing of bio-medical species without compromising the molecular structure.
Time-varying formation control with smooth switching communication
Authors: Zhang YuFeng , Feng Zhe , Jin JunWei , Gao WenTao , Xu Hao , Yu DengXiu
Published: October 2021

This paper studies the communication smooth switching problem of time-varying formation control. When the formation system performs topology switching, sudden changes in communication will cause communication failure and affect formation control. To avoid this adverse impact, we introduce a smooth transition function of communication topology. At the same time, for the formation system with unknown nonlinear dynamics, an adaptive backstepping controller combining the backstepping control method and the fuzzy logic system is designed. Then, based on Lyapunov stability theory, we prove the stability of the designed controller. The results of the simulation experiments can verify the effectiveness of the designed controller.
Utilizing laser scribing for graphene ablation
Authors: Panyathip Rangsan , Choopun Supab , Singjai Pisith , Sakulsermsuk Sumet
Published: October 2021

We present the investigation of graphene ablation by laser scribing from a LightScribe DVD. In laser scribed graphene (LSG) samples, laser scribed holes (LSHs) were observed as dark features filled with residuals from copper etching. The LSHs tend to form a series of discontinuous lines aligning to laser scribed traces on the disk. The calculated fluence of laser scribing was about 93 and 124 mJ/cm2 for a pulse train and a single pulse, respectively. These fluences are in the range of fluence threshold of graphene ablation by femtosecond laser and are much higher than that of cw laser. From characterizations and electrical measurements, evidence of extended defects in graphene from LSHs in LSG was observed. From testing of graphene-based gas sensors, we can see that the response of LSG to ethanol is almost 100 times higher than that of graphene. This work provides a low-cost, facile method of graphene ablation by utilizing laser scribing. By improving sample preparation, our method could be applied to patterning graphene into microstrips, which have applications in novel devices such as THz sources and gas sensors.
Adventures in Translocation: Studies of the Translocator Protein (TSPO) 18 kDa
Authors: Danon Jonathan J. , Tregeagle Dane F. L. , Kassiou Michael
Published: October 2021

The 18 kDa translocator protein (TSPO) is an evolutionarily conserved transmembrane protein found embedded in the outer mitochondrial membrane. A secondary target for the benzodiazepine diazepam, TSPO has been a protein of interest for researchers for decades, particularly owing to its well-established links to inflammatory conditions in the central and peripheral nervous systems. It has become a key biomarker for assessing microglial activation using positron emission tomography (PET) imaging in patients with diseases ranging from atherosclerosis to Alzheimer’s disease. This Account describes research published by our group over the past 15 years surrounding the development of TSPO ligands and their use in probing the function of this high-value target.
Tetrastigma hemsleyanum flavones exert antihepatic carcinoma property both in vitro and in vivo
Authors: Liu Yangyang , Li Yonglu , Chen Wen , Ye Xiang , Jia Ruoyi , Yu Lushuang , Tang Qiong , Tu Pengcheng , Jiang Yong , Chu Qiang , Zheng Xiaodong
Published: October 2021

Tetrastigma hemsleyanum (T. hemsleyanum) has been regarded as an anticancer food in China. However, its corresponding mechanisms remains unclear. Thus, in this study, the antitumor activity of flavones-rich fraction of root of T. hemsleyanum (FRTH) was investigated in vitro and in vivo. The results indicated that FRTH could inhibit the proliferation and migration of human hepatoellular carcinomas (HepG2) cells in vitro by the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway. FRTH could increase the level of reactive oxygen species and change the mitochondrial membrane potential in HepG2 cells. In addition, FRTH treatment (300 mg/kg and 600 mg/kg, body weight) significantly suppressed tumor growth on HepG2 tumor-bearing nude mice. Besides, immunohistochemistry assays and western blotting revealed that FRTH enhanced the expression level of Bcl-2 associated X protein/B-cell lymphoma-2 (Bax/Bcl-2), cytochrome C, caspase-3, caspase-9, and cleaved-caspase-3, and downregulated the expression level of platelet endothelial cell adhesion molecule-1 (CD31), ki67, and vascular endothelial growth factor (VEGF) factor in HepG2 tumor-bearing mice. Our study suggests T. hemsleyanum as a kind of promising candidate medicine for liver cancer treatment.
Questions to Measure Enjoyment of and Satisfaction With Physical Activity: Are They Appropriate for Use in an Older Population?
Authors: Huffman Mary Katherine , Christ Sharon L , Ferraro Kenneth F , Klenosky David B , Marceau Kristine , Amireault Steve
Published: October 2021

Background and Objectives

Enjoyment of and satisfaction with physical activity have been proposed as two actionable mechanisms to promote sustained engagement in physical activity. An accurate understanding of how, why, and for whom these two mechanisms work (or not) in response to a particular intervention strategy is contingent on having suitable measures for the population of interest. This study aims to determine whether the Physical Activity Enjoyment Scale-8 and a novel approach to the measurement of satisfaction with physical activity are suitable for use among older adults (Mage = 66.25 years; range = 55–91 years).

Research Design and Methods

Participants answered an online questionnaire twice across 4 weeks. Measurement invariance was assessed within a structural equation modeling framework; convergent validity was assessed by correlating the latent variables enjoyment and satisfaction with each other and with physical activity behavior.

Results

Both measures were invariant between gender and across time. Enjoyment and satisfaction were related to each other (r = 0.72) and to physical activity (r = 0.48 and 0.64, respectively).

Discussion and Implications

Results support the suitability of these measures as tools to assess enjoyment of and satisfaction with physical activity among older adults.
A Serum Marker for Early Pancreatic Cancer With a Possible Link to Diabetes
Authors: Nam Hoonsik , Hong Soon-Sun , Jung Kyung Hee , Kang Sunmi , Park Min Seok , Kang Suyeon , Kim Han Sun , Mai Van-Hieu , Kim Juyoung , Lee Ho , Lee Woohyung , Suh Young Ju , Lim Joo Han , Kim Soo-Youl , Kim Song Cheol , Kim So Hun , Park Sunghyouk
Published: October 2021

Background

Pancreatic cancer (PC) has a grim prognosis, and an early diagnostic biomarker has been highly desired. The molecular link between diabetes and PC has not been well established.

Methods

Bioinformatics screening was performed for a serum PC marker. Experiments in cell lines (5 PC and 1 normal cell lines), mouse models, and human tissue staining (37 PC and 10 normal cases) were performed to test asprosin production from PC. Asprosin’s diagnostic performance was tested with serums from multi-center cohorts (347 PC, 209 normal, and 55 additional diabetic patients) and evaluated according to PC status, stages, and diabetic status, which was compared with that of CA19-9.

Results

Asprosin, a diabetes-related hormone, was found from the bioinformatics screening, and its production from PC was confirmed. Serum asprosin levels from multi-center cohorts yielded an age-adjusted diagnostic area under the curve (AUC) of 0.987 (95% confidence interval [CI] = 0.961 to 0.997), superior to that of CA19-9 (AUC = 0.876, 95% CI = 0.847 to 0.905), and a cut-off of 7.18 ng/mL, at which the validation set exhibited a sensitivity of 0.957 and a specificity of 0.924. Importantly, the performance was maintained in early-stage and non-metastatic PC, consistent with the tissue staining. A slightly lower performance against additional diabetic patients (n = 55) was restored by combining asprosin and CA19-9 (AUC = 0.985, 95% CI = 0.975 to 0.995).

Conclusions

Asprosin is presented as an early-stage PC serum marker that may provide clues for PC-induced diabetes. Larger prospective clinical studies are warranted to solidify its utility.
CRISPR-Cas systems are widespread accessory elements across bacterial and archaeal plasmids
Authors: Pinilla-Redondo Rafael , Russel Jakob , Mayo-Muñoz David , Shah Shiraz A , Garrett Roger A , Nesme Joseph , Madsen Jonas S , Fineran Peter C , Sørensen Søren J
Published: October 2021

Many prokaryotes encode CRISPR-Cas systems as immune protection against mobile genetic elements (MGEs), yet a number of MGEs also harbor CRISPR-Cas components. With a few exceptions, CRISPR-Cas loci encoded on MGEs are uncharted and a comprehensive analysis of their distribution, prevalence, diversity, and function is lacking. Here, we systematically investigated CRISPR-Cas loci across the largest curated collection of natural bacterial and archaeal plasmids. CRISPR-Cas loci are widely but heterogeneously distributed across plasmids and, in comparison to host chromosomes, their mean prevalence per Mbp is higher and their distribution is distinct. Furthermore, the spacer content of plasmid CRISPRs exhibits a strong targeting bias towards other plasmids, while chromosomal arrays are enriched with virus-targeting spacers. These contrasting targeting preferences highlight the genetic independence of plasmids and suggest a major role for mediating plasmid-plasmid conflicts. Altogether, CRISPR-Cas are frequent accessory components of many plasmids, which is an overlooked phenomenon that possibly facilitates their dissemination across microbiomes.
SCovid: single-cell atlases for exposing molecular characteristics of COVID-19 across 10 human tissues
Authors: Qi Changlu , Wang Chao , Zhao Lingling , Zhu Zijun , Wang Ping , Zhang Sainan , Cheng Liang , Zhang Xue
Published: October 2021

SCovid (http://bio-annotation.cn/scovid) aims at providing a comprehensive resource of single-cell data for exposing molecular characteristics of coronavirus disease 2019 (COVID-19) across 10 human tissues. COVID-19, an epidemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been found to be accompanied with multiple-organ failure since its first report in Dec 2019. To reveal tissue-specific molecular characteristics, researches regarding to COVID-19 have been carried out widely, especially at single-cell resolution. However, these researches are still relatively independent and scattered, limiting the comprehensive understanding of the impact of virus on diverse tissues. To this end, we developed a single-cell atlas of COVID-19. Firstly we collected 21 single-cell datasets of COVID-19 across 10 human tissues paired with control datasets. Then we constructed a pipeline for the analysis of these datasets to reveal molecular characteristics of COVID-19 based on manually annotated cell types. The current version of SCovid documents 1 042 227 single cells of 21 single-cell datasets across 10 human tissues, 11 713 stably expressed genes and 3778 significant differentially expressed genes (DEGs). SCovid provides a user-friendly interface for browsing, searching, visualizing and downloading all detailed information.
Pharmacoresistant seizures and IDH mutation in low-grade gliomas
Authors: Correia Carlos Eduardo , Umemura Yoshie , Flynn Jessica R , Reiner Anne S , Avila Edward K
Published: October 2021

Background

Many low-grade gliomas (LGG) harbor isocitrate dehydrogenase (IDH) mutations. Although IDH mutation is known to be epileptogenic, the rate of refractory seizures in LGG with IDH mutation vs wild-type had not been previously compared. We therefore compared seizure pharmacoresistance in IDH-mutated and wild-type LGGs.

Methods

Single-institution retrospective study of patients with histologic proven LGG, known IDH mutation status, seizures, and ≥2 neurology clinic encounters. Seizure history was followed until histological high-grade transformation or death. Seizures requiring ≥2 changes in anti-epileptic drugs were considered pharmacoresistant. Incidence rates of pharmacoresistant seizures were estimated using competing risks methodology.

Results

Of 135 patients, 25 patients (19%) had LGGs classified as IDH wild-type. Of those with IDH mutation, 104 (94.5%) were IDH1 R132H; only 6 were IDH2 R172K. 120 patients (89%) had tumor resection, and 14 (10%) had biopsy. Initial post-surgical management included observation (64%), concurrent chemoradiation (23%), chemotherapy alone (9%), and radiotherapy alone (4%). Seizures became pharmacoresistant in 24 IDH-mutated patients (22%) and in 3 IDH wild-type patients (12%). The 4-year cumulative incidence of intractable seizures was 17.6% (95% CI: 10.6%-25.9%) in IDH-mutated and 11% (95% CI: 1.3%-32.6%) in IDH wild-type LGG (Gray’s P-value = .26).

Conclusions

22% of the IDH-mutated patients developed pharmacoresistant seizures, compared to 12% of the IDH wild-type tumors. The likelihood of developing pharmacoresistant seizures in patients with LGG-related epilepsy is independent to IDH mutation status, however, IDH-mutated tumors were approximately twice as likely to experience LGG-related pharmacoresistant seizures.
Feasibility and Acceptability of Community Coronavirus Disease 2019 Testing Strategies (FACTS) in a University Setting
Authors: Hirst Jennifer A , Logan Mary , Fanshawe Thomas R , Mwandigha Lazaro , Wanat Marta , Vicary Charles , Perera Rafael , Tonkin-Crine Sarah , Lee Joseph Jonathan , Tracey Irene , Duff Gordon , Tufano Peter , Besharov Marya , Tarassenko Lionel , Nicholson Brian D , Hobbs F D Richard
Published: October 2021

Background

During the coronavirus disease 2019 (COVID-19) pandemic in 2020, the UK government began a mass severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing program. This study aimed to determine the feasibility and acceptability of organized regular self-testing for SARS-CoV-2.

Methods

This was a mixed-methods observational cohort study in asymptomatic students and staff at University of Oxford, who performed SARS-CoV-2 antigen lateral flow self-testing. Data on uptake and adherence, acceptability, and test interpretation were collected via a smartphone app, an online survey, and qualitative interviews.

Results

Across 3 main sites, 551 participants (25% of those invited) performed 2728 tests during a follow-up of 5.6 weeks; 447 participants (81%) completed at least 2 tests, and 340 (62%) completed at least 4. The survey, completed by 214 participants (39%), found that 98% of people were confident to self-test and believed self-testing to be beneficial. Acceptability of self-testing was high, with 91% of ratings being acceptable or very acceptable. A total of 2711 (99.4%) test results were negative, 9 were positive, and 8 were inconclusive. Results from 18 qualitative interviews with students and staff revealed that participants valued regular testing, but there were concerns about test accuracy that impacted uptake and adherence.

Conclusions

This is the first study to assess feasibility and acceptability of regular SARS-CoV-2 self-testing. It provides evidence to inform recruitment for, adherence to, and acceptability of regular SARS-CoV-2 self-testing programs for asymptomatic individuals using lateral flow tests. We found that self-testing is acceptable and people were able to interpret results accurately.
Risk of stroke with antivenom usage after venomous snakebite in Taiwan: a population-based cohort study
Authors: Hung W -H , Sung J , Chen W -Y , Chiu L -T , Yip H -T , Wei J C -C , Hung Y -M , Chang R
Published: October 2021

Background and purpose

Stroke is a rare complication of snakebites, but may lead to serious sequelae. We aimed to explore the relationship between venomous snakebite and the risk for acute stroke, in a nationwide population-based cohort study.

Methods

This retrospective cohort study used claims data between 1 January 2000 and 31 December 2012, from the Taiwan National Health Insurance Research Database. The study included data of patients aged 18 years or older with venomous snakebite (n = 535), matched for propensity score with controls without venomous snakebite (n = 2140). The follow-up period was the duration from the initial diagnosis of venomous snakebite and administration of antivenom to the date of an acute stroke, or until 31 December 2013. The competing risk model was used to estimate the hazard ratio (HR) and 95% confidence intervals (CIs) of stroke, ischemic stroke and hemorrhagic stroke, after adjusting for demographic and other possible stroke risk factors.

Results

The adjusted HR for the venomous snakebite group compared with the control group was 2.68 for hemorrhagic stroke (95% CI = 1.35-5.33). Stratified analysis showed that the older age group (>65 years old) had a higher risk of hemorrhagic stroke. A 2.72-fold significant increase in the risk for hemorrhagic stroke was observed following venomous snakebite with antivenom usage (95% CI = 1.41–5.26).

Conclusion

Venomous snakebite is associated with an increased risk of hemorrhagic stroke after the use of antivenom. Further study of the underlying mechanism is warranted.
A hymenopteran odorant alerts flies to bury eggs
Authors: Davis Shaun M. , Chism Gregory T. , Maurer Megan M. , Trejo Julio E. , Garcia Ricardo J. , Schlenke Todd A.
Published: October 2021

Ants are ubiquitous and consume insects at all life stages, presumably creating a strong selective pressure for ant avoidance behaviors across insects. The insect egg stage can be especially defenseless against predation given that eggs are usually immobile and unguarded, suggesting insect mothers may have evolved oviposition strategies to minimize the ant predation risk to their offspring. Given the lack of parental care in most insects, these oviposition strategies would likely be innate rather than learned, since insect mothers are not usually present to assess predation of their eggs. Here, we use the vinegar flyDrosophila melanogasteras a model system for examining parental defensive responses to ant presence. Flies usually lay eggs partially inserted into the food substrate, although some are laid on top of the food and a few are inserted deeply into the food. We found that exposure to ants significantly alters fly oviposition depth: the proportion of eggs on the food surface decreased while the proportion of buried eggs increased. Buried eggs survive ant foraging bouts better than surface eggs, showing that this oviposition depth behavior is adaptive. This induced behavior is conserved across the genus Drosophila and is dependent on the fly olfactory system: anosmic mutant flies fail to bury their eggs in the presence of ants, and ant odor extracts are sufficient to induce egg burying. To further delineate the ant lineages to which flies respond, we exposed flies to the odors from numerous species of ants and other insects. Surprisingly, flies buried their eggs in response to the odors of nearly all hymenopterans tested, including hymenopteran groups that flies rarely interact with in nature like bees and paper wasps. Our data suggest that hymenopterans possess a conserved and ancient odorant, and that drosophilids evolved a mechanism for sensing this odorant early in their evolution as a means of protecting their offspring from ant predation. This study sheds light on the ecology and mechanisms underlying a sscommon biotic interaction in nature, that between insect parents ands the ants that would consume their offspring.
Cell-Penetrating D-Peptides Retain Antisense Morpholino Oligomer Delivery Activity
Authors: Schissel Carly K. , Farquhar Charlotte E. , Malmberg Annika B. , Loas Andrei , Pentelute Bradley L.
Published: October 2021

Cell-penetrating peptides (CPPs) can cross the cell membrane to enter the cytosol and deliver otherwise non-penetrant macromolecules such as proteins and oligonucleotides. For example, recent clinical trials have shown that a CPP attached to phosphorodiamidate morpholino oligomers (PMO) resulted in higher muscle concentration, increased exon-skipping and dystrophin production relative to another study of the PMO alone in patients of Duchenne muscular dystrophy. Therefore, effective design and study of CPPs could help enhance therapies for difficult-to-treat diseases. So far, the study of CPPs for PMO delivery has been restricted to predominantly canonical L-peptides. We hypothesized that mirror-image D-peptides could have similar PMO delivery activity as well as enhanced proteolytic stability, facilitating their characterization and quantification from biological milieu. We found that several enantiomeric peptide sequences could deliver a PMO-biotin cargo with similar activities, while remaining stable against serum proteolysis. The biotin label allowed for affinity capture of fully intact PMO-peptide conjugates from whole cell and cytosolic lysates. By profiling a mixture of these constructs in cells, we determined their relative intracellular concentrations. When combined with PMO activity, these concentrations provide a new metric for delivery efficiency which may be useful for determining which peptide sequence to pursue in further pre-clinical studies.

Abstract Figure
Recombinant adjuvanted zoster vaccine and reduced risk of COVID-19 diagnosis and hospitalization in older adults
Authors: Bruxvoort Katia J. , Ackerson Bradley , Sy Lina S. , Bhavsar Amit , Tseng Hung Fu , Florea Ana , Luo Yi , Tian Yun , Solano Zendi , Widenmaier Robyn , Shi Meng , Van Der Most Robbert , Schmidt Johannes Eberhard , Danier Jasur , Breuer Thomas , Qian Lei
Published: October 2021

Background

Vaccines may elicit long-term boosting of innate immune responses that can help protect against COVID-19. We evaluated the association between recombinant adjuvanted zoster vaccine (RZV) and COVID-19 outcomes at Kaiser Permanente Southern California.

Methods

In a cohort design, adults aged ≥50 years who received ≥1 RZV dose prior to 3/1/2020 were matched 1:2 to unvaccinated individuals and followed until 12/31/2020. Adjusted hazard ratios (aHR) and 95% confidence intervals (CIs) for COVID-19 outcomes were estimated using Cox proportional hazards regression. In a test-negative design, cases had a positive SARS-CoV-2 test and controls had only negative tests, from 3/1/2020-12/31/2020. Adjusted odds ratios (aOR) and 95% CIs for prior receipt of RZV were estimated using logistic regression.

Results

In the cohort design, 149,244 RZV recipients were matched to 298,488 unvaccinated individuals. The aHRs (95% CI) for COVID-19 diagnosis and hospitalization were 0.84 (0.81-0.87) and 0.68 (0.64-0.74), respectively. In the test-negative design, 8.4% of 75,726 test-positive cases and 13.1% of 340,898 test-negative controls had received ≥1 RZV dose. The aOR (95% CI) was 0.84 (0.81-0.86).

Conclusion

RZV vaccination was associated with a 16% lower risk of COVID-19 diagnosis and 32% lower risk of hospitalization, suggesting RZV elicits heterologous protection, possibly through trained immunity.
BinChecker: a new algorithm for quality assessment of microbial draft genomes
Authors: Klingenberg Heiner , Meinicke Peter
Published: October 2021

In the reconstruction of microbial genomes from metagenomic sequence data, the estimation of the final completeness and possible contamination is crucial for quality control. In metagenomics candidate genomes are usually obtained from a metagenome assembly and a subsequent binning of the assembled contigs. BinChecker provides a novel approach to quality assessment that is based on a fast protein domain search and a clustering approach for identification of marker domain (“feature”) sets. The feature sets that are used for estimation are not pre-computed for a given database of reference genomes, but are individually found for each bin by adaptive clustering and feature selection. In particular, the adaptivity facilitates the creation and extension of the underlying database, which just requires to add protein feature profiles of reference genomes. Tests with simulated bins indicate that the prediction accuracy of BinChecker meets the current state of the art while providing significant advantages in terms of speed and flexibility.
Anatomical and functional connectivity support the existence of a salience network node within the caudal ventrolateral prefrontal cortex
Authors: Trambaiolli Lucas R. , Peng Xiaolong , Lehman Julia F. , Liu Hesheng , Haber Suzanne N.
Published: October 2021

Three large-scale brain networks are considered essential to cognitive flexibility: the ventral and dorsal attention (VAN and DAN) and salience (SN) networks. The ventrolateral prefrontal cortex (vlPFC) is a known component of the VAN and DAN, but there is an important gap in the current knowledge regarding its involvement in the SN. In this study, we used a translational and multimodal approach to fulfill this gap and demonstrate the existence of a SN node within the vlPFC. First, we used tract-tracing methods in non-human primates (NHP) to quantify the anatomic connectivity strength between the different vlPFC areas and the frontal and insular cortices. The strongest connections with the dorsal anterior cingulate cortex (dACC) and anterior insula (AI) locations comprising the two main cortical SN nodes were derived from the caudal area 47/12. This location also has strong axonal projections to subcortical structures of the salience network, including the dorsomedial thalamus, hypothalamus, sublenticular extended amygdala, and periaqueductal gray. Second, we used a seed-based functional connectivity analysis in NHP resting-state functional MRI (rsfMRI) data to validate the caudal area 47/12 as an SN node. Third, we used the same approach in human rsfMRI data to identify a homologous structure in caudal area 47/12, also showing strong connections with the SN cortical nodes, thus confirming the caudal area 47/12 as the SN node in the vlPFC. Taken together, the vlPFC contains nodes for all three cognitive networks, the VAN, DAN, and SN. Thus, the vlPFC is in a position to switch between these three cognitive networks, pointing to a key role as an attentional hub. Its tight additional connections to the orbitofrontal, dorsolateral, and ventral premotor cortices, places the vlPFC at the center for switching behaviors based on environmental stimuli, computing value and cognitive control.
Morphological control of receptor-mediated endocytosis
Authors: Agostinelli Daniele , Elfring Gwynn J. , Bacca Mattia
Published: October 2021

Receptor-mediated endocytosis is the primary process for nanoparticle uptake in cells and one of the main entry mechanisms for viral infection. The cell membrane adheres to the particle (nanoparticle or virus) and then wraps it to form a vesicle delivered to the cytosol. Previous findings identified a minimum radius for a spherical particle below which endocytosis cannot occur. This is due to the insufficient driving force, from receptor-ligand affinity, to overcome the energy barrier created by membrane bending. In this paper, we extend this result to the case of clathrin-mediated endocytosis, which is the most common pathway for virus entry. Moreover, we investigate the effect of ligand inhibitors on the particle surface, motivated by viral antibodies, peptides or phage capsids nanoparticles. We determine the necessary conditions for endocytosis by considering the additional energy barrier due to the membrane bending to wrap such inhibiting protrusions. We find that the density and size of inhibitors determine the size range of internalized particles, and endocytosis is completely blocked above critical thresholds. The assembly of a clathrin coat with a spontaneous curvature increases the energy barrier and sets a maximum particle size (in agreement with experimental observations on smooth particles). Our investigation suggests that morphological considerations can inform the optimal design of neutralizing viral antibodies and new strategies for targeted nanomedicine.
Locating hydrogen positions in the autunite mineral metatorbernite [Cu(UO2)2(PO4)2·8H2O]: a combined approach using neutron powder diffraction and computational modelling
Authors: MacIver-Jones Fiona M. , Sutcliffe Polly , Graham Margaret C. , Morrison Carole A. , Kirk Caroline A.
Published: October 2021

Metatorbernite [Cu(UO2)2(PO4)2·8H2O] is a promising remediation material for environmental uranium contamination. Previous X-ray diffraction studies have been unable to definitively locate hydrogen positions within metatorbernite, which are key to determining the hydrogen-bond network that helps to stabilize the structure. Here, hydrogen positions have been determined using a combination of neutron powder diffraction and the computational modelling technique ab initio random structure searching (AIRSS). Atomic coordinates determined through Rietveld analysis of neutron powder diffraction data are in excellent agreement with the minimum energy configuration predicted by AIRSS; thus, simulations confirm that our proposed model likely represents the global minimum configuration. Two groups of water molecules exist within the metatorbernite structure: free water and copper-coordinating water. Free water molecules are held within the structure by hydrogen bonding only, whilst the coordinating water molecules bond to copper in the equatorial positions to produce a 4 + 2 Jahn–Teller octahedra. The successful agreement between neutron powder diffraction data and AIRSS suggests that this combined approach has excellent potential for the study of other (trans)uranium materials in which hydrogen bonding plays a key role in phase stability.
Michaelis-like complex of SARS-CoV-2 main protease visualized by room-temperature X-ray crystallography
Authors: Kneller Daniel W. , Zhang Qiu , Coates Leighton , Louis John M. , Kovalevsky Andrey
Published: October 2021

SARS-CoV-2 emerged at the end of 2019 to cause an unprecedented pandemic of the deadly respiratory disease COVID-19 that continues to date. The viral main protease (Mpro) is essential for SARS-CoV-2 replication and is therefore an important drug target. Understanding the catalytic mechanism of Mpro, a cysteine protease with a catalytic site comprising the noncanonical Cys145–His41 dyad, can help in guiding drug design. Here, a 2.0 Å resolution room-temperature X-ray crystal structure is reported of a Michaelis-like complex of Mpro harboring a single inactivating mutation C145A bound to the octapeptide Ac-SAVLQSGF-CONH2 corresponding to the nsp4/nsp5 autocleavage site. The peptide substrate is unambiguously defined in subsites S5 to S3′ by strong electron density. Superposition of the Michaelis-like complex with the neutron structure of substrate-free Mpro demonstrates that the catalytic site is inherently pre-organized for catalysis prior to substrate binding. Induced fit to the substrate is driven by P1 Gln binding in the predetermined subsite S1 and rearrangement of subsite S2 to accommodate P2 Leu. The Michaelis-like complex structure is ideal for in silico modeling of the SARS-CoV-2 Mpro catalytic mechanism.
X-ray molecular orbital analysis. II. Application to diformohydrazide, (NHCHO)2
Authors: Tanaka Kiyoaki , Wasada-Tsutsui Yuko
Published: October 2021

The molecular orbitals (MOs) of diformohydrazide have been determined from the electron density measured by X-ray diffraction. The experimental and refinement procedures are explained in detail and the validity of the obtained MOs is assessed from the crystallographic point of view. The X-ray structure factors were measured at 100 K by a four-circle diffractometer avoiding multiple diffraction, the effect of which on the structure factors is comparable to two-centre structure factors. There remained no significant peaks on the residual density map and the R factors reduced significantly. Among the 788 MO coefficients, 731 converged, of which 694 were statistically significant. The C—H and N—H bond distances are 1.032 (2) and 1.033 (3) Å, respectively. The electron densities of theoretical and experimental MOs and the differences between them are illustrated. The overall features of the electron density obtained by X-ray molecular orbital (XMO) analysis are in good agreement with the canonical orbitals calculated by the restricted Hartree Fock (RHF) method. The bonding-electron distribution around the middle of each bond is well represented and the relative phase relationships of the π orbitals are reflected clearly in the electron densities on the plane perpendicular to the molecular plane. However, differences are noticeable around the O atom on the molecular plane. The orbital energies obtained by XMO analysis are about 0.3 a.u. higher than the corresponding canonical orbitals, except for MO10 to MO14 which are about 0.7 a.u. higher. These exceptions are attributed to the N—H...O′′ intermolecular hydrogen bond, which is neglected in the MO models of the present study. The hydrogen bond is supported by significant electron densities at the saddle points between the H(N) and O′′ atoms in MO7, 8, 14 and 17, and by that of O′′-p extended over H(N) in MO21 and 22, while no peaks were found in MO10, 11, 13 and 15. The electron density of each MO clearly exhibits its role in the molecule. Consequently, the MOs obtained by XMO analysis give a fundamental quantum mechanical insight into the real properties of molecules.
The cultural landscape of coffee in Tolima, Colombia: heritage assessment, sustainability and management
Authors: Velandia Silva César Augusto , Diab Mark C.
Published: October 2021

Purpose

The purpose of this paper is to determine the basis for a management agenda for the Tolima Coffee Cultural Landscape (CCLT) in Colombia. To this end, a delimitation model has been developed. However, the approach taken to institute the agenda of the CCLT, as a comprehensive academic and policy-based theme, is based on the formulation of a social agenda that supports its construction.

Design/methodology/approach

A theoretical framework is proposed that addresses the sociocultural complexities of the Tolima cultural landscape. This is based on an ethnohistorical approach that elucidates the development of this landscape as a collective construction of pre-Hispanic origin. Therefore, this investigation has been perceived through the theoretical and conceptual framework of the cultural landscape concept and the unique historical and cultural phenomenon that help to define all landscapes. More specifically, the authors have demonstrated the close links that exist between nature and culture, requiring increasingly accurate methods in order to adapt the landscape definition to the specific Latin American context, rather than adhering to the institutional framework proposed by UNESCO.

Findings

The assessment methods currently in use support the interpretation of a set of qualitative and quantitative attributes inherent to the Tolima region. However, additional methods still remain similar to those of the Coffee Cultural Landscape of Colombia (CCLC) that has already been inscribed on UNESCO's World Heritage List. The CCLC is considered to be a representative landscape—or “type” landscape—that “mirrors” the CCLT. Taken as a whole, this theoretical construction combined with the official designation allows local communities to understand the spatial phenomena of the CCLT. This will have the effect of enabling communities at all levels, from local government to landholders and farmers, to authorize its existence and allow for its continuing development and governance. The additional approval for further academic research, combined with the totality of these elements, also has the added effect of empowering communities, their economic future and their cultural interests.

Originality/value

The management agenda that the authors are proposing may form the beginning of regional policy initiatives that reflect a positive strategy for highlighting the value of cultural heritage, thereby ensuring the protection of cultural properties and landscapes and allowing for a more sustainable environment and livelihood for its occupants.
Measuring the motivation to avoid duping: scale development and validation
Authors: Madrigal Robert , Wardley Marcus , Armstrong Soule Catherine Anne
Published: October 2021

Purpose

This paper aims to develop and validate a psychometrically sound scale measuring buyers’ motivation to avoid being duped (MAD) in a marketplace transaction.

Design/methodology/approach

Standard scale construction methodology was followed in developing the MAD Scale. Eight studies were conducted.

Findings

Three underlying MAD factors were discovered: suspicion of sellers, anticipated aversive emotions and deception detection. For purposes of analyses, data were collapsed across factors. High MAD individuals exhibited more vigilance in decision-making, were less trusting of strangers and displayed a greater desire to appear perfect to others. Those high in MAD were also more apt to have a prevention regulatory focus. Test-retest reliability was satisfactory, and no social desirability bias was observed. Finally, in an economic game with real financial consequences, those higher (vs lower) in MAD invested less after being duped, thus supporting criterion validity.

Originality/value

Marketplace deception has been identified as an existential threat facing consumers. Yet, few studies have examined how consumers cope with this threat. There currently exists no scales to measure consumer motivation to avoid being duped. The current research defines MAD and differentiates it from related constructs. The MAD scale will be useful in a variety of research contexts related to marketplace deception.