bluuebunny/crossref_metadata_2025 huggingface dataset:
Nanobodies from camelid mice and llamas neutralize SARS-CoV-2 variants
Authors: Xu Jianliang , Xu Kai , Jung Seolkyoung , Conte Andrea , Lieberman Jenna , Muecksch Frauke , Lorenzi Julio Cesar Cetrulo , Park Solji , Schmidt Fabian , Wang Zijun , Huang Yaoxing , Luo Yang , Nair Manoj S. , Wang Pengfei , Schulz Jonathan E. , Tessarollo Lino , Bylund Tatsiana , Chuang Gwo-Yu , Olia Adam S. , Stephens Tyler , Teng I-Ting , Tsybovsky Yaroslav , Zhou Tongqing , Munster Vincent , Ho David D. , Hatziioannou Theodora , Bieniasz Paul D. , Nussenzweig Michel C. , Kwong Peter D. , Casellas Rafael
Published: June 2021

Since the start of the COVID-19 pandemic, SARS-CoV-2 has caused millions of deaths worldwide. Although a number of vaccines have been deployed, the continual evolution of the receptor-binding domain (RBD) of the virus has challenged their efficacy. In particular, the emerging variants B.1.1.7, B.1.351 and P.1 (first detected in the UK, South Africa and Brazil, respectively) have compromised the efficacy of sera from patients who have recovered from COVID-19 and immunotherapies that have received emergency use authorization1–3. One potential alternative to avert viral escape is the use of camelid VHHs (variable heavy chain domains of heavy chain antibody (also known as nanobodies)), which can recognize epitopes that are often inaccessible to conventional antibodies4. Here, we isolate anti-RBD nanobodies from llamas and from mice that we engineered to produce VHHs cloned from alpacas, dromedaries and Bactrian camels. We identified two groups of highly neutralizing nanobodies. Group 1 circumvents antigenic drift by recognizing an RBD region that is highly conserved in coronaviruses but rarely targeted by human antibodies. Group 2 is almost exclusively focused to the RBD–ACE2 interface and does not neutralize SARS-CoV-2 variants that carry E484K or N501Y substitutions. However, nanobodies in group 2 retain full neutralization activity against these variants when expressed as homotrimers, and—to our knowledge—rival the most potent antibodies against SARS-CoV-2 that have been produced to date. These findings suggest that multivalent nanobodies overcome SARS-CoV-2 mutations through two separate mechanisms: enhanced avidity for the ACE2-binding domain and recognition of conserved epitopes that are largely inaccessible to human antibodies. Therefore, although new SARS-CoV-2 mutants will continue to emerge, nanobodies represent promising tools to prevent COVID-19 mortality when vaccines are compromised.
Three-dimensional folding dynamics of the Xenopus tropicalis genome
Authors: Niu Longjian , Shen Wei , Shi Zhaoying , Tan Yongjun , He Na , Wan Jing , Sun Jialei , Zhang Yuedong , Huang Yingzhang , Wang Wenjing , Fang Chao , Li Jiashuo , Zheng Piaopiao , Cheung Edwin , Chen Yonglong , Li Li , Hou Chunhui
Published: June 2021

Animal interphase chromosomes are organized into topologically associating domains (TADs). How TADs are formed is not fully understood. Here, we combined high-throughput chromosome conformation capture and gene silencing to obtain insights into TAD dynamics in Xenopus tropicalis embryos. First, TAD establishment in X. tropicalis is similar to that in mice and flies and does not depend on zygotic genome transcriptional activation. This process is followed by further refinements in active and repressive chromatin compartments and the appearance of loops and stripes. Second, within TADs, higher self-interaction frequencies at one end of the boundary are associated with higher DNA occupancy of the architectural proteins CTCF and Rad21. Third, the chromatin remodeling factor ISWI is required for de novo TAD formation. Finally, TAD structures are variable in different tissues. Our work shows that X. tropicalis is a powerful model for chromosome architecture analysis and suggests that chromatin remodeling plays an essential role in de novo TAD establishment.
Backward spatial perception can be augmented through a novel visual-to-auditory sensory substitution algorithm
Authors: Netzer Ophir , Heimler Benedetta , Shur Amir , Behor Tomer , Amedi Amir
Published: June 2021

Can humans extend and augment their natural perceptions during adulthood? Here, we address this fascinating question by investigating the extent to which it is possible to successfully augment visual spatial perception to include the backward spatial field (a region where humans are naturally blind) via other sensory modalities (i.e., audition). We thus developed a sensory-substitution algorithm, the “Topo-Speech” which conveys identity of objects through language, and their exact locations via vocal-sound manipulations, namely two key features of visual spatial perception. Using two different groups of blindfolded sighted participants, we tested the efficacy of this algorithm to successfully convey location of objects in the forward or backward spatial fields following ~ 10 min of training. Results showed that blindfolded sighted adults successfully used the Topo-Speech to locate objects on a 3 × 3 grid either positioned in front of them (forward condition), or behind their back (backward condition). Crucially, performances in the two conditions were entirely comparable. This suggests that novel spatial sensory information conveyed via our existing sensory systems can be successfully encoded to extend/augment human perceptions. The implications of these results are discussed in relation to spatial perception, sensory augmentation and sensory rehabilitation.
Isolated sphenoid sinus opacification is often asymptomatic and is not referred for otolaryngology consultation
Authors: Ashida Naoki , Maeda Yohei , Kitamura Takahiro , Hayama Masaki , Tsuda Takeshi , Nakatani Ayaka , Obata Sho , Takeda Kazuya , Akazawa Hitoshi , Inaba Fumitaka , Hosomi Naohiro , Uno Atsuhiko , Inohara Hidenori
Published: June 2021

Isolated sphenoid sinus opacifications (ISSOs) are clinically important because they can lead to serious complications. However, some patients with ISSOs are asymptomatic, and not all patients are properly referred to the otolaryngology department. Because past studies of ISSOs focused only on patients who received treatment, in this study we selected ISSO cases based on radiology reports, then determined whether these patients had symptoms and were appropriately referred for specialty care. We conducted a retrospective analysis of data collected from patients who underwent computed tomography or magnetic resonance imaging from January 2007 to March 2017 at Osaka General Medical Center. We searched for the terms “sphenoid” or “sphenoidal” using F-REPORT to identify patients who had a sphenoid disease. We checked all selected images and diagnosed ISSOs. Examination of 1115 cases revealed 223 cases of ISSOs, of whom 167 (74.9%) were asymptomatic. We categorized patients with ISSOs into four groups: inflammation, mucocele, fungal diseases, and unclassifiable; the final category was used when edges were irregular or complete opacity was encountered. In the unclassifiable group, the majority of cases required otolaryngology consultation, but 37 of 47 unclassifiable patients did not have an otolaryngology visit. ISSOs are often identified by chance on imaging tests performed by non-otolaryngologists. However, our study revealed that many patients with ISSOs who should be treated by otolaryngologists were not referred to the otolaryngology department. Accordingly, it is important to promote awareness of the disease among other types of clinicians.
Variations in photoreceptor throughput to mouse visual cortex and the unique effects on tuning
Authors: Rhim I. , Coello-Reyes G. , Nauhaus I.
Published: June 2021

Visual input to primary visual cortex (V1) depends on highly adaptive filtering in the retina. In turn, isolation of V1 computations requires experimental control of retinal adaptation to infer its spatio-temporal-chromatic output. Here, we measure the balance of input to mouse V1, in the anesthetized setup, from the three main photoreceptor opsins—M-opsin, S-opsin, and rhodopsin—as a function of two stimulus dimensions. The first dimension is the level of light adaptation within the mesopic range, which governs the balance of rod and cone inputs to cortex. The second stimulus dimension is retinotopic position, which governs the balance of S- and M-cone opsin input due to the opsin expression gradient in the retina. The fitted model predicts opsin input under arbitrary lighting environments, which provides a much-needed handle on in-vivo studies of the mouse visual system. We use it here to reveal that V1 is rod-mediated in common laboratory settings yet cone-mediated in natural daylight. Next, we compare functional properties of V1 under rod and cone-mediated inputs. The results show that cone-mediated V1 responds to 2.5-fold higher temporal frequencies than rod-mediated V1. Furthermore, cone-mediated V1 has smaller receptive fields, yet similar spatial frequency tuning. V1 responses in rod-deficient (Gnat1−/−) mice confirm that the effects are due to differences in photoreceptor opsin contribution.
An initial assessment of the involvement of transglutaminase2 in eosinophilic bronchitis using a disease model developed in C57BL/6 mice
Authors: Chen Lan , Liu Shuyan , Xiao Linzhuo , Chen Kanyao , Tang Juanjuan , Huang Chuqin , Luo Wei , Ferrandon Dominique , Lai Kefang , Li Zi
Published: June 2021

The detailed pathogenesis of eosinophilic bronchitis (EB) remains unclear. Transglutaminase 2 (TG2) has been implicated in many respiratory diseases including asthma. Herein, we aim to assess preliminarily the relationship of TG2 with EB in the context of the development of an appropriate EB model through ovalbumin (OVA) sensitization and challenge in the C57BL/6 mouse strain. Our data lead us to propose a 50 μg dose of OVA challenge as appropriate to establish an EB model in C57BL/6 mice, whereas a challenge with a 400 μg dose of OVA significantly induced asthma. Compared to controls, TG2 is up-regulated in the airway epithelium of EB mice and EB patients. When TG2 activity was inhibited by cystamine treatment, there were no effects on airway responsiveness; in contrast, the lung pathology score and eosinophil counts in bronchoalveolar lavage fluid were significantly increased whereas the cough frequency was significantly decreased. The expression levels of interleukin (IL)-4, IL-13, IL-6, mast cell protease7 and the transient receptor potential (TRP) ankyrin 1 (TRPA1), TRP vanilloid 1 (TRPV1) were significantly decreased. These data open the possibility of an involvement of TG2 in mediating the increased cough frequency in EB through the regulation of TRPA1 and TRPV1 expression. The establishment of an EB model in C57BL/6 mice opens the way for a genetic investigation of the involvement of TG2 and other molecules in this disease using KO mice, which are often generated in the C57BL/6 genetic background.
SEAMHCRD deterministic compartmental model based on clinical stages of infection for COVID-19 pandemic in Sultanate of Oman
Authors: Varghese Abraham , Kolamban Shajidmon , Sherimon Vinu , Lacap Eduardo M. , Ahmed Saad Salman , Sreedhar Jagath Prasad , Al Harthi Hasina , Al Shuaily Huda Salim
Published: June 2021

The present novel coronavirus (COVID-19) infection has engendered a worldwide crisis on an enormous scale within a very short period. The effective solution for this pandemic is to recognize the nature and spread of the disease so that appropriate policies can be framed. Mathematical modelling is always at the forefront to understand and provide an adequate description of the transmission of any disease. In this research work, we have formulated a deterministic compartmental model (SEAMHCRD) including various stages of infection, such as Mild, Moderate, Severe and Critical to study the spreading of COVID-19 and estimated the model parameters by fitting the model with the reported data of ongoing pandemic in Oman. The steady-state, stability and final pandemic size of the model has been proved mathematically. The various transmission as well as transition parameters are estimated during the period from June 4th to July 30th, 2020. Based on the currently estimated parameters, the pandemic size is also predicted for another 100 days. Sensitivity analysis is performed to identify the key model parameters, and the parameter gamma due to contact with the symptomatic moderately infected is found to be more significant in spreading the disease. Accordingly, the corresponding basic reproduction number has also been computed using the Next Generation Matrix (NGM) method. As the value of the basic reproduction number (R0) is 0.9761 during the period from June 4th to July 30th, 2020, the disease-free equilibrium is stable. Isolation and tracing the contact of infected individuals are recommended to control the spread of disease.
The queen conch mitogenome: intra- and interspecific mitogenomic variability in Strombidae and phylogenetic considerations within the Hypsogastropoda
Authors: Machkour-M’Rabet Salima , Hanes Margaret M. , Martínez-Noguez Josué Jacob , Cruz-Medina Jorge , García-De León Francisco J.
Published: June 2021

Aliger gigas is an economically important and vulnerable marine species. We present a new mitogenome of A. gigas from the Mexican Caribbean and use the eight publicly available Strombidae mitogenomes to analyze intra- and interspecific variation. We present the most complete phylogenomic understanding of Hypsogastropoda to date (17 superfamilies, 39 families, 85 genera, 109 species) to revisit the phylogenetic position of the Stromboidea and evaluate divergence times throughout the phylogeny. The A. gigas mitogenome comprises 15,460 bp including 13 PCGs, 22 tRNAs, and two rRNAs. Nucleotide diversity suggested divergence between the Mexican and Colombian lineages of A. gigas. Interspecific divergence showed high differentiation among Strombidae species and demonstrated a close relationship between A. gigas and Strombus pugilis, between Lambis lambis and Harpago chiragra, and among Tridentarius dentatus/Laevistrombus canarium/Ministrombus variabilis. At the intraspecific level, the gene showing the highest differentiation is ATP8 and the lowest is NAD4L, whereas at the interspecific level the NAD genes show the highest variation and the COX genes the lowest. Phylogenomic analyses confirm that Stromboidea belongs in the non-Latrogastropoda clade and includes Xenophoridea. The phylogenomic position of other superfamilies, including those of previously uncertain affiliation, is also discussed. Finally, our data indicated that Stromboidea diverged into two principal clades in the early Cretaceous while Strombidae diversified in the Paleocene, and lineage diversification within A. gigas took place in the Pleistocene.
Corneal biomechanical parameters in keratoconus eyes with abnormal elevation on the back corneal surface only versus both back and front surfaces
Authors: Sedaghat Mohammad-Reza , Momeni-Moghaddam Hamed , Roberts Cynthia J. , Maddah Nasim , Ambrósio Renato , Hosseini Seyed Rafi
Published: June 2021

Corneal biomechanical parameters were compared in 100 keratoconus eyes with abnormal elevation on the back corneal surface only (group 1), versus both the back and front surfaces (group 2). Scheimpflug tomography with Pentacam HR, corneal biomechanical assessments using Corvis ST and Ocular Response Analyzer (ORA) and corneal epithelium thickness maps using anterior segment optical coherence tomography were assessed. There were no significant differences in the IOP measured using Corvis ST and ORA, age or sex between the two groups. Statistically significant differences were found in all corneal shape parameters and all new parameters of Corvis ST: corneal stiffness parameter at first applanation (SP-A1), integrated inverse radius (IR) and deformation amplitude ratio (DAR)) between groups (p < 0.001). The classic parameters of ORA including corneal hysteresis (CH) and corneal resistance factor (CRF) were about 1.00 mmHg higher in group 1 (p < 0.001). In conclusion, keratoconus eyes with abnormal elevation limited to the back corneal surface have lower grade, stiffer corneal biomechanical parameters and less asymmetric shape. This is consistent with progressive biomechanical weakening from the first detectable back surface elevation to manifestation on the front surface as the severity overwhelms the ability of the epithelium to compensate.
Background stimulus delays detection of target stimulus in a familiar odor–odor combination
Authors: Gotow Naomi , Hoshi Ayaka , Kobayakawa Tatsu
Published: June 2021

Familiarity of odor–odor combinations is enhanced through food intake in daily life. As familiarity increases, the perceptual boundary between two odors may become ambiguous; therefore, we hypothesized that exposure to one odor would delay detection of the other in a high-familiarity combination but not in a low-familiarity combination. To test this hypothesis, we measured the speed of odor detection using two types of background stimuli (black tea odor and odorless air) and two types of target stimuli (lemon odor and almond odor). For Japanese participants, the combination of black tea and lemon odor has high familiarity, whereas the combination of black tea and almond odors has low familiarity. Reaction time for detection of target stimulus was measured by inserting a pulsed target stimulus into the flow of the background stimulus (i.e., replacing the background stimulus with the target stimulus for a short time). Reaction time for detection of lemon odor was significantly longer under the black tea odor condition than under the odorless air condition. Reaction time for detection of almond odor was similar between the black tea odor and odorless air conditions. These results are in line with the hypothesis that familiarity of an odor–odor combination affects odor detection speed. Further investigations are required to reach more robust conclusions.
Horizontal spin of ratchet motor by vertical agitation
Authors: Takahashi Toshinobu , Okita Erika , Yamamoto Daigo , Okamoto Yasunao , Shioi Akihisa
Published: June 2021

The horizontal spin of a ratchet motor by vertical vibration is reported. A macroscopic ratchet gear is placed on a granular bed, where nearly half of the gear is penetrated in the bed. The gear and granular bed are mechanically vibrated. The gear shows a random motion or one-way spin that depend on the diameter of the granules, vibration frequency, and degree of vertical motion allowed for the gear. Even when one-way spin is observed, the spin direction depends on the abovementioned factors. Although the dependency is complicated, it is deterministic because the motion or flows of granular matter determines it. The characteristics observed in the experiments are explained by a simple model that accounts for the statistical variance in the motion of the granular matter. Extraction of systematic motion from small and non-useful motions such as mechanical agitation will be developed into energy harvest technology and may facilitate the science of a spontaneously moving system in a uniform potential field.
Novel robust time series analysis for long-term and short-term prediction
Authors: Okamura Hiroshi , Osada Yutaka , Nishijima Shota , Eguchi Shinto
Published: June 2021

Nonlinear phenomena are universal in ecology. However, their inference and prediction are generally difficult because of autocorrelation and outliers. A traditional least squares method for parameter estimation is capable of improving short-term prediction by estimating autocorrelation, whereas it has weakness to outliers and consequently worse long-term prediction. In contrast, a traditional robust regression approach, such as the least absolute deviations method, alleviates the influence of outliers and has potentially better long-term prediction, whereas it makes accurately estimating autocorrelation difficult and possibly leads to worse short-term prediction. We propose a new robust regression approach that estimates autocorrelation accurately and reduces the influence of outliers. We then compare the new method with the conventional least squares and least absolute deviations methods by using simulated data and real ecological data. Simulations and analysis of real data demonstrate that the new method generally has better long-term and short-term prediction ability for nonlinear estimation problems using spawner–recruitment data. The new method provides nearly unbiased autocorrelation even for highly contaminated simulated data with extreme outliers, whereas other methods fail to estimate autocorrelation accurately.
Profiling, isolation and characterisation of beneficial microbes from the seed microbiomes of drought tolerant wheat
Authors: Hone Holly , Mann Ross , Yang Guodong , Kaur Jatinder , Tannenbaum Ian , Li Tongda , Spangenberg German , Sawbridge Timothy
Published: June 2021

Climate change is predicted to increase the incidence and severity of drought conditions, posing a significant challenge for agriculture globally. Plant microbiomes have been demonstrated to aid crop species in the mitigation of drought stress. The study investigated the differences between the seed microbiomes of drought tolerant and drought susceptible wheat lines. Furthermore, it highlighted and quantified the degree of drought tolerance conferred by specific microbes isolated from drought tolerant wheat seed microbiomes. Metagenomic and culture-based methods were used to profile and characterise the seed microbiome composition of drought tolerant and drought susceptible wheat lines under rainfed and drought conditions. Isolates from certain genera were enriched by drought tolerant wheat lines when placed under drought stress. Wheat inoculated with isolates from these targeted genera, such as Curtobacterium flaccumfaciens (Cf D3-25) and Arthrobacter sp. (Ar sp. D4-14) demonstrated the ability to promote growth under drought conditions. This study indicates seed microbiomes from genetically distinct wheat lines enrich for beneficial bacteria in ways that are both line-specific and responsive to environmental stress. As such, seed from stress-phenotyped lines represent an invaluable resource for the identification of beneficial microbes with plant growth promoting activity that could improve commercial crop production.
Lipopolysaccharide stimulation test on cultured PBMCs assists the discrimination of cryopyrin-associated periodic syndrome from systemic juvenile idiopathic arthritis
Authors: Wu Chao-Yi , Fan Wen-Lang , Chiu Ying-Ming , Yang Huang-Yu , Lee Wen-I. , Huang Jing-Long
Published: June 2021

Systemic juvenile idiopathic arthritis (sJIA) and cryopyrin-associated periodic syndrome (CAPS) share many common manifestations. We aim to identify an applicable method to assist disease discrimination. Inflammatory cytokines were measured in the plasma of patients with CAPS, sJIA with persistent disease course and healthy controls. Supernatants collected from non-stimulated peripheral blood mononuclear cells (PBMCs) and those undergone inflammasome stimulation tests utilizing lipopolysaccharide (LPS) with and without adenosine triphosphate (ATP) were investigated. Inflammatory cytokines in patient plasma fail to differentiate sJIA from CAPS. PBMCs from sJIA secrets higher amount of IL-1β and IL-18 while CAPS PBMCs produces more caspase-1 without stimulation. IL-1β, IL-18, and caspase-1 were significantly elevated among CAPS PBMCs (all p < 0.05) upon LPS stimulation, but not when additional ATPs were provided. Levels of cytokines and PBMC responses to the stimulation assays were similar among all sJIA patients regardless of their history of macrophage activation syndrome. Unstimulated PBMC activities and the LPS inflammasome stimulation assay without exogenic ATPs can assist the differentiation of CAPS from sJIA with persistent disease course.
An initial study on the agreement of body temperatures measured by infrared cameras and oral thermometry
Authors: Adams Scott , Bucknall Tracey , Kouzani Abbas
Published: June 2021

The COVID-19 pandemic has led to the rapid adoption and rollout of thermal camera-based Infrared Thermography (IRT) systems for fever detection. These systems use facial infrared emissions to detect individuals exhibiting an elevated core-body temperature, which is present in many symptomatic presentations of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Despite the rollout of these systems, there is little independent research supporting their efficacy. The primary objective of this study was to assess the precision and accuracy of IRT screening solutions in a real-world scenario. The method used was a single-centre, observational study investigating the agreement of three IRT systems compared to digital oral thermometer measurements of body temperature. Over 5 days, 107 measurements were taken from individuals wearing facial masks. During each entry, two measurements of the subject’s body temperature were made from each system to allow for the evaluation of the measurement precision, followed by an oral thermometer measurement. Each participant also answered a short demographic survey. This study found that the precision of the IRT systems was wider than 0.3 °C claimed accuracy of two of the systems. This study also found that the IRT measurements were only weakly correlated to those of the oral temperature. Additionally, it was found that demographic characteristics (age, gender, and mask-type) impacted the measurement error. This study indicates that using IRT systems in front-line scenarios poses a potential risk, where a lack of measurement accuracy could possibly allow febrile individuals to pass through undetected. Further research is required into methods which could increase accuracy and improve the techniques viability.
Housing quality and behavior affect brain health and anxiety in healthy Japanese adults
Authors: Pineda Juan Cesar D. , Kokubun Keisuke , Ikaga Toshiharu , Yamakawa Yoshinori
Published: June 2021

Countless studies in animals have shown how housing environments and behaviors can significantly affect anxiety and brain health, giving valuable insight as to whether this is applicable in the human context. The relationship between housing, behavior, brain health, and mental wellbeing in humans remains poorly understood. We therefore explored the interaction of housing quality, weekend/holiday sedentary behavior, brain structure, and anxiety in healthy Japanese adults. Whole-brain structural magnetic resonance imaging (MRI) methods based on gray matter volume and fractional anisotropy were used as markers for brain health. Correlation tests were conducted, and then adjusted for multiple comparisons using the False Discovery Rate method. Housing quality and weekend/holiday sedentary behavior were associated with fractional anisotropy, but not with gray matter volume. Fractional anisotropy showed significant associations with anxiety. Lastly, both weekend/holiday sedentary behavior and housing quality were indirectly associated with anxiety through fractional anisotropy. These results add to the limited evidence surrounding the relationship among housing, behavior, and the brain. Furthermore, these results show that behavior and housing qualities can have an indirect impact on anxiety through neurobiological markers such as fractional anisotropy.
BSE can propagate in sheep co-infected or pre-infected with scrapie
Authors: Chong Angela , Foster James D. , Goldmann Wilfred , Gonzalez Lorenzo , Jeffrey Martin , O’Connor Matthew J. , Bishop Keith , Maddison Ben C. , Houston E. Fiona , Gough Kevin C. , Hunter Nora
Published: June 2021

To understand the possible role of mixed-prion infections in disease presentation, the current study reports the co-infection of sheep with bovine spongiform encephalopathy (BSE) and scrapie. The bovine BSE agent was inoculated subcutaneously into sheep with ARQ/ARQ or VRQ/ARQ PRNP genotypes either at the same time as subcutaneous challenge with scrapie, or three months later. In addition, VRQ/VRQ sheep naturally infected with scrapie after being born into a scrapie-affected flock were challenged subcutaneously with BSE at eight or twenty one months-of-age. Sheep were analysed by incubation period/attack rate, and western blot of brain tissue determined the presence of BSE or scrapie-like PrPSc. Serial protein misfolding cyclic amplification (sPMCA) that can detect very low levels of BSE in the presence of an excess of scrapie agent was also applied to brain and lymphoreticular tissue. For VRQ/ARQ sheep challenged with mixed infections, scrapie-like incubation periods were produced, and no BSE agent was detected. However, whilst ARQ/ARQ sheep developed disease with BSE-like incubation periods, some animals had a dominant scrapie western blot phenotype in brain, but BSE was detected in these sheep by sPMCA. In addition, VRQ/VRQ animals challenged with BSE after natural exposure to scrapie had scrapie-like incubation periods and dominant scrapie PrPSc in brain, but one sheep had BSE detectable by sPMCA in the brain. Overall, the study demonstrates for the first time that for scrapie/BSE mixed infections, VRQ/ARQ sheep with experimental scrapie did not propagate BSE but VRQ/VRQ sheep with natural scrapie could propagate low levels of BSE, and whilst BSE readily propagated in ARQ/ARQ sheep it was not always the dominant PrPSc strain in brain tissue. Indeed, for several animals, a dominant scrapie biochemical phenotype in brain did not preclude the presence of BSE prion.
Atomistic insight into salinity dependent preferential binding of polar aromatics to calcite/brine interface: implications to low salinity waterflooding
Authors: Koleini Mohammad Mehdi , Badizad Mohammad Hasan , Mahani Hassan , Dastjerdi Ali Mirzaalian , Ayatollahi Shahab , Ghazanfari Mohammad Hossein
Published: June 2021

This paper resolve the salinity-dependent interactions of polar components of crude oil at calcite-brine interface in atomic resolution. Molecular dynamics simulations carried out on the present study showed that ordered water monolayers develop immediate to a calcite substrate in contact with a saline solution. Carboxylic compounds, herein represented by benzoic acid (BA), penetrate into those hydration layers and directly linking to the calcite surface. Through a mechanism termed screening effect, development of hydrogen bonding between –COOH functional groups of BA and carbonate groups is inhibited by formation of a positively-charged Na+ layer over CaCO3 surface. Contrary to the common perception, a sodium-depleted solution potentially intensifies surface adsorption of polar hydrocarbons onto carbonate substrates; thus, shifting wetting characteristic to hydrophobic condition. In the context of enhanced oil recovery, an ion-engineered waterflooding would be more effective than injecting a solely diluted saltwater.
Marine habitat use and feeding ecology of introduced anadromous brown trout at the colonization front of the sub-Antarctic Kerguelen archipelago
Authors: Davidsen Jan Grimsrud , Bordeleau Xavier , Eldøy Sindre Håvarstein , Whoriskey Frederick , Power Michael , Crossin Glenn T. , Buhariwalla Colin , Gaudin Philippe
Published: June 2021

In 1954, brown trout were introduced to the Kerguelen archipelago (49°S, 70°E), a pristine, sub-Antarctic environment previously devoid of native freshwater fishes. Trout began spreading rapidly via coastal waters to colonize adjacent watersheds, however, recent and unexpectedly the spread has slowed. To better understand the ecology of the brown trout here, and why their expansion has slowed, we documented the marine habitat use, foraging ecology, and environmental conditions experienced over one year by 50 acoustically tagged individuals at the colonization front. Trout mainly utilized the marine habitat proximate to their tagging site, ranging no further than 7 km and not entering any uncolonized watersheds. Nutritional indicators showed that trout were in good condition at the time of tagging. Stomach contents and isotope signatures in muscle of additional trout revealed a diet of amphipods (68%), fish (23%), isopods (6%), and zooplankton (6%). The small migration distances observed, presence of suitable habitat, and rich local foraging opportunities suggest that trout can achieve their resource needs close to their home rivers. This may explain why the expansion of brown trout at Kerguelen has slowed.
The influence of Coulomb interaction screening on the excitons in disordered two-dimensional insulators
Authors: Kirichenko E. V. , Stephanovich V. A.
Published: June 2021

We study the joint effect of disorder and Coulomb interaction screening on the exciton spectra in two-dimensional (2D) structures. These can be van der Waals structures or heterostructures of organic (polymeric) semiconductors as well as inorganic substances like transition metal dichalcogenides. We consider 2D screened hydrogenic problem with Rytova–Keldysh interaction by means of so-called fractional Scrödinger equation. Our main finding is that above synergy between screening and disorder either destroys the exciton (strong screening) or promote the creation of a bound state, leading to its collapse in the extreme case. Our second finding is energy levels crossing, i.e. the degeneracy (with respect to index$$\mu $$μ) of the exciton eigenenergies at certain discrete value of screening radius. Latter effects may also be related to the quantum manifestations of chaotic exciton behavior in above 2D semiconductor structures. Hence, they should be considered in device applications, where the interplay between dielectric screening and disorder is important.
Prognostic significance of p53, Sox11, and Pax5 co-expression in mantle cell lymphoma
Authors: Jing Caixia , Zheng Yuhuan , Feng Yu , Cao Xia , Xu Caigang
Published: June 2021

Mantle cell lymphoma (MCL) is a relatively rare subtype of non-Hodgkin’s lymphoma. To identify molecular biomarkers in MCL, we performed immunohistochemistry tissue arrays using biopsies from 64 MCL patients diagnosed in West China Hospital from 2012 to 2016. TP53 mutation status in those patients was also examined by sequencing. The sequencing results showed TP53 mutations were highly heterogeneous in MCL. We identified four novel TP53 mutations in MCL: P151R, G199R, V218E, and G325R. The MCL patients with TP53 mutations had inferior progression-free survival (PFS, p = 0.002) and overall survival (OS, p = 0.011). Tissue array results showed the expression of p53, Sox11, or Pax5 alone did not correlate with the patient PFS and OS. However, the MCL patients with triple-positive expression of p53/Sox11/Pax5 had inferior PFS (p = 0.008) and OS (p = 0.002). Such risk stratification was independent to the mantle cell lymphoma international prognostic index (MIPI), Ki-67 value, and TP53 mutation status of the patients. The triple-positive patients might represent a subtype of high-risk MCL. Our findings might indicate a novel way to stratify MCL and predict patients’ prognosis.
Critical supply chains for mitigating PM2.5 emission-related mortalities in India
Authors: Mitoma Haruka , Nagashima Fumiya , Kagawa Shigemi , Nansai Keisuke
Published: June 2021

Air pollution and its health-related effects are a major concern globally, and many people die from air pollution-related diseases each year. This study employed a structural path analysis combined with a health impact inventory database analysis to estimate the number of consumption-based PM2.5 emission-related deaths attributed to India’s power supply sector. We identified critical supply chain paths for direct (production) electricity use and indirect (consumption) use. We also considered both domestic and foreign final demand and its effect on PM2.5 emission-related deaths. Several conclusions could be drawn from our results. First, the effect of indirect electricity usage on PM2.5 emission-related deaths is approximately four times larger than that for direct usage. Second, a large percentage of pollution-related deaths can be attributed to India’s domestic final demand usage; however, electricity usage in the intermediate and final demand sectors is inextricably linked. Third, foreign final demand sectors from the Middle East, the USA, and China contribute indirectly toward PM2.5 emission-related deaths, specifically in the rice export supply chain. The results show that the Indian government should implement urgent measures to curb electricity use in rice supply chains in order to reduce the number of PM2.5 emission-related deaths.
Synthesis and comparative study on the structural and optical properties of ZnO doped with Ni and Ag nanopowders fabricated by sol gel technique
Authors: Al-Ariki S. , Yahya Nabil A. A. , Al-A’nsi Sua’ad A. , Jumali M. H. Hj , Jannah A. N. , Abd-Shukor R.
Published: June 2021

In this work we have tried to prepare Ni and Ag doped ZnO nanopowders using the sol gel technique. The influence of Ni and Ag (1, 3 and 5 mol.%) on the crystalline structure and optical properties of ZnO was investigated. The samples were characterized by XRD, FTIR and UV–visible spectrophotometer. XRD patterns confirmed the wurtzite formation of doped and undoped ZnO nanopowders. The average crystallite sizes of the prepared samples found from XRD were 19 nm for undoped ZnO, from 17 to 22 nm for Ni-ZnO and from 19 to 26 nm for Ag-ZnO. The average crystallite size of Ag-ZnO increased with increasing Ag contents. Different optical properties of Ni-ZnO and Ag-ZnO nanopowders were observed for different Ni and Ag content. The band gaps of Ni-ZnO and Ag-ZnO nanopowders were lower than that of the undoped ZnO (3.1 eV). The band gaps of Ag-ZnO were lower than that of Ni-ZnO. The optical properties of ZnO were enhanced by Ni (mol.%) in the UV region and by Ag (3 and 5 mol.%) in the visible region.
Speciation and environmental risk of heavy metals in biochars produced by pyrolysis of chicken manure and water-washed swine manure
Authors: Wang Andong , Zou Dongsheng , Zeng Xinyi , Chen Bin , Zheng Xiaochen , Li Longcheng , Zhang Liqing , Xiao Zhihua , Wang Hua
Published: June 2021

This study was conducted to investigate the speciation, bioavailability and environmental risk of heavy metals (HMs) in chicken manure (CM) and water-washed swine manure (WSM) and their biochars produced at different pyrolysis temperatures (200 to 800 °C). As the pyrolysis temperature increased, the remaining proportion, toxicity characteristic leaching procedure (TCLP), HCl and diethylenetriamine pentaacetic acid (DTPA) of HMs gradually declined. This result proved that the speciation of HMs in chicken manure biochars (CMB) and water-washed swine manure biochars (WSMB) was influenced by pyrolysis temperature. The proportions of stable fractions were enhanced with increased pyrolysis temperature and weakened the HM validity for vegetation at 800 °C. Finally, the results of the risk assessment showed that the environmental risk of HMs in CMB and WSMB decreased with increasing pyrolysis temperature. Therefore, pyrolysis at 800 °C can provide a practical approach to lessen the initial and underlying heavy metal toxicity of CMB and WSMB to the environment.
Combination treatment with U0126 and rt-PA prevents adverse effects of the delayed rt-PA treatment after acute ischemic stroke
Authors: Orset Cyrille , Arkelius Kajsa , Anfray Antoine , Warfvinge Karin , Vivien Denis , Ansar Saema
Published: June 2021

In acute ischemic stroke, the only FDA-approved drug; recombinant tissue plasminogen activator (rt-PA) is limited by restricted time-window due to an enhanced risk of hemorrhagic transformation which is thought to be caused by metalloproteinase (MMP). In experimental stroke inhibitors of the mitogen–activated protein kinase kinase extracellular signal–regulated kinase kinase (MEK) 1/2 pathways reduce the MMPs. This study evaluated whether a MEK1/2 inhibitor in combination with rt-PA can prevent the detrimental effects of delayed rt-PA therapy in stroke. Thromboembolic stroke was induced in C57 black/6J mice and the MEK1/2 inhibitor U0126 was administrated 3.5 h and rt-PA 4 h post stroke-onset. Treatment with rt-PA demonstrated enhanced MMP-9 protein levels and hemorrhagic transformation which was prevented when U0126 was given in conjunction with rt-PA. By blocking the MMP-9 with U0126 the safety of rt-PA administration was improved and demonstrates a promising adjuvant strategy to reduce the harmful effects of delayed rt-PA treatment in acute ischemic stroke.
Osteogenic differentiation of human mesenchymal stromal cells and fibroblasts differs depending on tissue origin and replicative senescence
Authors: Grotheer Vera , Skrynecki Nadine , Oezel Lisa , Windolf Joachim , Grassmann Jan
Published: June 2021

The need for an autologous cell source for bone tissue engineering and medical applications has led researchers to explore multipotent mesenchymal stromal cells (MSC), which show stem cell plasticity, in various human tissues. However, MSC with different tissue origins vary in their biological properties and their capability for osteogenic differentiation. Furthermore, MSC-based therapies require large-scale ex vivo expansion, accompanied by cell type-specific replicative senescence, which affects osteogenic differentiation. To elucidate cell type-specific differences in the osteogenic differentiation potential and replicative senescence, we analysed the impact of BMP and TGF-β signaling in adipose-derived stromal cells (ASC), fibroblasts (FB), and dental pulp stromal cells (DSC). We used inhibitors of BMP and TGF-β signaling, such as SB431542, dorsomorphin and/or a supplemental addition of BMP-2. The expression of high-affinity binding receptors for BMP-2 and calcium deposition with alizarin red S were evaluated to assess osteogenic differentiation potential. Our study demonstrated that TGF-β signaling inhibits osteogenic differentiation of ASC, DSC and FB in the early cell culture passages. Moreover, DSC had the best osteogenic differentiation potential and an activation of BMP signaling with BMP-2 could further enhance this capacity. This phenomenon is likely due to an increased expression of activin receptor-like kinase-3 and -6. However, in DSC with replicative senescence (in cell culture passage 10), osteogenic differentiation sharply decreased, and the simultaneous use of BMP-2 and SB431542 did not result in further improvement of this process. In comparison, ASC retain a similar osteogenic differentiation potential regardless of whether they were in the early (cell culture passage 3) or later (cell culture passage 10) stages. Our study elucidated that ASC, DSC, and FB vary functionally in their osteogenic differentiation, depending on their tissue origin and replicative senescence. Therefore, our study provides important insights for cell-based therapies to optimize prospective bone tissue engineering strategies.
Improvement of hyperlipidemia by aerobic exercise in mice through a regulatory effect of miR-21a-5p on its target genes
Authors: Zhao Jinfeng , Song Yicun , Zeng Yu , Chen Longchang , Yan Feng , Chen Anping , Wu Baoai , Wang Yaxin
Published: June 2021

Hyperlipidemia is a risk factor for cardiovascular disease, and miR-21a-5p plays an important role in the occurrence and progression of hyperlipidemia. Here, we aimed to investigate the mechanism of aerobic exercise improved hyperlipidemia through enhancing miR-21a-5p expression. In this study, high-fat/high-cholesterol diet mice received 8 weeks of aerobic exercise intervention, then we collected plasma and liver samples, we found that there had a notable improvement in weight gain, blood lipid level, and liver steatosis in hyperlipidemia mice after 8 weeks of aerobic exercise intervention. Besides, aerobic exercise significantly up-regulated the expression of miR-21a-5p and provoked favorable changes in the expression of target genes. Knockdown of miR-21a-5p resulted in dysregulation of lipid metabolism and increased expression of FABP7, HMGCR, ACAT1, and OLR1. While aerobic exercise could alleviate miR-21a-5p knock-down induced lipid metabolism disorder. Taken together, these results demonstrated that aerobic exercise improved hyperlipidemia through miR-21a-5p-induced inhibition of target genes FABP7, HMGCR, ACAT1, and OLR1.
Crystal structures of aconitase X enzymes from bacteria and archaea provide insights into the molecular evolution of the aconitase superfamily
Authors: Watanabe Seiya , Murase Yohsuke , Watanabe Yasunori , Sakurai Yasuhiro , Tajima Kunihiko
Published: June 2021

Aconitase superfamily members catalyze the homologous isomerization of specific substrates by sequential dehydration and hydration and contain a [4Fe-4S] cluster. However, monomeric and heterodimeric types of function unknown aconitase X (AcnX) have recently been characterized as a cis-3-hydroxy-L-proline dehydratase (AcnXType-I) and mevalonate 5-phosphate dehydratase (AcnXType-II), respectively. We herein elucidated the crystal structures of AcnXType-I from Agrobacterium tumefaciens (AtAcnX) and AcnXType-II from Thermococcus kodakarensis (TkAcnX) without a ligand and in complex with substrates. AtAcnX and TkAcnX contained the [2Fe-2S] and [3Fe-4S] clusters, respectively, conforming to UV and EPR spectroscopy analyses. The binding sites of the [Fe-S] cluster and substrate were clearlydifferent from those that were completely conserved in other aconitase enzymes; however, theoverall structural frameworks and locations of active sites were partially similar to each other.These results provide novel insights into the evolutionary scenario of the aconitase superfamilybased on the recruitment hypothesis.
Describing the movement of molecules in reduced-dimension models
Authors: Savage Natasha S.
Published: June 2021

When addressing spatial biological questions using mathematical models, symmetries within the system are often exploited to simplify the problem by reducing its physical dimension. In a reduced-dimension model molecular movement is restricted to the reduced dimension, changing the nature of molecular movement. This change in molecular movement can lead to quantitatively and even qualitatively different results in the full and reduced systems. Within this manuscript we discuss the condition under which restricted molecular movement in reduced-dimension models accurately approximates molecular movement in the full system. For those systems which do not satisfy the condition, we present a general method for approximating unrestricted molecular movement in reduced-dimension models. We will derive a mathematically robust, finite difference method for solving the 2D diffusion equation within a 1D reduced-dimension model. The methods described here can be used to improve the accuracy of many reduced-dimension models while retaining benefits of system simplification.
Synchrotron X-ray Imaging Combined with Multiscale Modeling Applied to Biological Soft Tissues
Authors: Gupta H. S. , Barbieri E. , Inamdar S. R. , Mo J.
Published: June 2021

Soft biological tissues have a hierarchical architecture from the molecular to the macroscale, with structure–function relations at each level crucial for function. In developing new soft biomaterials for medical applications, understanding, and emulating these mechanisms will provide essential guidance. In this chapter we review how time- and position-resolved synchrotron small-angle X-ray scattering (SAXS) combined with multiscale mechanical modelling can illuminate such small-scale mechanisms, using the examples of articular cartilage and the mutable connective tissue of echinoderms. In articular cartilage, SAXS reveals a gradient in fibrillar-level pre-strain, which is suppressed either by physiological static loading or by enzymatic modifications mimicking ageing, and modelling of the fibril/proteoglycan network shows that the pre-strain reflects the local internal swelling pressure. In mutable connective tissue, our results show that interfibrillar stiffening and de-stiffening enable its rapid alterations in mechanical properties, whose kinetics can be captured by analytical modelling of the structure. The combination of multiscale modelling and in situ SAXS thus shows potential in investigating and elucidating the mechanisms enabling function in both natural tissues as well as in new soft biomaterials mimicking their structure.