bluuebunny/crossref_metadata_2025 huggingface dataset:
Discrete roles of Ir76b ionotropic coreceptor impact olfaction, blood feeding, and mating in the malaria vector mosquito
Anopheles coluzzii
Authors: Ye Zi , Liu Feng , Sun Huahua , Ferguson Stephen T. , Baker Adam , Ochieng Samuel A. , Zwiebel Laurence J.
Published: June 2022

Significance

Chemosensory systems play crucial roles across mosquito life cycles, with underlying molecular receptors often forming functional complexes that require cognate coreceptors. To better understand chemosensory pathways in the malaria vector mosquito
Anopheles coluzzii
, gene editing were used to localize and functionally characterize the ionotropic receptor coreceptor
AcIr76b
. Expression of
AcIr76b
was observed in antennal grooved pegs, coeloconic sensilla, and other accessory olfactory appendages. When
AcIr76b
was inactivated, mutant mosquitoes displayed altered neuronal responses to amines.. Beyond olfactory phenotypes,
AcIr76b
mutants display significantly impaired mating and blood feeding capabilities. Our data reveal discrete roles of
AcIr76b
across chemosensory pathways, suggesting ionotropic pathways as targets for the design of vector control strategies.
From the laboratory to the consumer: Innovation, supply chain, and adoption with applications to natural resources
Authors: Zilberman David , Reardon Thomas , Silver Jed , Lu Liang , Heiman Amir
Published: June 2022

Significance

Research on innovation has two strands: institutions undertaking innovation as a research and development process and companies commercializing innovative products. We combine these strands, analyzing a sequence going from an innovation supply chain to a product supply chain from laboratory to market. We argue that these supply chains are symbiotic, and the relationship between entities is affected by economic considerations. Our framework allows an understanding of how research, regulatory policies, and economic conditions affect the emergence of innovations, the creation of institutions (markets, firms, contracts) to carry out these innovations, and the diffusion of the resulting products. Our approach may improve the design of strategies to induce climate change and food security solutions.
Membrane particles evoke a serotype-independent cross-protection against pneumococcal infection that is dependent on the conserved lipoproteins MalX and PrsA
Authors: Narciso Ana Rita , Iovino Federico , Thorsdottir Sigrun , Mellroth Peter , Codemo Mario , Spoerry Christian , Righetti Francesco , Muschiol Sandra , Normark Staffan , Nannapaneni Priyanka , Henriques-Normark Birgitta
Published: June 2022

Significance

Pneumococcal infections are major contributors to morbidity and mortality worldwide. Introduction of pneumococcal conjugated vaccines (PCVs) into the childhood vaccination program has led to a decrease in invasive pneumococcal disease (IPD) in vaccinated children but concurrently to an increase of nonvaccine-type IPD, also in nonvaccinated age groups such as the elderly. Thus, novel vaccine approaches are urgently needed, especially for the elderly, targeting all pneumococci causing IPD. Here, we show that pneumococcal membrane particles (MPs) evoke a serotype-independent cross-protection against IPD. This protection is dependent on the presence of the two conserved lipoproteins MalX and PrsA. We suggest that MPs can be used for pneumococcal vaccine development.
Cryo-EM structure of DNA-bound Smc5/6 reveals DNA clamping enabled by multi-subunit conformational changes
Authors: Yu You , Li Shibai , Ser Zheng , Kuang Huihui , Than Thane , Guan Danying , Zhao Xiaolan , Patel Dinshaw J.
Published: June 2022

Significance

The Smc5/6 complex plays multiple roles in DNA replication and repair. Its genome-protecting functions rely on its interaction with DNA; however, how this complex engages DNA is poorly understood. We report on a cryogenic electron microscopy structure of DNA-bound budding yeast Smc5/6 complex, revealing that its subunits form a clamp to encircle a double-helical DNA. We define the multi-subunit interactions forming the DNA clamp and the DNA binding sites distributed among subunits. We identify subunit transformations upon DNA capture and functional effects conferred by its multiple DNA contact sites. Our findings, in conjunction with studies on other structural maintenance of chromosomes (SMC) complexes, suggest a common SMC DNA-clamp mechanism with individual complex specific features that enable diverse genome organization and protection functions by SMC family complexes.
A unified theory of free energy functionals and applications to diffusion
Authors: Li Andrew B. , Miroshnik Leonid , Rummel Brian D. , Balakrishnan Ganesh , Han Sang M. , Sinno Talid
Published: June 2022

Free energy functionals of the Ginzburg–Landau type lie at the heart of a broad class of continuum dynamical models, such as the Cahn–Hilliard and Swift–Hohenberg equations. Despite the wide use of such models, the assumptions embodied in the free energy functionals frequently either are poorly justified or lead to physically opaque parameters. Here, we introduce a mathematically rigorous pathway for constructing free energy functionals that generalizes beyond the constraints of Ginzburg–Landau gradient expansions. We show that the formalism unifies existing free energetic descriptions under a single umbrella by establishing the criteria under which the generalized free energy reduces to gradient-based representations. Consequently, we derive a precise physical interpretation of the gradient energy parameter in the Cahn–Hilliard model as the product of an interaction length scale and the free energy curvature. The practical impact of our approach is demonstrated using both a model free energy function and the silicon–germanium alloy system.
The nonclassical MHC class I Qa-1 expressed in layer 6 neurons regulates activity-dependent plasticity via microglial CD94/NKG2 in the cortex
Authors: Marin Ioana A. , Gutman-Wei Alan Y. , Chew Kylie S. , Raissi Aram J. , Djurisic Maja , Shatz Carla J.
Published: June 2022

Significance

Molecules regulated by neuronal activity are necessary for circuits to adapt to changing inputs. Specific classical major histocompatibility class I (MHCI) molecules play roles in circuit and synaptic plasticity, but the function of most members of this family remains unexplored in brain. Here, we show that a nonclassical MHCI molecule, Qa-1 (H2-T23), is expressed in a subset of excitatory neurons and regulated by visually driven activity in the cerebral cortex. Moreover, CD94/NKG2 heterodimers, cognate receptors for Qa-1, are expressed in microglia. A functional interaction between Qa-1 and CD94/NKG2 is necessary for regulating the magnitude of ocular dominance plasticity during the critical period in the visual cortex, implying an interaction in which activity-dependent changes in neurons may be monitored by microglia.
Ion flux–energy distributions across grounded grids in an RF plasma source with DC-grounded electrodes
Authors: Soni Kunal , Antunes Rodrigo , Steiner Roland , Moser Lucas , Marot Laurent , Meyer Ernst
Published: June 2022

We present an experimental investigation of the ion flux–energy distribution functions (IFEDFs) obtained across grounded grids in an asymmetric capacitively coupled RF source using a helium discharge. The powered electrode in the RF source is DC-grounded via a λ/4 filter, which lifts its DC potential to zero. Grids of different dimensions (hole width, thickness, and geometric transparency) were used to confine the plasma, while the IFEDF of the ion beam departing the grid and reaching the reactor walls was studied using a retarding field energy analyser. The IFEDF obtained was double-peaked, indicating the presence of fast ions arriving from the plasma source, and cold ions generated upon charge exchange collisions between the fast ions and neutrals. The flux, as well as the peak energies of the two ion groups, depended significantly on the process parameters: RF power, He pressure, the distance between grids and walls, and the dimensions of the grids. The results indicate that confining plasma with grids can reduce the ion flux at the walls by over 60%, significantly lowering the wall sputtering rate. This was confirmed with a dedicated long-exposure plasma discharge with a gridded plasma reactor, wherein less than 1 nm of Cu deposition was found on the DC-grounded powered electrode, and the surface reflectivity was preserved to pristine values. In contrast, a similar experiment in a gridless reactor resulted in Cu deposition of 35 nm with a drastic drop in surface reflectivity. These studies are of great importance for the application of similar RF plasma sources with in-situ cleaning of diagnostic mirrors in fusion devices, as well as in a variety of plasma processing applications.
Continuous-variable quantum key distribution over a 15 km multi-core fiber
Authors: Sarmiento S , Etcheverry S , Aldama J , López I H , Vidarte L T , Xavier G B , Nolan D A , Stone J S , Li M J , Loeber D , Pruneri V
Published: June 2022

The secure transfer of information is critical to the ever-increasing demands of the digital world. Continuous-variable quantum key distribution (CV-QKD) is a promising technology that can provide high secret key rates over metropolitan areas, using conventional telecom components. In this study, we demonstrate the utilization of CV-QKD over a 15 km multi-core fiber (MCF), in which we take advantage of one core to remotely frequency lock Bob's local oscillator with Alice's transmitter. We also demonstrate the capacity of the MCF to boost the secret key rate by parallelizing CV-QKD across multiple cores. Our results indicate that MCFs are promising for the metropolitan deployment of QKD systems.
Erbium-ytterbium co-doped photonic crystal fiber amplifier supporting amplification for orbital angular momentum
Authors: Zhao Lijuan , Liang Ruoyu , Xu Zhiniu
Published: June 2022

In order to reduce the loss in orbital angular momentum (OAM) long-distance communication systems, an OAM erbium-ytterbium co-doped fiber amplifier (OAM-EYDFA) based on photonic crystal fiber (PCF) is proposed and investigated for the first time in this work. We set up a three-dimensional electromagnetic field model of the PCF in Comsol and solved it by the finite element method. Then, we designed a three-dimensional model of the OAM-EYDFA based on the proposed PCF using Comsol and MATLAB. The results reveal that the proposed OAM-EYDFA has a flat-high gain of about 47 dB, a differential mode gain of lower than 0.3 dB and a noise figure of lower than 3.4 dB. Compared with existing studies, its gain is increased by at least 25 dB, and other properties are also improved. The proposed OAM-EYDFA can provide a reference for OAM-based long-distance communication systems.
A 3 Giga Sample Per Second 14-bit Digital Receiver with 9 GHz Input Bandwidth for Solar Radio Observation
Authors: Zhang Yuanyuan , Zhang Lei , Shang Ziqian , Lu Guang , Wu Zhao , Su Yanrui , Chen Yao , Yan Fabao
Published: June 2022

A new digital receiver with excellent performances has been designed and developed for solar radio observation, which can receive the radio signal from direct current (DC) to 9 GHz in the direct acquisition way. On the digital receiver, the analog-to-digital converter (ADC) with 14-bit, two input channels and 3 Giga Samples per second (Gsps) are used to acquire observed signal, and the field-programmable-gate-array chip XCKU115 acts as the processing module. The new digital receiver can be used to directly sample the solar radio signals of frequency under 9 GHz. When receiving the solar radio signal above 9 GHz, the new digital receiver can save 1–2 stages of frequency down-conversion, and effectively improve many indexes of the solar radio observation system, i.e., the time resolution, analog front-end circuit, weight and volume of the analog circuit system. Compared with the digital receiver with sampling rate below 1 Gsps used in existing solar radio telescope, the new digital receiver reduces the frequency switching times of large bandwidth, which is beneficial to improving the frequency and time resolutions. The ADC sampling resolution of 14 bits, providing a large dynamic range, is very beneficial to observing smaller solar eruptions. This receiver, which would be used in the solar radio observation system, well meets the latest requirements with the resolutions of time (≤1 ms) and frequency (≤0.5 MHz) for fine observation of radio signals.
Integrated modelling and multiscale gyrokinetic validation study of ETG turbulence in a JET hybrid H-mode scenario
Authors: Citrin J. , Maeyama S. , Angioni C. , Bonanomi N. , Bourdelle C. , Casson F.J. , Fable E. , Görler T. , Mantica P. , Mariani A. , Sertoli M. , Staebler G. , Watanabe T.
Published: June 2022

Previous studies with first-principle-based integrated modelling suggested that electron temperature gradient (ETG) turbulence may lead to an anti-gyroBohm isotope scaling in JET high-performance hybrid H-mode scenarios. A dedicated comparison study against higher-fidelity turbulence modelling invalidates this claim. Ion-scale turbulence with magnetic field perturbations included, can match the power balance fluxes within temperature gradient error margins. Multiscale gyrokinetic simulations from two distinct codes produce no significant ETG heat flux, demonstrating that simple rules-of-thumb are insufficient criteria for its onset.
Experimental and theoretical study of weakly coherent mode in I-mode edge plasmas in the EAST tokamak
Authors: Liu Z.X. , Liu Y.J. , Xiao J.Y. , Xia T.Y. , Li Y.L. , Xu X.Q. , Wu M.Q. , Li G.Q. , Wu M.F. , Zhang T. , Gao X. , Gong X.Z. , Liu H.Q. , Zang Q. , Liu A.D. , Zhou C. , Lan T. , Li H. , Xie J.L. , Mao W.Z. , Ding W.X. , Zhuang G. , Li J.G. , Liu W.D. , the EAST Team
Published: June 2022

The I-mode is a promising operation mode for fusion in the future, featuring high-temperature and low-density confinement, but the reason why the temperature and density are decoupled remains an important aspect to be explored. The experimental results from the experimental advanced superconducting tokamak (EAST) showed that the weakly coherent mode (WCM) is directly related to sustaining the I-mode and that the peak amplitude of the WCM is proportional to the temperature in the pedestal. Simulating the experimental data from EAST with the six-field model of BOUT++, we find a density perturbation close to the frequency of the WCM observed in the experiment. By testing all the physical terms in this model, we find that the density perturbation and particle transport are directly related to the drift Alfvén wave (DAW) mode. We also use the SymPIC program (Xiao et al Plasma Sci. Technol.
20 110501; Phys. Plasmas
22 112504; Plasma Sci. Technol.
23 055102) to simulate the same experimental data and find that the frequency range of the WCM is close to both experimental and BOUT++ results. Therefore, the WCM of the I-mode can be considered to be driven by the DAW, which helps improve the transport of the I-mode.
Invited Commentary: Is Bias Towards the Null From Nondifferential Misclassification Wishful Thinking?
Authors: Hamra Ghassan B
Published: June 2022

In their article, Yland et al. (Am J Epidemiol. 2022;191(8):1485–1495) bring renewed attention to the oft-cited heuristic “nondifferential misclassification biases results towards the null.” They make a compelling case, as others have before, that this heuristic is misguided. Herein, I briefly discuss the history of this heuristic, discuss why I believe it became and stayed popular, and note the very limited circumstances for which it may be appropriate.
Pharmacokinetics and tissue distribution of orally administrated imidazole dipeptides in carnosine synthase gene knockout mice
Authors: Sakano Taiken , Egusa Ai Saiga , Kawauchi Yoko , Wu Jiawei , Nishimura Toshihide , Nakao Nobuhiro , Kuramoto Ayumu , Kawashima Takumi , Shiotani Shigenobu , Okada Yukio , Sato Kenichiro , Yanai Nobuya
Published: June 2022

Imidazole dipeptides (ID) are abundant in skeletal muscle and the brain and have various functions, such as antioxidant, pH-buffering, metal-ion chelation. However, the physiological significance of ID has not been fully elucidated. In this study, we orally administered ID to conventional carnosine synthase gene-deficient mice (Carns-KO mice) to investigate the pharmacokinetics. Carnosine or anserine was administered at a dose of 500 mg (approximately 2 mmol) per kilogram of mouse body weight, and ID contents in the tissues were measured. No ID were detected in untreated Carns-KO mice. In the ID treatment groups, the ID concentrations in the tissues increased in a time-dependent manner in the gastrocnemius muscle, soleus muscle, and cerebrum after ID administration. Our findings suggest that the Carns-KO mice are a valuable animal model for directly evaluate the effects of dietary ID and for elucidating the physiological functions of oral ID administration.
Dietary oleamide attenuates obesity induced by housing mice in small cages
Authors: Kobayashi Yasuyuki , Kubota Mai , Sugimoto Keiichiro , Kitakaze Tomoya , Harada Naoki , Yamaji Ryoichi
Published: June 2022

Physical inactivity due to prolonged sedentary behavior induces obesity. Therefore, we investigated whether housing mice in small cages to mimic sedentary behavior induced obesity and whether dietary oleamide (cis-9,10-octadeceneamide) suppressed the induced obesity. A single oral administration of oleamide (50 mg/kg) to mice resulted in the accumulation of the exogenous oleamide in abdominal visceral fat. Next, mice were housed in small cages and oleamide (50 mg/kg/d) was orally administered for 12 weeks. Housing mice in small cages impaired glucose tolerance and increased food efficiency. It also increased body weight and abdominal fat mass. Dietary oleamide improved the impairment and inhibited their increases in mice housed in small cages. Furthermore, dietary oleamide suppressed the mRNA expression of inflammation-related factors in abdominal fat of mice housed in small cages. Hence, these results indicate that although housing mice in small cages induces obesity and increases abdominal fat mass, dietary oleamide suppresses the obesity.
Improving E. coli organic solvent tolerance by 1,4-dihydroxy-2-naphthoic acid
Authors: Doukyu Noriyuki , Fujisawa Hideyuki , Saito Ryota
Published: June 2022

Improving the organic solvent tolerance of bacteria is beneficial for the bioproduction of various valuable chemicals. In this study, we found that 1,4-dihydroxy-2-naphthoic acid (DHNA), known as a prebiotic, increased organic solvent tolerance in Escherichia coli. The AcrAB‒TolC multidrug efflux pump contributes to the intrinsic organic solvent tolerance of E. coli. The addition of DHNA increased this pump's expression level. Transcriptional activators MarA, SoxS, and Rob proteins are known to control the expression of marA/soxS/rob regulon genes, including acrAB and tolC. Evaluation of the organic solvent tolerances of DmarA mutant, DsoxS mutant, and Drob mutant showed that DmarA mutant and DsoxS mutant did not improve organic solvent tolerance by the addition of DHNA. In addition, DHNA increased the promoter activities of both marA and soxS. These results indicated that DHNA induces the AcrAB‒TolC pump through both the marRAB system and the soxRS system.
Palo: spatially aware color palette optimization for single-cell and spatial data
Authors: Hou Wenpin , Ji Zhicheng
Published: June 2022

In the exploratory data analysis of single-cell or spatial genomic data, single-cells or spatial spots are often visualized using a two-dimensional plot where cell clusters or spot clusters are marked with different colors. With tens of clusters, current visualization methods often assign visually similar colors to spatially neighboring clusters, making it hard to identify the distinction between clusters. To address this issue, we developed Palo that optimizes the color palette assignment for single-cell and spatial data in a spatially aware manner. Palo identifies pairs of clusters that are spatially neighboring to each other and assigns visually distinct colors to those neighboring pairs. We demonstrate that Palo leads to improved visualization in real single-cell and spatial genomic datasets.

Availability and implementation

Palo R package is freely available at Github (https://github.com/Winnie09/Palo) and Zenodo (https://doi.org/10.5281/zenodo.6562505).

Supplementary information

Supplementary data are available at Bioinformatics online.
Effector-GAN: prediction of fungal effector proteins based on pretrained deep representation learning methods and generative adversarial networks
Authors: Wang Yansu , Luo Ximei , Zou Quan
Published: June 2022

Motivation

Phytopathogenic fungi secrete effector proteins to subvert host defenses and facilitate infection. Systematic analysis and prediction of candidate fungal effector proteins are crucial for experimental validation and biological control of plant disease. However, two problems are still considered intractable to be solved in fungal effector prediction: one is the high-level diversity in effector sequences that increases the difficulty of protein feature learning, and the other is the class imbalance between effector and non-effector samples in the training dataset.

Results

In our study, pretrained deep representation learning methods are presented to represent multiple characteristics of sequences for predicting fungal effectors and generative adversarial networks are adapted to create synthetic feature samples to address the data imbalance problem. Compared with the state-of-the-art fungal effector prediction methods, Effector-GAN shows an overall improvement in accuracy in the independent test set.

Availability and implementation

Effector-GAN offers a user-friendly interface to inspect potential fungal effector proteins (http://lab.malab.cn/~wys/webserver/Effector-GAN). The Python script can be downloaded from http://lab.malab.cn/~wys/gitlab/effector-gan.

Supplementary information

Supplementary data are available at Bioinformatics online.
‘One-stop-shop’ diagnosis and stage-adapted surgical therapy for small nodules of early stage lung cancer in a hybrid operating room
Authors: Caviezel C , Kostopanagiotou K , Puippe G D , Werner R S , Opitz I
Published: June 2022

Objective

Emergent lung cancer screening programs increased detection of small pulmonary nodules. Anatomical resection in case of early-stage lung cancer with only one intervention becomes increasingly desirable. Current literature lacks procedure data about both diagnosis and subsequent indicated resection. After starting our hybrid operating room program, we reviewed the efficacy of detection, diagnosis and therapy in one-step.

Methods

Undiagnosed pulmonary nodules suspicious of lung cancer, which were not detectable by conventional video-assisted thoracoscopic surgery (VATS) due to localization and size, were scheduled for a hybrid procedure consisting of a cone-beam CT-guided hookwire insertion and C-arm assisted thoracoscopic wedge resection for frozen section. All procedures were analyzed for perioperative outcomes including success rate of image-guided nodule resection and rate of concomitant correct anatomical resection.

Results

Between July 2020 and July 2021, 23 patients with 25 nodules underwent image-guided VATS (iVATS) in the hybrid room. Twenty-two nodules were successfully marked by hookwire, three nodules were detected by ultrasound in one case and palpation in two cases. In 16 patients (70%) wedge resection with frozen section showed malignancy. Five patients with previous history of operated lung cancer received only a diagnostic wedge, as frozen section could not differentiate between primary or metastatic lung cancer. Eleven patients (48%) had early-stage primary lung cancer (8 adenocarcinoma, one typical carcinoid, one small-cell lung cancer and one squamous-cell lung cancer). Ten of them (91%) received a synchronous completion anatomical resection (seven lobectomies, three segmentectomies). In one patient, malignancy was only confirmed in final histology.

Conclusion

One-stop-shop diagnosis and treatment by iVATS with frozen section and concomitant completion anatomical resection in a hybrid operating room for otherwise non-well approachable early stage lung cancer is patient-convenient for the increasingly detected small pulmonary nodules.
The yin and the yang of early classical pathway complement disorders
Authors: Sullivan Kathleen E
Published: June 2022

The classical pathway of the complement cascade has been recognized as a key activation arm, partnering with the lectin activation arm and the alternative pathway to cleave C3 and initiate the assembly of the terminal components. While deficiencies of classical pathway components have been recognized since 1966, only recently have gain-of-function variants been described for some of these proteins. Loss-of-function variants in C1, C4, and C2 are most often associated with lupus and systemic infections with encapsulated bacteria. C3 deficiency varies slightly from this phenotypic class with membranoproliferative glomerulonephritis and infection as the dominant phenotypes. The gain-of-function variants recently described for C1r and C1s lead to periodontal Ehlers Danlos syndrome, a surprisingly structural phenotype. Gain-of-function in C3 and C2 are associated with endothelial manifestations including hemolytic uremic syndrome and vasculitis with C2 gain-of-function variants thus far having been reported in patients with a C3 glomerulopathy. This review will discuss the loss-of-function and gain-of-function phenotypes and place them within the larger context of complement deficiencies.
Isolation of an ectoine-producing Sinobaca sp. and identification of genes that are involved in ectoine biosynthesis
Authors: Chen Shan-Yu , Peng Tzu-Chia , Huang Shan-Ze , Chien Chih-Ching
Published: June 2022

A moderate halophilic bacterium that could accumulate ectoine and hydroxyectoine was isolated from soil near a salt mine and was identified as a Sinobaca sp. (designed strain H24) according to 16S rRNA gene sequence analysis. The bacterium grew well in the presence of 1–2 M NaCl, while growth in a medium that contained 2 M NaCl led to higher accumulation of ectoines. The yields of ectoine and hydroxyectoine by Sinobaca sp. H24 reached 11.27 mg/l and 1.34 mg/l, respectively, when cultured in the following medium: NaCl (2 M), peptone (5 g/l), yeast extract (1 g/l), NH4Cl (0.02 M), KH2PO4 (1 M), K2HPO4 (0.1 M), and glycerol (1% w/v). Genes that are involved in ectoine biosynthesis of Sinobaca sp. H24 were also identified, and their sequences were determined by a metagenomics approach. The results demonstrated that Sinobaca sp. H24 possesses ectoine metabolism genes for both ectoine biosynthesis (ectA, ectB, ectC, and ectD) and ectoine degradation (doeA). Genes that are related to ectoine biosynthesis, such as lysC and asd, were also characterized. The identification and characterization results for ectoine/hydroxyectoine biosynthesis genes are in agreement with the physiology of Sinobaca sp. H24 as a potential candidate for ectoine production for industrial applications. This report established for the first time the accumulation of ectoine/hydroxyectoine in Sinobaca sp. and characterized the genes that are involved in ectoine/hydroxyectoine biosynthesis in Sinobaca sp. H24.
Cross-genus inhibitory activity of polyoxins against aflatoxin production by Aspergillus parasiticus and fumonisin production by Fusarium fujikuroi
Authors: Yoshinari Tomoya , Watanabe Maiko , Hara-Kudo Yukiko
Published: June 2022

Co-exposure to aflatoxin and fumonisin is a health concern where corn is a staple food, and a method to prevent co-contamination of these mycotoxins in foods is urgently needed. Polyoxins are chitin synthase inhibitors produced by Streptomyces cacaoi var. asoensis. The aflatoxin production inhibitory activity of a commercially available polyoxin D and four polyoxins purified from polyoxin AL water-soluble powder, an agricultural chemical containing polyoxins, was tested. The five polyoxins dose-dependently inhibited aflatoxin production by Aspergillus parasiticus and the IC50 values of polyoxin A, B, D, K and L were 16, 74, 110, 9 and 280 µmol L−1, respectively. Polyoxins also inhibited fumonisin production by Fusarium fujikuroi, and the IC50 values of polyoxin B, D, K and L were 270, 42, 65 and 62 µmol L−1, respectively. Polyoxins repressed the transcription of genes encoding proteins required for aflatoxin biosynthesis in A. parasiticus and fumonisin biosynthesis in F. fujikuroi. Polyoxin K and D also inhibited conidiation in A. parasiticus and F. fujikuroi, respectively. These results suggest that a mixture of polyoxins may effectively prevent co-contamination of aflatoxin and fumonisin in foods.
Plasmodium falciparumPfRUVBL proteins bind at the TARE region andvargene promoter located in the subtelomeric region
Authors: Saxena Himani , Gupta Ashish
Published: June 2022

In order to survive and establish infection, the Plasmodium parasite employs various strategies to evade the host immune response. The var genes family, a repertoire of 60 genes, expresses parasite-specific protein PfEMP1, a variable surface antigen, on the membrane of infected erythrocytes, and by continuously switching the variants of PfEMP1, help the parasite to avoid detection and destruction by the host immune system during the intra-erythrocytic developmental cycle. Although chromatin modifications are recognised to be a prominent phenomenon in regulation of mono-allelic expression of these var genes, the precise histone codes and molecular players and mechanisms guiding these modifications have yet to be unravelled in depth. In this study, we have functionally characterised RUVBL proteins of Plasmodium falciparum and shown that PfMYST (an essential lysine acetyl transferase) and PfRUVBL protein complex occupy the TARE region and var gene promoter in the ring stage of the parasite. Further, we have demonstrated that the PfMYST/PfRUVBL complex interacts with core histones, H3 and H4. Overall the findings of this study add further information by identifying the potential role of epigenetic regulators, PfMYST and PfRUVBL, in the regulation of monoallelic expression of var genes in the malaria parasite.
Genome-wide transcriptional regulation in Saccharomyces cerevisiae in response to carbon dioxide
Authors: Tan Lin-Rui , Liu Jing-Jing , Deewan Anshu , Lee Jae Won , Xia Peng-Fei , Rao Christopher V , Jin Yong-Su , Wang Shu-Guang
Published: June 2022

Sugar metabolism by Saccharomyces cerevisiae produces ample amounts of CO2 under both aerobic and anaerobic conditions. High solubility of CO2 in fermentation media, contributing to enjoyable sensory properties of sparkling wine and beers by S. cerevisiae, might affect yeast metabolism. To elucidate the overlooked effects of CO2 on yeast metabolism, we examined glucose fermentation by S. cerevisiae under CO2 as compared to N2 and O2 limited conditions. While both CO2 and N2 conditions are considered anaerobic, less glycerol and acetate but more ethanol were produced under CO2 condition. Transcriptomic analysis revealed that significantly decreased mRNA levels of GPP1 coding for glycerol-3-phosphate phosphatase in glycerol synthesis explained the reduced glycerol production under CO2 condition. Besides, transcriptional regulations in signal transduction, carbohydrate synthesis, heme synthesis, membrane and cell wall metabolism, and respiration were detected in response to CO2. Interestingly, signal transduction was uniquely regulated under CO2 condition, where upregulated genes (STE3, MSB2, WSC3, STE12, and TEC1) in the signal sensors and transcriptional factors suggested that MAPK signaling pathway plays a critical role in CO2 sensing and CO2-induced metabolisms in yeast. Our study identifies CO2 as an external stimulus for modulating metabolic activities in yeast and a transcriptional effector for diverse applications.
Predicting Lumber Grade Occurrence and Volume in Sugar Maple and Yellow Birch Logs
Authors: Havreljuk Filip , Achim Alexis , Pothier David
Published: June 2022

The North American temperate deciduous forests are an important source of hardwoods sought after by the appearance wood products industries. The purpose of this study was to model the relationships between log characteristics and sawn board attributes in sugar maple (Acer saccharum Marsh.) and yellow birch (Betula alleghaniensis Britt.). We harvested sixty-four sugar maple and thirty-two yellow birch trees from two locations in southern Quebec, Canada, which were then processed into 189 sawlogs and 2,236 boards. We developed statistical models linking log characteristics to the volume recovery of the various lumber grades and color specifications according to the National Hardwood Lumber Association rules. In both species, board grades were strongly related to log length, position of the log in the stem, and small-end diameter and decay of the log. Color classes were related to small-end diameter of the log and red heartwood diameter of the log at both ends for sugar maple, and to log length, diameter of the log at the small-end, and red heartwood diameter at the large-end of the log for yellow birch. These models outperformed a log classification used in practice for predicting lumber volume recovery from different log grades.
Genetic diversity of Listeria monocytogenes isolates from farm products in Shanghai, China
Authors: Suo Yujuan , Qu Yang , Bai Yalong , Zhou Xiujuan , Lin Ting , Wang Jing , Chen Wanyi , Zhou Changyan
Published: June 2022

Farm products are considered important vehicles for the transmission of Listeria monocytogenes (L. monocytogenes). The typing of L. monocytogenes from farm products contributes to the surveillance and source tracing of the pathogen. In this study, 77 L. monocytogenes strains from seven farm product categories in Shanghai were analyzed by serological typing, multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE), and whole-genome nucleotide polymorphism (wgSNP). The results showed that the 77 isolates were classified into four serovars (1/2a, 1/2c, 1/2b, and 4b), and of these, 1/2a (n=47) was the most prevalent. Seventeen sequence types (STs) were generated by MLST with two novel STs (ST1402 and ST1403), and 20 of 77 L. monocytogenes isolates had high genetic identity with previously documented outbreak isolates according to the minimum spanning tree from the MLST results. Moreover, 34 PFGE patterns (PF1–PF34) were differentiated, and based on a similarity value higher than 80% by the unweighted pair group method dendrogram, the discriminatory index was relatively low (equal to 0.775). Furthermore, 14 isolates were chosen and further analyzed by wgSNP based on the previous typing results, which demonstrated that wgSNP and MLST yielded mostly consistent typing results but higher resolution than PFGE. In conclusion, 77 L. monocytogenes isolates from farm products collected in nine districts in Shanghai were highly genetically diverse, and 20 of these isolates had high relatedness with previously documented outbreak strains worldwide. The results indicate a possible cross-contamination risk of L. monocytogenes and a potential public health concern resulting from farm products during the supply chain in Shanghai, China.
The First Annotated Genome Assembly of Macrophomina tecta Associated with Charcoal Rot of Sorghum
Authors: Poudel Barsha , Purushotham Neeraj , Jones Ashley , Nasim Jamila , Adorada Dante L. , Sparks Adam H. , Schwessinger Benjamin , Vaghefi Niloofar
Published: June 2022

Charcoal rot is an important soilborne disease caused by a range of Macrophomina species, which affects a broad range of commercially important crops worldwide. Even though Macrophomina species are fungal pathogens of substantial economic importance, their mechanism of pathogenicity and host spectrum are poorly understood. There is an urgent need to better understand the biology, epidemiology, and evolution of Macrophomina species, which, in turn, will aid in improving charcoal rot management strategies. Here, we present the first high-quality genome assembly and annotation of Macrophomina tecta strain BRIP 70781 associated with charcoal rot symptoms on sorghum. Hybrid assembly integrating long reads generated by Oxford Nanopore Technology and short Illumina paired-end reads resulted in 43 contigs with a total assembly size of ∼54 Mb, and an N50 of 3.4 Mb. In total, 12,926 protein-coding genes and 7,036 repeats were predicted. Genome comparisons detected accumulation of DNA transposons in Macrophomina species associated with sorghum. The first reference genome of M. tecta generated in this study will contribute to more comparative and population genomics studies of Macrophomina species.
The German Response to Austria’s Annexation of Cracow in 1846
Authors: Šedivý Miroslav
Published: June 2022

The annexation of the Free City of Cracow by Austria in November 1846 has been regarded by historians as one of the most important international events in the period before the outbreak of revolutions in 1848. The annihilation of an independent state has been seen as a flagrant violation of international law that led to a weakening of Europeans’ faith in the justice of the post-Napoleonic order. Consequently, it is surprising that even as this evaluation has become rooted in historical scholarship, the public response to this affair has scarcely been analysed. The aim of this article is to reveal the impact of the annexation on the broad public in the German Confederation and the decline in people’s trust in justice in international relations. Germans across various political camps primarily perceived the annexation of Cracow not from the perspective of political modernization but in terms of geopolitical security. Their concern was not just with the position of the individual German states in relation to Prussia, Austria, Britain, France and Russia or the position of the entire German Confederation in relation to France, Britain and Russia, but also with their position within the political-legal system of European politics. The ensuing debate on the necessity for external security against threats from other European powers and nations became the most important outcome of this affair in Germany, with an egoistic, power-oriented response to the annexation of Cracow paving the way for conflicts among the Germans, Poles and other nations in 1848.
Imaging subsurface structure over the Xiadian fault using P waves extracted from urban traffic noise
Authors: Song Youngseok , Seol Soon Jee , Byun Joongmoo , Hayashi Koichi , Tan Shunjia
Published: June 2022

The imaging of subsurface structures is an essential task in subsurface engineering projects; it provides information regarding the locations of active faults and layer boundaries. Among the methods available for imaging of subsurface structures, the body wave imaging method using urban traffic noise has recently attracted attention because it permits continuous measurement at low cost in urban areas. However, because the urban traffic noise signal used for imaging on the engineering scale has characteristics that differ from the ambient noise used on the crustal scale, the conventional crustal-scale data processing workflow should be modified through systematic data analysis. In this study, traffic noise sources were systematically analysed using field data obtained over the Xiadian fault in Hebei province, China. The traffic noise signals were recorded in various patterns because of diverse incoming directions and show marked amplitude changes depending on time of recording. The overlapping signals originating from opposite directions generate spurious events and noise in the seismic interferometry images; constant processing parameters cannot respond to the large amplitude changes. In this study, to remove surface waves with markedly changing amplitude, we applied actively varying threshold values to each set of traces using the moving average of amplitude changes within the trace. In addition, the signals originating from diverse directions were separated into negative and positive slopes through the f–k filter; the interference generated by overlapping signals was minimized by applying data processing (e.g. median filtering and high amplitude removal) separately to the negative and positive slopes of each simultaneously acquired trace gather. Due to the modified data processing workflow, most spurious events were successfully suppressed in the final stacked image compared with those produced using the conventional data processing workflow, and reflections were imaged more clearly. Fault spatial locations and layer boundary depth variation in the final image obtained by the modified processing workflow were similar to those reported in previous studies.
Simulation of seismic velocity changes in brittle rocks subjected to triaxial stresses using 3-D microstructural models
Authors: Bai Qingsheng , Zhang Cun , Konietzky Heinz , Young R Paul
Published: June 2022

Numerical simulation of non-linear elastic wave propagation in rocks is indispensable for understanding stress/damage dependence of wave velocity changes and the associated micromechanisms. A numerical microstructural model is presented here to investigate seismic velocity changes due to stress and damage. By introducing pre-existing cracks and considering the valid microstructures in the bonded particle model, the proposed method successfully reproduces velocity changes of experiments on dry Lac du Bonnet granite and dry Darley Dale sandstone in both loading and unloading processes. Velocity increasing results from the closure of pre-existing cracks during loading stages, while the reopen of cracks during the unloading process causes velocity decreasing. Particle velocity vectors are used to illustrate wave propagation in a micromechanical way. P wave wave fronts are observed from the source to travel through the model, and wave intersections are clearly shown in the medium when the tensile wave front meets the compressive wave. The microstructure of the model shows a significant effect on rock mechanical behaviour and velocities and lends credibility to the velocity simulation. The valid microstructure produces realistic mechanical behaviour and velocity changes. Also, it replicates the initial hardening in the axial stress versus the axial strain curve, while invalid microstructures (e.g. cement overlap) underestimate the elastic modulus. The simulations also show that the wave velocities scale with the square root of the corresponding component of the coordination number, which can be used to quantify the mechanisms behind the velocity changes. Direct relations were established between velocity changes and opened crack density, which displays a similar tendency compared with predictions of the effective elastic theory. The microstructural model provides the ability to simulate the macro behaviour of rock under loadings in a more realistic manner and to directly examine the microprocesses underlying velocity changes.
Mutation burden analysis of six common mental disorders in African Americans by whole genome sequencing
Authors: Liu Yichuan , Qu Hui-Qi , Chang Xiao , Qu Jingchun , Mentch Frank D , Nguyen Kenny , Tian Lifeng , Glessner Joseph , Sleiman Patrick M A , Hakonarson Hakon
Published: June 2022

Mental disorders present a global health concern and have limited treatment options. In today’s medical practice, medications such as antidepressants are prescribed not only for depression but also for conditions such as anxiety and attention deficit hyperactivity disorder (ADHD). Therefore, identifying gene targets for specific disorders is important and offers improved precision. In this study, we performed a genetic analysis of six common mental disorders—ADHD, anxiety, depression, delays in mental development, intellectual disabilities (IDs) and speech/language disorder—in the ethnic minority of African Americans (AAs) using whole genome sequencing (WGS). WGS data were generated from blood-derived DNA from 4178 AA individuals, including 1384 patients with the diagnosis of at least one mental disorder. Mutation burden analysis was applied based on rare and deleterious mutations in the AA population between cases and controls, and further analyzed in the context of patients with single mental disorder diagnosis. Certain genes uncovered demonstrated significant P-values in mutation burden analysis. In addition, exclusive recurrences in specific type of disorder were scanned through gene–drug interaction databases to assess for availability of potential medications. We uncovered 15 genes harboring deleterious mutations, including 3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMGCR) and Uronyl 2-Sulfotransferase (UST) for ADHD; Farnesyltransferase, CAAX Box, Beta (FNTB) for anxiety; Xin Actin Binding Repeat Containing 2 (XIRP2), Natriuretic Peptide C (NPPC), Serine/Threonine Kinase 33 (STK33), Pannexin 1 (PANX1) and Neurotensin (NTS) for depression; RUNX Family Transcription Factor 3 (RUNX3), Tachykinin Receptor 1 (TACR1) and NADH:Ubiquinone Oxidoreductase Core Subunit S7 (NDUFS7) for delays in mental development; Hepsin (HPN) for ID and Collagen Type VI Alpha 3 Chain (COL6A3), Damage Specific DNA Binding Protein 1 (DDB1) and NADH:Ubiquinone Oxidoreductase Subunit A11 (NDUFA11) for speech/language disorder. Taken together, we have established critical insights into the development of new precision medicine approaches for mental disorders in AAs.
Current and future perspectives of chimeric antigen receptors against glioblastoma
Authors: Zhang Josephine , Siller-Farfán Jesús A
Published: June 2022

Glioblastoma multiforme (GBM) is the most malignant form of cancer in the central nervous system; even with treatment, it has a 5-year survival rate of 7.2%. The adoptive cell transfer (ACT) of T cells expressing chimeric antigen receptors (CARs) has shown a remarkable success against hematological malignancies, namely leukemia and multiple myeloma. However, CAR T cell therapy against solid tumors, and more specifically GBM, is still riddled with challenges preventing its widespread adoption. Here, we first establish the obstacles in ACT against GBM, including on-target/off-tumor toxicity, antigen modulation, tumor heterogeneity, and the immunosuppressive tumor microenvironment. We then present recent preclinical and clinical studies targeting well-characterized GBM antigens, which include the interleukin-13 receptor α2 and the epidermal growth factor receptor. Afterward, we turn our attention to alternative targets in GBM, including less-explored antigens such as B7-H3 (CD276), carbonic anhydrase IX, and the GD2 ganglioside. We also discuss additional target ligands, namely CD70, and natural killer group 2 member D ligands. Finally, we present the possibilities afforded by novel CAR architectures. In particular, we examine the use of armored CARs to improve the survival and proliferation of CAR T cells. We conclude by discussing the advantages of tandem and synNotch CARs when targeting multiple GBM antigens.