bluuebunny/crossref_metadata_2025 huggingface dataset:
REGULATION OF GENE ACTIVITY BY DOSAGE COMPENSATION AT THE CHROMOSOMAL LEVEL IN DROSOPHILA
Authors: Stewart Barbara R , Merriam John R
Published: January 2021

Two models of dosage compensation have been tested by the measurement of G6PD and 6PGD enzymatic specific activities in flies hyperploid for regions of the X chromosome. Females duplicated for the proximal half of the X chromosome (2½ X's) have an increased level of G6PD and a normal level of 6PGD. Females duplicated for the distal half of the X chromosome (2½ X's) have a normal level of G6PD and an increased level of 6PGD. Males bearing duplications of various segments of the X chromosome show control levels of G6PD and 6PGD, except where the duplicated region includes the structural gene for G6PD or 6PGD. These results fail to provide evidence for either the presence of discrete X-linked compensator (regulator) genes reducing the activity of other X-linked genes, or for a factor in limiting supply necessary for the transcription of all the genes on the X chromosome. Superfemales (3 X chromosomes) have the same G6PD and 6PGD activity levels as their diploid sisters. It would appear that the regulation of gene activity by dosage compensation is a chromosomal phenomenon in that the level of activity per gene copy for loci on the X chromosome is modulated in a stepwise fashion according to the total number of X chromosomes present.
GENE DUPLICATION AS A MECHANISM OF GENETIC ADAPTATION IN SACCHAROMYCES CEREVISIAE
Authors: Hansche Paul E
Published: January 2021

It has been shown that specific mutations of the gene that codes for the general acid monophosphatase (Aphtase) of S. cerevisiae can increase the affinity of this enzyme for β-glycerophosphate (BGP) and thereby provide this organism with the capacity to exploit extremely low concentrations of this organic phosphate (Francis and Hansche 1973). In this report two additional avenues are demonstrated to be available to this organism for increasing its capacity to exploit low concentrations of organic phosphates. One avenue is through mutations that increase the amount of Aphtase that associates with the cell wall, where it catalizes the hydrolysis of exogenous organic phosphates. The other avenue is through duplication of the gene that codes for Aphtase, doubling the amount of Aphtase synthesized. — The spontaneous duplication of the structural gene of Aphtase and the incorporation of the duplicate into this experimental population as a means of exploiting low concentrations of exogenous organic phosphates provides direct support for the first step of the mechanism through which new metabolic functions are postulated to evolve.
Modified frequency–Bessel transform method for dispersion imaging of Rayleigh waves from ambient seismic noise
Authors: Xi Chaoqiang , Xia Jianghai , Mi Binbin , Dai Tianyu , Liu Ya , Ning Ling
Published: January 2021

Ambient noise surface wave methods have gained much attention among geophysical and civil engineering communities because of their capability of determining near-surface shear wave velocities in highly populated urban areas. Higher mode information of surface waves is important in dispersion curve inversion for shear wave velocity structure. The frequency–Bessel (F-J) transform method is an effective tool for multimode surface wave extraction, which has been applied to multiscale investigations of the Earth structure. The measured dispersion energy with the F-J method, however, would usually be contaminated by a type of ‘crossed’ artefacts at high frequencies, which are caused by spatial aliasing and bidirectional velocity scan of dispersion analysis methods. The ‘crossed’ artefacts usually cross and smear the true dispersion energy in the frequency–velocity domain. We propose a modified F-J (MFJ) transform method in which the Bessel function is replaced by the Hankel function for dispersion analysis of empirical Green's function. The MFJ method performs a unidirectional velocity scanning on the outgoing wave to avoid the ‘crossed’ artefacts. Synthetic and real-world examples demonstrate the effectiveness of the proposed MFJ method in improving the accuracy of Rayleigh wave multimode dispersion measurements.
Downregulation of long non-protein coding RNA MVIH impairs glioblastoma cell proliferation and invasion through an miR-302a-dependent mechanism
Authors: Cardoso Ana M , Morais Catarina M , Rebelo Olinda , Tão Hermínio , Barbosa Marcos , Pedroso de Lima Maria C , Jurado Amália S
Published: January 2021

Glioblastoma (GB) is the most frequent and malignant type of brain tumor, for which no effective therapy exists. The high proliferative and invasive nature of GB, as well as its acquired resistance to chemotherapy, makes this type of cancer extremely lethal shortly after diagnosis. Long non-protein coding RNAs (lncRNA) are a class of regulatory RNAs whose levels can be dysregulated in the context of diseases, unbalancing several physiological processes. The lncRNA associated with microvascular invasion in hepatocellular carcinoma (lncRNA-MVIH), overexpressed in several cancers, was described to co-precipitate with phosphoglycerate kinase 1 (PGK1), preventing secretion of this enzyme to the extracellular environment and promoting cell migration and invasion. We hypothesized that, by silencing the expression of lncRNA-MVIH, the secretion of PGK1 would increase, reducing GB cell migration and invasion capabilities. We observed that lncRNA-MVIH silencing in human GB cells significantly decreased glycolysis, cell growth, migration, and invasion and sensitized GB cells to cediranib. However, no increase in extracellular PGK1 was observed as a consequence of lncRNA-MVIH silencing, and therefore, we investigated the possibility of a mechanism of miRNA sponge of lncRNA-MVIH being in place. We found that the levels of miR-302a loaded onto RISC increased in GB cells after lncRNA-MVIH silencing, with the consequent downregulation of several miR-302a molecular targets. Our findings suggest a new mechanism of action of lncRNA-MVIH as a sponge of miR-302a. We suggest that lncRNA-MVIH knockdown may be a promising strategy to address GB invasiveness and chemoresistance, holding potential towards its future application in a clinical context.
Mitochondria: their role in spermatozoa and in male infertility
Authors: Boguenet Magalie , Bouet Pierre-Emmanuel , Spiers Andrew , Reynier Pascal , May-Panloup Pascale
Published: January 2021

BACKGROUND

The best-known role of spermatozoa is to fertilize the oocyte and to transmit the paternal genome to offspring. These highly specialized cells have a unique structure consisting of all the elements absolutely necessary to each stage of fertilization and to embryonic development. Mature spermatozoa are made up of a head with the nucleus, a neck, and a flagellum that allows motility and that contains a midpiece with a mitochondrial helix. Mitochondria are central to cellular energy production but they also have various other functions. Although mitochondria are recognized as essential to spermatozoa, their exact pathophysiological role and their functioning are complex. Available literature relative to mitochondria in spermatozoa is dense and contradictory in some cases. Furthermore, mitochondria are only indirectly involved in cytoplasmic heredity as their DNA, the paternal mitochondrial DNA, is not transmitted to descendants.

OBJECTIVE AND RATIONAL

This review aims to summarize available literature on mitochondria in spermatozoa, and, in particular, that with respect to humans, with the perspective of better understanding the anomalies that could be implicated in male infertility.

SEARCH METHODS

PubMed was used to search the MEDLINE database for peer-reviewed original articles and reviews pertaining to human spermatozoa and mitochondria. Searches were performed using keywords belonging to three groups: ‘mitochondria’ or ‘mitochondrial DNA’, ‘spermatozoa’ or ‘sperm’ and ‘reactive oxygen species’ or ‘calcium’ or ‘apoptosis’ or signaling pathways’. These keywords were combined with other relevant search phrases. References from these articles were used to obtain additional articles.

OUTCOMES

Mitochondria are central to the metabolism of spermatozoa and they are implicated in energy production, redox equilibrium and calcium regulation, as well as apoptotic pathways, all of which are necessary for flagellar motility, capacitation, acrosome reaction and gametic fusion. In numerous cases, alterations in one of the aforementioned functions could be linked to a decline in sperm quality and/or infertility. The link between the mitochondrial genome and the quality of spermatozoa appears to be more complex. Although the quantity of mtDNA, and the existence of large-scale deletions therein, are inversely correlated to sperm quality, the effects of mutations seem to be heterogeneous and particularly related to their pathogenicity.

WIDER IMPLICATIONS

The importance of the role of mitochondria in reproduction, and particularly in gamete quality, has recently emerged following numerous publications. Better understanding of male infertility is of great interest in the current context where a significant decline in sperm quality has been observed.
Science, social networks, and collaboration: an analysis of publications in fisheries science from 1990 to 2018
Authors: Olson Julia , Pinto da Silva Patricia
Published: January 2021

Understanding the nature of collaboration underpinning scientific work in fisheries is critical to building the social foundations for effective scientific progress in addressing complex socio-ecological systems. We examine the nature of interdisciplinary work in fisheries through an analysis of nearly three decades of peer-reviewed papers authored by researchers affiliated with NOAA Fisheries’ Northeast Fisheries Science Center in the United States. Using social network analysis, and approaches novel to scientometrics such as grounded theory building, we map and analyse the relationships between authors of different disciplinary backgrounds, visualize these changing networks over time, and evaluate the nature of collaboration with a particular emphasis given to the integration of the social sciences. Our analysis suggests that areas of research such as ecosystem-based management and climate change have helped create synergies between the natural and social sciences, pointing to the importance of organizational changes promoting multiple perspectives, the institutionalization of integrated approaches, and openness to diverse understandings.
Comparative Functional Anatomy of Marmoset Brains
Authors: Kaas Jon H
Published: January 2021

Marmosets and closely related tamarins have become popular models for understanding aspects of human brain organization and function because they are small, reproduce and mature rapidly, and have few cortical fissures so that more cortex is visible and accessible on the surface. They are well suited for studies of development and aging. Because marmosets are highly social primates with extensive vocal communication, marmoset studies can inform theories of the evolution of language in humans. Most importantly, marmosets share basic features of major sensory and motor systems with other primates, including those of macaque monkeys and humans with larger and more complex brains. The early stages of sensory processing, including subcortical nuclei and several cortical levels for the visual, auditory, somatosensory, and motor systems, are highly similar across primates, and thus results from marmosets are relevant for making inferences about how these systems are organized and function in humans. Nevertheless, the structures in these systems are not identical across primate species, and homologous structures are much bigger and therefore function somewhat differently in human brains. In particular, the large human brain has more cortical areas that add to the complexity of information processing and storage, as well as decision-making, while making new abilities possible, such as language. Thus, inferences about human brains based on studies on marmoset brains alone should be made with a bit of caution.
Intrapulmonary Vaccination Induces Long-lasting and Effective Pulmonary Immunity Against Staphylococcus aureus Pneumonia
Authors: Fan Xin , Li Ning , Xu Meiyi , Yang Decheng , Wang Beinan
Published: January 2021

Background

Staphylococcus aureus causes community- and hospital-acquired pneumonia linked to a high mortality rate. The emergence and rapid transmission of multidrug-resistant S. aureus strains has become a serious health concern, highlighting the challenges associated with the development of a vaccine to combat S. aureus pneumonia.

Methods

This study evaluated the effects of intrapulmonary immunization on the immune response and protection against S. aureus lung infection in a respiratory mouse model using a subunit vaccine.

Results

Compared with the intranasal immunized mice, the intrapulmonarily immunized mice had lower levels of pulmonary bacterial colonization and lethality, accompanied by alleviated lung inflammation with reduced proinflammatory cytokines and increased levels of interleukin-10 and antimicrobial peptide following intrapulmonary challenge. Optimal protection was associated with increased pulmonary antibodies and resident memory T cells. Moreover, intrapulmonary immunization provided long-lasting pulmonary protection for at least 6 months, with persistent cellular and humoral immunity in the lungs.

Conclusions

Vaccine reaching the deep lung by intrapulmonary immunization plays a significant role in the induction of efficacious and long-lasting immunity against S. aureus in the lung parenchyma. Hence, intrapulmonary immunization can be a strategy for the development of a vaccine against S. aureus pneumonia.

Immunization through the intrapulmonary route with a subunit of S. aureus vaccine elicited tissue resident memory T cells and antigen-specific antibodies in the lungs, and provided optimal and long-term protection against S. aureus pneumonia.
Identification and Characterization of Chemical Constituents in HuaTanJiangQi Capsules by UPLC-QTOF-MS Method
Authors: Li Chenhui , Fang Wei , Wu Qingqing , Yao Zhaomin , Wu Jie , Huang Peng , Wang Dianlei , Li Zegeng
Published: January 2021

Background

HuaTanJiangQi (HTJQ) is a classical Chinese medicine compound preparation, mainly used for clinically treating and improving chronic obstructive pulmonary disease (COPD) in China.

Objective

To establish a rapid and efficient analytical method for the identification and characterization of chemical constituents in HTJQ based on ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS).

Method

UPLC-QTOF-MS was used to rapidly separate and identify the chemical constituents of HTJQ via a gradient elution system. The accurate mass data of the protonated and deprotonated molecules and fragment ions were detected in positive and negative ion modes. Compounds of HTJQ can be identified and assigned by analyzing accurate mass measurements and ion fragmentation mechanisms and comparing them with a chemical compositions database.

Results

A total of 61 compounds in HTJQ were separated and identified, including 14 flavonoids, 16 organic acids, four isothiocyanic acids, eight butyl phthalides, two alkaloids, 10 terpenoids, four methoxyphenols and furanocoumarins, and three other compounds. The chemical compounds of HTJQ were identified and elucidated comprehensively for the first time.

Conclusions

A rapid, accurate, and efficient UPLC-QTOF-MS method has been developed for the identification of chemical components and applied to simultaneously evaluate the quality and effectiveness of HTJQ.

Highlights

Systematic identification of chemical constituents in HTJQ can provide a scientific and reasonable basis for the application of HTJQ in the clinical treatment of COPD.
Solo dwarfs II: the stellar structure of isolated Local Group dwarf galaxies
Authors: Higgs C R , McConnachie A W , Annau N , Irwin M , Battaglia G , Côté P , Lewis G F , Venn K
Published: January 2021

The Solo (Solitary Local) Dwarf Galaxy survey is a volume-limited, wide-field g- and i-band survey of all known nearby (<3 Mpc) and isolated (>300 kpc from the Milky Way or M31) dwarf galaxies. This set of 44 dwarfs is homogeneously analysed for quantitative comparisons to the satellite dwarf populations of the Milky Way and M31. In this paper, an analysis of the 12 closest Solo dwarf galaxies accessible from the Northern hemisphere is presented, including derivation of their distances, spatial distributions, morphology, and extended structures, including their inner integrated light properties and their outer resolved star distributions. All 12 galaxies are found to be reasonably well described by two-dimensional Sérsic functions, although UGC 4879 in particular shows tentative evidence of two distinct components. No prominent extended stellar substructures, which could be signs of either faint satellites or recent mergers, are identified in the outer regions of any of the systems examined.
The correlation of high-redshift galaxies with the thermal Sunyaev–Zel’dovich effect traces reionization
Authors: Baxter Eric J , Weinberger Lewis , Haehnelt Martin , Iršič Vid , Kulkarni Girish , Pandey Shivam , Roy Anirban
Published: January 2021

We explore a potential new probe of reionization: the cross-correlation of high-redshift galaxies with maps of the thermal Sunyaev–Zel’dovich (tSZ) effect. We consider two types of high-redshift galaxies: Lyman break galaxies (LBGs) and Lyman-α emitters (LAEs). LBGs and LAEs will be detected in large numbers at high redshift (z ≈ 4–7) by ongoing and future surveys. We consider a future LBG sample from The Rubin Observatory Legacy Survey of Space and Time, and a selection of LAEs modelled after the Subaru SILVERRUSH programme, but covering a much larger sky fraction. The tSZ effect is sensitive to a line-of-sight integral of the ionized gas pressure, and is measured across large patches of sky using multifrequency cosmic microwave background (CMB) surveys. We consider forecast tSZ maps from CMB Stage 4 and more futuristic observations. Using a suite of hydrodynamical simulations, we show that LBGs and LAEs are correlated with the tSZ signal from reionization. The cross-spectra between LBGs/LAEs with tSZ maps contain information about the reionization history of the Universe, such as the distribution of bubble sizes, and could be used to directly measure the timing of reionization. The amplitude of the signal is small, however, and its detectability is hindered by low-redshift contributions to tSZ maps and by instrumental noise. If the low-redshift contribution to the observed tSZ signal is suppressed by masking of massive haloes, a combination of overlapping futuristic CMB and galaxy surveys could probe this signal.
Magnetic flux inversion in a peculiar changing look AGN
Authors: Scepi Nicolas , Begelman Mitchell C , Dexter Jason
Published: January 2021

We argue that the changing-look event in the active galactic nucleus (AGN) 1ES 1927+654, followed by a dip of three orders of magnitude in the X-ray luminosity, is controlled by a change in the accretion rate and an inversion of magnetic flux in a magnetically arrested disc (MAD). Before the changing-look event, strong magnetic flux on the black hole powers X-ray emission via the Blandford–Znajek process, while the UV emission is produced by a radiatively inefflcient magnetized disc. An advection event, bringing flux of the opposite polarity, propagates inward leading, first, to a rise in the UV/optical luminosity and, then, to a dip in the X-ray luminosity. We find that the observed time-scale between the beginning of the changing-look event and the minimum in the X-ray luminosity, ≈200 d, is in agreement with the time needed to cancel the magnetic flux in a MAD extending to ≈180 rg. Although flux inversion events might be rare due to the large ratio of flux-to-mass that is needed, we argue that AGN showing an unusually high ratio of X-ray to UV luminosity are prime candidates for such events. We suggest that similar events may lead to jet interruptions in radio-loud objects.
Fine-Scale Genetic Structure and Demographic History in the Miyako Islands of the Ryukyu Archipelago
Authors: Matsunami Masatoshi , Koganebuchi Kae , Imamura Minako , Ishida Hajime , Kimura Ryosuke , Maeda Shiro
Published: January 2021

The Ryukyu Archipelago is located in the southwest of the Japanese islands and is composed of dozens of islands, grouped into the Miyako Islands, Yaeyama Islands, and Okinawa Islands. Based on the results of principal component analysis on genome-wide single-nucleotide polymorphisms, genetic differentiation was observed among the island groups of the Ryukyu Archipelago. However, a detailed population structure analysis of the Ryukyu Archipelago has not yet been completed. We obtained genomic DNA samples from 1,240 individuals living in the Miyako Islands, and we genotyped 665,326 single-nucleotide polymorphisms to infer population history within the Miyako Islands, including Miyakojima, Irabu, and Ikema islands. The haplotype-based analysis showed that populations in the Miyako Islands were divided into three subpopulations located on Miyakojima northeast, Miyakojima southwest, and Irabu/Ikema. The results of haplotype sharing and the D statistics analyses showed that the Irabu/Ikema subpopulation received gene flows different from those of the Miyakojima subpopulations, which may be related with the historically attested immigration during the Gusuku period (900 − 500 BP). A coalescent-based demographic inference suggests that the Irabu/Ikema population firstly split away from the ancestral Ryukyu population about 41 generations ago, followed by a split of the Miyako southwest population from the ancestral Ryukyu population (about 16 generations ago), and the differentiation of the ancestral Ryukyu population into two populations (Miyako northeast and Okinawajima populations) about seven generations ago. Such genetic information is useful for explaining the population history of modern Miyako people and must be taken into account when performing disease association studies.
Inhibitory investigation of niacin derivatives on metalloenzyme indoleamine 2,3-dioxygenase 1 for its immunomodulatory function
Authors: Yan Daojing , Xu Jiakun , Tan Xiangshi
Published: January 2021

Inhibitors of indoleamine 2,3-dioxygenase 1 (IDO1) have received wide attention for their roles in cancer immunotherapy. It highlights the important role of metalloenzymes in performing human physiological functions. Herein, the recombinant human IDO1 was expressed and purified successfully, and the protein molecule was characterized by SDS-PAGE, MALDI-TOF mass spectrometry, and metalloenzymology. A series of niacin derivatives were investigated with regard to their inhibition on metalloenzyme IDO1, and the resulting potential anti-cancer activities in cell lines. Among the niacin derivatives, 4,4,4-trifluoro-1-(pyridin-3-yl)-butane-1,3-dione (compound 9) was found to be the most effective inhibitor to IDO1 in HepG-2 cells, with an EC50 of 11 µM with low cytotoxicity. The IC50 value of compound 9 with trifluoroethyl group in enzymatic inhibition was shown to be ∼5 times more potent than a positive control 4-phenylimidazole. The interaction between compound 9 and IDO1 was verified by isothermal titration calorimetry and molecular docking study. The most favorable molecular docking results revealed that functional groups of compound 9 contributed to the binding of 9 to IDO1 through IDO1–heme coordination, H-bond interactions and hydrophobic contacts. Our finding provides a strategy for the development of new inhibitor candidates for the therapeutic inhibition of IDO1.
Micro-homology intermediates: RecA’s transient sampling revealed at the single molecule level
Authors: Lee Andrew J , Endo Masayuki , Hobbs Jamie K , Davies A Giles , Wälti Christoph
Published: January 2021

Recombinase A (RecA) is central to homologous recombination. However, despite significant advances, the mechanism with which RecA is able to orchestrate a search for homology remains elusive. DNA nanostructure-augmented high-speed AFM offers the spatial and temporal resolutions required to study the RecA recombination mechanism directly and at the single molecule level. We present the direct in situ observation of RecA-orchestrated alignment of homologous DNA strands to form a stable recombination product within a supporting DNA nanostructure. We show the existence of subtle and short-lived states in the interaction landscape, which suggests that RecA transiently samples micro-homology at the single RecA monomer-level throughout the search for sequence alignment. These transient interactions form the early steps in the search for sequence homology, prior to the formation of stable pairings at >8 nucleotide seeds. The removal of sequence micro-homology results in the loss of the associated transient sampling at that location.
Meningioma: A Pathology Perspective
Authors: Toland Angus , Huntoon Kristin , Dahiya Sonika M
Published: January 2021

Meningiomas are dural-based neoplasms that account for ∼37% of all intracranial tumors in the adult population. They can occur anywhere within the central nervous system and have a predilection for females. The World Health Organization classifies meningiomas into 3 grades based on increased risk of recurrence and associated mortality in grade III tumors. Although most tumors are categorized as low-grade, up to ∼15%-20% demonstrate more aggressive behavior. With the long-recognized association with neurofibromatosis type 2 gene mutation, putative driver mutations can be attributed to ∼80% of tumors. Several germline mutations have also been identified in some cases of familial meningiomatosis such as SMARCE1, SUFU, PTEN, and BAP1. Finally, in addition to genetic data, epigenetic alterations, specifically deoxyribonucleic acid methylation, are being increasingly recognized for their prognostic value, potentially adding objectivity to a currently subjective grading scheme.
The university third mission and the European Structural Funds in peripheral regions: Insights from Finland
Authors: Salomaa Maria , Charles David
Published: January 2021

Current EU policies aim to support regional research, development, and innovation activities. The Cohesion Policy, implemented through Structural Funds (SFs) Operational Programmes, seeks to foster local level innovation. In parallel, universities have become important drivers of regional development through their ‘third mission’ driven by the different policy levels. This article investigates the tensions between the primary institutional logics of the university and the institutional logic of the SF programmes in peripheral regions as experienced by a multi-disciplinary university network from Finland. The findings from the case study reveal competing and co-evolving institutional logics of the two frameworks; university-led SF activities increase collaboration with local stakeholders, but the implementation of SF projects remains challenging (e.g. strict guidelines, higher education (HE) policies driving research excellence). Further investigation of these results in different regional contexts could provide new tools for managing the university third mission more efficiently, through SF programmes and beyond.
Evaluating the Sensitivity and Specificity of Promising Circulating Biomarkers to Diagnose Liver Injury in Humans
Authors: Llewellyn Heather P , Vaidya Vishal S , Wang Zhenyu , Peng Qinghai , Hyde Craig , Potter David , Wang Jianying , Zong Qing , Arat Seda , Martin Matt , Masek-Hammerman Katherine , Warner Roscoe , Johnson Kent , Kullak-Ublick Gerd A , Aithal Guruprasad P , Dear James W , Ramaiah Shashi K
Published: January 2021

Early diagnosis of drug-induced liver injury (DILI) continues to be a major hurdle during drug development and postmarketing. The objective of this study was to evaluate the diagnostic performance of promising biomarkers of liver injury—glutamate dehydrogenase (GLDH), cytokeratin-18 (K18), caspase-cleaved K18 (ccK18), osteopontin (OPN), macrophage colony-stimulating factor (MCSF), MCSF receptor (MCSFR), and microRNA-122 (miR-122) in comparison to the traditional biomarker alanine aminotransferase (ALT). Biomarkers were evaluated individually and as a multivariate model in a cohort of acetaminophen overdose (n = 175) subjects and were further tested in cohorts of healthy adults (n = 135), patients with liver damage from various causes (n = 104), and patients with damage to the muscle (n = 74), kidney (n = 40), gastrointestinal tract (n = 37), and pancreas (n = 34). In the acetaminophen cohort, a multivariate model with GLDH, K18, and miR-122 was able to detect DILI more accurately than individual biomarkers alone. Furthermore, the three-biomarker model could accurately predict patients with liver injury compared with healthy volunteers or patients with damage to muscle, pancreas, gastrointestinal tract, and kidney. Expression of K18, GLDH, and miR-122 was evaluated using a database of transcriptomic profiles across multiple tissues/organs in humans and rats. K18 mRNA (Krt18) and MiR-122 were highly expressed in liver whereas GLDH mRNA (Glud1) was widely expressed. We performed a comprehensive, comparative performance assessment of 7 promising biomarkers and demonstrated that a 3-biomarker multivariate model can accurately detect liver injury.
Isolation and Characterization of Bacteriophages Infecting Burkholderia glumae, the Major Causal Agent of Bacterial Panicle Blight in Rice
Authors: Jungkhun Nootjarin , Farias Antonio R. G. , Barphagha Inderjit , Patarapuwadol Sujin , Ham Jong Hyun
Published: January 2021

Bacterial panicle blight (BPB), caused by Burkholderia glumae, is one of the most severe seed-borne bacterial diseases of rice in the world, which can decrease rice production by ≤75%. Nevertheless, there are few effective measures to manage this disease. In an attempt to develop an alternative management tool for BPB, we isolated and characterized phages from soil and water that are effective to lyse several strains of B. glumae. After tests of host ranges, the phages NBP1-1, NBP4-7, and NBP4-8 were selected for further comprehensive characterization, all of which could lyse B. glumae BGLa14-8 (phage sensitive) but not B. glumae 336gr-1 (phage insensitive). This result indicates that the phages killing B. glumae cells have specific host ranges at the strain level within the bacterial species. In the greenhouse condition of this study, foliar application of the phage NBP4-7 reduced the severity of BPB caused by B. glumae BGLa14-8 ≤62% but did not cause any significant effect on the infection by B. glumae 336gr-1. Electron microscopy and whole-genome sequencing were also performed to characterize the three selected phages. Transmission electron microscopy revealed that the selected phages belong to the family Myoviridae. Furthermore, whole-genome sequence analysis indicated that the three phages belong to a same species and are closely related to the Burkholderia phage KL3, a member of the Myoviridae family.
Identification of Grapevine Pinot gris virus in Free-Living Vitis spp. Located in Riparian Areas Adjacent to Commercial Vineyards
Authors: Diaz-Lara Alfredo , Dangl Gerald S. , Yang Judy , Golino Deborah , Al Rwahnih Maher
Published: January 2021

Grapevine Pinot gris virus (GPGV) is a recently identified pathogen of grapevines in California. To advance our knowledge about the epidemiology of GPGV, we investigated if free-living Vitis spp. can represent a source of inoculum. In 2019, a field survey of GPGV infection was conducted in Napa County and 60 free-living vines in riparian habitats near commercial vineyards with GPGV infection were sampled. The samples were tested by real-time reverse transcription (RT)-PCR, identifying 23 free-living Vitis spp. positive for GPGV. GPGV infection was confirmed in these plants via end-point RT-PCR and Sanger sequencing. Based on sequence analysis, the detected GPGV isolates were more related to asymptomatic variants of the virus. Vitis species ancestry was determined by DNA fingerprinting. The GPGV-infected materials included V. californica, V. californica × V. vinifera hybrids and hybrid rootstock cultivars. Here, GPGV is reported for the first time in free-living Vitis spp. The results of this study will support the development of management strategies for GPGV in California and beyond.
Diversity of fungi associated with macroalgae from an estuarine environment and description of Cladosporium rubrum sp. nov. and Hypoxylon aveirense sp. nov.
Authors: Vicente Tânia F. L. , Gonçalves Micael F. M. , Brandão Cláudio , Fidalgo Cátia , Alves Artur
Published: January 2021

Fungal communities associated with macroalgae remain largely unexplored. To characterize algicolous fungal communities using culture dependent methods, macroalgae were collected from different sampling sites in the Ria de Aveiro estuary, Portugal. From a collection of 486 isolates that were obtained, 213 representative isolates were selected through microsatellite-primed PCR (MSP-PCR) fingerprinting analysis. The collection yielded 33 different genera, which were identified using the ITS region of the rDNA. The results revealed that the most abundant taxa in all collections were Acremonium-like species: Alternaria, Cladosporium, Leptobacillium and Penicillium. The fungal community composition varied with macroalgae species. Through multilocus phylogenetic analyses based on ITS, tub2, tef1-α and actA sequences, in addition to detailed morphological data, we propose Cladosporium rubrum sp. nov. (type strain=CMG 28=MUM 19.39) and Hypoxylon aveirense sp. nov. (type strain=CMG 29=MUM 19.40) as novel species.
Inhibition of canine distemper virus replication by blocking pyrimidine nucleotide synthesis with A77 1726, the active metabolite of the anti-inflammatory drug leflunomide
Authors: Li Yao , Yi Li , Cheng Sipeng , Wang Yongshan , Wang Jiongjiong , Sun Jing , Zhang Quan , Xu Xiulong
Published: January 2021

Canine distemper virus (CDV) is the aetiological agent that causes canine distemper (CD). Currently, no antiviral drugs have been approved for CD treatment. A77 1726 is the active metabolite of the anti-rheumatoid arthritis (RA) drug leflunomide. It inhibits the activity of Janus kinases (JAKs) and dihydroorotate dehydrogenase (DHO-DHase), a rate-limiting enzyme inde novopyrimidine nucleotide synthesis. A77 1726 also inhibits the activity of p70 S6 kinase (S6K1), a serine/threonine kinase that phosphorylates and activates carbamoyl-phosphate synthetase (CAD), a second rate-limiting enzyme in thede novopathway of pyrimidine nucleotide synthesis. Our present study focuses on the ability of A77 1726 to inhibit CDV replication and its underlying mechanisms. Here we report that A77 1726 decreased the levels of the N and M proteins of CDV and lowered the virus titres in the conditioned media of CDV-infected Vero cells. CDV replication was not inhibited by Ruxolitinib (Rux), a JAK-specific inhibitor, but by brequinar sodium (BQR), a DHO-DHase-specific inhibitor, and PF-4708671, an S6K1-specific inhibitor. Addition of exogenous uridine, which restores intracellular pyrimidine nucleotide levels, blocked the antiviral activity of A77 1726, BQR and PF-4708671. A77 1726 and PF-4708671 inhibited the activity of S6K1 in CDV-infected Vero cells, as evidenced by the decreased levels of CAD and S6 phosphorylation. S6K1 knockdown suppressed CDV replication and enhanced the antiviral activity of A77 1726. These observations collectively suggest that the antiviral activity of A77 1726 against CDV is mediated by targeting pyrimidine nucleotide synthesis via inhibiting DHO-DHase activity and S6K1-mediated CAD activation.
Identifying novel β-lactamase substrate activity through in silico prediction of antimicrobial resistance
Authors: Tsang Kara K. , Maguire Finlay , Zubyk Haley L. , Chou Sommer , Edalatmand Arman , Wright Gerard D. , Beiko Robert G. , McArthur Andrew G.
Published: January 2021

Diagnosing antimicrobial resistance (AMR) in the clinic is based on empirical evidence and current gold standard laboratory phenotypic methods. Genotypic methods have the potential advantages of being faster and cheaper, and having improved mechanistic resolution over phenotypic methods. We generated and applied rule-based and logistic regression models to predict the AMR phenotype from

Escherichia coli

and

Pseudomonas aeruginosa

multidrug-resistant clinical isolate genomes. By inspecting and evaluating these models, we identified previously unknown β-lactamase substrate activities. In total, 22 unknown β-lactamase substrate activities were experimentally validated using targeted gene expression studies. Our results demonstrate that generating and analysing predictive models can help guide researchers to the mechanisms driving resistance and improve annotation of AMR genes and phenotypic prediction, and suggest that we cannot solely rely on curated knowledge to predict resistance phenotypes.
The LEAFY floral regulator displays pioneer transcription factor properties
Authors: Lai Xuelei , Blanc-Mathieu Romain , GrandVuillemin Loïc , Huang Ying , Stigliani Arnaud , Lucas Jérémy , Thévenon Emmanuel , Loue-Manifel Jeanne , Daher Hussein , Brun-Hernandez Eugenia , Vachon Gilles , Latrasse David , Benhamed Moussa , Dumas Renaud , Zubieta Chloe , Parcy François
Published: January 2021

Pioneer transcription factors (TFs) are a special category of TFs with the capacity to bind to closed chromatin regions in which DNA is wrapped around histones and often highly methylated. Subsequently, they are able to modify the chromatin state to initiate gene expression. In plants, LEAFY (LFY) is a master floral regulator and has been suggested to act as a pioneer TF in Arabidopsis. Here, we demonstrate that LFY is able to bind both methylated and non-methylated DNA using a combination ofin vitrogenome-wide binding experiments and structural modeling. Comparisons between regions bound by LFYin vivoand chromatin accessibility data suggest that LFY binds a subset of regions occupied by nucleosomes. We confirm that LFY is able to bind nucleosomal DNAin vitrousing reconstituted nucleosomes. Finally, we show that constitutive LFY expression in seedling tissues is sufficient to induce chromatin accessibility in the LFY direct target genes,APETALA1andAGAMOUS. Taken together, our study suggests that LFY possesses key pioneer TF features that contribute to launch the floral gene expression program.
The Fourth Industrial Revolution and private commercial banks: the good, bad and ugly
Authors: Rahman Asif , Abedin Md. Joynal
Published: January 2021

Purpose

This study aims to assess how new and emerging technologies can contribute to achieving the financial goals of the private commercial banking sector in Bangladesh. It considers the perception among the top management about the Fourth Industrial Revolution (4IR) and further measures the readiness of private commercial banks (PCBs) to become resilient.

Design/methodology/approach

This study attempts to measure the perception and readiness of the commercial banking sector because of the 4IR based on the stratified sampling method. The research is qualitative and selected PCBs listed in the Dhaka Stock Exchange. 4IR in the context of the banking sector in Bangladesh is a problem that has not been studied more clearly, intended to establish priorities, develop operational definitions and improve the final research design.

Findings

This research has identified a significant gap of study in the preparedness among the private commercial banking sector in Bangladesh to confront the 4IR while indicating the most significant risks and managerial insights. The findings show technologies will dramatically change the nature of work. Traditional system of banking from the branch will be shifting into banking from everywhere. Hence, digital products and services will foster value-driven business. The result of the study also states the readiness of the banking sector is in the preliminary stage and endorses some of the coping approaches.

Research limitations/implications

Different schools of thought regarding the role of the 4IR and its future consequences have been observed. The corporate sector in Bangladesh has an inclusive lack of understanding regarding the 4IR.

Practical implications

The insights may provide directions to banking financial institutions of Bangladesh to thrive during the 4IR. This study is intended to assist policymakers, decision-makers and employees of PCBs to increase awareness and preparedness for future challenges that may appear from the 4IR where the 41 competitive PCBs play vital role in turning the fast emerging Bangladesh economy.

Originality/value

The contribution of this paper associates with academics and bankers to increase understanding of coping in the context of the escalating use of emerging technology-driven banking services within the PCBs in Bangladesh by determining perception and testing different forms of readiness including a variety of important outcomes such as risks.
Profiles of traumatic dental injuries among children aged 0–15 years in Cappadocia, Turkey: A retrospective cohort study
Authors: Gümüş Hüsniye , Öztürk Gülce , Kürem Büşra
Published: January 2021

Background/Aim

Traumatic dental injuries are among the most serious dental public health problems in children. The aim of this retrospective study was to evaluate the dental trauma profile of primary and permanent teeth among children aged 0–15 years who presented to a university hospital.

Material and Methods

The study included 650 patients (1,000 primary and permanent teeth) who presented with a history of dental trauma to the Department of Pediatric Dentistry, Faculty of Dentistry, Erciyes University between 2016 and 2019. Traumatized teeth were assessed according to the Andreasen classification. The following information was recorded: age, gender, teeth affected by trauma, etiologies of trauma, place and season of trauma, type of trauma, type of treatment, and time between the trauma and treatment.

Results

In total, 650 patients (240 females, 410 males) and 1,000 incisors (212 primary teeth, 788 permanent teeth) were evaluated. The average age of the patients was 8.89 ± 3.41 years, and dental injuries were more frequent between 8 and 10 years of age. The maxillary central incisors, both primary (40.1%) and permanent (42.8%), were the most frequently affected teeth. The main cause of traumatic dental injuries was falls. Most accidents occurred at school and home. The most common type of dental injuries recorded was luxation injuries in the primary teeth (21.5%) and enamel‐dentin fractures (35.9%) in the permanent teeth. Only 48 teeth were treated during the first hour after injury.

Conclusions

The most common type of traumatic injury affecting permanent teeth was enamel‐dentin fractures, and primary teeth were luxation injury. Only 4.8% of teeth were treated within the first hour after trauma.
Structural requirements for membrane binding of human guanylate‐binding protein 1
Authors: Sistemich Linda , Dimitrov Stanchev Lyubomir , Kutsch Miriam , Roux Aurélien , Günther Pomorski Thomas , Herrmann Christian
Published: January 2021

Human guanylate‐binding protein 1 (hGBP1) is a key player in innate immunity and fights diverse intracellular microbial pathogens. Its antimicrobial functions depend on hGBP1’s GTP binding‐ and hydrolysis‐induced abilities to form large, structured polymers and to attach to lipid membranes. Crucial for both of these biochemical features is the nucleotide‐controlled release of the C terminally located farnesyl moiety. Here, we address molecular details of the hGBP1 membrane binding mechanism by employing recombinant, fluorescently labeled hGBP1, and artificial membranes. We demonstrate the importance of the GTPase activity and the resulting structural rearrangement of the hGBP1 molecule, which we term the open state. This open state is supported and stabilized by homodimer contacts involving the middle domain of the protein and is further stabilized by binding to the lipid bilayer surface. We show that on the surface of the lipid bilayer a hGBP1 monolayer is built in a pins in a pincushion‐like arrangement with the farnesyl tail integrated in the membrane and the N‐terminal GTPase domain facing outwards. We suggest that similar intramolecular contacts between neighboring hGBP1 molecules are responsible for both polymer formation and monolayer formation on lipid membranes. Finally, we show that tethering of large unilamellar vesicles occurs after the vesicle surface is fully covered by the monolayer. Both hGBP1 polymer formation and hGBP1‐induced vesicle tethering have implications for understanding the molecular mechanism of combating bacterial pathogens.

Databases

Structural data are available in RCSB Protein Data Bank under the accession numbers: 6K1Z, 2D4H.
Temperature and precipitation at specific growth stages influence soybean tocopherol and lutein concentrations
Authors: Tang Ruixue , Seguin Philippe , Morrison Malcolm J. , Fan Shimin
Published: January 2021

Soybean [Glycine max (L.) Merr.] is an important source of health beneficial compounds, including tocopherols and lutein. Seeds with elevated concentrations of these health beneficial compounds may be required to meet the increasing needs of the functional food market. A study was conducted for a period of 11 years in Ottawa, ON, Canada to examine the relationship between temperature and precipitation during specific growth stage intervals (GSI) and the concentration of tocopherol (toc) and lutein in the seeds at harvest. Tocopherol concentrations in soybean were most influenced by air temperature changes, while lutein concentration was more sensitive to precipitation. Heat stress via the accumulation of temperatures greater than 31°C during the mid‐vegetative to physiological maturity GSI was positively correlated (r2 = 0.94) with α‐toc concentration. Lutein concentration was negatively correlated (r2 = 0.61) with mean cumulative precipitation (cppt) during the seed development to maturation GSI. Overall, reproductive stages were more responsive to climatic variables than vegetative stages. In addition, the cultivars with higher toc or lutein concentrations were less affected by climatic variables than cultivars with lower concentrations. Climatic factors and abiotic stress during specific growth stages may have significant impact on concentrations of health beneficial compounds in mature seeds and this should be considered in the production of soybean for the functional food market.