bluuebunny/crossref_metadata_2025 huggingface dataset:
Restricted nucleation and piRNA-mediated establishment of heterochromatin during embryogenesis inDrosophila miranda
Authors: Wei Kevin H.-C. , Chan Carolus , Bachtrog Doris
Published: February 2021

Heterochromatin is a key architectural feature of eukaryotic genomes, crucial for silencing of repetitive elements and maintaining genome stability. Heterochromatin shows stereotypical enrichment patterns around centromeres and repetitive sequences, but the molecular details of how heterochromatin is established during embryogenesis are poorly understood. Here, we map the genome-wide distribution of H3K9me3-dependent heterochromatin in individual embryos ofD. mirandaat precisely staged developmental time points. We find that canonical H3K9me3 enrichment patterns are established early on before cellularization, and mature into stable and broad heterochromatin domains through development. Intriguingly, initial nucleation sites of H3K9me3 enrichment appear as early as embryonic stage3 (nuclear cycle 9) over transposable elements (TE) and progressively broaden, consistent with spreading to neighboring nucleosomes. The earliest nucleation sites are limited to specific regions of a small number of TE families and often appear over promoter regions, while late nucleation develops broadly across most TEs. Early nucleating TEs are highly targeted by maternal piRNAs and show early zygotic transcription, consistent with a model of co-transcriptional silencing of TEs by small RNAs. Interestingly, truncated TE insertions lacking nucleation sites show significantly reduced enrichment across development, suggesting that the underlying sequences play an important role in recruiting histone methyltransferases for heterochromatin establishment.
Functional basis for calmodulation of the TRPV5 calcium channel
Authors: Roig Sara R , Thijssen Niky , Erp Merijn van , Fransen Jack , Hoenderop Joost G , van der Wijst Jenny
Published: February 2021

Within the transient receptor potential (TRP) superfamily of ion channels, TRPV5 is a highly Ca2+-selective channel important for active reabsorption of Ca2+in the kidney. Its channel activity is controlled by a negative feedback mechanism involving calmodulin (CaM) binding. Combining advanced microscopy techniques and biochemical assays, this study characterized the dynamic bilobal CaM regulation and binding stoichiometry. We demonstrate for the first time that functional (full-length) TRPV5 interacts with CaM in the absence of Ca2+, and this interaction is intensified at increasing Ca2+concentrations sensed by the CaM C-lobe that achieves channel pore blocking. Channel inactivation occurs without CaM N-lobe calcification. Moreover, we reveal a 1:2 stoichiometry of TRPV5:CaM binding by implementingsingle molecule photobleaching counting, a technique with great potential for studying TRP channel regulation. In conclusion, our study proposes a new model for CaM- dependent regulation –calmodulation– of the Ca2+-selective TRPV5 that involves apoCaM interaction and lobe-specific actions.
Understanding distribution and occupancy of Himalayan Monal in Uttarkashi district, Uttarakhand
Authors: Sharief Amira , Singh Hemant , Joshi Bheem Dutt , Mukherjee Tanoy , Chandra Kailash , Thakur Mukesh , Sharma Lalit Kumar
Published: February 2021

The Himalayan Monal is a conservation priority species in its entire distribution range. Its population is declining in many areas due to various anthropogenic threats. The information on species distribution and its abundance is lacking in many areas which are vital for conservation and management planning. Hence, through the present study, we have assessed the abundance and occupancy of Himalayan monal in Uttarkashi district (Uttarakhand). We used camera traps and conventional sign surveys for documenting the species during 2018-2019. We installed a total of 69 camera traps (2819 trap nights) and surveyed 54 trails (650 km) which represents entire habitat and topographic variability of the landscape. The occupancy and detection probability was modelled using the habitat variables. The top model showed that occupancy probability of Himalayan monal was positively influenced by the slope (β =27.52 ±16.25) and negatively influenced by Reserve Forest (RF) (β= −8.14 SE ± 4.99). The observed naïve occupancy of Himalayan Monal was 0.69 in the study area, which was slightly lower than the estimated occupancy. However, in the null model, the site occupancy estimated was found to be 0.82±0.08 and with detection probability 0.23±0.03. The overall abundance of monal was estimated about 171.58 ±10.2 in the study area with an average density of 0.62/ km2. The activity pattern analysis indicates that monal remains very active between 6.00 hrs −12.00 hrs and relatively less active during mid-day when humans are most active 11.30 hrs-16.30 hrs. The present study is a first attempt to estimate occupancy and abundance using camera traps as well as sign survey for the species primarily from non-Protected Area (PA). We found that Himalayan monal is abundant outside the PAs, which is a good indication for its long-term viability and also identified areas for conservation and management prioritization in Uttarkashi.
Human pluripotent stem cell-derived cardiomyocytes align under cyclic strain when guided by cardiac fibroblasts
Authors: Mostert Dylan , Groenen Bart , Klouda Leda , Passier Robert , Goumans Marie-Jose , Kurniawan Nicholas A. , Bouten Carlijn V.C
Published: February 2021

The human myocardium is a mechanically active tissue typified by anisotropic organization of the resident cells (cardiomyocytes (CMs) and cardiac fibroblasts (cFBs)) and the extracellular matrix (ECM). Upon ischemic injury, the anisotropic tissue is replaced by disorganized scar tissue, eventually resulting in loss of coordinated contraction. Efforts to re-establish tissue anisotropy in the injured myocardium are hampered by a lack of understanding on how CM and/or cFB structural organization is affected by the two major physical cues inherent in the myocardium: ECM organization and cyclic mechanical strain. Herein, we investigate the singular and combined effect of ECM (dis)organization and cyclic strain in a 2D humanin vitroco-culture model of the myocardial microenvironment. We show that (an)isotropic ECM protein patterning can guide the orientation of CMs and cFBs, both in mono- and co-culture. Subsequent application of uniaxial cyclic strain – mimicking the local anisotropic deformation of beating myocardium – causes no effect when applied parallel to the anisotropic ECM. However, when cultured on isotropic substrates, cFBs, but not CMs, orient away from the direction of cyclic uniaxial strain (strain avoidance). In contrast, CMs show strain avoidance via active remodeling of their sarcomeres only when co-cultured with at least 30% cFBs. Paracrine signaling or N-cadherin-mediated communication between CMs and cFBs were no contributing factors, but our findings suggest that the mechanoresponsive cFBs provide structural guidance for CM orientation and elongation. Our study therefore highlights a synergistic mechanobiological interplay between CMs and cFBs in shaping tissue organization, which is of relevance for regenerating functionally organized myocardium.
In-cell structures of a conserved supramolecular array at the mitochondria-cytoskeleton interface in mammalian sperm
Authors: Leung Miguel Ricardo , Chiozzi Riccardo Zenezini , Roelofs Marc C. , Hevler Johannes F. , Ravi Ravi Teja , Maitan Paula , Zhang Min , Henning Heiko , Bromfield Elizabeth G. , Howes Stuart C. , Gadella Bart M. , Heck Albert J.R. , Zeev-Ben-Mordehai Tzviya
Published: February 2021

Mitochondria-cytoskeleton interactions modulate cellular physiology by regulating mitochondrial transport, positioning, and immobilization. However, there is very little structural information defining mitochondria-cytoskeleton interfaces in any cell type. Here, we use cryo-focused ion beam milling-enabled cryo-electron tomography to image mammalian sperm, where mitochondria wrap around the ciliary cytoskeleton. We find that mitochondria are tethered to their neighbors through inter-mitochondrial linkers and are anchored to the cytoskeleton through ordered arrays on the outer mitochondrial membrane. We use subtomogram averaging to resolve in-cell structures of these arrays from three mammalian species, revealing they are conserved across species despite variations in mitochondrial dimensions and cristae organization. We find that the arrays consist of boat-shaped particles anchored on a network of membrane pores whose arrangement and dimensions are consistent with voltage dependent anion channels. Proteomics and in-cell cross-linking mass spectrometry suggest that the conserved arrays are composed of glycerol kinase-like proteins. Ordered supramolecular assemblies may serve to stabilize similar contact sites in other cell types where mitochondria need to be immobilized in specific subcellular environments, such as in muscles and neurons.
LC-MS Based Draft Map of theArabidopsis thalianaNuclear Proteome and Protein Import in Pattern Triggered Immunity
Authors: Ayash Mohamed , Abukhalaf Mohammad , Thieme Domenika , Proksch Carsten , Heilmann Mareike , Schattat Martin , Hoehenwarter Wolfgang
Published: February 2021

Despite its central role as the ark of genetic information and gene expression the plant nucleus is surprisingly understudied. We isolated nuclei from theArabidopsis thalianadark grown cell culture left untreated and treated with flg22 and nlp20, two elicitors of pattern triggered immunity (PTI) in plants, respectively. An LC-MS based discovery proteomics approach was used to measure the nuclear proteome fractions. An enrichment score based on the relative abundance of cytoplasmic, mitochondrial and golgi markers in the nuclear protein fraction allowed us to curate the nuclear proteome producing high quality catalogs of around 3,000 nuclear proteins under untreated and both PTI conditions. The measurements also covered low abundant proteins including more than 100 transcription factors and transcriptional co-activators. Protein import into the nucleus in plant immunity is known. Here we sought to gain a broader impression of this phenomenon employing our proteomics data and found 157 and 73 proteins to be putatively imported into the nucleus upon stimulus with flg22 and nlp20, respectively. Furthermore, the abundance of 93 proteins changed significantly in the nucleus following elicitation of immunity. These results suggest promiscuous ribosome assembly and retrograde signaling from the mitochondrion to the nucleus including Prohibitins and Cytochrome C, in the two forms of PTI.
Screening of the antimicrobial activity of marine sponge extracts from Martinique
Authors: Piron Julie , Pastour Jessica , Tysklind Niklas , Smith-Ravin Juliette , Priam Fabienne
Published: February 2021

Marine sponges are known for their antimicrobial, antifungal, and cytotoxic activity. In this study, the activity of aqueous and ethanoic extracts of 3 sponges from Martinique were tested on 5 bacterial strains:Bascillus cereus(CIP 783),Echerichia coli(CIP 54127),Pseudomonas aeruginosa(CIP A22),Staphylococcus aureus(CIP 67.8) andStaphylococcus saprophyticus(CIP 76125). The antimicrobial activity ofAgelas clathrodes, Desmapsamma anchorata, andVerongula rigida, was demonstrated using the disc diffusion method and by determining the minimum inhibitory concentration and the minimum bactericidal concentration. The ethanoic extract ofAgelas clathrodeshad an inhibitory activity specifically onStaphylococcus aureusandStaphylococcus saprophyticus. No activity was observed for the other extracts. Further chemical analyses will be carried out in order to identify the active molecules of these sponges.
Extended Graphical Lasso for Multiple Interaction Networks for High Dimensional Omics Data
Authors: Xu Yang , Jiang Hongmei , Jiang Wenxin
Published: February 2021

There has been a spate of interest in association networks in biological and medical research, for example, genetic interaction networks. In this paper, we propose a novel method, the extended joint hub graphical lasso (EDOHA), to estimate multiple related interaction networks for high dimensional omics data across multiple distinct classes. To be specific, we construct a convex penalized log likelihood optimization problem and solve it with an alternating direction method of multipliers (ADMM) algorithm. The proposed method can also be adapted to estimate interaction networks for high dimensional compositional data such as microbial interaction networks. The performance of the proposed method in the simulated studies shows that EDOHA has remarkable advantages in recognizing class-specific hubs than the existing comparable methods. We also present three applications of real datasets. Biological interpretations of our results confirm those of previous studies and offer a more comprehensive understanding of the underlying mechanism in disease.

Author summary

Reconstruction of multiple association networks from high dimensional omics data is an important topic, especially in biology. Previous studies focused on estimating different networks and detecting common hubs among all classes. Integration of information over different classes of data while allowing difference in the hub nodes is also biologically plausible. Therefore, we propose a method, EDOHA, to jointly construct multiple interaction networks with capacity in finding different hub networks for each class of data. Simulation studies show the better performance over conventional methods. The method has been demonstrated in three real world data.
Between virus correlations in the outcome of infection across host species: evidence of virus genotype by host species interactions
Authors: Imrie Ryan M. , Roberts Katherine E. , Longdon Ben
Published: February 2021

Virus host shifts are a major source of outbreaks and emerging infectious diseases, and predicting the outcome of novel host and virus interactions remains a key challenge for virus research. The evolutionary relationships between host species can explain variation in transmission rates, virulence, and virus community composition between hosts, but the potential for different viruses to interact with host species effects has yet to be established. Here, we measure correlations in viral load of fourCripavirusisolates across experimental infections of 45Drosophilidaehost species. We find positive correlations between every pair of viruses tested, suggesting that broadly susceptible host clades could act as reservoirs and donors for certain types of viruses. Additionally, we find evidence of genotype-by-genotype interactions between viruses and host species, highlighting the importance of both host and virus traits in determining the outcome of virus host shifts. More closely related viruses tended to be more strongly correlated, providing tentative evidence that virus evolutionary relatedness may be a useful proxy for determining the likelihood of novel virus emergence, which warrants further research.

Impact Summary

Many new infectious diseases are caused by viruses jumping into novel host species. Estimating the probability that jumps will occur, what the characteristics of new viruses will be, and how they are likely to evolve after jumping to new host species are major challenges. To solve these challenges, we require a detailed understanding of the interactions between different viruses and hosts, or metrics that can capture some of the variation in these interactions. Previous studies have shown that the evolutionary relationships between host species can be used to predict traits of infections in different hosts, including transmission rates and the damage caused by infection. However, the potential for different viruses to influence the patterns of these host species effects has yet to be determined. Here, we use four viruses of insects in experimental infections across 45 different fruit fly host species to begin to answer this question. We find similarities in the patterns of replication and persistence between all four viruses, suggesting susceptible groups of related hosts could act as reservoirs and donors for certain types of virus. However, we also find evidence that different virus genotypes interact in different ways with some host species. Viruses that were more closely related tended to behave in similar ways, and so we suggest that virus evolutionary relatedness may prove to be a useful metric for predicting the traits of novel infections and should be explored further in future studies.
Complement Decay-Accelerating Factor is a modulator of influenza A virus lung immunopathology
Authors: Santos Nuno Brito , Vaz da Silva Zoé Enderlin , Gomes Catarina , Reis Celso A. , Amorim Maria João
Published: February 2021

Clearance of viral infections, such as SARS-CoV-2 and influenza A virus (IAV), must be fine-tuned to eliminate the pathogen without causing immunopathology. As such, an aggressive initial innate immune response favors the host in contrast to a detrimental prolonged inflammation. The complement pathway bridges innate and adaptive immune system and contributes to the response by directly clearing pathogens or infected cells, as well as recruiting proinflammatory immune cells and regulating inflammation. However, the impact of modulating complement activation in viral infections is still unclear. In this work, we targeted the complement decay-accelerating factor (DAF/CD55), a surface protein that protects cells from non-specific complement attack, and analyzed its role in IAV infections. We found that DAF modulates IAV infectionin vivo,via an interplay with the antigenic viral proteins hemagglutinin (HA) and neuraminidase (NA), in a strain specific manner. Our results reveal that, contrary to what could be expected, DAF potentiates complement activation, increasing the recruitment of neutrophils, monocytes and T cells. We also show that viral NA acts on the heavily sialylated DAF and propose that it exacerbates complement activation, leading to lung immunopathology. Remarkably, this mechanism has no impact on viral loads but rather on the host resilience to infection and may have direct implications in zoonotic influenza transmissions.

Author summary

Exacerbated complement activation and immune deregulation are at the basis of several pathologies induced by respiratory viruses. Here, we report that complement decay-accelerating factor (DAF), which inhibits complement activation in healthy cells, increases disease severity upon Influenza A virus (IAV) infection. Remarkably, DAF interaction with IAV proteins, hemagglutinin (HA) and neuraminidase (NA), resulted in excessive complement activation and recruitment of innate and adaptive immune cells, without affecting viral loads. Furthermore, we observed that viral NA directly cleaves DAF and promotes complement activation, providing a possible link between IAV-DAF interaction and pathology. Therefore, our results unveil a novel pathway that could modulate disease severity, which may help to understand the increased pathogenicity of zoonotic and pandemic IAV infections.
Human cytomegalovirus blocks canonical TGFβ signaling during lytic infection to limit induction of type I interferons
Authors: Pham Andrew H. , Mitchell Jennifer , Botto Sara , Pryke Kara M. , Defilippis Victor R. , Hancock Meaghan H.
Published: February 2021

Human cytomegalovirus (HCMV) microRNAs (miRNAs) significantly rewire host signaling pathways to support the viral lifecycle and regulate host cell responses. Here we show that SMAD3 expression is regulated by HCMV miR-UL22A and contributes to the IRF7-mediated induction of type I IFNs and IFN-stimulated genes (ISGs) in human fibroblasts. Addition of exogenous TGFβ interferes with the replication of a miR-UL22A mutant virus in a SMAD3-dependent manner in wild type fibroblasts, but not in cells lacking IRF7, indicating that downregulation of SMAD3 expression to limit IFN induction is important for efficient lytic replication. These findings uncover a novel interplay between SMAD3 and innate immunity during HCMV infection and highlight the role of viral miRNAs in modulating these responses.

Author Summary

Cells trigger the interferon (IFN) response to induce the expression of cellular genes that limit virus replication. In turn, viruses have evolved numerous countermeasures to avoid the effects of IFN signaling. Using a microRNA (miRNA) mutant virus we have uncovered a novel means of regulating the IFN response during human cytomegalovirus (HCMV) infection. Lytic HCMV infection induces the production of TGFβ, which binds to the TGFβ receptor and activates the receptor-associated SMAD SMAD3. SMAD3, together with IRF7, induces the expression of IFNβ and downstream IFN-stimulated genes in human fibroblasts. To counteract this, HCMV miR-UL22A, along with other HCMV gene products, directly targets SMAD3 for downregulation. Infection of fibroblasts with a miR-UL22A mutant virus results in enhanced type I IFN production in a SMAD3-dependent manner and the virus is impaired for growth in the presence of TGFβ, but only when both SMAD3 and IRF7 are present, highlighting the unique interaction between TGFβ and innate immune signaling.
Trial-by-trial fluctuations in post-stimulus attention during memory encoding predict subsequent associative context memory performance
Authors: Elshiekh Abdelhalim , Rajah M. Natasha
Published: February 2021

Episodic memory formation rate varies over time partly due to fluctuations in attentional state during memory encoding. Emerging evidence suggests that fluctuations in pre- and/or post-stimulus attention during encoding impact subsequent memory performance. It remains unclear how these fluctuations may differentially impact the subsequent retrieval of items alone, compared to items + their contextual details (associative context memory). In this study, we explored this in 30 healthy younger adults (21-34 years old). We developed the Montreal Attention at Encoding (MAET) task where on each encoding trial, participants responded as quickly as possible to a central fixation cross that expanded in size after a random duration. They then had to encode a picture of an object and its spatial location. Memory for the object-location associations was tested during retrieval. Response time (RT) to the fixation cross presented prior to each object gauged pre-stimulus attention levels on a trial-by-trial basis, while RT to the fixation cross that ensued each object indexed post-stimulus attention levels. Within-subject logistic regressions were used to predict context and item memory performance from pre- and post-stimulus RTs. Results revealed that encoding pre-stimulus attentional levels did not differentially predict context vs. item memory. However, post-stimulus RTs did predict subsequent context retrieval such that, longer post-stimulus RT to the fixation was related to poorer subsequent context retrieval. This study introduces a novel paradigm for investigating the impact of attentional state at encoding on subsequent memory performance and indicate a link between post-stimulus delays in attention-related RT and associative encoding success.
Probe the effect of clustering on EphA2 receptor signaling efficiency by subcellular control of ligand-receptor mobility
Authors: Chen Zhongwen , Oh Dongmyung , Biswas Kabir H. , Zaidel-Bar Ronen , Groves Jay T.
Published: February 2021

Clustering of ligand:receptor complexes on the cell membrane is widely presumed to have functional consequences for subsequent signal transduction. However, it is experimentally challenging to selectively manipulate receptor clustering without altering other biochemical aspects of the cellular system. Here, we develop a microfabrication strategy to produce substrates displaying mobile and immobile ligands that are separated by roughly one micron and thus experience an identical cytoplasmic signaling state, enabling precision comparison of downstream signaling reactions. Applying this approach to characterize the ephrinA1:EphA2 signaling system reveals that EphA2 clustering enhances receptor phosphorylation. Single molecule imaging clearly resolves increased molecular binding dwell time at EphA2 clusters for both Grb2:SOS and NCK:NWASP signaling modules. This type of intracellular comparison enables a substantially higher degree of quantitative analysis than is possible when comparisons must be made between different cells and essentially eliminates the effects of cellular response to ligand manipulation.
The winding roads to adulthood: a twin study
Authors: Rimfeld Kaili , Malancini Margherita , Packer Amy E. , Gidziela Agnieszka , Allegrini Andrea G. , Ayorech Ziada , Smith-Woolley Emily , McMillan Andrew , Ogden Rachel , Dale Philip S. , Eley Thalia C. , Plomin Robert
Published: February 2021

In the 21stcentury, emerging adulthood has stretched from the late teens through the twenties. Although this extended transition to adulthood can create stress, it can also offer opportunities to explore vocations and relationships that provide a better fit to individuals’ proclivities, including their genetic propensities.

Here we report the results of the first systematic investigation of genetic and environmental influences on 57 psychological traits covering major issues in emerging adulthood such as aspirations, thoughts and attitudes, relationships and personality. We also investigate how these traits relate to physical and mental health, educational attainment and wellbeing using a sample of nearly 5000 pairs of UK twins aged 21-25 from the Twins Early Development Study.

All 57 traits showed significant genetic influence, with an average heritability of 34% (SNP heritability ∼10%). Most of the variance (59% on average) was explained by non-shared environmental influences. These diverse traits were associated with mental health (average correlation .20), wellbeing (.16), physical health (.12) and educational attainment (.06). Shared genetic factors explained the majority of these correlations (∼50%). Together, these emerging adulthood traits explained on average 30% of the variance in the outcomes (range = 8 to 69%), suggesting that these traits relate to the outcomes additively.

We conclude that the environmental uncertainties of emerging adulthood in the 21stcentury do not diminish the importance of genetics. As adolescents travel down long and winding roads to adulthood, their trip is substantially influenced by genetic proclivities that nudge them down different paths leading to different destinations.
Characterization of heliorhodopsins detected via functional metagenomics in freshwater Actinobacteria, Chloroflexi and Archaea
Authors: Chazan Ariel , Rozenberg Andrey , Mannen Kentaro , Nagata Takashi , Tahan Ran , Yaish Shir , Larom Shirley , Inoue Keiichi , Béjà Oded , Pushkarev Alina
Published: February 2021

Rhodopsins are widespread in microbes residing in diverse aquatic environments across the globe. Recently, a new unusual rhodopsin family, the heliorhodopsins (HeRs), was discovered, distributed among diverse bacteria, archaea, eukarya and even viruses. Here, using functional metagenomics on samples from Lake Ha’Hula and Ein Afek reserve, we found and characterized ten HeRs representing divergent members of the family. The expressed HeRs absorb light in the green and yellow wavelengths and originate from Actinobacteria, Chloroflexi and Archaea. The photocycle of the HeR from Chloroflexi revealed a low accumulation of the M-intermediate that we connect to the lack of two conserved histidine residues in transmembrane helices 1 and 2 in this protein. Another of HeR, from Actinobacteria, exhibited an unusually fast photocycle (166 ms, 5 times faster than HeR-48C12). To further explore the still unresolved question of the HeR function, we performed an analysis of protein families among genes neighboring HeRs, in our clones and thousands of other microbes. This analysis revealed a putative connection between HeRs and genes involved in oxidative stress. At the same time, very few protein families were found to distinguish genes surrounding prokaryotic HeRs from those surrounding rhodopsin pumps. The strongest association was found with the DegV family involved in activation of fatty acids and uncharacterized family DUF2177, which allowed us to hypothesize that HeRs are involved in membrane lipid remodeling. This work further establishes functional metagenomics as a simple and fruitful method of screening for new rhodopsins.

Significance

The recently discovered divergent rhodopsin family of heliorhodopsins is abundant in freshwater environments. In this study, we sampled a habitat rich in dissolved organic matter to increase our chances of finding spectrally shifted rhodopsins. Using functional metagenomics, diverse heliorhodopsins absorbing green and yellow light were discovered. The metagenomic clones originated from diverse prokaryotic groups: Actinobacteria, Chloroflexi and even Archaea, emphasizing the versatility of theE. coliexpression system used. Photocycles of representative heliorhodopsins were measured and exhibited diverse kinetic characteristics. Analysis of genes neighboring heliorhodopsins in diverse prokaryotes revealed their putative connection to membrane lipid re-modeling and oxidative stress. Our findings suggest that functional metagenomics is a productive method for the discovery of new and diverse rhodopsins.
Distinct metabolic flux modes through the tricarboxylic acid cycle in mesophyll and guard cells revealed by GC-MS-based13C-positional isotopomer analysis
Authors: G. Daubermann André , F. Lima Valéria , Schwarzländer Markus , Erban Alexander , Kopka Joachim , Fernie Alisdair R. , Anjos Leticia dos , Daloso Danilo M.
Published: February 2021

13C-Metabolic flux analysis (13C-MFA) have greatly contributed to revealing the regulation of plant metabolism. However, mass spectrometry (MS) approaches have hitherto been limited in their power to deduce flux information due to lack of positional information.

Here we established an MS-based13C-positional isotopomer labelling approach and performed a multi-species/cell-types analysis based on previous13C-MFA to compare flux modes through the tricarboxylic acid (TCA) cycle and associated pathways in mesophyll (MCs) and guard cells (GCs).

Both cell types showed high13C-enrichment in pyruvate. However, GCs and sink MCs, but not source MCs showed high13C-incorporation into Glu/Gln following provision of13C-sucrose. Only GCs showed higher13C-enrichment in the carbon 1 atom of Gln, which is derived from PEPc-mediated CO2fixation. Increased13C-enrichment in the carbon 1 of Glu was also observed in bothtrxo1andntra ntrbmutants, but not in wild type Arabidopsis plants, following provision of13C-glucose.

Our results suggest that the mitochondrial thioredoxin system restricts the fluxes from PEPc and glycolysis to Glu in illuminated MCs and reveal that fluxes throughout the TCA cycle of GCs resemble those of sink MCs but operate different non-cyclic flux modes to support Gln synthesis in the light.
A mixture of generative models strategy helps humans generalize across tasks
Authors: Herce Castañón Santiago , Cardoso-Leite Pedro , Altarelli Irene , Green C. Shawn , Schrater Paul , Bavelier Daphne
Published: February 2021

What role do generative models play in generalization of learning in humans? Our novel multi-task prediction paradigm—where participants complete four sequence learning tasks, each being a different instance of a common generative family—allows the separate study ofwithin-task learning(i.e., finding the solution to each of the tasks), andacross-task learning(i.e., learning a task differently because of past experiences). The very first responses participants make in each task are not yet affected by within-task learning and thus reflect their priors. Our results show that these priors change across successive tasks, increasingly resembling the underlying generative family. We conceptualize multi-task learning as arising from a mixture-of-generative-models learning strategy, whereby participants simultaneously entertain multiple candidate models which compete against each other to explain the experienced sequences. This framework predicts specific error patterns, as well as a gating mechanism for learning, both of which are observed in the data.
Drought is a stronger driver of plant morphology and nutritional composition than warming in two common pasture species
Authors: Catunda Karen L. M. , Churchill Amber C. , Zhang Haiyang , Power Sally A. , Moore Ben D.
Published: February 2021

Under warmer and drier future conditions, global livestock and dairy production are threatened by impacts on the productivity and nutritional quality of pastures. However, morphological and nutritional adjustments within plants in response to warming and drought vary among species and less is known how these relate to production and forage quality. To investigate this, we grew two common pasture species, tall fescue (Festuca arundinacea: grass) and lucerne (Medicago sativa: legume), in a climate-controlled facility, under different temperatures (ambient and elevated) and watering regimes (well-watered and droughted). We found that drought had a strong negative impact on biomass production, morphology and nutritional quality while warming only significantly affected both species when response metrics were considered in concert, although to a lesser degree than the drought. Furthermore, interactions between warming and drought were only seen for lucerne, with the greatest reduction in biomass and most dead material and dry matter content. In tall fescue, drought had bigger impacts on nutritional composition than morphological traits, while in lucerne, drought affected all morphological traits and most nutritional parameters. These findings suggest that in future climate scenarios, drought may be a stronger driver of changes in the morphology and nutritional composition of pasture grasses and legumes, compared to modest levels of warming.
Pilot study: Trehalose-induced remodelling of the human microbiota affects Clostridioides difficile infection outcome in an in vitro colonic model
Authors: Buckley Anthony M. , Moura Ines B. , Arai Norie , Spittal William , Clark Emma , Nishida Yoshihiro , Harris Hannah C. , Bentley Karen , Davis Georgina , Wang Dapeng , Mitra Suparna , Higashiyama Takanobu , Wilcox Mark H.
Published: February 2021

Within the human intestinal tract, dietary, microbial- and host-derived compounds are used as signals by many pathogenic organisms, including Clostridioides difficile. Trehalose has been reported to enhance virulence of certain C. difficile ribotypes; however, such variants are widespread and not correlated with clinical outcomes for patients suffering from C. difficile infection (CDI). Here, we make preliminary observations to how to trehalose supplementation affects the microbiota in an in vitro model and show that trehalose can reduce the outgrowth of C. difficile, preventing simulated CDI. Three clinically reflective human gut models simulated the effects of sugar (trehalose or glucose) or saline ingestion on the microbiota. Models were instilled with sugar or saline and further exposed to C. difficile spores. The recovery of the microbiota following antibiotic treatment and CDI induction was monitored in each model. The human microbiota remodeled to utilise the bioavailable trehalose. Clindamycin induction caused simulated CDI in models supplemented with either glucose or saline; however, trehalose supplementation did not result in CDI, although limited spore germination did occur. The absence of CDI in trehalose model was associated with enhanced abundances of Finegoldia, Faecalibacterium and Oscillospira, and reduced abundances of Klebsiella and Clostridium spp., compared with the other models. Functional analysis of the microbiota in the trehalose model revealed differences in the metabolic pathways, such as amino acid metabolism, which could be attributed to prevention of CDI. Our data show that trehalose supplementation remodelled the microbiota, which prevented simulated CDI, potentially due to enhanced recovery of nutritionally competitive microbiota against C. difficile.
Vancomycin resistance inEnterococcus faeciumfrom the Dallas, Texas area is conferred predominantly on pRUM-like plasmids
Authors: Islam Moutusee , Sharon Belle , Abaragu Ada , Sistu Harita , Akins Ronda L. , Palmer Kelli
Published: February 2021

Vancomycin-resistantE. faecium(VREfm) is a significant public health concern because of limited treatment options. Genomic surveillance can be used to monitor VREfm transmission and evolution. Genomic analysis of VREfm has not been reported for the Dallas/Fort Worth/Arlington, Texas, area, which is currently the 4th largest metropolitan area in the United States. Our study aimed to address this gap in knowledge by analyzing the genomes of 46 VREfm and one vancomycin-sensitive comparator collected during routine fecal surveillance of high-risk patients upon admission to a Dallas, Texas hospital system (August to October, 2015). 31 complete and 16 draft genome sequences were generated. The closed VREfm genomes possessed up to 12 extrachromosomal elements each. Overall, 251 closed putative plasmid sequences assigned to previously described and newly definedrepfamily types were obtained. Phylogenetic analysis identified 10 different sequence types (STs) among the isolates, with the most prevalent being ST17 and ST18. Strikingly, all but three of the VREfm isolates encodedvanA-type vancomycin resistance within Tn1546-like elements on a pRUM-like (rep17) plasmid backbone. Relative to a previously reported typing scheme for thevanA-encoding Tn1546, new variants of the Tn1546were identified that harbored a combination of 7 insertion sequences (IS), including 3 novel IS elements reported in this study (ISEfa16, ISEfa17andISEfa18). We conclude that pRUM-like plasmids are important vectors for vancomycin resistance in the Dallas, Texas area and should be a focus of plasmid surveillance efforts.

Importance

Vancomycin is an antibiotic used to treat infections caused by multidrug-resistant Gram-positive bacteria. Vancomycin resistance is common in clinical isolates of the Gram-positive pathogenEnterococcus faecium. InE. faecium, vancomycin resistance genes can be disseminated by plasmids with different host ranges and transfer efficiencies. Surveillance of resistance plasmids is critical to understanding antibiotic resistance transmission. This study analyzed the genome sequences of VREfm collected from the Dallas, Texas area, with particular focus on the mobile elements associated with vancomycin resistance genes. We find that a single plasmid family, the pRUM-like family, is associated with vancomycin resistance in the majority of isolates sampled. Our work suggests that the pRUM-like plasmids should continue to be studied to understand their mechanisms of maintenance, transmission, and evolution in VREfm.
Electronic structure of Schiff-base peroxo{2,2′-[1,2-phenylenebis(nitrilomethanylylidene)]bis(6-methoxyphenolato)}titanium(IV) monohydrate: a possible model structure of the reaction center for the theoretical study of hemoglobin
Authors: Kožíšková Júlia Adamko , Breza Martin , Valko Marián , Herich Peter , Bučinský Lukáš , Kožíšek Jozef
Published: February 2021

An extensive characterization of [Ti(C22H18N2O6)]·H2O was performed by topological analysis according to Bader's quantum theory of atoms in molecules (QTAIM) from the experimentally (multipole model) and theoretically (DFT) determined electron density. To the best of our knowledge, this study is the first example of an experimental electronic structure of a coordination compound in which a peroxo anion is bonded to a 3dcentral atom. The titanium coordination polyhedron could be described as a deformed tetrahedral pyramid if the midpoint of the peroxide O—O bond (side-onmode) is considered to be in the quasi-apical position. According to the multipole model (MM) results, the titanium atom has a positive QTAIM charge of 2.05 e−which does not correspond to the formal Ti (IV) oxidation state. On the other hand, the peroxo oxygen atoms O(1) and O(2) haveMMQTAIM charges of −0.27 and −0.12, respectively. This asymmetric charge density distribution on the peroxo oxygens is in agreement with the distorted orientation of the O2moiety with respect to the titanium atom. Despite the fact that the overallMMcharge of the O2moiety is more remote from the formal −2 charge than from neutral O2, the O—O distance remains close to that in the peroxo O22−anion. In the case of DFT results, the titanium atom charge is also found to be close to +2, the O2x−moiety charge is around −1, the optimized O—O distance is shorter by onlyca0.04 Å than the experimental value of 1.5005 (16) Å, and the DFTd-populations on titanium are found to be lower than the experimentalMMvalue. This study is the first experimental electronic structure of a transition metal peroxo complex.
On modelling disordered crystal structures through restraints from molecule-in-cluster computations, and distinguishing static and dynamic disorder
Authors: Dittrich Birger
Published: February 2021

Distinguishing disorder into static and dynamic based on multi-temperature X-ray or neutron diffraction experiments is the current state of the art, but is only descriptive, not predictive. Here, several disordered structures are revisited from the Cambridge Crystallographic Data Center `drug subset', the Cambridge Structural Database and own earlier work, where experimental intensities of Bragg diffraction data were available. Using the molecule-in-cluster approach, structures with distinguishable conformations were optimized separately, as extracted from available or generated disorder models of the respective disordered crystal structures. Re-combining these `archetype structures' by restraining positional and constraining displacement parameters for conventional least-squares refinement, based on the optimized geometries, then often achieves a superior fit to the experimental diffraction data compared with relying on experimental information alone. It also simplifies and standardizes disorder refinement. Ten example structures were analysed. It is observed that energy differences between separate disorder conformations are usually within a small energy window ofRT(T= crystallization temperature). Further computations classify disorder into static or dynamic, using single experiments performed at one single temperature, and this was achieved for propionamide.
The tetrameric structure of the novel haloalkane dehalogenase DpaA from Paraglaciecola agarilytica NO2
Authors: Mazur Andrii , Prudnikova Tatyana , Grinkevich Pavel , Mesters Jeroen R. , Mrazova Daria , Chaloupkova Radka , Damborsky Jiri , Kuty Michal , Kolenko Petr , Kuta Smatanova Ivana
Published: February 2021

Haloalkane dehalogenases (EC 3.8.1.5) are microbial enzymes that catalyse the hydrolytic conversion of halogenated compounds, resulting in a halide ion, a proton and an alcohol. These enzymes are used in industrial biocatalysis, bioremediation and biosensing of environmental pollutants or for molecular tagging in cell biology. The novel haloalkane dehalogenase DpaA described here was isolated from the psychrophilic and halophilic bacterium Paraglaciecola agarilytica NO2, which was found in marine sediment collected from the East Sea near Korea. Gel-filtration experiments and size-exclusion chromatography provided information about the dimeric composition of the enzyme in solution. The DpaA enzyme was crystallized using the sitting-drop vapour-diffusion method, yielding rod-like crystals that diffracted X-rays to 2.0 Å resolution. Diffraction data analysis revealed a case of merohedral twinning, and subsequent structure modelling and refinement resulted in a tetrameric model of DpaA, highlighting an uncommon multimeric nature for a protein belonging to haloalkane dehalogenase subfamily I.
Resilience of commercial banks of Bangladesh to the shocks caused by COVID-19 pandemic: an application of MCDM-based approaches
Authors: Ghosh Ratan , Saima Farjana Nur
Published: February 2021

Purpose

The purpose of this study is to analyze and forecast the financial sustainability and resilience of commercial banks of Bangladesh in response to the negative effects of COVID-19 pandemic.

Design/methodology/approach

Eighteen publicly listed commercial banks of Dhaka Stock Exchange (DSE) have been taken as a sample for this study. To measure the riskiness of banks' credit portfolio, nine industries of DSE have been considered to determine probable loss of revenue arising from the COVID-19 pandemic shock. Moreover, two commonly used multiple-criteria-decision-making (MCDM) tools namely TOPSIS method and HELLWIG method have been used for analyzing the data.

Findings

Based on the performance scores under TOPSIS and HELLWIG method, banks are categorized into three groups (six banks each) namely top resilient, moderate resilient and low resilient. It is found that EBL and DBBL are the most resilient banks, and ONEBANK is the worst resilient bank in Bangladesh in managing the COVID-19 pandemic shock.

Research limitations/implications

This study concludes that banks with low capital adequacy, low liquidity ratio, low performance and higher NPLs are more vulnerable to the shocks caused by the COVID-19 pandemic. The management of commercial banks should emphasize on maintaining higher capital base and reducing default loans.

Originality/value

Resilience of the Bangladeshi banking sector under any adverse economic event has been examined by only using stress testing approach. This study is empirical evidence where both TOPSIS and HELLWIG MCDM methods have been used to make the result conclusive.
Infinite horizon impulse control problem with jumps and continuous switching costs
Authors: Amami Rim , Pontier Monique , Abidi Hani
Published: February 2021

Purpose

The purpose of this paper is to show the existence results for adapted solutions of infinite horizon doubly reflected backward stochastic differential equations with jumps. These results are applied to get the existence of an optimal impulse control strategy for an infinite horizon impulse control problem.

Design/methodology/approach

The main methods used to achieve the objectives of this paper are the properties of the Snell envelope which reduce the problem of impulse control to the existence of a pair of right continuous left limited processes. Some numerical results are provided to show the main results.

Findings

In this paper, the authors found the existence of a couple of processes via the notion of doubly reflected backward stochastic differential equation to prove the existence of an optimal strategy which maximizes the expected profit of a firm in an infinite horizon problem with jumps.

Originality/value

In this paper, the authors found new tools in stochastic analysis. They extend to the infinite horizon case the results of doubly reflected backward stochastic differential equations with jumps. Then the authors prove the existence of processes using Envelope Snell to find an optimal strategy of our control problem.