bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clues to reaction specificity in PLP-dependent fold type I aminotransferases of monosaccharide biosynthesis
Authors: Srivastava Jaya , Balaji Petety V. 
Published: September 2021

AbstractNovel functions can emerge in an enzyme family while conserving catalytic mechanism, motif or fold. PLP-dependent enzymes have evolved into seven fold-types and catalyse diverse reactions using the same mechanism for the formation of external aldimine. Nucleotide sugar aminotransferases (which will be henceforth referred to as aminotransferases) belong to fold type I and mediate the biosynthesis of several monosaccharides. They use diverse substrates but are highly selective to the C3 or C4 carbon to which amine group is transferred. Profile HMMs were able to identify aminotransferases but could not capture reaction specificity. A search for discriminating features led to the discovery of sequence motifs that are located near the pyranose binding site suggesting their role in imparting reaction specificity. Using a position weight matrix for this motif, we were able to assign reaction specificity to a large number of aminotransferases. Inferences from this analysis set way for future experiments that can shed light on mechanisms of functional diversification in nucleotide sugar aminotransferases of fold type I.
Aphid transmission of a Potexvirus, Foxtail mosaic virus, in the presence of the Potyvirus helper component proteinase
Authors: Jiang Jun , Yu Eric , Casteel Clare L. 
Published: September 2021

AbstractTo establish successful infections, plant viruses compete with the host plants for limited resources and thus alter the physiological state of the plants. After successful infection, insect vectors are required for the transmission of some plant viruses to the next host plant. One of the largest groups of plant viruses, the potyvirus, can be transmitted by aphids. During transmission, the potyvirus protein helper component proteinase (HC-Pro) binds to the yet-to-be-defined aphid receptor on the stylet, as well as to the virus particles through the Asp-Ala-Gly (DAG) motif of the viral coat protein. Previously it was determined that a naturally occurring DAG motif in the non-aphid transmissible potexvirus, Potato aucuba mosaic potexvirus (PAMV), is functional when the HC-Pro is provided through co-infection with a potyvirus. Further, the DAG motif of PAMV can be successfully transferred to another non-aphid transmissible potexvirus, Potato virus X (PVX), to convey aphid transmission capabilities. We expand on this previous work by demonstrating, the DAG motif from two different potyviruses, Sugarcane mosaic virus and Turnip mosaic virus, as well as the DAG motif from the previous potexvirus PAMV, can be added to another non-aphid transmissible potexvirus, Foxtail mosaic virus (FoMV), to make it aphid transmissible. Transmission efficiency varied from less than 10% to over 80% depending on the DAG motif and host plant used in transmission, suggesting not all DAG motifs are equal for engineering aphid transmission. The underlying mechanisms mediating this variation still need to be explored.
Involvement of Brn3a-positive spinal dorsal horn neurons in the transmission of visceral pain in inflammatory bowel disease model mice
Authors: Nishida Kazuhiko , Matsumura Shinji , Kobayashi Takuya 
Published: September 2021

ABSTRACTThe spinal dorsal horn (SDH) plays a crucial role in the transmission and processing of somatosensory information. Although spinal neural circuits that process several distinct types of somatic sensations have been studied extensively, those responsible for visceral pain transmission remain poorly understood. In the present study, we analyzed dextran sodium sulfate (DSS)-induced inflammatory bowel disease (IBD) mouse models to characterize the spinal dorsal horn neurons involved in visceral pain transmission. Immunostaining for c-fos, a marker of neuronal activity, demonstrated that numerous c-fos-positive cells were found bilaterally in the lumbosacral spinal dorsal horn, and their distribution was particularly abundant in the shallow dorsal horn. Characterization of these neurons by several molecular markers revealed that the percentage of the Pit1-Oct1-Unc86 domain (POU domain)-containing transcription factor Brn3a-positive neurons among the c-fos-positive neurons in the shallow dorsal horn was 30-40% in DSS-treated mice, which was significantly higher than that in the somatic pain model mice. We further demonstrated by neuronal tracing that, within the shallow dorsal horn, Brn3a-positive neurons were more highly represented in spino-solitary projection neurons than in spino-parabrachial projection neurons. These results raise the possibility that Brn3a-positive spinal dorsal horn neurons make a large contribution to visceral pain transmission, part of which is mediated through the spino-solitary pathway.
Reversible supramolecular assembly of the anti-microbial peptide plectasin into helical non-amyloid fibrils
Authors: Pohl Christin , Effantin Gregory , Kandiah Eaazhisai , Meier Sebastian , Zeng Guanghong , Streicher Werner , Peters Günther H.J. , Schoehn Guy , Mueller-Dieckmann Christoph , Noergaard Allan , Harris Pernille 
Published: September 2021

ABSTRACTSelf-assembly and fibril formation play important roles in protein behavior. Amyloid fibrils formation is well-studied due to its role in neurodegenerative diseases and characterized by refolding of the protein into predominant β-sheet form. However, much less is known about the assembly of proteins into other types of supramolecular structures. Using cryo-electron microscopy at a resolution of 1.97 Å, we show that a triple-mutant of the anti-microbial peptide plectasin assembles reversibly into helical non-amyloid fibrils. Plectasin contains a cysteine-stabilized α-helix-β-sheets structure, which remains intact upon fibril formation. Two fibrils form a right-handed superstructure with each fibril consisting of double helical, left-handed structures. The fibril formation is reversible and follows sigmoidal kinetics with a pH-dependent equilibrium between soluble monomer and protein fibril. The anti-microbial activity does not appear compromised by fibril formation. This is the first high-resolution structure of this type of α/β protein fibrils.
Ecology dictates the value of memory for foraging bees
Authors: Pull Christopher D. , Petkova Irina , Watrobska Cecylia , Pasquier Grégoire , Fernandez Marta Perez , Leadbeater Ellouise 
Published: September 2021

Abstract“Ecological intelligence” hypotheses posit that animal learning and memory evolves to meet the demands posed by foraging, and together with social intelligence and cognitive buffer hypotheses, provide a key framework for understanding cognitive evolution. However, identifying the critical environments where cognitive investment reaps significant benefits has proved challenging. Here, we capitalise upon seasonal variation in forage availability for a social insect model (Bombus terrestris) to establish how the benefits of short-term memory vary with resource availability. Through analysis of over 1700 foraging trips carried out over two years, we show that short-term memory predicts foraging efficiency – a key determinant of colony fitness – in plentiful spring foraging conditions, but that this relationship is reversed during the summer floral dearth. Our results suggest that selection for enhanced cognitive abilities is unlikely to be limited to harsh environments where food is hard to find or extract, highlighting instead that the complexity of rich and plentiful environments could be a broad driver in the evolution of certain cognitive traits.
Actions of camptothecin derivatives on larvae and adults of the arboviral vectorAedes aegypti
Authors: Partridge Frederick A. , Poulton Beth C. , Lake Milly A.I. , Lees Rebecca A. , Mann Harry-Jack , Lycett Gareth J. , Sattelle David B 
Published: September 2021

AbstractMosquito-borne viruses including dengue, Zika and Chikungunya viruses as well as parasites such as malaria andOnchocerca volvulusendanger health and economic security around the globe and emerging mosquito-borne pathogens have pandemic potential. However, the rapid spread of insecticide resistance threatens our ability to control mosquito vectors. Larvae ofAedes aegypti(New Orleans strain) were screened with the Medicines for Malaria Venture Pandemic Response Box, an open-source compound library, using INVAPP, an invertebrate automated phenotyping platform suited to high-throughput chemical screening of larval motility.Of the 400 compounds screened, we identified rubitecan (a synthetic derivative of camptothecin) as a hit compound that significantly reducedAe. aegyptilarval motility compared to DMSO controls. Both rubitecan and camptothecin displayed concentration dependent reduction in larval motility with estimated EC50s of 25.5 ± 5.0 μM and 22.3 ± 5.4 μM respectively. We extended our investigation to adult mosquitoes and found that camptothecin increased lethality when delivered in a blood meal toAe. aegyptiadults at 100 μM and 10 μM and completely blocked egg laying when fed at 100 μM.Camptothecin and its derivatives, inhibitors of topoisomerase I, have known activity against several agricultural pests and are also approved for the treatment of several cancers. Crucially, they can inhibit Zika virus replication in human cells, so there is potential for dual targeting of both the vector and an important arbovirus that it carries. Both humans and mosquitoes express the highly conserved topoisomerase I target, however, the design of derivatives with differing pharmacokinetic properties may offer a promising route towards the development of insect-specificity of this chemistry.
Biochemical characterization of a human septin octamer
Authors: Fischer Martin , Frank Dominik , Rösler Reinhild , Johnsson Nils , Gronemeyer Thomas 
Published: September 2021

1AbstractSeptins are part of the cytoskeleton and polymerize into non-polar filaments of heteromeric hexamers or octamers. They belong to the class of P-loop GTPases but the roles of GTP binding and hydrolysis on filament formation and dynamics are not well understood.The basic human septin building block is the septin rod, a hetero-octamer composed of SEPT2, SEPT6, SEPT7, and SEPT9 with a stoichiometry of 2:2:2:2 (2-7-6-9-9-6-7-2).Septin rods polymerize by end-to-end and lateral joining into linear filaments and higher ordered structures such as rings, sheets, and gauzes.We purified a recombinant human septin octamer from E. coli for in vitro experimentation that is able to polymerize into filaments. We could show that the C-terminal region of the central SEPT9 subunit contributes to filament formation and that the human septin rod decreases the rate of in vitro actin polymerization.We provide further first kinetic data on the nucleotide uptake- and exchange properties of human hexameric and octameric septin rods. We could show that nucleotide uptake prior to hydrolysis is a dynamic process and that a bound nucleotide is exchangeable. However, the hydrolyzed γ-phosphate is not released from the native protein complex. We consequently propose that GTP hydrolysis in human septins does not follow the typical mechanism known from other small GTPases.
Short-term instantaneous prophylaxis and efficient treatment against SARS-CoV-2 in hACE2 mice conferred by an intranasal nanobody (Nb22)
Authors: Wu Xilin , Wang Yaxing , Cheng Lin , Ni Fengfeng , Zhu Linjing , Ma Sen , Huang Bilian , Ji Mengmeng , Hu Huimin , Li Yuncheng , Xu Shijie , Shi Haixia , Zhang Doudou , Liu Linshuo , Nawaz Waqas , Hu Qinxue , Ye Sheng , Liu Yalan , Wu Zhiwei 
Published: September 2021

AbstractCurrent COVID-19 vaccines need to take at least one month to complete inoculation and then become effective. Around 51% global population are still not fully vaccinated. Instantaneous protection is an unmet need among those who are not fully vaccinated. In addition, breakthrough infections caused by SARS-CoV-2 are widely reported. All these highlight the unmet needing for short-term instantaneous prophylaxis (STIP) in the communities where SARS-CoV-2 is circulating. Previously, we reported nanobodies isolated from an alpaca immunized with the spike protein, exhibiting ultrahigh potency against SARS-CoV-2 and its variants. Herein, we found that Nb22, among our previously reported nanobodies, exhibited ultrapotent neutralization against Delta variant with an IC50 value of 0.41 ng/ml (5.13 pM). Furthermore, the crystal structural analysis revealed that the binding of Nb22 to WH01 and Delta RBDs both effectively blocked the binding of RBD to hACE2. Additionally, intranasal Nb22 exhibited protection against SARS-CoV-2 Delta variant in the post-exposure prophylaxis (PEP) and pre-exposure prophylaxis (PrEP). Of note, intranasal Nb22 also demonstrated high efficacy against SARS-CoV-2 Delta variant in STIP for seven days administered by single dose and exhibited long-lasting retention in the respiratory system for at least one month administered by four doses, providing a means of instantaneous short-term prophylaxis against SARS-CoV-2. Thus, ultrahigh potency, long-lasting retention in the respiratory system as well as stability at room-temperature make the intranasal or inhaled Nb22 to be a potential therapeutic or STIP agent against SARS-CoV-2.Brief summaryNb22 exhibits ultrahigh potency against Delta variant in vitro and is exploited by crystal structural analysis; furthermore, animal study demonstrates high effectiveness in the treatment and short-term instantaneous prophylaxis in hACE2 mice via intranasal administration.HighlightsNb22 exhibits ultrapotent neutralization against Delta variant with an IC50 value of 0.41 ng/ml (5.13 pM).Structural analysis elucidates the ultrapotent neutralization of Nb22 against Delta variant.Nb22 demonstrates complete protection in the treatment of Delta variant infection in hACE2 transgenic mice.We complete the proof of concept of STIP against SARS-CoV-2 using intranasal Nb22 with ultrahigh potency and long-lasting retention in respiratory system.Graphic Abstract
Prider – multiplexed primer design using linearly scaling approximation of set coverage
Authors: Smolander Niina , Tamminen Manu 
Published: September 2021

AbstractDesigning oligonucleotide primers and probes is one of the key steps of various laboratory experiments such as multiplexed PCR or digital multiplexed ligation assays. When designing primers and probes to complex, heterogeneous DNA data sets, an optimization problem arises where the smallest number of oligonucleotides covering the largest diversity of the input dataset needs to be identified. Tools that provide this optimization in an efficient manner for large input data are currently lacking.Here we present Prider, an R package for designing primers and probes with a nearly optimal coverage for complex and large sequence sets. Prider initially prepares a full primer coverage of the input sequences, the complexity of which is subsequently reduced by removing components of high redundancy or narrow coverage. The primers from the resulting near-optimal coverage are easily accessible as data frames and their coverage across the input sequences can be visualized as heatmaps using Prider’s plotting function. Prider scales linearly to increasing sequence data and therefore permits efficient design of primers to large and highly diverse DNA datasets.Prider is available on GitHub under the permissive BSD-3-clause license:https://github.com/manutamminen/prider
Kinetic tracking of Plasmodium falciparum antigen presentation reveals determinants of protein export and membrane insertion
Authors: Shao Jinfeng , Arora Gunjan , Manzella-Lapeira Javier , Brzostowski Joseph A. , Desai Sanjay A. 
Published: September 2021

AbstractIntracellular malaria parasites export many proteins into their host cell, inserting several into the erythrocyte plasma membrane to enable interactions with their external environment. While static techniques have identified some surface-exposed proteins, other candidates have eluded definitive localization and membrane topology determination. Moreover, both export kinetics and the mechanisms of membrane insertion remain largely unexplored. We introduce Reporter of Insertion and Surface Exposure (RISE), a method for continuous nondestructive tracking of antigen exposure on infected cells. RISE utilizes a small 11 aa NanoLuc fragment inserted into a target protein and detects surface exposure through high-affinity complementation. We tracked insertion of CLAG3, a malaria parasite protein linked to nutrient uptake, throughout the P. falciparum cycle in human erythrocytes. Our approach also revealed key determinants of trafficking and surface exposure. Removal of a C-terminal transmembrane domain aborted export. Unexpectedly, certain increases in the exposed reporter size improved surface exposure by up to 50-fold, revealing that both size and charge of the extracellular epitope influence membrane insertion. Insertion of parasite proteins at the host cell surface and antigen accessibility is regulated by multiple factors, enabling intracellular parasite survival and immune evasion under a broad range of conditions.
Wnt signaling rescues amyloid beta induced stem cell loss
Authors: Kaur Prameet , Chua Ellora Hui Zhen , Lim Wen Kin , Harmston Nathan , Tolwinski Nicholas S. 
Published: September 2021

AbstractPreviously, we established an optogenetic model to induce Amyloid-β intracellular oligomerization to model distinct disease etiologies (Limet al. 2020). Here we examine the effect of Wnt signaling on Amyloid in this model. We observe that Wnt activation rescues the detrimental effects of Amyloid expression and oligomerization. We analyze the gene expression changes downstream of Wnt that contribute to this rescue and find changes in aging related genes, protein misfolding, metabolism and inflammation. We propose that Wnt expression reduces inflammation through repression of Toll activating factors and confirm that chronic Toll activation reduces lifespan. We propose that the protective effect observed for Lithium treatment functions at least in part through Wnt activation and inhibition of inflammation.
Chaos in small microbial communities
Authors: Karkaria Behzad D. , Manhart Angelika , Fedorec Alex J. H. , Barnes Chris P. 
Published: September 2021

AbstractPredictability is a fundamental requirement in biological engineering. As we move to building coordinated multicellular systems, the potential for such systems to display chaotic behaviour becomes a concern. Therefore understanding which systems show chaos is an important design consideration. We developed a methodology to explore the potential for chaotic dynamics in small microbial communities governed by resource competition, intercellular communication and competitive bacteriocin interactions. We show that we can expect to find chaotic states in relatively small synthetic microbial systems, understand the governing dynamics and provide insights into how to control such systems. This work is the first to query the existence of chaotic behaviour in synthetic microbial communities and has important ramifications for the fields of biotechnology, bioprocessing and synthetic biology.
The second lineage differentiation of bovine embryos fails in the absence of OCT4/POU5F1
Authors: Simmet Kilian , Kurome Mayuko , Zakhartchenko Valeri , Reichenbach Horst-Dieter , Springer Claudia , Bähr Andrea , Blum Helmut , Philippou-Massier Julia , Wolf Eckhard 
Published: September 2021

ABSTRACTThe mammalian blastocyst undergoes two lineage segregations, i.e., formation of the trophectoderm and subsequently differentiation of the hypoblast (HB) from the inner cell mass, leaving the epiblast (EPI) the remaining pluripotent lineage. To clarify expression patterns of markers specific for these lineages in bovine embryos, we analyzed day 7, 9 and 12 blastocysts completely derived ex vivo by staining for OCT4, NANOG, SOX2 (EPI) and GATA6, SOX17 (HB) and identified genes specific for these developmental stages in a global transcriptomics approach. To study the role of OCT4, we generated OCT4-deficient (OCT4 KO) embryos via somatic cell nuclear transfer or in vitro fertilization. OCT4 KO embryos reached the expanded blastocyst stage by day 8 but lost of NANOG and SOX17 expression, while SOX2 and GATA6 were unaffected. Blastocysts transferred to recipient cows from day 6 to 9 expanded, but the OCT4 KO phenotype was not rescued by the uterine environment. Exposure of OCT4 KO embryos to exogenous FGF4 or chimeric complementation with OCT4 intact embryos did not restore NANOG or SOX17 in OCT4-deficient cells. Our data show, that OCT4 is required cell-autonomously for the maintenance of pluripotency of the EPI and differentiation of the HB in bovine embryos.
Fibroadipogenic Progenitors contribute to microvascular repair during skeletal muscle regeneration
Authors: Ollitrault David , Buffa Valentina , Correra Rosamaria , Sayed Angeliqua , Hoareau Bénédicte , Pöhle-Kronawitter Sophie , Stricker Sigmar , Hulot Jean-Sebastien , Valente Mariana , Marazzi Giovanna , Sassoon David 
Published: September 2021

AbstractSkeletal muscle injury results in a disruption of the muscle bed vascular network. A local source of vascular progenitors during muscle regeneration has not been clearly identified. Fibroadipogenic progenitors (FAPs) are required for proper regeneration, however they can also directly contribute to fibrotic and fatty infiltration in response to chronic muscle injury and muscle disease. We show here that acute muscle injury leads to hypoxia and glucose deprivation, triggering FAP proliferation and differentiation into endothelial cells in vitro and in vivo. In response to glucose deprivation, FAPs down regulate fibrotic and fat associated genes and acquire an endothelial cell fate, which is dependent upon mTORC2-HIF2α-eNOS pathway. These findings bring new insights into the mechanisms of vascular regeneration during muscle regeneration and define a highly plastic resident progenitor population that responds to oxygen/glucose-deprivation induced cell stress by promoting an endothelial cell fate.
GMQN: A reference-based method for correcting batch effects as well as probes bias in HumanMethylation BeadChip
Authors: Xiong Zhuang , Li Mengwei , Ma Yingke , Li Rujiao , Bao Yiming 
Published: September 2021

AbstractIllumina HumanMethylation BeadChip is one of the most cost-effective ways to quantify DNA methylation levels at the single-base level across the human genome, which makes it a routine platform for epigenome-wide association studies. It has accumulated tens of thousands of DNA methylation array samples in public databases, thus provide great support for data integration and further analysis. However, majority of public DNA methylation data are deposited as processed data without background probes which are widely used in data normalization. Here we present Gaussian mixture quantile normalization (GMQN), a reference based method for correcting batch effects as well as probes bias in HumanMethylation BeadChip. Availability and implementation: https://github.com/MengweiLi-project/gmqn.