bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative genomics of five Valsa species gives insights on their pathogenicity evolution
Authors: Sun Guangchao , Xie Shichang , Tang Lin , Zhao Chao , Zhang Mian , Huang Lili 
Published: May 2022

ABSTRACTValsa is a genus of ascomycetes fungi within the family Valsaceae that includes many wood destructive pathogens. The species such as Valsa mali and Valsa pyri that colonize fruit trees are threatening the global fruit production. Rapid host adaptation and fungicide resistance emergence are the main characteristics that make them devastating and hard to control. Efficient disease management can be achieved from early infection diagnosis and fungicide application, but lack of understandings of their genetic diversity and genomic features that underpin their pathogenicity evolution and drug resistance is essentially impeding the progress of effective and sustainable disease control. Here, we report genome assemblies of Valsa malicola, Valsa persoonii and Valsa sordida which represents close relatives of the two well known Valsa mali and Valsa pyri that cause canker disease with different host preferences. Comparative genomics analysis revealed that segmental rearrangements, inversions and translocations frequently occurred among Valsa spp. genomes. Genes identified in highly active regions exhibited high sequence differentiation and are enriched in membrane transporter proteins involved in anti-drug and nutrient transportation activities. Consistently, we also found membrane transporter gene families have been undergoing significant expansions in Valsa clade. Furthermore, unique genes that possessed or retained by each of the five Valsa species are more likely part of the secondary metabolic (SM) gene clusters which suggests SM one of the critical components that diverge along with the evolution of <I>Valsa</I> species. Repeat sequence content contributes significantly to genome size variation across the five species. The wide spread AT-rich regions resulted from repeat induced point C to T mutation (RIP) exhibited a specific proximity to secondary metabolic gene clusters and this positional proximity is correlated with the diversification of SM clusters suggesting a potential companion evolution between repeat sequence and secondary metabolism cluster. Lastly, we show that LaeA, the global regulator of secondary metabolic gene cluster, exhibiting diverged manner of regulation on the expression of clusters in vegetative and invasive mycelia of the devastating V. mali indicating the complexity of secondary metabolism in fungal species.
Jak2V617F Reversible Activation Shows an Essential Requirement for Jak2V617F in Myeloproliferative Neoplasms
Authors: Dunbar Andrew , Bowman Robert L. , Park Young , Izzo Franco , Myers Robert M. , Karzai Abdul , Kim Won Jun , Maestre Inés Fernández , Waarts Michael R. , Nazir Abbas , Xiao Wenbin , Brodsky Max , Farina Mirko , Cai Louise , Cai Sheng F. , Wang Benjamin , An Wenbin , Yang Julie L , Mowla Shoron , Eisman Shira E. , Mishra Tanmay , Houston Remie , Guzzardi Emily , Martinez Benitez Anthony R. , Viny Aaron , Koche Richard , Landau Dan A. , Levine Ross L. 
Published: May 2022

ABSTRACTJanus kinases (JAKs) mediate cytokine signaling, cell growth and hematopoietic differentiation.1 Gain-of-function mutations activating JAK2 signaling are seen in the majority of myeloproliferative neoplasm (MPN) patients, most commonly due to the JAK2V617F driver allele.2 While clinically-approved JAK inhibitors improve symptoms and outcomes in MPNs, remissions are rare, and mutant allele burden does not substantively change with chronic JAK inhibitor therapy in most patients.3, 4 This has been postulated to be due to incomplete dependence on constitutive JAK/STAT signaling, alternative signaling pathways, and/or the presence of cooperating disease alleles;5 however we hypothesize this is due to the inability of current JAK inhibitors to potently and specifically abrogate mutant JAK2 signaling. We therefore developed a conditionally inducible mouse model allowing for sequential activation, and then inactivation, of Jak2V617F from its endogenous locus using a Dre-rox/Cre-lox dual orthogonal recombinase system. Deletion of oncogenic Jak2V617Fabrogates the MPN disease phenotype, induces mutant-specific cell loss including in hematopoietic stem/progenitor cells, and extends overall survival to an extent not observed with pharmacologic JAK inhibition. Furthermore, reversal of Jak2V617F in MPN cells with antecedent loss of Tet26, 7 abrogates the MPN phenotype and inhibits mutant stem cell persistence suggesting cooperating epigenetic-modifying alleles do not alter dependence on mutant JAK/STAT signaling. Our results suggest that mutant-specific inhibition of JAK2V617F represents the best therapeutic approach for JAK2V617F-mutant MPN and demonstrate the therapeutic relevance of a dual-recombinase system to assess mutant-specific oncogenic dependencies in vivo.
The acute phase response in bats (Carollia perspicillata) varied with the time and dose of the immune-challenge
Authors: Viola Matheus F. , Herrera M. L. Gerardo , da Cruz-Neto Ariovaldo P. 
Published: May 2022

ABSTRACTThe acute phase response (APR) is a core component of the innate immune response and represents the first line of immune defense used in response to infections. Although several studies with vertebrates reported fever, decrease in food intake and body mass, as well as increase in neutrophil/lymphocyte ratio and total white blood cell count after lipopolysaccharide (LPS) inoculation there was great variability in the magnitude of these responses. Some of these differences might reflect, to some extent, differences in time of endotoxin inoculation (during activity or resting periods) and dose; however, no study in the literature has evaluated the synergistic effect of these two factors in vertebrates. Therefore, our study tested the interplay between LPS dose and time of injection on selected physiological (fever and increase in total white blood cell count and neutrophil/lymphocyte ratio), and behavioral (food intake) components of APR using a Neotropical fruit-eating bat (Carollia perspicillata) as a model organism. We predicted that LPS would trigger a dose- and time-dependent response on APR components. APR components were assessed in resting and activity periods after injection of three doses of LPS (5, 10 and 15 mg/kg LPS). The results showed that LPS-evoked changes in skin temperature, food intake, neutrophil lymphocyte ratio depend markedly on the LPS dose and/or time that LPS is administered.
C5aR1 antagonism alters microglial polarization and mitigates disease progression in a mouse model of Alzheimer’s disease
Authors: Gomez-Arboledas Angela , Carvalho Klebea , Balderrama-Gutierrez Gabriela , Chu Shu-Hui , Liang Heidi Yahan , Schartz Nicole D. , Selvan Purnika , Petrisko Tiffany J. , Pan Miranda A. , Mortazavi Ali , Tenner Andrea J. 
Published: May 2022

AbstractMultiple studies have recognized the involvement of the complement cascade during Alzheimer’s disease pathogenesis; however, the specific role of C5a-C5aR1 signaling in the progression of this neurodegenerative disease is still not clear. Furthermore, its potential as a therapeutic target to treat AD still remains to be elucidated. Canonically, generation of the anaphylatoxin C5a as the result of complement activation and interaction with its receptor C5aR1 triggers a potent inflammatory response. Previously, genetic ablation of C5aR1 in a mouse model of Alzheimer’s disease exerted a protective effect by preventing cognitive deficits. Here, using PMX205, a potent, specific C5aR1 antagonist, in the Tg2576 mouse model of Alzheimer’s disease we show a striking reduction in dystrophic neurites in parallel with the reduced amyloid load, rescue of the excessive pre-synaptic loss associated with AD cognitive impairment and the polarization of microglial gene expression towards a DAM-like phenotype that are consistent with the neuroprotective effects seen. These data support the beneficial effect of a pharmacological inhibition of C5aR1 as a promising therapeutic approach to treat Alzheimer’s disease. Supportive of the safety of this treatment is the recent FDA-approval of another other C5a receptor 1 antagonist, Avacopan, as a treatment for autoimmune inflammatory diseases.One Sentence SummaryC5aR1 antagonist shifts microglial gene expression toward neuroprotection.
Profiles of secoiridoids and alkaloids in tissue of susceptible and resistant green ash progeny reveal patterns of induced responses to emerald ash borer inFraxinus pennsylvanica
Authors: Stanley Robert K. , Carey David W. , Mason Mary E. , Poland Therese M. , Koch Jennifer L. , Jones A. Daniel , Romero-Severson Jeanne 
Published: May 2022

AbstractThe emerald ash borer (Agrilus planipennis, EAB) invasion in North America threatens most North AmericanFraxinusspecies, including green ash (F. pennsylvanica), the mostly widely distributed species (1, 2). A small number of green ash (“lingering ash”, 0.1-1%) survive years of heavy EAB attack (3) and kill more EAB larvae when challenged in greenhouse studies than susceptible controls (4). We combined untargeted metabolomics with intensive phenotyping of segregating F1progeny from susceptible or lingering ash parents to detect chemotypes associated with defensive responses to EAB. We examined three contrasting groups: low larval kill (0-25% of larvae killed), high larval kill (55-95% of larvae killed) and uninfested. Contrasting the chemotypes of these groups revealed evidence of an induced response to EAB. Infested trees deployed significantly higher levels of select secoiridoids than uninfested trees. Within the infested group, the low larval kill (LLK) individuals deployed significantly higher levels of select secoiridoids than the high larval kill (HLK) individuals. The HLK individuals deployed significantly higher concentrations of three metabolites annotated as aromatic alkaloids compared to the LLK and uninfested individuals. We propose a two-part model for the North AmericanFraxinusresponse to EAB wherein every individual has the capacity to detect and respond to EAB, but only certain trees mount an effective defense, killing enough EAB larvae to prevent or minimize lethal damage to the vascular system. Integration of intensive phenotyping of structured populations with metabolomics reveals the multi-faceted nature of the defenses deployed in naïve host populations against invasive species.SignificanceLong-lived forest trees employ evolutionarily conserved templates to synthesize an array of defensive metabolites. The regulation of these metabolites, honed against native pests and pathogens, may be ineffective against novel species, as illustrated by the high mortality (>99%) in green ash infested by the invasive emerald ash borer (EAB). However, high standing genetic variation may produce a few individuals capable of an effective defense, as seen in the rare surviving green ash. In an investigation of this plant-insect interaction, we annotated metabolites associated with generalized but ineffective responses to EAB, and others associated with successful defensive responses. Untargeted metabolomics combined with intensive phenotyping of structured populations provides a framework for understanding resistance to invasive species in naïve host populations.
Using NAMs to characterize chemical bioactivity at the transcriptomic, proteomic and phosphoproteomic levels
Authors: Li Yuan , Zhang Zhenpeng , Jiang Songhao , Xu Feng , Tulum Liz , Li Kaixuan , Liu Shu , Li Suzhen , Chang Lei , Liddell Mark , Tu Fengjuan , Gu Xuelan , Carmichael Paul Lawford , White Andrew , Peng Shuangqing , Zhang Qiang , Li Jin , Zuo Tao , Kukic Predrag , Xu Ping 
Published: May 2022

ABSTRACTOmic-based technologies are of particular interest and importance for non-animal chemical hazard and risk characterization based on the premise that any apical endpoint change must be underpinned by some alterations measured at the omic levels. In this work we studied cellular responses to caffeine and coumarin by generating and integrating multi-omic data from transcriptomic, proteomic and phosphoproteomic experiments. We have shown that the methodology presented here is able to capture the complete chain of events from the first compound-induced changes at the phosphoproteome level to changes in gene expression induced by transcription factors and lastly to changes in protein abundance that further influence changes at the cellular level. In HepG2 cells we found the metabolism of lipids and general cellular stress to be dominant biological processes in response to caffeine and coumarin exposure, respectively. The phosphoproteomic changes were detected early in time, at very low concentrations and provided a fast adaptive cellular response to chemical exposure. Changes in protein abundance were found much less frequently than the transcriptomic changes and can be used, together with the transcriptomic changes, to facilitate a more complete understanding of pathway responses to chemical exposure.GRAPHIC ABSTRACT
Maize immune signalling peptide ZIP1 evolved de novo from a retrotransposon
Authors: Depotter Jasper R.L. , Misas Villamil Johana C. , Doehlemann Gunther 
Published: May 2022

AbstractPlants are subjected to different types of threats that require appropriate physiological responses to counteract them. Signalling peptides are produced under specific conditions and elicit physiological changes.PROZIP1encodes such a signalling peptide, Zip1, that induces salicylic acid defence responses in maize (Zea mays) leading to a better protection against biotrophic pathogens. Despite salicylic acid pathway being conserved amongst plants, we observed that Zip1 only occurs in theZeagenus.PROZIP1’s evolution is associated with transposons, as it resides in the terminal repeat of a retrotransposon from the Gyma family. We traced back the mutations that were encountered by this transposon and found thatPROZIP1emergedde novoinZea. This emergence likely occurred less than 728,000 years ago. In conclusion, we describe the evolution of a recently emerged plant immune signalling peptide from a transposon sequence.
pastclim: an R package to easily access and use paleoclimatic reconstructions
Authors: Leonardi Michela , Hallett Emily Y. , Beyer Robert , Krapp Mario , Manica Andrea 
Published: May 2022

AbstractThe recent development of continuous paleoclimatic reconstructions covering hundreds of thousands of years paved the way to a large number of studies from disciplines ranging from paleoecology to linguistics, from archaeology to conservation and from population genetics to human evolution. Unfortunately, such climatic data can be challenging to extract and analyze for scholars unfamiliar with such specific climatic file formats.Here we presentpastclim, an R package facilitating the access and use of two sets of paleoclimatic reconstructions covering respectively the last 120,000 and 800,000 years. The package contains a set of functions allowing to quickly and easily recover the climate for the whole world or specific areas for time periods of interest, extract data from locations scattered in space and/or time, retrieve time series from individual sites, and easily manage the ice or land coverage.The package can easily be adapted to paleoclimatic reconstructions different from the ones already included, offering a handy platform to include the climate of the past into existing analyses and pipelines.
Serial depletion of Baltic herring since the Viking Age revealed by ancient DNA and population genomics
Authors: Atmore Lane M. , Martínez-García Lourdes , Makowiecki Daniel , André Carl , Lõugas Lembi , Barrett James H. , Star Bastiaan 
Published: May 2022

AbstractMarine resource consumption has been a key component in European diet and culture since the Middle Ages, when fish consumption increased dramatically. Yet, the early origins of marine industries and the long-term ecological consequences of historical and contemporary fisheries remain debated. The Baltic Sea was home to the first “industrial” fishery ∼800 years ago targeting the Baltic herring, a species that is still economically and culturally important today. We combine modern whole genome data with ancient DNA (aDNA) to identify the first known long-distance herring trade in the region, illustrating that large-scale fish trade began during the Viking Age. We resolve population structure within the Baltic and observe demographic independence for four local herring stocks over at least 200 generations. It has been suggested that overfishing at Øresund in the 16thcentury resulted in a demographic shift from autumn-spawning to spring-spawning herring dominance in the Baltic. We show that while the Øresund fishery had a negative impact on the western Baltic herring stock, the existence of autumn-spawning refugia in other regions of the Baltic delayed the demographic shift to spring spawning dominance until the 20thcentury. Importantly, modelling demographic trajectories over time, we identify a consistent pattern of serial depletion within the Baltic that is associated with changes in fishing pressure and climate, and conclude that herring exploitation at both historical and recent intensities is not sustainable. Our results highlight the complex and enduring impacts humans have had on the marine environment well before the industrial era.
DCAlign v1.0: Aligning biological sequences using co-evolution models and informative priors
Authors: Muntoni Anna Paola , Pagnani Andrea 
Published: May 2022

SummaryDCAlign is a new alignment method able to cope with the conservation and the co-evolution signals that characterize the columns of a multiple sequence alignment of homologous sequences. However, the pre-processing steps required to align a candidate sequence are computationally demanding. We show in v1.0 how to dramatically reduce the overall computing time by including an empirical prior over an informative set of variables mirroring the presence of insertions and deletions.Availability and implementationDCAlign v1.0 is implemented in Julia and it is fully available at https://github.com/infernet-h2020/DCAlignContactanna.muntoni@polito.it
PGC-1β maintains mitochondrial metabolism and restrains inflammatory gene expression
Authors: Guak Hannah , Sheldon Ryan D. , Beddows Ian , Ark Alexandra Vander , Shen Hui , Jones Russell G. , St-Pierre Julie , Ma Eric H. , Krawczyk Connie M. 
Published: May 2022

AbstractMetabolic programming of the innate immune cells known as dendritic cells (DCs) changes in response to different stimuli, influencing their function. While the mechanisms behind increased glycolytic metabolism in response to inflammatory stimuli are well-studied, less is known about the programming of mitochondrial metabolism in DCs. We used lipopolysaccharide (LPS) and interferon-β (IFN-β), which differentially stimulate the use of glycolysis and oxidative phosphorylation (OXPHOS), respectively, to identify factors important for mitochondrial metabolism. We found that the expression of peroxisome proliferator-activated receptor gamma coactivator 1β (PGC-1β), a transcriptional co-activator and known regulator of mitochondrial metabolism, decreases when DCs are activated with LPS, when OXPHOS is diminished, but not with IFN-β, when OXPHOS is maintained. We examined the role of PGC-1β in bioenergetic metabolism of DCs and found that PGC-1β deficiency in DCs indeed impairs mitochondrial respiration. PGC-1β-deficient DCs are more glycolytic compared to controls, likely to compensate for reduced OXPHOS. PGC-1β deficiency also causes decreased capacity for ATP production at steady state and in response to IFN-β treatment. Loss of PGC-1β in DCs leads to increased expression of genes in inflammatory pathways, and reduced expression of genes encoding proteins important for mitochondrial metabolism and function. Collectively, these results demonstrate that PGC-1β is a key positive regulator of mitochondrial metabolism in DCs.
Discovery and pre-clinical evaluation of antibodies to the NKG2A inhibitory receptor
Authors: Baek Du-San , Kim Ye-Jin , Li Wei , Macatangay Bernard JC , Cyktor Joshua C. , Hines Margaret G. , Mellors John W. , Dimitrov Dimiter S. 
Published: May 2022

AbstractNK and CD8+ T cells are important cells for cytolysis of cancer cells. The tumor microenvironment can upregulate surface expression on these cells of NKG2A, an inhibitory receptor that can dampen immune responses to cancer leading to immune evasion. To block NKG2A-mediated inhibition, we discovered and characterized two fully human antibodies using phage and yeast display that bind to NKG2A. These antibodies are highly specific for human CD94/NKG2A heterodimer complex, displaying no binding to the activating NKG2C receptor. A mutagenesis study revealed that the serine residue at 170 position (S170) of NKG2A is critical for the selectivity of anti-NKG2A antibodies. In vitro cytotoxic assays showed that NKG2A antibody inhibitors activated primary NK cells and promoted ADCC function of specific antibodies that bind to antigens expressed on cancer cells.Summary headingFully human antibodies to the NKG2A inhibitory receptor
Ancestral state reconstruction suggests repeated losses of recruitment communication during ant evolution (Hymenoptera: Formicidae)
Authors: Glaser Simone M , Grüter Christoph 
Published: May 2022

AbstractEusocial insects have evolved different strategies to share information about their environment and workers can recruit nestmates to food sources or new nest sites. Ants are the most species-rich social insect group and are known to use pheromones, visual and tactile signals to communicate and inform nestmates about resources. However, how these different strategies evolved and whether there was a predominant evolutionary sequence that led to present day recruitment strategies is not well understood. In our study we explored two competing hypotheses about the ancestral recruitment communication: (1) ant ancestors did not recruit nestmates and species evolved more complex recruitment strategies over time vs. (2) early ants used mass-recruitment, which was lost repeatedly in some lineages. We combined an extensive search of the scientific literature and ancestral state reconstruction to estimate the ancestral recruitment strategy, focusing on the categories (i) no recruitment, (ii) tandem running, (iii) group-recruitment and (iv) chemical mass-recruitment. Stochastic character mapping suggests that mass-recruitment was ancestral in ants (59-61%), whereas “no recruitment” was unlikely to be the ancestral condition (21%). Similarly, marginal ancestral state reconstruction suggests that mass-recruitment (44-81%) or group-recruitment (48-50%) represented the original state. Our results are consistent with the finding that early ants lived in colonies containing up to several thousand individuals, which are typically associated with mass-recruiting in ants. However, our ability to robustly identify patterns in the evolution of communication in ants remains hampered by a lack of natural history information for most ant species.