bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pseudomonascan prevent the parasitic fungus, while keeping the crop fungus unaffected, in the gardens ofOdontotermes obesus
Authors: Agarwal Renuka , Gupta Manisha , Antony Abin , Sen Ruchira , Raychoudhury Rhitoban 
Published: January 2021

AbstractInsects that farm monocultures of fungi are canonical examples of nutritional symbiosis as well as independent evolution of agriculture in non-human animals. But just like in human agriculture, these fungal crops face constant threat of invasion by weeds which, if unchecked, takes over the crop fungus. In fungus-growing termites, the crop fungus (Termitomyces) faces such challenges from the parasitic fungusPseudoxylaria. The mechanism by whichPseudoxylariais suppressed is not known. However, evidence suggests that some bacterial secondary symbionts can serve as defensive mutualists by preventing the growth ofPseudoxylaria. However, such secondary symbionts must possess the dual, yet contrasting, capabilities of suppressing the weedy fungus while keeping the growth of the crop fungus unaffected. This study describes the isolation, identification and culture-dependent estimation of the roles of several such putative defensive mutualists from the colonies of the wide-spread fungus-growing termite from India,Odontotermes obesus. From the 38 bacterial cultures tested, a strain ofPseudomonasshowed significantly greater suppression of the weedy fungus than the crop fungus. Moreover, a 16S rRNA pan-microbiome survey, using the Nanopore platform, revealedPseudomonasto be a part of the core microbiota ofOdontotermes obesus. A meta-analysis of microbiota composition across different species ofOdontotermesalso confirms the wide-spread prevalence ofPseudomonaswithin this termite. These evidence indicate thatPseudomonascould be playing the role of defensive mutualist withinOdontotermes.
Circadian dynamics of the teleost skin immune-microbiome interface
Authors: Ellison Amy R , Wilcockson David , Cable Jo 
Published: January 2021

AbstractCircadian rhythms of host immune activity and their microbiomes are likely pivotal to health and disease resistance. The integration of chronotherapeutic approaches to disease mitigation in managed animals, however, is yet to be realised. In aquaculture, light manipulation is commonly used to enhance growth and control reproduction but may have unknown negative consequences for animal health. Infectious diseases are a major barrier to sustainable aquaculture and understanding the circadian dynamics of fish immunity and crosstalk with the microbiome is urgently needed. We demonstrate daily rhythms in fish skin immune expression and microbiomes, that are modulated by photoperiod and parasitic infection. We identify putative associations of host clock and immune gene profiles with microbial composition. Our results suggest circadian perturbation that shifts the magnitude and timing of immune and microbiota activity, is detrimental to fish health. This study represents a valuable foundation for investigating the utility of chronotherapies in aquaculture, and more broadly contributes to our understanding of circadian health in vertebrates.
Effect of concentration and hydraulic reaction time on the removal of pharmaceutical compounds in a membrane bioreactor inoculated with activated sludge
Authors: Rios-Miguel Ana B. , Jetten Mike S.M. , Welte Cornelia U. 
Published: January 2021

AbstractPharmaceuticals are often not fully removed in wastewater treatment plants (WWTPs) and are thus being detected at trace levels in water bodies all over the world posing a risk to numerous organisms. These organic micropollutants (OMPs) reach WWTPs at concentrations sometimes too low to serve as growth substrate for microorganisms, thus co-metabolism is thought to be the main conversion mechanism. In this study, the microbial removal of six pharmaceuticals was investigated in a membrane bioreactor at increasing concentrations (4-800 nM) of the compounds and using three different hydraulic retention times (HRT; 1, 3.5, 5 days). The bioreactor was inoculated with activated sludge from a Dutch WWTP and fed with ammonium, acetate, and methanol as main growth substrates to stimulate and mimic co-metabolism in a WWTP. Each pharmaceutical compound had a different average removal efficiency: acetaminophen (100%) > fluoxetine (50%) > metoprolol (25%) > diclofenac (20%) > metformin (15%) > carbamazepine (10%). Higher pharmaceutical influent concentrations proportionally increased the removal rate of each compound, but surprisingly not the removal percentage. Furthermore, only metformin removal improved to 80-100% when HRT or biomass concentration was increased in the reactor. Microbial community changes were followed with 16S rRNA gene amplicon sequencing in response to the increment of supplied pharmaceutical concentration: it was found thatNitrospiraeandPlanctomycetes16S rRNA relative gene abundance decreased, whereasAcidobacteriaandBacteroidetesincreased. Remarkably, theDokdonellagenus, previously implicated in acetaminophen metabolism, showed a 30-fold increase in abundance at the highest (800 nM) concentration of pharmaceuticals applied. Taken together, these results suggest that the incomplete removal of most pharmaceutical compounds in WWTPs is neither dependent on concentration nor HRT. Accordingly, we propose a chemical equilibrium or a growth substrate limitation as the responsible mechanisms of the incomplete removal. Finally,Dokdonellacould be the main acetaminophen degrader under activated sludge conditions, and non-antimicrobial pharmaceuticals might still be toxic to relevant WWTP bacteria.
Doxorubicin Induces Senescence in Intestinal Epithelial Cells
Authors: Biraud Mandy , Cortes Jocsa , Cray Paul , Kunzmann Guy , Mohammed Javid , Dekaney Christopher M. 
Published: January 2021

AbstractDoxorubicin treatment induces DNA damage and apoptosis in rapidly dividing cell types like intestinal epithelial cells. This has been demonstrated bothin vivoandin vitro. In certain cell types some cells do not undergo DNA damage-induced apoptosis in response to doxorubicin but instead become senescent. Induction of senescence in these cells can lead to dysfunction and chronic inflammation, which can lead to more damage. We questioned whether a single dose of doxorubicin would be able to induce apoptosis and senescence in intestinal epithelial cellsin vitro. For these studies, we exposed IEC-6 small intestinal epithelial cells to doxorubicin to evaluate whether senescence is induced in a relatively homogeneous population of intestinal epithelial cells. Although some cells underwent apoptosis, those that did not showed traits of senescence. Our studies showed that doxorubicin treatment increased cell size and increased expression of senescence-associated β-galactosidase. Concomitantly, we observed increased mRNA expression of several genes associated with a senescence-associated secretory phenotype includingIL-6,Ptges,Faim2, andCdkn1aand decreased expression ofSirt1. We also observed release of HMGB1, a cellular alarmin, from treated cells. Together, these data suggest that doxorubicin induces senescence in intestinal epithelial cells. Furthermore, our data indicate that cellular responses to a DNA damaging agent, such as doxorubicin, can differ within a population of cells suggesting differing levels of sensitivity within a relatively homogenous cell population. Further studies are needed to delineate the mechanisms that determine whether a cell moves down an apoptotic or senescent pathway following DNA damage.
Serum hormone levels in infertile women between conceived with and without hormone replacement therapy: Safety of estradiol and progesterone replacement therapy in frozen-thawed embryo transfer cycles for breast cancer survivors
Authors: Ito Ayumu , Katagiri Yukiko , Fukuda Yusuke , Morita Mineto 
Published: January 2021

AbstractObjectiveRecent advances in cancer treatment and reproductive medicine have made the post-treatment quality of life an important concern for cancer survivors. We aimed to evaluate the safety of sex hormone (estradiol and progesterone) replacement therapy (HRT) in women who conceived by assisted reproductive technology (ART) with hormone receptor-positive breast cancer.MethodsWe measured serum E2 and P4 levels at 4–10 weeks of gestation in women who conceived naturally or after timed intercourse or intrauterine insemination for infertility without HRT for luteal support (non-HR group; n=135). We conducted a retrospective comparison of the values from the non-HR group with those of women who conceived by ART with HRT for infertility (HR group; n=75).ResultsSerum E2 levels were significantly higher in the non-HR group than in the HR group at 5, 6, and 8 weeks of gestation. Similarly, serum P4 levels were significantly higher in the non-HR group than in the HR group at 4, 5, and 6 weeks of gestation.ConclusionsThis study suggests that in cancer reproductive medicine for hormone-dependent breast cancer survivors, HRT administered during the first trimester of a pregnancy after primary disease treatment may not increase the sex hormone levels to levels above those seen in spontaneous pregnancy.
White matter hyperintensity volume and early-onset post-stroke depression in Thai older patients
Authors: Jaroonpipatkul Chaichana , Onwanna Jaruwan , Tunvirachaisakul Chavit , Jittapiromsak Nutchawan , Rakvongthai Yothin , Chutinet Aurauma , Supasitthumrong Thitiporn 
Published: January 2021

ABSTRACTObjectivePost-stroke depression (PSD) is one of the most frequent psychiatric symptoms after a stroke event. The role of white matter hyperintensities (WMHs) associated with PSD in older patients remains unclear. This study aimed to examine the volume and location of white matter microstructure abnormalities among older patients with early-onset PSD.MethodsOlder (≥55 years) patients with acute cerebral infarction and hospitalized in King Chulalongkorn Memorial Hospital’s stroke unit from October 2019 to September 2020 were recruited. Participants were assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS) within three months after the onset of stroke. All patients had MRI scans. The brain images were segmented into four regions via left/right, frontal/dorsal plains. Two WMHs volume detections (visual rating vs. semi-automated WMHs volumetric detection) were employed on the fluid-attenuated inversion recovery images (FLAIR) for each segment. The study then investigated the association between WMHs volume and MADRS score with regression analysis.ResultsThe study included twenty-nine patients with acute stroke. Total WMHs volume and segmented regions were not statistically associated with the MADRS score. However, there was a trend in different WHMs volume of the left anterior segment between depressed and non-depressed groups (t-test 2.058, p = 0.055). Further, demographic and clinical data showed no association with depressive symptoms.ConclusionThe volume of WHMs might not contribute to the development of early-onset PSD in older patients. This study showed a potential of a quantitative MRI analysis in clinical practice. Further investigation with a larger group of patients is needed.
m6A RNA methylation facilitates pre-mRNA 3’-end formation and is essential for viability ofToxoplasma gondii
Authors: Holmes Michael J. , Padgett Leah R. , Bastos Matheus S. , Sullivan William J. 
Published: January 2021

AbstractToxoplasma gondiiis an obligate intracellular parasite that can cause serious opportunistic disease in the immunocompromised or through congenital infection. To progress through its life cycle,Toxoplasmarelies on multiple layers of gene regulation that includes an array of transcription and epigenetic factors. Over the last decade, the modification of mRNA has emerged as another important layer of gene regulation called epitranscriptomics. Here, we report that epitranscriptomics machinery exists inToxoplasma,namely the methylation of adenosines (m6A) in mRNA transcripts. We identified novel components of the m6A methyltransferase complex and determined the distribution of m6A marks within the parasite transcriptome. m6A mapping revealed the modification to be preferentially located near the 3’-boundary of mRNAs within the consensus sequence, YGCAUGCR. Knockdown of the m6A writer enzyme METTL3 resulted in diminished m6A marks, loss of a target transcript, and a complete arrest of parasite replication. Furthermore, we examined the two proteins inToxoplasmathat possess YTH domains, which bind m6A marks, and showed them to be integral members of the cleavage and polyadenylation machinery that catalyzes the 3’-end processing of pre-mRNAs. Together, these findings establish that the m6A epitranscriptome is essential for parasite viability by contributing to the processing of mRNA 3’-ends.Author SummaryToxoplasma gondiiis a parasite of medical importance that causes disease upon immuno-suppression. Uncovering essential pathways that the parasite uses for its basic biological processes may reveal opportunities for new anti-parasitic drug therapies. Here, we describe the machinery thatToxoplasmauses to modify specific adenosine residues within its messenger RNAs (mRNA) by N6-adenosine methylation (m6A). We discovered that m6A mRNA methylation is prevalent in multiple stages of the parasite life cycle and is required for parasite replication. We also establish that m6A plays a major role in the proper maturation of mRNA. Two proteins that bind m6A modifications on mRNA associate with factors responsible for the cleavage and final processing steps of mRNA maturation. Since all of the machinery is conserved from plants toToxoplasmaand other related parasites, we propose that this system operates similarly in these organisms.
Metabolic flexibility via mitochondrial BCAA carrier SLC25A44 is required for optimal fever
Authors: Yoneshiro Takeshi , Kataoka Naoya , Walejko Jacquelyn M. , Ikeda Kenji , Brown Zachary , Yoneshiro Momoko , Crown Scott B. , McGarrah Robert W. , White Phillip J. , Nakamura Kazuhiro , Kajimura Shingo 
Published: January 2021

ABSTRACTImporting necessary metabolites into the mitochondrial matrix is a crucial step of fuel choice during stress adaptation. Branched chain-amino acids (BCAA, Valine, Leucine, and Isoleucine) are essential for anabolic processes like protein synthesis, but they are also imported into the mitochondria for catabolic reactions. What controls the distinct subcellular BCAA utilization during stress adaptation is insufficiently understood. The present study reports the role of SLC25A44, a recently identified mitochondrial BCAA carrier (MBC), in the regulation of mitochondrial BCAA catabolism and adaptive response to fever. We found that mitochondrial BCAA oxidation in brown adipose tissue (BAT) is significantly enhanced during fever in response to the pyrogenic mediator prostaglandin E2(PGE2) and psychological stress. Genetic deletion of MBC in a BAT-specific manner blunts mitochondrial BCAA oxidation and non-shivering thermogenesis following intracerebroventricular PGE2administration. At a cellular level, MBC is required for mitochondrial BCAA deamination as well as the synthesis of mitochondrial amino acids and TCA intermediates. Together, these results illuminate the role of MBC as a determinant of metabolic flexibility to mitochondrial BCAA catabolism and optimal febrile responses. This study also offers an opportunity to control fever by rewiring the subcellular BCAA fate.
GATA2 deficiency during embryogenesis elevates Interferon Regulatory Factor-8 to subvert a progenitor cell differentiation program
Authors: Johnson Kirby D. , Bresnick Emery H. 
Published: January 2021

AbstractCell type-specific transcription factors control stem and progenitor cell transitions by establishing networks containing hundreds of genes and proteins. Network complexity renders it challenging to discover essential versus modulatory or redundant components. This scenario is exemplified by GATA2 regulation of hematopoiesis during embryogenesis. Previously, we demonstrated that loss ofGata2, −77 enhancer disrupts the GATA2-dependent genetic network governing erythro-myeloid differentiation. The aberrant network includes the transcription factor Interferon Regulatory Factor-8 and a host of innate immune regulators. Mutant progenitors lose the capacity to balance production of diverse myelo-erythroid progeny. To elucidate mechanisms, we asked if IRF8 is essential, contributory or not required.Irf8ablation, in the context of the −77 mutant allele, reversed granulocytic deficiencies of −77−/−embryos and rescued an imbalance of dendritic cell progenitors. Despite many dysregulated components that control vital processes, including transcription and signaling, aberrant elevation of a single transcription factor deconstructed the differentiation program.
Antagonistic relationship of NuA4 with the Non-Homologous End-Joining machinery at DNA damage sites
Authors: Ahmad Salar , Côté Valerie , Cheng Xue , Bourriquen Gaëlle , Sapountzi Vasileia , Altaf Mohammed , Côté Jacques 
Published: January 2021

AbstractThe NuA4 histone acetyltransferase complex, apart from its known role in gene regulation, has also been directly implicated in the repair of DNA double-strand breaks (DSBs), favoring homologous recombination (HR) in S/G2 during the cell cycle. Here, we investigate the antagonistic relationship of NuA4 with non-homologous end joining (NHEJ) factors. We show that budding yeast Rad9, the 53BP1 ortholog, can inhibit NuA4 acetyltransferase activity when bound to chromatinin vitro. While we previously reported that NuA4 is recruited at DSBs during the S/G2 phase, we can also detect its recruitment in G1 when genes for NHEJ factors Rad9, Yku80 and Nej1 are mutated. This is accompanied with the binding of single-strand DNA binding protein RPA and Rad52, indicating DNA end resection in G1 as well as recruitment of the HR machinery. This NuA4 recruitment to DSBs in G1 depends on both Xrs2 and Lcd1/Ddc2 and is linked to the hyper-resection phenotype of NHEJ mutants. It also implicates NuA4 in the resection-based single-strand annealing (SSA) repair pathway along Rad52. Interestingly, we identified two novel non-histone acetylation targets of NuA4, Nej1 and Yku80. Acetyl-mimicking mutant of Nej1 inhibits repair of DNA breaks by NHEJ, decreases its interaction with other core NHEJ factors such as Yku80 and Lif1 and favors end resection. Altogether, these results establish a strong reciprocal antagonistic regulatory function of NuA4 and NHEJ factors in repair pathway choice and suggests a role of NuA4 in alternative repair mechanism that involves DNA-end resection in G1.Author SummaryDNA double-strand breaks (DSBs) are one of the most harmful form of DNA damage. Cells employ two major repair pathways to resolve DSBs: Homologous Recombination (HR) and Non-Homologous End Joining (NHEJ). Here we wanted to dissect further the role played by the NuA4 (Nucleosome acetyltransferase of histone H4) complex in the repair of DSBs. Budding yeast NuA4 complex, like its mammalian homolog TIP60 complex, has been shown to favor repair by HR. Here, we show that indeed budding yeast NuA4 and components of the NHEJ repair pathway share an antagonistic relationship. Deletion of NHEJ components enables increased recruitment of NuA4 in the vicinity of DSBs, possible through two independent mechanisms, where NuA4 favors the end resection process which implicates it in repair by single-strand annealing (SSA), an alternate homology-based repair pathway. Additionally, we also present two NHEJ core components as new targets of NuA4 acetyltransferase activity and suggest that these acetylation events can disassemble the NHEJ repair complex from DSBs, favoring repair by HR. Our study demonstrates the importance of NuA4 in the modulation of DSB repair pathway choice.
From heterogeneity to homogeneity: coordination of siderophore gene expression among clonal cells of the bacteriumPseudomonas aeruginosa
Authors: Mridha Subham , Kümmerli Rolf 
Published: January 2021

AbstractThere has been great progress in understanding how bacterial groups coordinate social actions, such as biofilm formation, swarming and public-goods secretion. Less clear, however, is whether the seemingly coordinated responses observed at the group level actually mirror what individual cells do. Here, we use a microscopy approach to simultaneously quantify the investment of individual cells of the bacteriumPseudomonas aeruginosainto two public goods, the siderophores pyochelin and pyoverdine. Using gene expression as a proxy for investment, we initially observed no coordination but high heterogeneity and bimodality in siderophore gene expression across cells. With increasing cell density, gene expression became homogenized across cells, accompanied by a shift from pyochelin to pyoverdine expression. We found positive correlations in the expression of pyochelin and pyoverdine genes across cells, and show that cell-to-cell variation is driven by differences in cellular metabolic states. We propose a model explaining how variation in internal iron stocks can spur initial erratic gene expression, while siderophore-mediated signalling and intra-cellular feedbacks later on can induce highly coordinated gene expression and synchronized shifts from pyochelin to pyoverdine. Our work provides new insights into bacterial collective decision-making processes and reveals a three-phase chronobiological siderophore investment cycle inP. aeruginosa.
MMP12 Knockout Prevent Weight and Muscle Loss Induced by Cancer Cachexia
Authors: Jiang Lingbi , Yang Mingming , He Shihui , Li Zhengyang , Li Haobin , Niu Ting , Xie Dehuan , Mei Yan , He Xiaodong , Wei Lili , Huang Pinzhu , Huang Mingzhe , Zhang Rongxin , Wang Lijing , Li Jiangchao 
Published: January 2021

AbstractWeight loss and muscle wasting can have devastating impacts on survival and quality of life of patients with cancer cachexia. Here, we have established a hybrid mouse of ApcMin/+mice and MMP12 knockout mice (ApcMin/+; MMP12-/-) and found that knockout MMP12 can suppress the weight and muscle loss of ApcMin/+mice. In detail, we found that interleukin 6 was highly upregulated in the serum of cancer patients and MMP12 was increased in muscle of tumor-bearing mice. Interestingly, the interleukin 6 secreted by tumor cells led to MMP12 overexpression in the macrophages, which further resulted in degradation of insulin and insulin-like growth factor 1 and interruption of glycolipid metabolism. Notably, depletion of MMP12 prevented weight loss of ApcMin/+mice. Our study uncovers the critical role of MMP12 in controlling weight and highlights the great potential of MMP12 in the treatment of cancer cachexia.
Information retrieval in an infodemic: the case of COVID-19 publications
Authors: Teodoro Douglas , Ferdowsi Sohrab , Borissov Nikolay , Kashani Elham , Alvarez David Vicente , Copara Jenny , Gouareb Racha , Naderi Nona , Amini Poorya 
Published: January 2021

ABSTRACTThe COVID-19 pandemic has led to an exponential surge and an enormous amount of published literature, both accurate and inaccurate, a term usually coined as an infodemic. In the context of searching for COVID-19 related scientific literature, we present an information retrieval methodology for effectively finding relevant publications for different information needs. Our multi-stage information retrieval architecture combines probabilistic weighting models and re-ranking algorithms based on neural masked language models. The methodology was evaluated in the context of the TREC-COVID challenge, achieving competitive results with the top ranking teams participating in the competition. Particularly, the ranking combination of bag-of-words and language models significantly outperformed a BM25-based baseline model (16 percentage points for the NDCG@20 metric), correctly retrieving more than 16 out of the top 20 documents retrieved. The proposed pipeline could thus support the effective search and discovery of relevant information in the case of an infodemic.