bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor Necrosis Factor-Mediated Survival of CD169
+
Cells Promotes Immune Activation during Vesicular Stomatitis Virus Infection
Authors: Shinde Prashant V. , Xu Haifeng C. , Maney Sathish Kumar , Kloetgen Andreas , Namineni Sukumar , Zhuang Yuan , Honke Nadine , Shaabani Namir , Bellora Nicolas , Doerrenberg Mareike , Trilling Mirko , Pozdeev Vitaly I. , van Rooijen Nico , Scheu Stefanie , Pfeffer Klaus , Crocker Paul R. , Tanaka Masato , Duggimpudi Sujitha , Knolle Percy , Heikenwalder Mathias , Ruland Jürgen , Mak Tak W. , Brenner Dirk , Pandyra Aleksandra A. , Hoell Jessica I. , Borkhardt Arndt , Häussinger Dieter , Lang Karl S. , Lang Philipp A. 
Published: November 2017

ABSTRACT

Innate immune activation is essential to mount an effective antiviral response and to prime adaptive immunity. Although a crucial role of CD169
+
cells during vesicular stomatitis virus (VSV) infections is increasingly recognized, factors regulating CD169
+
cells during viral infections remain unclear. Here, we show that tumor necrosis factor is produced by CD11b
+
Ly6C
+
Ly6G
+
cells following infection with VSV. The absence of TNF or TNF receptor 1 (TNFR1) resulted in reduced numbers of CD169
+
cells and in reduced type I interferon (IFN-I) production during VSV infection, with a severe disease outcome. Specifically, TNF triggered RelA translocation into the nuclei of CD169
+
cells; this translocation was inhibited when the paracaspase MALT-1 was absent. Consequently, MALT1 deficiency resulted in reduced VSV replication, defective innate immune activation, and development of severe disease. These findings indicate that TNF mediates the maintenance of CD169
+
cells and innate and adaptive immune activation during VSV infection.

IMPORTANCE
Over the last decade, strategically placed CD169
+
metallophilic macrophages in the marginal zone of the murine spleen and lymph nodes (LN) have been shown to play a very important role in host defense against viral pathogens. CD169
+
macrophages have been shown to activate innate and adaptive immunity via “enforced virus replication,” a controlled amplification of virus particles. However, the factors regulating the CD169
+
macrophages remain to be studied. In this paper, we show that after vesicular stomatitis virus infection, phagocytes produce tumor necrosis factor (TNF), which signals via TNFR1, and promote enforced virus replication in CD169
+
macrophages. Consequently, lack of TNF or TNFR1 resulted in defective immune activation and VSV clearance.
Human Papillomavirus Replication Regulation by Acetylation of a Conserved Lysine in the E2 Protein
Authors: Thomas Yanique , Androphy Elliot J. 
Published: November 2017

ABSTRACT
The papillomavirus (PV) E2 protein is a sequence-specific DNA binding protein that recruits cellular factors to its genome in infected epithelial cells. E2 also binds to and loads the viral E1 DNA helicase at the origin of replication. Posttranslational modifications (PTMs) of PV E2 have been identified as potential regulators of E2 functions. We recently reported lysine 111 (K111) as a target of p300 acetylation in bovine PV (BPV). The di-lysines at 111 and 112 are conserved in almost all papillomaviruses. We pursued a mutational approach to query the functional significance of lysine in human PV (HPV) E2. Amino acid substitutions that prevent acetylation, including arginine, were unable to stimulate transcription and E1-mediated DNA replication. The arginine K111 mutant retained E2 transcriptional repression, nuclear localization, DNA and chromatin binding, and association with E2 binding partners involved in PV transcription and replication. While the replication-defective E2-K111R mutant recruited E1 to the viral replication origin, surprisingly, unwinding of the duplex DNA did not occur. In contrast, the K111 glutamine (K111Q) mutant increased origin melting and stimulated replication compared to wild-type E2. These experiments reveal a novel activity of E2 necessary for denaturing the viral origin that likely depends on acetylation of highly conserved lysine 111.

IMPORTANCE
HPV is one of the most common sexually transmitted infections in the United States. Over 200 HPVs have been described, and they manifest in a variety of ways; they can be asymptomatic or can result in benign lesions (papillomas) or progress to malignancy. Although 90% of infections are asymptomatic and resolve easily, HPV16 and -18 alone are responsible for 70% of all cervical cancers, which are almost entirely caused by HPV infection. Interestingly, 60 to 90% of other cancers have been linked to HPV. The goal of this research is to further elucidate the mechanisms that regulate and mediate viral replication.
Epstein-Barr Virus Protein EB2 Stimulates Translation Initiation of mRNAs through Direct Interactions with both Poly(A)-Binding Protein and Eukaryotic Initiation Factor 4G
Authors: Mure Fabrice , Panthu Baptiste , Zanella-Cléon Isabelle , Delolme Frédéric , Manet Evelyne , Ohlmann Théophile , Gruffat Henri 
Published: November 2017

ABSTRACT
Epstein-Barr virus (EBV) expresses several mRNAs produced from intronless genes that could potentially be unfavorably translated compared to cellular spliced mRNAs. To overcome this situation, the virus encodes an RNA-binding protein (RBP) called EB2, which was previously found to both facilitate the export of nuclear mRNAs and increase their translational yield. Here, we show that EB2 binds both nuclear and cytoplasmic cap-binding complexes (CBC and eukaryotic initiation factor 4F [eIF4F], respectively) as well as the poly(A)-binding protein (PABP) to enhance translation initiation of a given messenger ribonucleoparticle (mRNP). Interestingly, such an effect can be obtained only if EB2 is initially bound to the native mRNPs in the nucleus. We also demonstrate that the EB2-eIF4F-PABP association renders translation of these mRNPs less sensitive to translation initiation inhibitors. Taken together, our data suggest that EB2 binds and stabilizes cap-binding complexes in order to increase mRNP translation and furthermore demonstrate the importance of the mRNP assembly process in the nucleus to promote protein synthesis in the cytoplasm.

IMPORTANCE
Most herpesvirus early and late genes are devoid of introns. However, it is now well documented that mRNA splicing facilitates recruitment on the mRNAs of cellular factors involved in nuclear mRNA export and translation efficiency. To overcome the absence of splicing of herpesvirus mRNAs, a viral protein, EB2 in the case of Epstein-Barr virus, is produced to facilitate the cytoplasmic accumulation of viral mRNAs. Although we previously showed that EB2 also specifically enhances translation of its target mRNAs, the mechanism was unknown. Here, we show that EB2 first is recruited to the mRNA cap structure in the nucleus and then interacts with the proteins eIF4G and PABP to enhance the initiation step of translation.
Identification of a Small Molecule That Compromises the Structural Integrity of Viroplasms and Rotavirus Double-Layered Particles
Authors: Eichwald Catherine , De Lorenzo Giuditta , Schraner Elisabeth M. , Papa Guido , Bollati Michela , Swuec Paolo , de Rosa Matteo , Milani Mario , Mastrangelo Eloise , Ackermann Mathias , Burrone Oscar R. , Arnoldi Francesca 
Published: November 2017

ABSTRACT

Despite the availability of two attenuated vaccines, rotavirus (RV) gastroenteritis remains an important cause of mortality among children in developing countries, causing about 215,000 infant deaths annually. Currently, there are no specific antiviral therapies available. RV is a nonenveloped virus with a segmented double-stranded RNA genome. Viral genome replication and assembly of transcriptionally active double-layered particles (DLPs) take place in cytoplasmic viral structures called viroplasms. In this study, we describe strong impairment of the early stages of RV replication induced by a small molecule known as an RNA polymerase III inhibitor, ML-60218 (ML). This compound was found to disrupt already assembled viroplasms and to hamper the formation of new ones without the need for
de novo
transcription of cellular RNAs. This phenotype was correlated with a reduction in accumulated viral proteins and newly made viral genome segments, disappearance of the hyperphosphorylated isoforms of the viroplasm-resident protein NSP5, and inhibition of infectious progeny virus production. In
in vitro
transcription assays with purified DLPs, ML showed dose-dependent inhibitory activity, indicating the viral nature of its target. ML was found to interfere with the formation of higher-order structures of VP6, the protein forming the DLP outer layer, without compromising its ability to trimerize. Electron microscopy of ML-treated DLPs showed dose-dependent structural damage. Our data suggest that interactions between VP6 trimers are essential, not only for DLP stability, but also for the structural integrity of viroplasms in infected cells.

IMPORTANCE
Rotavirus gastroenteritis is responsible for a large number of infant deaths in developing countries. Unfortunately, in the countries where effective vaccines are urgently needed, the efficacy of the available vaccines is particularly low. Therefore, the development of antivirals is an important goal, as they might complement the available vaccines or represent an alternative option. Moreover, they may be decisive in fighting the acute phase of infection. This work describes the inhibitory effect on rotavirus replication of a small molecule initially reported as an RNA polymerase III inhibitor. The molecule is the first chemical compound identified that is able to disrupt viroplasms, the viral replication machinery, and to compromise the stability of DLPs by targeting the viral protein VP6. This molecule thus represents a starting point in the development of more potent and less cytotoxic compounds against rotavirus infection.
First Insights into the Diverse Human Archaeome: Specific Detection of Archaea in the Gastrointestinal Tract, Lung, and Nose and on Skin
Authors: Koskinen Kaisa , Pausan Manuela R. , Perras Alexandra K. , Beck Michael , Bang Corinna , Mora Maximilian , Schilhabel Anke , Schmitz Ruth , Moissl-Eichinger Christine 
Published: November 2017

ABSTRACT

Human-associated archaea remain understudied in the field of microbiome research, although in particular methanogenic archaea were found to be regular commensals of the human gut, where they represent keystone species in metabolic processes. Knowledge on the abundance and diversity of human-associated archaea is extremely limited, and little is known about their function(s), their overall role in human health, or their association with parts of the human body other than the gastrointestinal tract and oral cavity. Currently, methodological issues impede the full assessment of the human archaeome, as bacteria-targeting protocols are unsuitable for characterization of the full spectrum of
Archaea
. The goal of this study was to establish conservative protocols based on specifically archaea-targeting, PCR-based methods to retrieve first insights into the archaeomes of the human gastrointestinal tract, lung, nose, and skin. Detection of
Archaea
was highly dependent on primer selection and the sequence processing pipeline used. Our results enabled us to retrieve a novel picture of the human archaeome, as we found for the first time
Methanobacterium
and
Woesearchaeota
(DPANN superphylum) to be associated with the human gastrointestinal tract and the human lung, respectively. Similar to bacteria, human-associated archaeal communities were found to group biogeographically, forming (i) the thaumarchaeal skin landscape, (ii) the (methano)euryarchaeal gastrointestinal tract, (iii) a mixed skin-gastrointestinal tract landscape for the nose, and (iv) a woesearchaeal lung landscape. On the basis of the protocols we used, we were able to detect unexpectedly high diversity of archaea associated with different body parts.

IMPORTANCE
In summary, our study highlights the importance of the primers and data processing pipeline used to study the human archaeome. We were able to establish protocols that revealed the presence of previously undetected
Archaea
in all of the tissue samples investigated and to detect biogeographic patterns of the human archaeome in the gastrointestinal tract and on the skin and for the first time in the respiratory tract, i.e., the nose and lungs. Our results are a solid basis for further investigation of the human archaeome and, in the long term, discovery of the potential role of archaea in human health and disease.
Manipulating the Bacterial Cell Cycle and Cell Size by Titrating the Expression of Ribonucleotide Reductase
Authors: Zhu Manlu , Dai Xiongfeng , Guo Weilun , Ge Zengxiang , Yang Mingxuan , Wang Haikuan , Wang Yi-Ping 
Published: November 2017

ABSTRACT

Understanding how bacteria coordinate growth with cell cycle events to maintain cell size homeostasis remains a grand challenge in biology. The period of chromosome replication (C period) is a key stage in the bacterial cell cycle. However, the mechanism of
in vivo
regulation of the C period remains unclear. In this study, we found that titration of the expression of ribonucleotide reductase (RNR), which changes the intracellular deoxynucleoside triphosphate (dNTP) pools, enables significant perturbations of the C period, leading to a substantial change in cell size and DNA content. Our work demonstrates that the intracellular dNTP pool is indeed an important parameter that controls the progression of chromosome replication. Specially, RNR overexpression leads to a shortened C period compared with that of a wild-type strain growing under different nutrient conditions, indicating that the dNTP substrate levels are subsaturated under physiological conditions. In addition, perturbing the C period does not significantly change the D period, indicating that these two processes are largely independent from each other. Overall, titration of ribonucleotide reductase expression can serve as a standard model system for studying the coordination between chromosome replication, cell division, and cell size.

IMPORTANCE
Bacteria must coordinate growth with cell cycle progression to maintain cell size hemostasis. Cell cycle and cell size regulation is a fundamental concern in biology. The period required for chromosome replication (the C period) is a key stage in the bacterial cell cycle. However, how the C period is controlled
in vivo
remains largely an open question in this field of bacterial cell cycle regulation. Through introducing a genetic circuit into
Escherichia coli
for titrating the expression of ribonucleotide reductase, we achieve substantial perturbation of the C period and cell size. Our work demonstrates that the intracellular dNTP pool is an important parameter that controls the progression of chromosome replication. Moreover, our work indicates that bacterial cells manage to maintain subsaturated dNTP levels under different nutrient conditions, leading to a submaximal speed of DNA replication fork movement.
Sex Reporting in Preclinical Microbiological and Immunological Research
Authors: Potluri Tanvi , Engle Kyrra , Fink Ashley L. , vom Steeg Landon G. , Klein Sabra L. 
Published: November 2017

ABSTRACT

Both sex (i.e., biological construct of male and female) and gender (i.e., social construct of masculine and feminine) impact the pathogenesis of diseases, including those caused by microbial infections. Following the 2015 NIH policy for consideration of sex as a biological variable in preclinical research, in 2018, authors of papers published in primary-research American Society for Microbiology (ASM) journals will be asked to report the sex of the research subjects and animals and of materials derived directly from them. To address the need for sex reporting in ASM journals, we systematically reviewed 2,928 primary-research articles published in six primary-research ASM journals (
Antimicrobial Agents and Chemotherapy
,
Clinical and Vaccine Immunology
,
Infection and Immunity
,
Journal of Bacteriology
,
Journal of Virology
, and
mBio
) in 2016. Approximately 37% of animal studies and 9% of primary cell culture papers published in 2016 would have been affected by the new sex-reporting policy. For animal studies (i.e., studies with any nonhuman vertebrate hosts), most published papers either did not report the sex of the animals or used only female animals, and a minority used only males or both sexes. For published studies using primary cells from diverse animal species (i.e., humans and nonhuman vertebrates), almost all studies failed to report the sex of donors from which the cells were isolated. We believe that reporting the sex of animals and even of the donors of derived cells could improve the rigor and reproducibility of research conducted in microbiology and immunology and published in ASM journals.
Keratolimbal allograft for limbal stem cell deficiency after severe corneal chemical injury: a systematic review
Authors: Shanbhag Swapna S , Saeed Hajirah N , Paschalis Eleftherios I , Chodosh James 
Published: November 2017

PurposeTo review the published literature on outcomes of keratolimbal allograft (KLAL) for the surgical treatment of limbal stem cell deficiency (LSCD) and corneal blindness after severe corneal chemical injury.MethodsLiterature searches were conducted in the following electronic databases: MEDLINE, EMBASE, Science Citation Index, CINAHL, LILACS and the Cochrane Library. Standard systematic review methodology was applied. The main outcome measure was the proportion of eyes with best-corrected visual acuity (BCVA) ≥20/200 at last follow-up. Other measures of allograft success were also collected.ResultsWe identified six reports in which KLAL outcomes in the eyes after chemical injury could be distinguished. There were no randomised controlled studies. The outcomes of KLAL in 36 eyes of 33 patients were analysed. One study with seven eyes did not specify KLAL follow-up specific to chemical injury. Median postoperative follow-up for the other 29 eyes in 26 patients was 42 months (range 6.2–114 months). In the same 29 eyes, 69% (20/29) had BCVA ≥20/200 at the last follow-up examination. Eighty-nine per cent of all eyes (32/36) underwent penetrating keratoplasty simultaneous or subsequent to KLAL.ConclusionsThe number of studies where outcomes of KLAL in eyes with severe corneal chemical injury could be discerned was limited, and variability was observed in outcome reporting. The quality of evidence to support the use of KLAL in LSCD in severe chemical corneal burns was low. Standardisation and longer follow-up are needed to better define evidence-based best practice when contemplating surgical intervention for blindness after corneal chemical injury.PROSPERO registration numberCRD42017054733.
DNA methylation defines regional identity of human intestinal epithelial organoids and undergoes dynamic changes during development
Authors: Kraiczy Judith , Nayak Komal M , Howell Kate J , Ross Alexander , Forbester Jessica , Salvestrini Camilla , Mustata Roxana , Perkins Sally , Andersson-Rolf Amanda , Leenen Esther , Liebert Anke , Vallier Ludovic , Rosenstiel Philip C , Stegle Oliver , Dougan Gordon , Heuschkel Robert , Koo Bon-Kyoung , Zilbauer Matthias 
Published: November 2017

ObjectiveHuman intestinal epithelial organoids (IEOs) are increasingly being recognised as a highly promising translational research tool. However, our understanding of their epigenetic molecular characteristics and behaviour in culture remains limited.DesignWe performed genome-wide DNA methylation and transcriptomic profiling of human IEOs derived from paediatric/adult and fetal small and large bowel as well as matching purified human gut epithelium. Furthermore, organoids were subjected to in vitro differentiation and genome editing using CRISPR/Cas9 technology.ResultsWe discovered stable epigenetic signatures which define regional differences in gut epithelial function, including induction of segment-specific genes during cellular differentiation. Established DNA methylation profiles were independent of cellular environment since organoids retained their regional DNA methylation over prolonged culture periods. In contrast to paediatric and adult organoids, fetal gut-derived organoids showed distinct dynamic changes of DNA methylation and gene expression in culture, indicative of an in vitro maturation. By applying CRISPR/Cas9 genome editing to fetal organoids, we demonstrate that this process is partly regulated by TET1, an enzyme involved in the DNA demethylation process. Lastly, generating IEOs from a child diagnosed with gastric heterotopia revealed persistent and distinct disease-associated DNA methylation differences, highlighting the use of organoids as disease-specific research models.ConclusionsOur study demonstrates striking similarities of epigenetic signatures in mucosa-derived IEOs with matching primary epithelium. Moreover, these results suggest that intestinal stem cell-intrinsic DNA methylation patterns establish and maintain regional gut specification and are involved in early epithelial development and disease.
Clinical course, therapeutic responses and outcomes in relapsing MOG antibody-associated demyelination
Authors: Ramanathan Sudarshini , Mohammad Shekeeb , Tantsis Esther , Nguyen Tina Kim , Merheb Vera , Fung Victor S C , White Owen Bruce , Broadley Simon , Lechner-Scott Jeannette , Vucic Steve , Henderson Andrew P D , Barnett Michael Harry , Reddel Stephen W , Brilot Fabienne , Dale Russell C 
Published: November 2017

ObjectiveWe characterised the clinical course, treatment and outcomes in 59 patients with relapsing myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelination.MethodsWe evaluated clinical phenotypes, annualised relapse rates (ARR) prior and on immunotherapy and Expanded Disability Status Scale (EDSS), in 218 demyelinating episodes from 33 paediatric and 26 adult patients.ResultsThe most common initial presentation in the cohort was optic neuritis (ON) in 54% (bilateral (BON) 32%, unilateral (UON) 22%), followed by acute disseminated encephalomyelitis (ADEM) (20%), which occurred exclusively in children. ON was the dominant phenotype (UON 35%, BON 19%) of all clinical episodes. 109/226 (48%) MRIs had no brain lesions. Patients were steroid responsive, but 70% of episodes treated with oral prednisone relapsed, particularly at doses <10 mg daily or within 2 months of cessation. Immunotherapy, including maintenance prednisone (P=0.0004), intravenous immunoglobulin, rituximab and mycophenolate, all reduced median ARRs on-treatment. Treatment failure rates were lower in patients on maintenance steroids (5%) compared with non-steroidal maintenance immunotherapy (38%) (P=0.016). 58% of patients experienced residual disability (average follow-up 61 months, visual loss in 24%). Patients with ON were less likely to have sustained disability defined by a final EDSS of ≥2 (OR 0.15, P=0.032), while those who had any myelitis were more likely to have sustained residual deficits (OR 3.56, P=0.077).ConclusionRelapsing MOG antibody-associated demyelination is strongly associated with ON across all age groups and ADEM in children. Patients are highly responsive to steroids, but vulnerable to relapse on steroid reduction and cessation.
Conversion of neutron stars to 2 + 1 flavor Nambu–Jona-Lasinio quark stars as a mechanism for gamma-ray bursts
Authors: Shu Xiao-Yu , Huang Yong-Feng , Zong Hong-Shi 
Published: November 2017

The phase transition from a neutron star to a quark star and its relation to gamma-ray bursts are investigated. A new model: the 2 + 1 flavor Nambu–Jona-Lasinio (NJL) model with the method of proper-time regularization (PTR) is utilized for the quark phase; while the Relativistic Mean Field (RMF) theory is used for the hadronic phase. The process of phase transition is studied by considering the chemical potential, paying special attention to the phase transition point and the emergence of strange quark matter. Characteristics of compact stars are illustrated, and the energy release during the phase transition is found to be [Formula: see text] erg.