bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship Between Physical Activity and Clinical Outcomes After ACL Reconstruction
Authors: Kuenze Christopher , Cadmus-Bertram Lisa , Pfieffer Karin , Trigsted Stephanie , Cook Dane , Lisee Caroline , Bell David
Published: November 2017

Context: Reductions in objectively measured moderate to vigorous physical activity (MVPA) have been reported among individuals with anterior cruciate ligament reconstruction (ACLR). Self-reported measures of physical activity are commonly used to assess participation in physical activity after ACLR despite the lack of evidence to support the validity of such measures within this population. Objective: The objective of this research was to determine the relationships between objectively measured MVPA, self-reported physical activity, and knee function among individuals with ACLR. Setting: University laboratory. Patients (or Other Participants): Thirty-one participants with a history of ACLR (sex: 23 females and 8 males; age = 19.8 [1.4] y) and 31 matched controls (sex: 23 females and 8 males; age = 20.6 [1.7] y) enrolled in this study. Intervention(s): None. Main Outcome Measures: Participants completed self-reported physical activity using the Tegner Activity Scale and the Marx Activity Rating Scale. Participant MVPA was objectively measured using an ActiGraph wGT3X-BT accelerometer for a 7-day period during which the monitor was worn for not less than 10 hours per day. Primary outcome measures were the amount of time spent in MVPA (minutes per week) and time spent in MVPA performed in bouts of ≥10 minutes (minutes per week). Relationships between the Tegner Activity Score, Marx Activity Rating Scale, and objectively measured MVPA variables were assessed using partial Spearman’s rank correlation coefficients after controlling for activity monitor wear time. Results: There were no significant relationships between objectively measured MVPA and self-reported physical activity (ρ ≤ 0.31, P ≥ .05) or self-reported knee-related function (ρ ≤ .41, P ≥ .05) among ACLR participants. Conclusions: Objectively measured physical activity is not significantly related to self-reported physical activity or self-reported knee function among individuals with a history of ACLR. Consideration of objective and self-reported physical activity within this population may provide key insights into disconnects between perception and the reality of physical activity engagement following ACLR.
Eight-Week Return to Play Following Latarjet Shoulder Reconstruction in an Australian Football Player: A Case Report
Authors: Murphy Myles , Stockden Marshall , Withers Ken , Breidahl William , Charlesworth Jonathon
Published: November 2017

Introduction: Anterior shoulder dislocation is a common injury in many sports, resulting in extended time lost from play with an extremely high recurrence rate in young athletes playing a high-risk sport. Latarjet shoulder reconstruction is a common surgical procedure used to prevent subsequent dislocation with an expected rehabilitation time frame of between 4 and 6 months before return to play. Case Description: A 21-year-old male Australian football player experienced 2 left-sided shoulder dislocations before undergoing a left Latarjet shoulder reconstruction. He was assessed clinically and with magnetic resonance imaging, which revealed significant tearing of the anterior labrum. The authors theorized that maximal glenohumeral stability occurs after bony healing of the coracoid onto the glenoid at 6 weeks. The patient then underwent an 8-week structured and graduated rehabilitation program aimed at preventing loss of shoulder range of motion, muscle, and functional capacity and returned to play at 8 weeks postinjury with no complications or recurrence at 12-month follow-up. Discussion: This is the first time an 8-week rehabilitation following Latarjet shoulder reconstruction has been reported. In athletes with anterior glenohumeral dislocation who require accelerated return to play, a Latarjet reconstruction with an 8-week rehabilitation protocol may be considered.
Examining the Presence of Back Pain in Competitive Athletes: A Focus on Stress and Recovery
Authors: Heidari Jahan , Belz Johanna , Hasenbring Monika , Kleinert Jens , Levenig Claudia , Kellmann Michael
Published: November 2017

Context:Explanatory approaches for back pain (BP) in athletes focus on biomechanical factors while neglecting psychological perspectives. Psychological factors have gained importance in the prediction of injuries in athletes and BP in the general population, with stress and recovery emerging as central risk factors. However, scarce evidence exists regarding the role of these aspects for the prevalent burden of BP.Objective:To investigate the association between stress and recovery parameters and the presence of BP.Design:Cross-sectional design.Setting: The questionnaires were distributed after the training sessions.Participants:A total of 345 competitive athletes (mean age = 18.31 y [SD = 5.40]) were investigated. The classification of the athletes’ competitive status was based on performance level.Interventions:Data were collected using questionnaires for the assessment of stress, recovery, and BP.Main Outcome Measures:The authors performed a multiple logistic regression to obtain odds ratios for stress and recovery parameters with regard to the outcome variable BP status.Results:For stress, the dimension “overall stress” (odds ratio = 1.83; 95% confidence interval, 1.30–2.59;P = .001) and the scale “physical complaints” (odds ratio = 1.68; 95% confidence interval, 1.25–2.25;P = .001) of the general version of the Recovery-Stress Questionnaire resulted to be significantly associated with BP. None of the recovery-related scales displayed a statistically significant relationship with BP.Conclusion:The outcomes of this study imply a modest association between stress and the presence of BP in competitive athletes. Practitioners may take these findings into account regarding the conception of training and for monitoring purposes.
The Role of Lumbopelvic-Hip Complex Stability in Softball Throwing Mechanics
Authors: Gilmer Gabrielle G. , Washington Jessica K. , Dugas Jeffrey R. , Andrews James R. , Oliver Gretchen D.
Published: November 2017

Context: Studies have found that a 20% reduction in energy generation from the lumbopelvic-hip complex during overhead throws leads to a 34% increase in load on the shoulder. Objective: The purpose of this study was to assess the effects of lumbopelvic-hip complex stability, via the single leg squat assessment, on throwing mechanics of softball athletes. Design: Prospective cohort study. Setting: Laboratory setting. Participants: A total of 50 softball athletes (164.0 [104.0] cm, 65.6 [11.3] kg, 16.3 [3.8] y, 8.61 [3.62] y of experience) performed 3 overhead throws and a single leg squat on each leg. Intervention: Four stability groups were derived: (1) stable on both legs (bilateral stability), (2) unstable on the throwing side leg (TS instability) and stable on the nonthrowing side leg, (3) unstable on the nonthrowing side leg (NTS instability) and stable on the throwing side leg, and (4) unstable on both legs (bilateral instability). All throws were analyzed across 4 throwing events: foot contact (FC), maximum external shoulder rotation (MER), ball release (BR), and maximum internal shoulder rotation (MIR). Main Outcome Measures: Mann–Whitney U tests revealed significant differences between the bilateral stability and the TS instability groups in trunk flexion at BR; the bilateral stability and the NTS instability groups in trunk flexion at BR, shoulder horizontal abduction at FC, shoulder rotation at FC, and pelvis flexion at MIR; the TS instability and the bilateral instability groups in trunk rotation at FC; and the NTS instability and the bilateral instability groups in trunk flexion at MER and shoulder rotation at FC. Conclusion: These findings demonstrate the different mechanisms in which energy can be lost through lumbopelvic-hip complex instability as evident in throwing mechanics. The findings from this study suggest that the current methods used for classification could act as a tool for coaches, physicians, and athletic trainers when assessing their athletes’ injury susceptibility.
A method of high-throughput functional evaluation of
EGFR
gene variants of unknown significance in cancer
Authors: Kohsaka Shinji , Nagano Masaaki , Ueno Toshihide , Suehara Yoshiyuki , Hayashi Takuo , Shimada Naoko , Takahashi Kazuhisa , Suzuki Kenji , Takamochi Kazuya , Takahashi Fumiyuki , Mano Hiroyuki
Published: November 2017

A method for high-throughput functional analysis identifies drug-insensitive EGFR mutations in tumors.
A 3D view of tumor heterogeneity
Authors: Chung Kwanghun
Published: November 2017

Solid tumor clearing and light-sheet microscopy improves interrogation of intratumoral heterogeneity.
Accurate PCR Detection of Influenza A/B and Respiratory Syncytial Viruses by Use of Cepheid Xpert Flu+RSV Xpress Assay in Point-of-Care Settings: Comparison to Prodesse ProFlu+
Authors: Cohen Daniel M. , Kline Jennifer , May Larissa S. , Harnett Glenn Eric , Gibson Jane , Liang Stephen Y. , Rafique Zubaid , Rodriguez Carina A. , McGann Kevin M. , Gaydos Charlotte A. , Mayne Donna , Phillips David , Cohen Jason
Published: November 2017

The Xpert Flu+RSV Xpress Assay is a fast, automated
in vitro
diagnostic test for qualitative detection and differentiation of influenza A and B viruses and respiratory syncytial virus (RSV) performed on the Cepheid GeneXpert Xpress System. The objective of this study was to establish performance characteristics of the Xpert Flu+RSV Xpress Assay compared to those of the Prodesse ProFlu+ real-time reverse transcription-PCR (RT-PCR) assay (ProFlu+) for the detection of influenza A and B viruses as well as RSV in a Clinical Laboratory Improvement Amendments (CLIA)-waived (CW) setting. Overall, the assay, using fresh and frozen nasopharyngeal (NP) swabs, demonstrated high concordance with results of the ProFlu+ assay in the combined CW and non-CW settings with positive percent agreements (PPA) (100%, 100%, and 97.1%) and negative percent agreements (NPA) (95.2%, 99.5%, and 99.6%) for influenza A and B viruses and RSV, respectively. In conclusion, this multicenter study using the Cepheid Xpert Flu+RSV Xpress Assay demonstrated high sensitivities and specificities for influenza A and B viruses and RSV in ∼60 min for use at the point-of-care in the CW setting.
Human Adenovirus Infection Causes Cellular E3 Ubiquitin Ligase MKRN1 Degradation Involving the Viral Core Protein pVII
Authors: Inturi Raviteja , Mun Kwangchol , Singethan Katrin , Schreiner Sabrina , Punga Tanel
Published: November 2017

Human adenoviruses (HAdVs) are common human pathogens encoding a highly abundant histone-like core protein, VII, which is involved in nuclear delivery and protection of viral DNA as well as in sequestering immune danger signals in infected cells. The molecular details of how protein VII acts as a multifunctional protein have remained to a large extent enigmatic. Here we report the identification of several cellular proteins interacting with the precursor pVII protein. We show that the cellular E3 ubiquitin ligase MKRN1 is a novel precursor pVII-interacting protein in HAdV-C5-infected cells. Surprisingly, the endogenous MKRN1 protein underwent proteasomal degradation during the late phase of HAdV-C5 infection in various human cell lines. MKRN1 protein degradation occurred independently of the HAdV E1B55K and E4orf6 proteins. We provide experimental evidence that the precursor pVII protein binding enhances MKRN1 self-ubiquitination, whereas the processed mature VII protein is deficient in this function. Based on these data, we propose that the pVII protein binding promotes MKRN1 self-ubiquitination, followed by proteasomal degradation of the MKRN1 protein, in HAdV-C5-infected cells. In addition, we show that measles virus and vesicular stomatitis virus infections reduce the MKRN1 protein accumulation in the recipient cells. Taken together, our results expand the functional repertoire of the HAdV-C5 precursor pVII protein in lytic virus infection and highlight MKRN1 as a potential common target during different virus infections.

IMPORTANCE
Human adenoviruses (HAdVs) are common pathogens causing a wide range of diseases. To achieve pathogenicity, HAdVs have to counteract a variety of host cell antiviral defense systems, which would otherwise hamper virus replication. In this study, we show that the HAdV-C5 histone-like core protein pVII binds to and promotes self-ubiquitination of a cellular E3 ubiquitin ligase named MKRN1. This mutual interaction between the pVII and MKRN1 proteins may prime MKRN1 for proteasomal degradation, because the MKRN1 protein is efficiently degraded during the late phase of HAdV-C5 infection. Since MKRN1 protein accumulation is also reduced in measles virus- and vesicular stomatitis virus-infected cells, our results signify the general strategy of viruses to target MKRN1.
Effective Priming of Herpes Simplex Virus-Specific CD8
+
T Cells
In Vivo
Does Not Require Infected Dendritic Cells
Authors: Whitney Paul G. , Makhlouf Christina , MacLeod Beth , Ma Joel Z. , Gressier Elise , Greyer Marie , Hochheiser Katharina , Bachem Annabell , Zaid Ali , Voehringer David , Heath William R. , Wagle Mayura V. , Parish Ian , Russell Tiffany A. , Smith Stewart A. , Tscharke David C. , Gebhardt Thomas , Bedoui Sammy
Published: November 2017

Resolution of virus infections depends on the priming of virus-specific CD8
+
T cells by dendritic cells (DC). While this process requires major histocompatibility complex (MHC) class I-restricted antigen presentation by DC, the relative contribution to CD8
+
T cell priming by infected DC is less clear. We have addressed this question in the context of a peripheral infection with herpes simplex virus 1 (HSV). Assessing the endogenous, polyclonal HSV-specific CD8
+
T cell response, we found that effective
in vivo
T cell priming depended on the presence of DC subsets specialized in cross-presentation, while Langerhans cells and plasmacytoid DC were dispensable. Utilizing a novel mouse model that allows for the
in vivo
elimination of infected DC, we also demonstrated
in vivo
that this requirement for cross-presenting DC was not related to their infection but instead reflected their capacity to cross-present HSV-derived antigen. Taking the results together, this study shows that infected DC are not required for effective CD8
+
T cell priming during a peripheral virus infection.

IMPORTANCE
The ability of some DC to present viral antigen to CD8
+
T cells without being infected is thought to enable the host to induce killer T cells even when viruses evade or kill infected DC. However, direct experimental
in vivo
proof for this notion has remained elusive. The work described in this study characterizes the role that different DC play in the induction of virus-specific killer T cell responses and, critically, introduces a novel mouse model that allows for the selective elimination of infected DC
in vivo
. Our finding that HSV-specific CD8
+
T cells can be fully primed in the absence of DC infection shows that cross-presentation by DC is indeed sufficient for effective CD8
+
T cell priming during a peripheral virus infection.
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

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

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

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

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

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

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

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

Purpose

To 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.

Methods

Literature 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.

Results

We 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.

Conclusions

The 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 number

CRD42017054733.
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

Objective

Human 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.

Design

We 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.

Results

We 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.

Conclusions

Our 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

Objective

We characterised the clinical course, treatment and outcomes in 59 patients with relapsing myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelination.

Methods

We 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.

Results

The 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).

Conclusion

Relapsing 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.
The devastating effect of exposure to high irradiation dose on liver and the performance of synthesized nano-Hap in relieve the associated symptoms in rats
Authors: Abdel-Gawad Eman I. , Awwad Sameh A.
Published: November 2017

Ionizing radiation is one of the environmental factors that may contribute to liver dysfunction through a mechanism involving oxidative stress. This investigation studied the possible therapeutic effects of nano-HAp on hepatotoxicity in rats induced with gamma (γ) radiation. The study was carried out using 3 groups with 10 rats in each. Group 1 comprised the non-irradiated control rats, whereas the rats in groups 2 and 3 received a single dose of 10 Gy γ-radiation. The rats in group 3 were treated with nano-HAp [100 mg·(kg body mass)−1] once a week for 2 weeks starting the day after irradiation. The results showed that the rats exposed to γ-radiation had fragmented DNA, and significantly decreased levels of liver tissue enzymes such as paraoxonase 1, gamma glutamyl, alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Pro-inflammatory factors such as interleukin (IL)-2, IL-6, tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ) in tissue were significantly increased compared with the controls. Also, exposure to γ-radiation significantly decreased the activity of superoxide dismutase and glutathione oxidase and increased lipid peroxidation in liver tissue. These effects were accompanied by severe histopathological changes to the hepatocytes. Intravenous injection of nano-HAp after irradiation has significant therapeutic potential against irradiation-induced liver damage because the treatment with nano-HAp restored antioxidant activity in the liver, antagonized the significant changes in the levels of IL-2, IL-6, TNF-α, IFN-γ, and restored the tissue level of paraoxonase 1, gamma glutamyl, ALT, and AST. Administering nano-HAp seemed to relieve the pathological changes induced by γ-radiation. Based on these results, it could be concluded that nano-HAp may have a therapeutic effect against liver dysfunction induced by γ-radiation through antagonizing the generation of free radicals and enhancing the antioxidant defense mechanisms.
The vesicular Sainte-Sophie dykes: a chemically distinct, near-surface facies of the Grenville Dyke Swarm?
Authors: Higgins Michael D. , Hankard Fatim , Ganerød Morgan , Van der Voo Rob
Published: November 2017

Undeformed and unmetamorphosed diabase dykes up to 5 m wide occur in an area of ∼100 km2 about 50 km northwest of Montreal near the village of Sainte-Sophie. The dykes are subvertical and oriented east–west. The most common phenocryst phase is plagioclase (1–2 mm, exceptionally 10 mm), followed by olivine, and in one dyke, pyroxene. Most dykes have vesicles 0.1–10 mm in diameter and fine-grained margins. Alteration is extensive: plagioclase is partly sericitized, olivine is serpentinized, and zeolites and carbonate are developed in the vesicles and matrix. Ar–Ar dating was challenging, but the weighted mean of two plateau ages indicates intrusion and cooling at 591.6 ± 2.5 Ma. The overall characteristics of these dykes suggest that they may be a facies of the much larger Grenville dyke swarm to the west. However, there are distinct chemical differences that suggest they were fed from a different, generally more enriched mantle source. This zone may be related to the one that produced the alkaline Monteregian intrusions some 470 million years later in the same region. If the Sainte-Sophie dykes are part of the Grenville dyke event, then the use of chemical fingerprints to identify components of this swarm must be used with caution. Another difference between the Sainte-Sophie and main Grenville dykes is the presence of vesicles and zeolites in the former, which suggests the dykes were emplaced close to the surface; hence, this crustal block has seen little erosion during the last 600 million years.
FINANCIAL INCLUSION, POVERTY, AND INCOME INEQUALITY
Authors: PARK CYN-YOUNG , MERCADO ROGELIO
Published: November 2017

This paper extends the existing literature on financial inclusion by analyzing the factors affecting financial inclusion and assessing the impact of financial inclusion on poverty and income inequality in the world and Asia. We construct a new financial inclusion indicators to assess various macroeconomic and country-specific factors affecting the degree of financial inclusion for 176 economies, including 37 of which from developing Asia. We test the impact of financial inclusion, along with other control variables, on poverty and income inequality. We do so for full sample of countries and then for developing Asia sample to access which factors are relevant for full sample and for developing Asia specifically. The estimation results show that per capita income, rule of law, and demographic characteristics significantly affect financial inclusion for both world and Asia samples. However, primary education completion and literacy significantly increases financial inclusion only in the full sample, not for the Asian sample. The findings also indicate that financial inclusion is significantly correlated with lower poverty and income inequality levels for the full sample. For developing Asia, however, there appears to be no link between financial inclusion and income inequality.
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.
Broadband anomalous reflection caused by unsymmetrical specific acoustic impedance in phononic crystals
Authors: Han S. K. , Wu C. W. , Chen Z.
Published: November 2017

We investigate through numerical simulation the anomalous reflection (AR) of acoustic waves with perfect phononic crystals (PCs). Broadband AR is observed in a wide angle for the oblique incidence. The AR is due to the unsymmetrical specific acoustic impedance (SAI) profile along the surface, which is caused by the high frequency incidence. The findings in this paper complement the theories for the AR of acoustic waves with PCs, and may find applications in acoustic engineerings.
Editorial: To Honor Our Mentor and Friend, Professor L. A. Zadeh
Authors: Wang Peizhuang , Guo Guirong , Shi Yong , Liu Zhenliang
Published: November 2017

On 6 September 2017, the global scholars and professionals were mourning the death of professor L. A. Zadeh. This paper briefly recalls the historical significance of fuzzy mathematics, Zadeh’s friendship with China and what his academic thoughts have been carried out in China.
Flexure Analysis of Laminated Plates Using Multiquadratic RBF Based Meshfree Method
Authors: Solanki Manoj Kumar , Kumar Rahul , Singh Jeeoot
Published: November 2017

The linear and nonlinear flexure analysis of laminated plates with twenty theories with the five variable higher order shear deformation theory (HSDT) is investigated using multiquadratic radial basis function based meshfree method. The mathematical formulation of the actual physical problem of the plate subjected to transverse loading is presented utilizing von Karman nonlinear kinematics. These non-linear governing differential equations of equilibrium are linearized using quadratic extrapolation technique. The different results for deflection and stresses are obtained for thin to a thick plate and compared with some published results. It is observed that some of the theories taken here are well suited for analysis of thin as well as a thick plate while some theories are suited only for thin plates.
On Baer–Kaplansky Classes of Modules
Authors: Tütüncü Derya Keskin , Tribak Rachid
Published: November 2017

We are interested in studying when the class of local modules is Baer–Kaplansky. We provide an example showing that even over a commutative semisimple ring R, we can find two non-isomorphic simple R-modules S1 and S2 such that the rings EndR(S1) and EndR(S2) are isomorphic. We show that over any ring R, the class of semisimple R-modules is Baer–Kaplansky if and only if so is the class of simple R-modules.
LIBS
Authors: Nguyen Anh , Alqurashi Raghda , Raghebi Zohreh , Banaei-Kashani Farnoush , Halbower Ann C. , Vu Tam
Published: November 2017

Excerpted from "A Lightweight and Inexpensive In-ear Sensing System For Automatic Whole-night Sleep Stage Monitoring," from ACM SenSys 2016, Proceedings of the 14th ACM Conference on Embedded Network Sensor Systems, with permission. http://dl.acm.org/citation.cfm?id=2994562 ACM 2016