bluuebunny/crossref_metadata_2025 huggingface dataset:
The reproducibility of skeletal muscle signal intensity on routine magnetic resonance imaging in Crohn's disease
Authors: Spooren Corinne E.G.M. , Lodewick Toine M. , Beelen Evelien M.J. , van Dijk David P.J. , Bours Martijn J.L. , Haans Jeoffrey J. , Masclee Ad A.M. , Pierik Marie J. , Bakers Frans C.H. , Jonkers Daisy M.A.E.
Published: April 2020

Background and Aim

Myosteatosis is a prognostic factor in cancer and liver cirrhosis. It can be determined noninvasively using computed tomography or, as shown recently, by magnetic resonance (MR) imaging. The primary aim was to analyze the reproducibility of skeletal muscle signal intensity on routine MR‐enterographies, as indicator of myosteatosis, in Crohn's disease (CD) and to explore the association between skeletal muscle signal intensity at diagnosis with time to intestinal resection.

Methods

CD patients undergoing MR‐enterography within 6 months from diagnosis and having a maximum of 5 years follow‐up were included. Skeletal muscle signal intensity was analyzed on T1‐weighted fat‐saturated post‐contrast images. Intra‐observer and inter‐observer reproducibilities were assessed by intra‐class correlation coefficient and Cohen's kappa. Intra‐observer and inter‐observer variabilities were determined by Pearson correlation coefficient and displayed by Bland–Altman plots. Time to intestinal resection was studied by Kaplan–Meier analysis.

Results

Median time between diagnosis and MR‐enterography was 5 weeks (inter‐quartile range 1–9) in 35 CD patients. Skeletal muscle signal intensity showed good intra‐class correlation and substantial agreement (for intra‐observer, intraclass correlation coefficient = 0.948, κ = 0.677; and inter‐observer reproducibility, intraclass correlation coefficient = 0.858, κ = 0.622). Resection free survival was shorter in the low skeletal muscle signal intensity group (P = 0.037).

Conclusion

Skeletal muscle signal intensity on routine MR‐enterographies is reproducible and was associated with unfavorable disease outcome, indicating potential clinical relevance.
Determination of detection thresholds of sinigrin in water‐based matrix and allyl isothiocyanate in water‐ and oil‐based matrices
Authors: Eib Sabrina , Ramos Gajek Sarah , Schneider Désirée Janet , Hensel Oliver , Seuss‐Baum Ingrid
Published: April 2020

In the present study, sensory detection thresholds for sinigrin in a water‐based matrix and allyl isothiocyanate (AITC) in water‐ and oil‐based matrices were determined using a three‐alternative forced choice test with ascending concentrations. The study consisted of a prestudy with 10 assessors (3 mustard “users”; 7 mustard “nonusers”) and a main study with 64 assessors (10 mustard “users”; 54 mustard “nonusers”). In addition, panelists were asked to locate (throat, tongue, throat, and tongue) the predominant sensation (sinigrin: bitterness; AITC: pungency). The group threshold for sinigrin in the water‐based matrix in the prestudy was 10.928 mg/100 ml. Moreover, the group thresholds for AITC in the water‐based matrix in the prestudy and main study were 0.135 and 0.121 mg/100 ml, respectively. The group thresholds for AITC in the oil‐based matrix in the prestudy and main studies were 0.497 and 0.582 mg/100 ml, respectively. However, mustard “users” and mustard “nonusers” showed no significant differences in thresholds. Sinigrin and AITC were both prevalently perceived on the tongue.

Practical applications

Threshold determination for the primary pungent substance allyl isothiocynanate (AITC) and the corresponding precursor sinigrin in cruciferous plants such as mustard, horseradish, and wasabi are important for product development and quality assurance, especially for new products. These parameters will help to estimate whether pungency is a relevant characteristic of the product. In particular, differentiation of the matrix (water‐ or oil‐based matrix) helps to evaluate whether the particular AITC concentration is noticeable in food products depending on the food composition. Further studies should be conducted to determine whether AITC is perceived at the same levels in different food systems. Sinigrin causes the unpleasant bitterness of brassica vegetables. Nevertheless, sinigrin is a desirable substance in food products owing to its potential health‐promoting effects. Therefore, knowledge about the detection threshold of sinigrin will facilitate the breeding of sinigrin‐containing products without unpleasant bitterness and may increase consumer acceptance.
Baseline sensitivities to azoxystrobin and tebuconazole in Sclerotinia sclerotiorum isolates from sunflower in Iran related to sensitivities to carbendazim and iprodione
Authors: Molaei Havva , Abrinbana Masoud , Ghosta Youbert
Published: April 2020

In this study, sensitivities of 156 Sclerotinia sclerotiorum isolates collected from sunflower fields of West Azarbaijan province, Iran, were assessed to carbendazim and iprodione, and the baseline sensitivities were established for azoxystrobin and tebuconazole. Resistance to carbendazim and iprodione was observed in 53.85% and 4.49% of the isolates, respectively. The 50% effective concentration (EC50) values of azoxystrobin for the isolates ranged from 0.017 to 3.515 μg/ml with a mean of 0.330 μg/ml, and 8.97% of the strains showed low levels of resistance to the fungicide. However, in the presence of salicylhydroxamic acid, all isolates were sensitive to azoxystrobin and EC50 values ranged from 0.015 to 0.263 μg/ml with a mean of 0.086 μg/ml. All isolates were found to be sensitive to tebuconazole, and EC50 values ranged from 0.003 to 0.177 μg/ml with a mean of 0.036 μg/ml. Among the multiple‐resistant isolates, the strains exhibiting resistance to both carbendazim and iprodione were detected in the highest frequency (4.49%). No correlation was observed between mycelial growth and aggressiveness with fungicide sensitivity of the isolates suggesting the absence of fitness cost associated with resistance to the studied fungicides. The results indicated that iprodione, azoxystrobin and tebuconazole could be effectively used in rotation or mixture in spray programmes to manage S. sclerotiorum in the region. The baselines established for azoxystrobin and tebuconazole would be useful in monitoring the fungal populations in the province to assess possible shifts in fungicide sensitivity of S. sclerotiorum isolates in the future.
Description of Freudenthalidium gen. nov. and Halluxium gen. nov. to Formally Recognize Clades Fr3 and H as Genera in the Family Symbiodiniaceae (Dinophyceae)
Authors: Nitschke Matthew R. , Craveiro Sandra C. , Brandão Cláudio , Fidalgo Cátia , Serôdio João , Calado António J. , Frommlet Jörg C.
Published: April 2020

The Symbiodiniaceae are a family of marine dinoflagellates known mostly for their endosymbiotic interactions with invertebrates and protists, but facultatively and exclusively free‐living life histories in this family are also evident. A recent systematic revision of the Symbiodiniaceae replaced the clade‐based nomenclature of seven divergent lineages of “Symbiodinium” sensu lato with one based on formally described genera. The revised taxonomy was not extended to the whole group because type species to describe a new genus for each of the remaining clades and subclades were lacking. In an effort to characterize benthic habitats of symbiodiniaceans in sediments at Heron Island (Great Barrier Reef, Australia), we isolated >100 monoclonal Symbiodiniaceae cultures. Four of these belonged to Symbiodiniaceae ‘subclade’ Fr3, and three to Clade H, based on nucleotide sequence similarity (ITS2, LSU, cp23S, and mtCOB), representing the first cultures of these taxa. Based on these isolates, we propose two new genera: Freudenthalidium gen. nov. and Halluxium gen. nov., circumscribing Clades Fr3 and H, respectively. Three new species are described: Freudenthalidium heronense, F. endolithicum, and Halluxium pauxillum. Kofoidian tabulations of motile cells confirm previous observations that amphiesmal vesicle arrangements are generally conserved across the family. These descriptions are an important step toward completing the systematic revision of the Symbiodiniaceae. That this contribution was enabled by isolates from an endopsammic habitat highlights the potential of discovering new symbiodiniacean species in the environment, the study of which will lead to a deeper understanding of free‐living versus symbiotic life histories in this ecologically important family of dinoflagellates.
Termite mound vegetation patterns are largely driven by stochastic rather than deterministic processes at regional scale in Africa: A meta‐analysis
Authors: Muvengwi Justice , Witkowski Edward T. F.
Published: April 2020

Questions

Although the biogeography of plant communities has been well studied, mechanisms controlling plant community diversity are still poorly understood. Stochastic and deterministic processes are hotly debated as being key in structuring communities across taxa. Here we ask, to what extent are plant communities on termite mounds shaped by either stochastic or deterministic processes within and between regions on the African continent?

Methods

We performed a meta‐analysis on 23 studies that satisfied our selection criteria out of 369 that we initially identified. All these studies sampled woody plants that occurred on termite mounds and the surrounding matrix. In order to disentangle the relative importance of deterministic and stochastic processes in generating beta diversity between mound–mound and matrix–matrix plots, within and between regions, we applied null models. We also assessed the relationship between species richness and environmental variables for each site.

Results

Of the environmental variables assessed at each site, only altitude had a significant (negative) relationship with species richness. Within each region comparison of mound–mound, matrix–matrix and matrix–mound species composition did not significantly deviate from the null models of random expectation. Between regions, the observed pattern was significantly higher than null expectation for both mound–mound and matrix–matrix plots between East and West Africa. Surprisingly, the comparison between southern Africa and both East and West Africa did not significantly deviate from the null expectation, regardless of increased spatial separation. We attributed the within‐region pattern to homogenizing dispersal and reliance on the same species pool (γ) for matrix and mound plots. The between‐regions pattern was influenced by both deterministic and stochastic processes.

Conclusion

Our results suggest that the processes responsible for vegetation composition between mound–mound, matrix–matrix and mound–matrix plots are stochastic in nature due to lack of difference from the null expectation. However, regional patterns are governed by both deterministic and stochastic processes.
A martingale representation theorem and valuation of defaultable securities
Authors: Choulli Tahir , Daveloose Catherine , Vanmaele Michèle
Published: April 2020

We consider a financial framework with two levels of information: the public information generated by the financial assets, and a larger flow of information that contains additional knowledge about a random time. This random time can represent many economic and financial settings, such as the default time of a firm for credit risk, and the death time of an insured for life insurance. As the random time cannot be seen before its occurrence, the progressive enlargement of filtration seems tailor‐fit to model the larger flow of information that incorporates both the public flow and the information about the random time. In this context, our interest focuses on the following challenges: (a) How to single out the various risks coming from the financial assets, the random time, and their correlations? (b) How these risks interplay and lead to the formation of any risk in the larger flow of information? It is clear that understanding how risks build‐up and interact, when one enlarges the flow of information, is vital for an efficient risk management and derivatives' evaluation in those informational markets. Our answers to these challenges are full and complete no matter what the model for the random time is and no matter how the random time is related to the public flow. In fact, we introduce “pure default” risks, and quantify and classify these risks afterward. Then we elaborate our martingale representation results, which state that any martingale in the large filtration stopped at the random time can be decomposed into orthogonal local martingales (i.e., local martingales whose product remains a local martingale). This constitutes our first principal contribution, while our second contribution consists in evaluating various defaultable securities according to the recovery policy, within our financial setting that encompasses any default model, using a martingale “basis.” Our pricing formulas explain the impact of various recovery policies on securities and determine the types of pure default risk they entail.
A spontaneous missense mutation in the chromodomain helicase DNA‐binding protein 8 (CHD8) gene: a novel association with congenital myasthenic syndrome
Authors: Lee C. Y. , Petkova M. , Morales‐Gonzalez S. , Gimber N. , Schmoranzer J. , Meisel A. , Böhmerle W. , Stenzel W. , Schuelke M. , Schwarz J. M.
Published: April 2020

Aims

Congenital myasthenic syndromes (CMS) are characterized by muscle weakness, ptosis and episodic apnoea. Mutations affect integral protein components of the neuromuscular junction (NMJ). Here we searched for the genetic basis of CMS in female monozygotic twins.

Methods

We employed whole‐exome sequencing for mutation detection and Sanger sequencing for segregation analysis. Immunohistology was done with antibodies against CHD8, rapsyn, β‐catenin (βCAT) and golgin on fi‐bro‐blasts, human and mouse muscle. We recorded superresolution images of the NMJ using 3D‐structured illumination microscopy.

Results

We discovered a spontaneous missense mutation in CHD8 [chr14:g.21,884,051G>A, GRCh37.p11 | c.1732C>T, NM_00117062 | p.(R578C)], the gene encoding chromodomain helicase DNA‐binding protein 8. This is the first missense mutation affecting Duplin, the short 110 kDa isoform of CHD8. It is known that CHD8/Duplin negatively regulates βCAT signalling in the WNT pathway and plays a role in chromatin remodelling. Inactivating CHD8 mutations are associated with autism spectrum disorder and intellectual disability in combination with facial dysmorphism, overgrowth and macrocephalus. No muscle‐specific phenotype has been reported to date. Co‐immunostaining with rapsyn on human and mouse muscle revealed a strong presence of CHD8 at the NMJ being located towards the sarcoplasmic side of the rapsyn cluster, where it co‐localizes with βCAT.

Conclusion

We hypothesize CHD8 to have a role in the maintenance of the structural integrity and function of the NMJ. Both patients benefited from treatment with 3,4‐diaminopyridine, a reversible blocker of voltage‐gated potassium channels at the nerve terminal that prolongs the action potential and increases acetylcholine release.
East/West Visiting Scholars in Pediatric Anesthesia Program (ViSiPAP): Developing tomorrow’s pediatric anesthesia leaders
Authors: Ferschl Marla B. , Lee Jennifer K. , Lockman Justin L. , Black Stephanie , Chatterjee Debnath , Agarwal Rita , Schwartz Lawrence I. , Fiadjoe John , Heitmiller Eugenie , Mershon Bommy Hong , Deutsch Nina , McCloskey John , Infosino Andrew
Published: April 2020

Promoting and retaining junior faculty are major challenges for many medical schools. High clinical workloads often limit time for scholarly projects and academic development, especially in anesthesiology. To address this, we created the East/West Visiting Scholars in Pediatric Anesthesia Program (ViSiPAP). The program's goal is to help “jumpstart” academic careers by providing opportunities for national exposure and recognition through invited lectures and collaborative opportunities. East/West ViSiPAP benefits the participating scholars, the home and hosting anesthesia departments, and pediatric anesthesia fellowship training programs. By fostering a sense of well‐being and inclusion in the pediatric anesthesia community, East/West ViSiPAP has the potential to increase job satisfaction, help faculty attain promotion, and reduce attrition. Faculty and trainees are exposed to new expertise and role models. Moreover, ViSiPAP provides opportunities for women and underrepresented in medicine faculty. This program can help develop today's junior faculty into tomorrow's leaders in pediatric anesthesia. We advocate for expanding the concept of ViSiPAP to other institutions in academic medicine.
Water security: A litmus test for international law
Authors: Magsig Bjørn‐Oliver
Published: April 2020

While water security is now being discussed at the highest political level, the debate on how the concept should actually be implemented to improve the management of our transboundary freshwater resources is still in its infancy. Further, the absence of law in much of this debate impedes efforts to utilize water security as a change agent for international water law and diplomacy – an unsatisfactory situation threatening global stability and international security. This article demonstrates that a fresh conceptualization of water security is not only required to bring about the desperately needed change in the underlying perceptions of sovereignty, but that it is also possible. However, this will only work if international law plays its part in turning the buzzword into a meaningful concept. By supporting the contemporary understanding of water security through strengthening normative developments regarding the concepts of common concern and cooperative sovereignty, these concepts of international law could simultaneously be better employed to tackle other increasingly complex global challenges.
Endobronchial coils for emphysema: Dual mechanism of action on lobar residual volume reduction
Authors: Hartman Jorine E. , Shah Pallav L. , Sciurba Frank , Herth Felix J.F. , Slebos Dirk‐Jan ,   RENEW Study Group
Published: April 2020

Residual lobar volume reduction in treated lobes measured by QCT was found to be the driving mechanism of action of endobronchial coils leading to positive clinical outcomes. However, the improvement in exercise capacity and quality of life seems to be affected by the presence of cardiac disease.

See related Editorial
Conservation science and technology identity instrument: Empirically measuring STEM identities in informal science learning programs
Authors: Rodriguez Laura S. , Morzillo Anita , Volin John C. , Campbell Todd
Published: April 2020

Our research centered on developing the Conservation Science and Technology Identity (CSTI) instruments as an empirical way to measure STEM identities and the intersection of identity constructs such as competence, performance, recognition, and ways of seeing and being. The surveys were used in a large funded multi‐year project for teens and adults learning geospatial technologies and conservation science to use in intergenerational community conservation projects. We investigated whether an informal STEM learning program was developing new STEM identities or advancing well‐developed identities. The instruments’ content validity was determined through a vetting process from national STEM identity research experts. Reliability was estimated with Cronbach coefficient alpha. Mann‐Whitney and Wilcoxon Signed Rank tests were used to determine participants’ STEM identities and the workshop’s effect on specific identity constructs. We found teens and adults had historically similar STEM identities, with stronger conservation science than technology. Both science and technology competences, as well as technology ways of seeing and being, significantly increased, suggesting CSTI can be a valuable instrument in empirically assessing STEM identities.
Online education platforms scale college STEM instruction with equivalent learning outcomes at lower cost
Authors: Chirikov Igor , Semenova Tatiana , Maloshonok Natalia , Bettinger Eric , Kizilcec René F.
Published: April 2020

Online platforms are an affordable and effective solution to expand STEM education.
The pharyngeal nervous system orchestrates feeding behavior in planarians
Authors: Miyamoto Mai , Hattori Miki , Hosoda Kazutaka , Sawamoto Mika , Motoishi Minako , Hayashi Tetsutaro , Inoue Takeshi , Umesono Yoshihiko
Published: April 2020

Specialization of modular functions in the peripheral nervous system orchestrates feeding behavior in planarians.
Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS–coronavirus 2
Authors: Shi Jianzhong , Wen Zhiyuan , Zhong Gongxun , Yang Huanliang , Wang Chong , Huang Baoying , Liu Renqiang , He Xijun , Shuai Lei , Sun Ziruo , Zhao Yubo , Liu Peipei , Liang Libin , Cui Pengfei , Wang Jinliang , Zhang Xianfeng , Guan Yuntao , Tan Wenjie , Wu Guizhen , Chen Hualan , Bu Zhigao
Published: April 2020

Alternative hosts and model animals

The severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) pandemic may have originated in bats, but how it made its way into humans is unknown. Because of its zoonotic origins, SARS-CoV-2 is unlikely to exclusively infect humans, so it would be valuable to have an animal model for drug and vaccine development. Shi
et al.
tested ferrets, as well as livestock and companion animals of humans, for their susceptibility to SARS-CoV-2 (see the Perspective by Lakdawala and Menachery). The authors found that SARS-CoV-2 infects the upper respiratory tracts of ferrets but is poorly transmissible between individuals. In cats, the virus replicated in the nose and throat and caused inflammatory pathology deeper in the respiratory tract, and airborne transmission did occur between pairs of cats. Dogs appeared not to support viral replication well and had low susceptibility to the virus, and pigs, chickens, and ducks were not susceptible to SARS-CoV-2.

Science
, this issue p.
1016
; see also p.
942
Functional Properties of Helicobacter pylori VacA Toxin m1 and m2 Variants
Authors: Caston Rhonda R. , Sierra Johanna C. , Foegeding Nora J. , Truelock Mandy D. , Campbell Anne M. , Frick-Cheng Arwen E. , Bimczok Diane , Wilson Keith T. , McClain Mark S. , Cover Timothy L.
Published: April 2020

Helicobacter pylori
colonizes the gastric mucosa and secretes a pore-forming toxin (VacA). Two main types of VacA, m1 and m2, can be distinguished by phylogenetic analysis. Type m1 forms of VacA have been extensively studied, but there has been relatively little study of m2 forms. In this study, we generated
H. pylori
strains producing chimeric proteins in which VacA m1 segments of a parental strain were replaced by corresponding m2 sequences. In comparison to the parental m1 VacA protein, a chimeric protein (designated m2/m1) containing m2 sequences in the N-terminal portion of the m region was less potent in causing vacuolation of HeLa cells, AGS gastric cells, and AZ-521 duodenal cells and had reduced capacity to cause membrane depolarization or death of AZ-521 cells.
Role of Pseudomonas aeruginosa Glutathione Biosynthesis in Lung and Soft Tissue Infection
Authors: Michie Kelly L. , Dees Justine L. , Fleming Derek , Moustafa Dina A. , Goldberg Joanna B. , Rumbaugh Kendra P. , Whiteley Marvin
Published: April 2020

The opportunistic pathogen
Pseudomonas aeruginosa
is a leading cause of morbidity and mortality worldwide. To survive in both the environment and the host,
P. aeruginosa
must cope with redox stress. In
P. aeruginosa
, a primary mechanism for protection from redox stress is the antioxidant glutathione (GSH). GSH is a low-molecular-weight thiol-containing tripeptide (
l
-γ-glutamyl-
l
-cysteinyl-glycine) that can function as a reversible reducing agent.
Aging Dampens the Intestinal Innate Immune Response during Severe Clostridioides difficile Infection and Is Associated with Altered Cytokine Levels and Granulocyte Mobilization
Authors: Abernathy-Close Lisa , Dieterle Michael G. , Vendrov Kimberly C. , Bergin Ingrid L. , Rao Krishna , Young Vincent B.
Published: April 2020

Clostridioides
(formerly
Clostridium
)
difficile
is the most common cause of hospital-acquired infection, and advanced age is a risk factor for
C. difficile
infection. Disruption of the intestinal microbiota and immune responses contribute to host susceptibility and severity of
C. difficile
infection. However, the specific impact of aging on immune responses during
C. difficile
infection remains to be well described.
Increase of CD26/Dipeptidyl Peptidase IV Expression on Human Gingival Fibroblasts upon Stimulation with Cytokines and Bacterial Components
Authors: Nemoto Eiji , Sugawara Shunji , Takada Haruhiko , Shoji Shigeru , Horiuch Hiroshi
Published: April 2020

CD26/dipeptidyl peptidase IV (DPPIV) is a cell surface ectoenzyme which participates in immune and inflammatory reactions. We found that CD26 was only partially expressed on human fibroblasts from periodontal tissues, whereas fibroblasts from lung and skin expressed CD26 constitutively as revealed by flow cytometry. We examined the possible upregulation of CD26 expression on human gingival fibroblasts in response to various stimulants. Interleukin-1α (IL-1α); tumor necrosis factor alpha; gamma interferon; lipopolysaccharide fromPorphyromonas gingivalis,Prevotella intermedia, andEscherichia coli; andPrevotellaglycoprotein augmented CD26 expression on gingival fibroblasts. Among the stimulants, IL-1α exhibited the most potent activity. Enzymatic activity of CD26 induced by IL-1α on fibroblasts was determined colorimetrically in terms of Gly-Pro hydrolysis of a synthetic chromogenic substrate, Gly-Prop-nitroanilide. Among various inhibitors tested, diprotin A and phenylmethylsulfonyl fluoride inhibited the enzymatic activity, suggesting that the enzyme induced by IL-1α was DPPIV. The upregulation of CD26 mRNA expression upon stimulation with IL-1α was also revealed by a quantitative reverse transcription-PCR assay. In the kinetic experiment, 48 h and several days were required for maximum CD26 mRNA accumulation and CD26 molecule expression on the cell surface, respectively. The addition of cycloheximide at 2 h before IL-1α stimulation almost completely inhibited the accumulation of CD26 mRNA. These results suggested that induction of CD26 on human gingival fibroblasts is regulated at the transcriptional level and is also dependent on a de novo-synthesized protein factor(s).
Expression of Recombinant EnterotoxigenicEscherichia coliColonization Factor Antigen I bySalmonella typhimuriumElicits a Biphasic T Helper Cell Response
Authors: Pascual David W. , Hone David M. , Hall Stacy , van Ginkel Frederik W. , Yamamoto Masafumi , Walters Nancy , Fujihashi Kohataro , Powell Robert J. , Wu Shaoguang , Vancott John L. , Kiyono Hiroshi , McGhee Jerry R.
Published: April 2020

Protective immunity to enterotoxigenicEscherichia coli(ETEC) is antibody (Ab) dependent; however, oral immunization with purified ETEC fimbriae fails to elicit protective immunity as a consequence of antigenic alteration by the gastrointestinal (GI) tract. Unless unaltered ETEC fimbriae can reach the inductive lymphoid tissues of the GI tract, immunity to ETEC cannot be induced. To produce immunity, live vectors, such asSalmonella typhimurium, can effectively target passenger antigens to the inductive lymphoid tissues of the GI tract. By convention, oral immunizations withSalmonellavectors induce CD4+T helper (Th) cell responses by gamma interferon (IFN-γ)-dominated pathways both to the vector and passenger antigen, resulting in serum immunoglobulin G2a (IgG2a) and modest mucosal IgA Ab responses. In the present study, mice orally immunized with aSalmonellavector engineered to stably express ETEC colonization factor antigen I (CFA/I) showed initially elevated serum IgG1 and mucosal IgA anti-CFA/I Ab responses. As expected, mice orally immunized with anE. coli-CFA/I construct elicited poor anti-CFA/I Ab responses. In fact, the addition of cholera toxin during oralE. coli-CFA/I immunization failed to greatly enhance mucosal IgA Ab responses. Seven days after immunization with theSalmonella-CFA/I construct, cytokine-specific ELISPOT showed induction of predominant Th2-type responses in both mucosal and systemic immune compartments supporting the early IgG1 and IgA anti-CFA/I Abs. By 4 weeks, the Th cell response became Th1 cell dominant from the earlier Th2-type responses, as evidenced by increased mucosal and systemic IFN-γ-producing T cells and a concomitant elevation of serum IgG2a Ab responses. This biphasic response offers an alternative strategy for directingSalmonellavector-induced host immunity along a Th2 cell-dependent pathway, allowing for early promotion of mucosal and systemic Abs.
Cytokine Profiles of AIDS Patients Are Similar to Those of Mice with DisseminatedCryptococcus neoformansInfection
Authors: Lortholary Olivier , Improvisi Luce , Rayhane Naima , Gray Francoise , Fitting Catherine , Cavaillon Jean Marc , Dromer Francoise
Published: April 2020

Cryptococcosis is an hematogenously disseminated meningoencephalitis during which the relationship between the disease severity and the immune response remains unclear. We thus analyzed, by enzyme-linked immunosorbent assay, proinflammatory (tumor necrosis factor alpha [TNF-α] and interleukin-6 [IL-6]) and anti-inflammatory (IL-10) cytokine levels in plasma at the time of diagnosis in 51 AIDS patients with culture-proven cryptococcosis. We used a murine model to determine the correlation between cytokine levels and fungal burden in blood and tissues and the kinetics of the immune response and of the formation of cerebral lesions. In AIDS patients, plasma TNF-α and IL-10, but not IL-6, levels were significantly higher in the case of fungemia or disseminated infection than in their absence, whereas the presence of meningitis had no influence on these levels. In mice, none of these cytokines were detected within the first day after inoculation. Later on, TNF-α and IL-10, but not IL-6, levels in plasma correlated significantly with the fungal burden in the blood and spleen but not the brain. In the brain, cytokine levels were low compared to those in other compartments, and tissue lesions and a degree of infection similar to those observed in humans were seen, further suggesting the relevance of this experimental model. Thus, AIDS patients with cryptococcosis produce an immune response that reflects the dissemination but not the meningeal involvement. This murine model of disseminated cryptococcosis can be used to investigate the pathophysiology of cryptococcosis and new therapeutic approaches.
Immunoglobulin Concentrations and Antigen-Specific Antibody Levels in Cervicovaginal Lavages of Rhesus Macaques Are Influenced by the Stage of the Menstrual Cycle
Authors: Lü F. Xusheng , Ma Zhongmin , Rourke Tracy , Srinivasan Seema , McChesney Michael , Miller Christopher J.
Published: April 2020

The levels of antigen-specific antibodies (Abs) and immunoglobulins in the cervical mucus of women vary with the menstrual cycle; the highest levels occur during menses, and the lowest occur during the periovulatory period. The rhesus macaque is a widely used animal model of female genital tract immunity. We sought to determine whether rhesus macaques have a cyclical pattern of changing cervicovaginal Ab and immunoglobulin levels that is similar to that of the human female. This study examined the relationship of the stages of the menstrual cycle to genital mucosal and systemic immunoglobulin concentrations and Ab levels in rhesus macaques. In all seven rhesus macaques studied, the immunoglobulins G and A and some antibodies in cervicovaginal lavages varied with the stages of the menstrual cycle, and in many cases this variation reached the level of statistical significance. In a pattern similar to that of women, the highest levels of Abs and immunoglobulins occurred during menses, and the lowest levels occurred around the time of ovulation. However, the Ab and immunoglobulin levels in serum and rectal lavages did not change with the menstrual cycle stage. The results of this study are consistent with the hypothesis that the ovarian hormones that drive the menstrual cycle influence genital tract immunity in female primates.
Characterization of the
angR
Gene of
Vibrio anguillarum
: Essential Role in Virulence
Authors: Wertheimer A. M. , Verweij W. , Chen Q. , Crosa L. M. , Nagasawa M. , Tolmasky M. E. , Actis L. A. , Crosa J. H.
Published: April 2020

The ability to utilize the iron bound by high-affinity iron-binding proteins in the vertebrate host is an important virulence factor for the marine fish pathogen
Vibrio anguillarum
. Virulence in septicemic infections is due to the presence of a highly efficient plasmid-encoded iron transport system. AngR, a 110-kDa protein component of this system, appears to play a role in both regulation of the expression of the iron transport genes
fatDCBA
and the production of the siderophore anguibactin. Therefore, study of the expression of the
angR
gene and the properties of its product, the AngR protein, may contribute to the understanding of the mechanisms of virulence of this pathogen. In this work, we present genetic and molecular evidence from transposition mutagenesis experiments and RNA analysis that
angR
, which maps immediately downstream of the
fatA
gene, is part of a polycistronic transcript that also includes the iron transport genes
fatDCBA
and
angT
, a gene located downstream of
angR
which showed domain homology to certain thioesterases involved in nonribosomal peptide synthesis of siderophores and antibiotics. In order to dissect the specific domains of AngR associated with regulation of iron transport gene expression, anguibactin production, and virulence, we also generated a panel of site-directed
angR
mutants, as well as deletion derivatives. Both virulence and anguibactin production were dramatically affected by each one of the
angR
modifications. In contrast to the need for an intact AngR molecule for anguibactin production and virulence, the regulation of iron transport gene expression does not require the entire AngR molecule, since truncation of the carboxy terminus carrying the nonribosomal peptide synthetase cores, as well as the site-directed mutations, resulted in derivatives that retained their ability to regulate gene expression which was only abolished after truncation of amino-terminal sequences containing helix-turn-helix and leucine zipper motifs and a specialized heterocyclization and condensation domain found in certain nonribosomal peptide synthetases. The evidence, while not rigorously eliminating the possibility that a separate regulatory polypeptide exists and is encoded somewhere within the 5′-end region of the
angR
gene, strongly supports the idea that AngR is a bifunctional protein and that it plays an essential role in the virulence mechanisms of
V. anguillarum
. We also show in this study that the
angT
gene, found downstream of
angR
, intervenes in the mechanism of anguibactin production but is not essential for virulence or iron transport gene expression.
ThepspCGene ofStreptococcus pneumoniaeEncodes a Polymorphic Protein, PspC, Which Elicits Cross-Reactive Antibodies to PspA and Provides Immunity to Pneumococcal Bacteremia
Authors: Brooks-Walter Alexis , Briles David E. , Hollingshead Susan K.
Published: April 2020

PspC is one of three designations for a pneumococcal surface protein whose gene is present in approximately 75% of allStreptococcus pneumoniaestrains. Under the name SpsA, the protein has been shown to bind secretory immunoglobulin A (S. Hammerschmidt, S. R. Talay, P. Brandtzaeg, and G. S. Chhatwal, Mol. Microbiol. 25:1113–1124, 1997). Under the name CbpA, the protein has been shown to interact with human epithelial and endothelial cells (C. Rosenow et al., Mol. Microbiol. 25:819–829, 1997). The gene is paralogous to thepspAgene inS. pneumoniaeand was thus calledpspC(A. Brooks-Walter, R. C. Tart, D. E. Briles, and S. K. Hollingshead, Abstracts of the 97th General Meeting of the American Society for Microbiology 1997). Sequence comparisons of five published and seven new alleles reveal that this gene has a mosaic structure, and modular domains have contributed to gene diversity during evolution. Two major clades exist: clade A alleles are larger and contain an extra module that is shared with manypspAalleles; clade B alleles are smaller and lack thispspA-like domain. All alleles have a proline-rich domain and a choline-binding repeat domain that show 0% divergence from similar domains in the PspA protein. Immunization of a rabbit with a recombinant clade B PspC molecule produced antiserum that cross-reacted with both PspC and PspA from 15 pneumococcal isolates. The cross-reactive antibodies afforded cross-protection in a mouse model system. Mice immunized with PspC were protected against challenge with a strain that expressed PspA but not PspC. The PspA- and PspC-cross-reactive antibodies were directed to the proline-rich domain present in both molecules.
Immunopathologic Alterations in Murine Models of Sepsis of Increasing Severity
Authors: Ebong Samuel , Call Douglas , Nemzek Jean , Bolgos Gerald , Newcomb David , Remick Daniel
Published: April 2020

We investigated inflammatory and physiologic parameters in sepsis models of increasing lethality induced by cecal ligation and puncture (CLP). Mice received imipenem for antibiotic therapy, and groups were sacrificed at 2, 4, 8, 12, 16, 20, and 24 h after CLP. The severity of sepsis increased with needle puncture size (lethality with 18-gauge puncture [18G], 100%; 21G, 50%; 25G, 5%; sham treatment, 0%). While the temperature (at 12 h) and the activity and diurnal rhythm (at day 4) of the 25G-treated CLP group recovered to normal, the 21G and 18G treatment groups exhibited severe hypothermia along with decreased activities. A direct correlation was also observed between the severity of sepsis and cytokine (interleukin 1β [IL-1β], tumor necrosis factor [TNF], IL-6, and IL-10) concentrations in both the peritoneum and the plasma. There were substantially higher cytokine levels in the more severe CLP models than in the sham-treated one. Peritoneal and plasma TNF levels were always less than 40 pg/ml in all models. None of the cytokines in the septic mice peaked within the first hour, which is in contrast to the results of most endotoxin models. Chemokine (KC and macrophage inflammatory protein 2) profiles also correlated with the severity of sepsis. Except for the chemokines, levels of inflammatory mediators were always higher at the site of inflammation (peritoneum) than in the circulation. Our study demonstrated that sepsis of increasing severity induced increased cytokine levels both within the local environment (peritoneum) and systemically (plasma), which in turn correlated with morbidity and mortality.
Peptide Localization and Gene Structure of Cryptdin 4, a Differentially Expressed Mouse Paneth Cell α-Defensin
Authors: Ouellette Andre J. , Darmoul Dalila , Tran Dat , Huttner Kenneth M. , Yuan Jun , Selsted Michael E.
Published: April 2020

Paneth cells in crypts of the small intestine express antimicrobial peptides, including α-defensins, termed cryptdins in mice. Of the known Paneth cell α-defensins, the cryptdin 4 gene is unique, because it is inactive in the duodenum and expressed at maximal levels in the distal small bowel (D. Darmoul and A. J. Ouellette, Am. J. Physiol. 271:G68–G74, 1996). With a cryptdin 4-specific antibody, immunohistochemical staining of ileal Paneth cells was strong and specific for cytoplasmic granules, demonstrating that this microbicidal peptide is a secretory product of Paneth cells in the distal small intestine. Consistent with the pattern of cryptdin 4 mRNA distribution along the length of the gut, the cryptdin 4 peptide was not detected in duodenum. Structurally, the cryptdin 4 gene resembles other Paneth cell α-defensin genes. Its two exons, transcriptional start site, intron, splice sites, and 3′ flanking sequences are characteristic of the highly conserved mouse α-defensin genes. However, in the region upstream of the transcriptional initiation site, the cryptdin 4 gene contains a repeated 130-bp element that is unique to this α-defensin gene. Every independent cryptdin 4 genomic clone examined carries the repeated element, which contains putative recognition sequences for TF-IID-EIIA, cMyc-RS-1, and IgHC.2/CuE1.1; the repeat proximal to the start of transcription replaces DNA at the corresponding position in other mouse α-defensin genes. We speculate that this unique duplicated element may have acis-acting regulatory role in the positional specificity of cryptdin 4 gene expression.
Analysis of Antibody Response to Invariable Regions of VlsE, the Variable Surface Antigen of
Borrelia burgdorferi
Authors: Liang Fang Ting , Philipp Mario T.
Published: April 2020

VlsE, the variable surface antigen of
Borrelia burgdorferi
, consists of two invariable domains at the amino and carboxyl termini and one central variable domain. The latter contains six invariable regions, IR
1
to IR
6
, and six variable regions. In the present study, the antigenicity of all of the invariable regions in
B. burgdorferi
-infected monkeys, humans, and mice was assessed by peptide-based enzyme-linked immunosorbent assays. Only one invariable region, IR
6
, was antigenic in all animals of the three host species. IR
2
and IR
4
were also antigenic in mice.
Delivery of a MalE CD4+-T-Cell Epitope into the Major Histocompatibility Complex Class II Antigen Presentation Pathway byBordetella pertussisAdenylate Cyclase
Authors: Loucká Jir̆ina , Schlecht Géraldine , Vodolánová Jana , Leclerc Claude , S̆ebo Peter
Published: April 2020

Recombinant adenylate cyclase toxoids are shown to deliver inserted foreign CD4+-T-cell epitopes into the major histocompatibility complex class II presentation pathway, inducing a specific CD4+-T-cell response in vivo and yielding in vitro stimulation of specific CD4+T cells at a 100-times-higher molar efficiency than the free peptide containing the epitope.
Novel Laminin-Binding Protein of
Streptococcus pyogenes
, Lbp, Is Involved in Adhesion to Epithelial Cells
Authors: Terao Yutaka , Kawabata Shigetada , Kunitomo Eiji , Nakagawa Ichiro , Hamada Shigeyuki
Published: April 2020

The
lbp
gene, which encodes a laminin-binding protein (Lbp) of
Streptococcus pyogenes
, was found in all
S. pyogenes
M types. An Lbp-deficient mutant showed a significantly lower efficiency of adhesion to HEp-2 cells than did the wild-type strain. These results indicate that Lbp is one of the important
S. pyogenes
adhesins.
High-Quality Draft Genome Sequences of Marine Fish Gut
Bacillus
sp. Strains ABP1 and ABP2 with Nonstarch Polysaccharide Hydrolytic Potential
Authors: Serra Cláudia R. , Matas Isabel M. , Albuquerque Pedro , Muñoz-Mérida Antonio , Oliva Teles Aires , Enes Paula , Tavares Fernando
Published: April 2020

Here, we present the genome sequences of two environmental
Bacillus
strains with broad hydrolytic capacity toward different nonstarch polysaccharides (NSPs) that were isolated from the gut of marine fish fed NSP-rich diets. Several genes that may contribute to the NSP-degrading behavior were identified through
in silico
analysis.
Draft Genome Sequences of Novel
Campylobacter
Species Isolated from Nonhuman Primates
Authors: Mannion Anthony , Shen Zeli , Sheh Alex , Fox James G.
Published: April 2020

Campylobacter
species are being increasingly isolated and associated with disease in humans and animals. Here, we describe four draft genome sequences of
Campylobacter
species from nonhuman primates. These include
Campylobacter troglodytis
, isolated from wild chimpanzees, and two likely new
Campylobacter
species isolated from a lemur, common marmoset, and cotton-top tamarin.
Near-Complete Genome Sequence of a Fish Nervous Necrosis Virus Isolated from Hybrid Grouper in China
Authors: Jia Peng , Chen Xiaoqi , Fu Jiajie , Yi Meisheng , Chen Wenbo , Jia Kuntong
Published: April 2020

The genome sequence of nervous necrosis virus strain HGN1910, isolated from hybrid grouper (
Epinephelus fuscoguttatus
♀ ×
E. lanceolatus
♂), was cloned, sequenced, and characterized. Two near-complete gene segments were obtained, RNA1 and RNA2. Phylogenetic analysis shows that the virus belongs to the red-spotted grouper nervous necrosis virus genotype of betanodavirus.
A Late Miocene magmatic flare-up in West Sulawesi triggered by Banda slab rollback
Authors: Zhang Xiaoran , Tien Chia-Yu , Chung Sun-Lin , Maulana Adi , Mawaleda Musri , Chu Mei-Fei , Lee Hao-Yang
Published: April 2020

Cenozoic magmatism occurs throughout West Sulawesi, Indonesia, yet its detailed evolution remains enigmatic due mainly to the scarcity of precise dating. Here, we report new whole-rock geochemical and zircon U-Pb-Hf isotopic data of plutonic/volcanic rocks and river sediments from West Sulawesi to constrain the petrogenesis and magmatic tempo. The magmatic rocks are intermediate to felsic (SiO2 = 58.1–68.0 wt%), high-K calc-alkaline to shoshonitic (K2O = 2.2–6.0 wt%), metaluminous to weakly peraluminous, and I-type in composition. Trace element concentrations and ratios (e.g., Nb/U = 1.7–4.3 and Ti/Zr < 28), along with negative zircon εHf(t) values (–17.0 to –0.4) and old crustal model ages (TDMC = 2.1–1.1 Ga), indicate a dominant magma source region from the underlying continental crystalline basement. U-Pb dating on zircons from ten magmatic rocks yielded weighted mean 206Pb/238U ages of 7.2–6.1 Ma, best representing the crystallization ages of host magmas, further consistent with the prominent age peaks (7.3–6.3 Ma) defined by detrital zircons from four sedimentary samples. Our new data, combined with available results, allow the identification of a noticeable climax of magmatism (flare-up) at ca. 7–6 Ma, forming a continuous magmatic belt throughout West Sulawesi. Given the absence of contemporaneous subduction and the coincidence of incipient opening of the South Banda Basin during ca. 7.15–6.5 Ma, the Late Miocene magmatic flare-up in West Sulawesi and coeval regional extension in eastern Indonesia are attributed to a resumed episode of Banda slab rollback.
Visual field fluctuations correlating with the menstrual cycle in a patient with optic pathway glioma
Authors: Jacobson Adam , Leonard Marcia , Robertson Patricia , Bohnsack Brenda L
Published: April 2020

Optic pathway gliomas are commonly associated with vision loss in children. We describe an 18-year-old woman with neurofibromatosis, type 1 and an optic nerve glioma who showed reproducible visual field defects that worsened midmenstrual cycle and returned to baseline during menses. To our knowledge, this is the first reported case of visual field fluctuations in a patient with an optic nerve glioma that correlated with her menstrual cycle.