bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of dietary interventions in the prevention of IgE‐mediated food allergy in children
Authors: Du Toit George , Foong Ru‐Xin , Lack Gideon
Published: March 2017

Over the last 30 years, the prevalence of food allergy has been on the rise and remains a disease that can have a significant impact on the quality of life of children and their families. There are several hypotheses that have been suggested to account for the increasing prevalence, but this review will focus on the impact that dietary factors have on food allergy development. In the past food allergy, prevalence has largely focused on allergen avoidance; however, there is increasing evidence from interventional studies that have shown that early introduction to potential food allergens may have a beneficial role in allergy prevention. This review aims to look at the evidence in support of early introduction of allergens into infant diets to prevent against the development of food allergy.
Health‐related quality of life among children with hereditary angioedema
Authors: Engel‐Yeger Batya , Farkas Henriette , Kivity Shmuel , Veszeli Nóra , Kőhalmi Kinga Viktória , Kessel Aharon
Published: March 2017

Background

The clinical expressions of hereditary angioedema with C1‐inhibitor deficiency (C1‐INH‐HAE) and its related burden may negatively affect patient quality of life. This study aimed to assess health‐related quality of life (HRQoL) in children with C1‐INH‐HAE.

Methods

Children (N = 98: 34 C1‐INH‐HAE patients, 64 healthy controls) aged 3–18 years were recruited in Israel and Hungary. All individuals completed a demographic questionnaire, a disease activity and site questionnaire, and the Pediatric Quality of Life Inventory (PedsQL™) 4.0 Generic Core Scales (child self‐report and maternal proxy report) to assess HRQoL.

Results

Among C1‐INH‐HAE patients, nine (26.5%) had 1–5 attacks/year, six (17.6%) had 6–18 attacks/year, eight (23.5%) had 25–60 attacks/year, and 11 (32.4%) were asymptomatic over the previous year. Children with C1‐INH‐HAE attacks demonstrated lower HRQoL than healthy control children across the total score, school, and psychosocial dimensions of the PedsQL™. The number of C1‐INH‐HAE attacks negatively correlated with the total HRQoL score (r = −0.48, p = 0.008), school‐related HRQoL (r = −0.39, p = 0.02), and psychosocial HRQoL (r = −0.43, p = 0.01). Patients with multisite laryngeal, abdominal, and peripheral C1‐INH‐HAE attacks had a lower HRQoL compared with those who experienced solely peripheral attacks across the total score (p = 0.04), physical (p = 0.04), and school (p = 0.02) domains. There was no significant difference between asymptomatic C1‐INH‐HAE patients and healthy controls.

Conclusions

Children with symptomatic C1‐INH‐HAE demonstrate impaired HRQoL compared with healthy controls. HRQoL was affected by the frequency and site of C1‐INH‐HAE attacks and mostly in the school and physical domains.
Overexpression of Populus trichocarpa CYP85A3 promotes growth and biomass production in transgenic trees
Authors: Jin Yan‐Li , Tang Ren‐Jie , Wang Hai‐Hai , Jiang Chun‐Mei , Bao Yan , Yang Yang , Liang Mei‐Xia , Sun Zhen‐Cang , Kong Fan‐Jing , Li Bei , Zhang Hong‐Xia
Published: March 2017

Brassinosteroids (BRs) are essential hormones that play crucial roles in plant growth, reproduction and response to abiotic and biotic stress. In Arabidopsis, AtCYP85A2 works as a bifunctional cytochrome P450 monooxygenase to catalyse the conversion of castasterone to brassinolide, a final rate‐limiting step in the BR‐biosynthetic pathway. Here, we report the functional characterizations of PtCYP85A3, one of the three AtCYP85A2 homologous genes from Populus trichocarpa. PtCYP85A3 shares the highest similarity with AtCYP85A2 and can rescue the retarded‐growth phenotype of the Arabidopsis cyp85a2‐2 and tomato dx mutants. Constitutive expression of PtCYP85A3, driven by the cauliflower mosaic virus 35S promoter, increased the endogenous BR levels and significantly promoted the growth and biomass production in both transgenic tomato and poplar. Compared to the wild type, plant height, shoot fresh weight and fruit yield increased 50%, 56% and 43%, respectively, in transgenic tomato plants. Similarly, plant height and stem diameter increased 15% and 25%, respectively, in transgenic poplar plants. Further study revealed that overexpression of PtCYP85A3 enhanced xylem formation without affecting the composition of cellulose and lignin, as well as the cell wall thickness in transgenic poplar. Our finding suggests that PtCYP85A3 could be used as a potential candidate gene for engineering fast‐growing trees with improved wood production.
Cardiac manifestations of inherited metabolic disease in children
Authors: Lloyd David FA , Vara Roshni , Mathur Sujeev
Published: March 2017

Inborn errors of metabolism (IEM) are responsible for around 5% of all cases of cardiomyopathy (CM) and for 15% of non‐idiopathic cases. Storage disorders such as Pompe disease (glycogen storage disease type II) typically cause hypertrophic CM, whereas the accumulation of toxic metabolites, as seen in the organic acidurias, is associated with dilated cardiomyopathy (DCM). Mixed pathology is also possible, particularly in late presentations. IEM such as Barth syndrome, a disorder of cardiolipin stability usually associated with DCM, have been associated with rarer types of CM such as endocardial fibroelastosis and left ventricular non‐compaction. Conduction disturbances can also occur, particularly in disorders of glycogen metabolism associated with PRKAG2 mutations. Cardiac screening of patients with metabolic diseases is important to guide treatment and stratify risk. Supportive cardiac treatment may be required, and although associated myocardial disease may improve or even resolve with correction of the underlying metabolic disturbance, progression to cardiac transplantation has been described. In this article we document all IEM known to be associated with cardiac disease in children, focusing on common and clinically important diagnoses. We also discuss the pathophysiology of the various types of CM, and present a recommended approach to screening in the pediatric population.
Vitamin D receptor polymorphisms in immune thrombocytopenic purpura
Authors: Yesil Sule , Tanyildiz Hikmet Gulsah , Tekgunduz Sibel Akpinar , Toprak Sule , Fettah Ali , Dikmen Asiye Ugras , Sahin Gurses
Published: March 2017

Background

Vitamin D receptor (VDR) polymorphisms have been studied in immune‐mediated disorders, but not yet in immune thrombocytopenic purpura (ITP). We investigated whether VDR variants were associated with ITP in children.

Methods

The study included 44 children with a diagnosis of ITP and 100 healthy controls. Five VDR polymorphisms (Cdx‐2, FokI, BsmI, ApaI and TaqI) were genotyped and used to evaluate the association of VDR variants with ITP.

Results

The distribution of the three Cdx‐2 genotype groups (GG, GA, and AA) was significantly different between ITP patients and controls (P = 0.025); the homozygous GG genotype of Cdx‐2 was overrepresented in ITP patients. The frequency of the A allele of Cdx‐2 was significantly different between patients and controls (P = 0.01). The A allele of Cdx‐2 was associated with a decreased risk of ITP (OR, 0.343; 95% CI: 0.150–0.782). No statistically significant difference was found between the ITP group and control group for Fok1, Bsm1, Apa1, and Taq1 polymorphisms (P > 0.5).

Conclusion

There appears to be an interaction between the Cdx‐2 variant of VDR and childhood immune thrombocytopenia.
Atypical features of benign rolandic epilepsy in Chinese children: Retrospective study
Authors: Zhao Xiuhe , Wang Aiqin , Wang Shengjun , Zhang Tongxia , Chi Zhaofu , Liu Yiming
Published: March 2017

Background

Benign rolandic epilepsy (BRE) is one of the most common focal epilepsies in childhood, but less typical clinical presentations may lead to misdiagnosis and incorrect treatment. The focus of this study was therefore to retrospectively investigate the less typical features of BRE in Chinese children.

Methods

Data on 316 Chinese children with BRE were collected and analyzed.

Results

A total of 7.3% of children complained of tension, fear and terror at the onset of a seizure, and 5.4% had been misdiagnosed with mesial temporal lobe epilepsy. Approximately 12.3% had post‐ictal Todd's paresis, with 6.6% having been misdiagnosed and given incorrect treatment. Nineteen children (6%) had neuroradiologic abnormalities, which could lead to a diagnosis of symptomatic epilepsy. Twenty‐five patients (8.0%) had cognitive deficits.

Conclusions

Greater recognition of, and further investigation into, the spectrum of BRE are needed.
The effect of lunisolar tidal acceleration on stem elongation growth, nutations and leaf movements in peppermint (Mentha × piperita L.)
Authors: Zajączkowska U. , Barlow P. W.
Published: March 2017

Orbital movement of the Moon generates a system of gravitational fields that periodically alter the gravitational force on Earth. This lunar tidal acceleration (Etide) is known to act as an external environmental factor affecting many growth and developmental phenomena in plants. Our study focused on the lunar tidal influence on stem elongation growth, nutations and leaf movements of peppermint.

Plants were continuously recorded with time‐lapse photography under constant illumination as well in constant illumination following 5 days of alternating dark–light cycles. Time courses of shoot movements were correlated with contemporaneous time courses of the Etide estimates. Optical microscopy and SEM were used in anatomical studies.

All plant shoot movements were synchronised with changes in the lunisolar acceleration. Using a periodogram, wavelet analysis and local correlation index, a convergence was found between the rhythms of lunisolar acceleration and the rhythms of shoot growth. Also observed were cyclical changes in the direction of rotation of stem apices when gravitational dynamics were at their greatest. After contrasting dark–light cycle experiments, nutational rhythms converged to an identical phase relationship with the Etide and almost immediately their renewed movements commenced. Amplitudes of leaf movements decreased during leaf growth up to the stage when the leaf was fully developed; the periodicity of leaf movements correlated with the Etide rhythms.

For the fist time, it was documented that lunisolar acceleration is an independent rhythmic environmental signal capable of influencing the dynamics of plant stem elongation. This phenomenon is synchronised with the known effects of Etide on nutations and leaf movements.
Sorghum (Sorghum bicolor) as a bean intercrop or rotation crop contributes to the survival of bean root rot pathogens and perpetuation of bean root rots
Authors: Ocimati W. , Tusiime G. , Opio F. , Ugen M. A. , Buruchara R.
Published: March 2017

Root rots (RR) are the main cause of declining bean (Phaseolus vulgaris) production in southwestern Uganda. Here, beans are mainly intercropped/rotated with maize (Zea mays), sorghum (Sorghum bicolor), sweet potato (Ipomoea batatas), potatoes (Solanum tuberosum) and garden peas (Pisum sativum). These crops also suffer from RR and bean RR pathogens have been isolated from some of these crops. This study aimed to determine the extent of RR on maize, sorghum and peas, and their potential to contribute to the survival of bean RR pathogens. Therefore, experiments were carried out in bean RR‐infested farmers’ fields as well as soils inoculated with bean RR pathogens (Pythium spp. and Fusarium spp.) under screen house conditions and a susceptible bean cultivar served as a control. High RR incidence/severity scores were recorded in beans and sorghum in both farmers’ fields and screen house experiments. The high field RR incidence/severity in sorghum correlated with the screen house scores. This study shows that RR is also a problem to other crops, especially sorghum, warranting attention. The findings also imply that sorghum plays a potential role as an alternate host to bean RR pathogens, increasing inoculum density of bean RR pathogens and potentially negatively impacting the bean RR problem. Intercropping or rotating beans with sorghum in this region is not recommended. However, maize was RR‐resistant and therefore appropriate as an intercrop/rotational crop to beans in the system. A holistic rather than commodity approach is recommended for managing RR in this cropping system.
Resting state intrinsic EEG impacts on go stimulus‐response processes
Authors: Karamacoska Diana , Barry Robert J. , Steiner Genevieve Z.
Published: March 2017

Neuropsychological research and practice rely on cognitive task performance measures as indicators of brain functioning. The neural activity underlying stimulus‐response processes can be assessed with ERPs, but the relations between these cognitive processes and the brain's intrinsic resting state EEG activity are less understood. This study focused on the neurocognitive functioning of 20 healthy young adults in an equiprobable go/no‐go task to map the ERP correlates of behavioral responses and examine contributions of the resting state intrinsic EEG to task‐related outcomes. Continuous EEG was recorded during pretask eyes‐closed (EC) and eyes‐open (EO) conditions, and in the subsequent task. Delta, theta, alpha, and beta band amplitudes were assessed for the EC state and also for the reactive change to EO. Go/no‐go ERPs were submitted to temporal principal components analysis, where the P2, N2, P3, and slow wave components of interest were extracted. The performance measure of reaction time (RT) variability was positively correlated with no‐go and go errors, and also with go P2 amplitude, linking these to stimulus discrimination efforts involved in appropriate response selection. An N2c‐P3b pairing was enhanced for shorter mean RTs, supporting their involvement in the decision to execute a response. A stepwise regression model identified EC midline delta as a predictor of P3b positivity, highlighting the relevance of delta in the neural mechanisms of attentional processes. These findings clarify the electrophysiology underlying decision‐making processes in executive function, and provide a platform for further research assessing performance outcomes in larger samples and in developmental/clinical contexts.
Sexual Assault on College Hookups: The Role of Alcohol and Acquaintances
Authors: Ford Jessie V.
Published: March 2017

This article takes a new approach to the study of college sexual assault by conducting an analysis of female students’ most recent “hookup.” By isolating a particular hookup event and examining the features of that event, I am able to examine predictors of sexual assault during hookups. My analysis focuses on the implications of alcohol consumption and knowing a male partner before a hookup, while controlling for multiple individual, school, and situational characteristics, using data from the Online College Social Life Survey collected 2005–2011. In my sample, 2.4% of women experienced sexual assault during their most recent hookup. Results show women do not experience an increased risk of physically forced intercourse until they have consumed nine or more drinks. In addition, women were more likely to report sexual assault during a hookup with a man they did not know well. Together, these findings suggest that men are more likely to assault women who are drunk, possibly because the double standard has made them respect such women less, or because they target women who are likely unable to resist or recall what happened. It also appears that the “in‐network stranger” may be the individual most dangerous to women in college hookups.
“The Mommy Deployment”: Military Spouses and Surrogacy in the United States
Authors: Ziff Elizabeth
Published: March 2017

This article examines narratives of women who are surrogates and are married to members of the military in the United States. I show how this group of women invoke and transpose their structured military experiences and institutional understandings of sacrifice, duty, and responsibility when constructing their surrogate experience. Using semistructured interviews with 33 military spouses who have been surrogates,​ I trace the parallels they narrate between their role as military spouse and their role as surrogate—with metaphors of deployment, relocation, and the “hurry up and wait” game, in addition to strict daily regimentation. Through this work, I highlight the often‐surprising transposition between militarized and surrogacy narratives invoked by surrogates and show how the practice of surrogacy allows them to tap into the narratives they have crafted through their experiences as a spouse to make a difference in the lives of others, contribute financially to their own families, and to gain a sense of importance outside of their everyday roles. The narratives provide for a better understanding of the commercially arranged surrogate experience in the United States and the state‐structured military spouse experience by exposing the skills, language, and habits utilized by this group of women.
Intersections of Multiple Oppressions: Racism, Sizeism, Ableism, and the “Illimitable Etceteras” in Encounters With Law Enforcement,
Authors: Whitesel Jason
Published: March 2017

This think piece on the intersectionality of multiple oppressive markers incorporates critical race feminism, fat studies, body/embodiment studies, and dis/ability studies. It discusses the cases of two African Americans deemed irresolvable nuisances, treated as threats to police, and dealt with, with undue force, resulting in their untimely deaths. Eleanor Bumpurs, 66, was a black female of older age, ample size, with physical and mental disabilities; she was arthritic, fighting off hallucinations, and was economically disadvantaged. Eric Garner, 43, was a black male of ample size, with physical disabilities; he was diabetic, asthmatic, with sleep apnea and a heart condition, all of which made employment difficult for him. Intersectional identities determined what happened when each crossed paths with law enforcement. Intersecting oppressions of racism/classism/fat hatred/ageism/ableism/healthism resulted in the murder of Bumpurs in 1984 and Garner in 2014. Following Garner's execution, police supporters used multiple, intersecting forms of discrimination to sidestep the brutality: “Garner would've died going up a flight of stairs—he died because of preexisting medical conditions.” This article argues that besides perpetuating the long history of portraying African American men as hulking brutes or as genetically inferior, such justifications aim to divert attention away from structural racism, cloaking it in sizeism/ableism/healthism.
Sustaining Farming on Marginal Land: Farmers’ Convictions, Motivations and Strategies in Northeastern Germany
Authors: Preissel Sara , Zander Peter , Knierim Andrea
Published: March 2017

Contrary to a scholarly debate that anticipated a trend towards the marginalisation of agriculture in many rural areas of Europe, farmers have continued to utilise agro‐economically marginal land, especially in a variety of areas in Europe's northwest. We explore why and how farmers secure the development of their farms while cultivating crops on the margins, based on qualitative empirical research in Brandenburg, Germany. By bringing together farmers’ motivations and convictions with their agricultural and agronomical practices, the study identifies three farming strategies for managing farms on marginal land, focused on independence, balancing multiple aims, or optimising land productivity. We develop a concept of farming strategy as an expression of personal motivations and convictions in a coherent, targeted, long‐term plan for farming. We discuss the implications of such an understanding for system‐oriented, micro‐sociological research and for the perpetuation of agriculture in marginalised rural areas.
Incidence and outcome of BK polyomavirus infection in a multicenter randomized controlled trial with renal transplant patients receiving cyclosporine‐, mycophenolate sodium‐, or everolimus‐based low‐dose immunosuppressive therapy
Authors: van Doesum Willem B. , Gard Lilli , Bemelman Frederike J. , de Fijter Johan W. , Homan van der Heide Jaap J. , Niesters Hubert G. , van Son Willem J. , Stegeman Coen A. , Groen Henk , Riezebos‐Brilman Annelies , Sanders Jan Stephan F.
Published: March 2017

Background

It remains unclear whether overall degree of immunosuppression or specific effects of individual immunosuppressive agents are causal for increased occurrence of BK polyomavirus (BKPyV) infection in renal transplant recipients (RTR).

Methods

A prospective, multicenter, open‐label randomized controlled trial in 361 de novo RTR was performed. A total of 224 RTR were randomized at 6 months into three treatment groups with dual therapy consisting of prednisolone (Pred) plus either cyclosporine (CsA), mycophenolate sodium (MPS), or everolimus (EVL). Primary outcomes were incidence of BK viruria, BK viremia, and BKPyV‐associated nephropathy (BKVAN).

Results

From 6 months, incidence of BK viruria in the MPS group (43.6%) was significantly higher than in the other groups (CsA: 16.9%, EVL: 19.8%) (P=.003). BKVAN was diagnosed in 3 patients, all treated with MPS (7.8%, P=.001). Longitudinal data analysis showed a lower BKPyV load and a significantly faster clearance of BK viruria in the CsA group compared to the MPS group (P=.03).

Conclusions

Treatment with MPS was associated with an increased incidence of BK viruria. Dual immunosuppressive therapy with CsA and Pred was associated with the lowest rate of BKPyV replication and the fastest clearance of the virus.
Concomitant loss of NDH complex‐related genes within chloroplast and nuclear genomes in some orchids
Authors: Lin Choun‐Sea , Chen Jeremy J. W. , Chiu Chi‐Chou , Hsiao Han C. W. , Yang Chen‐Jui , Jin Xiao‐Hua , Leebens‐Mack James , de Pamphilis Claude W. , Huang Yao‐Ting , Yang Ling‐Hung , Chang Wan‐Jung , Kui Ling , Wong Gane Ka‐Shu , Hu Jer‐Ming , Wang Wen , Shih Ming‐Che
Published: March 2017

The chloroplast NAD(P)H dehydrogenase‐like (NDH) complex consists of about 30 subunits from both the nuclear and chloroplast genomes and is ubiquitous across most land plants. In some orchids, such as Phalaenopsis equestris, Dendrobium officinale and Dendrobium catenatum, most of the 11 chloroplast genome‐encoded ndh genes (cp‐ndh) have been lost. Here we investigated whether functional cp‐ndh genes have been completely lost in these orchids or whether they have been transferred and retained in the nuclear genome. Further, we assessed whether both cp‐ndh genes and nucleus‐encoded NDH‐related genes can be lost, resulting in the absence of the NDH complex. Comparative analyses of the genome of Apostasia odorata, an orchid species with a complete complement of cp‐ndh genes which represents the sister lineage to all other orchids, and three published orchid genome sequences for P. equestris, D. officinale and D. catenatum, which are all missing cp‐ndh genes, indicated that copies of cp‐ndh genes are not present in any of these four nuclear genomes. This observation suggests that the NDH complex is not necessary for some plants. Comparative genomic/transcriptomic analyses of currently available plastid genome sequences and nuclear transcriptome data showed that 47 out of 660 photoautotrophic plants and all the heterotrophic plants are missing plastid‐encoded cp‐ndh genes and exhibit no evidence for maintenance of a functional NDH complex. Our data indicate that the NDH complex can be lost in photoautotrophic plant species. Further, the loss of the NDH complex may increase the probability of transition from a photoautotrophic to a heterotrophic life history.
Identification of a drimenol synthase and drimenol oxidase from Persicaria hydropiper, involved in the biosynthesis of insect deterrent drimanes
Authors: Henquet Maurice G. L. , Prota Neli , van der Hooft Justin J. J. , Varbanova‐Herde Marina , Hulzink Raymond J. M. , de Vos Martin , Prins Marcel , de Both Michiel T. J. , Franssen Maurice C. R. , Bouwmeester Harro , Jongsma Maarten
Published: March 2017

The sesquiterpenoid polygodial, which belongs to the drimane family, has been shown to be an antifeedant for a number of herbivorous insects. It is presumed to be synthesized from farnesyl diphosphate via drimenol, subsequent C‐12 hydroxylation and further oxidations at both C‐11 and C‐12 to form a dialdehyde. Here, we have identified a drimenol synthase (PhDS) and a cytochrome P450 drimenol oxidase (PhDOX1) from Persicaria hydropiper. Expression of PhDS in yeast and plants resulted in production of drimenol alone. Co‐expression of PhDS with PhDOX1 in yeast yielded drimendiol, the 12‐hydroxylation product of drimenol, as a major product, and cinnamolide. When PhDS and PhDOX1 were transiently expressed by agro‐infiltration in Nicotiana benthamiana leaves, drimenol was almost completely converted into cinnamolide and several additional drimenol derivatives were observed. In vitro assays showed that PhDOX1 only catalyses the conversion from drimenol to drimendiol, and not the further oxidation into an aldehyde. In yeast and heterologous plant hosts, the C‐12 position of drimendiol is therefore likely to be further oxidized by endogenous enzymes into an aldehyde and subsequently converted to cinnamolide, presumably by spontaneous hemiacetal formation with the C‐11 hydroxyl group followed by oxidation. Purified cinnamolide was confirmed by NMR and shown to be deterrent with an effective deterrent dose (ED50) of about 200–400 μg g−1 fresh weight against both whiteflies and aphids. The putative additional physiological and biochemical requirements for polygodial biosynthesis and stable storage in plant tissues are discussed.
Gastrostomy tube placement for long‐term oral drug administration in non‐human primates
Authors: Kim Jong‐Min , Shin Jun‐Seop , Min Byoung‐Hoon , Kim Jung‐Sik , Yoon Il‐Hee , Jeong Won‐Young , Lee Ga‐Eul , Kim Min‐Sun , Kim Ju‐Eun , Park Chung‐Gyu
Published: March 2017

Background

Non‐human primates (NHPs) are often used as recipients in preclinical transplantation research that in most cases involves administration of various drugs including immunosuppressants. Long‐term oral drug administration, particularly tacrolimus, is challenging in the transplant recipient NHPs. Oral drug administration method using the mixture of drug and fruit juice has been used in NHPs, but this is not always effective in all monkeys. To those monkeys who are poorly compliant, oral drug administration in restraint or administration using gastrostomy tube should be necessary. The aim of this study was to compare the efficacy of between oral drug administration in restraint and administration using gastrostomy tube and to report complications and solutions to overcome the problems related to gastrostomy tube for long‐term oral drug dosing in rhesus monkeys.

Methods

Fifteen of 4‐ to 5‐year‐old male and female healthy rhesus monkeys weighing 5.0‐6.8 kg were used as recipients for porcine pancreatic islet transplantation. Oral drug administration in restraint was used for four monkeys, and gastrostomy tube was placed to other 11 monkeys (8‐French Feeding tube, n=6; Tri‐Funnel Replacement Gastrostomy tube, n=5). Oral immunosuppressive drugs such as sirolimus and tacrolimus were administered through the tube. The efficacy and the extent of ease for administration and related complications were compared between two groups.

Results and Conclusions

The complication of gastrostomy included a transient inflammation in the skin and peritonitis caused by a leakage around implantation site (one case), which could be overcome by changing suture method and tube type to interlocking box suture and Tri‐Funnel Replacement Gastrostomy tube, respectively. Despite these complications, oral drug administration using gastrostomy tube allowed us to perform accurate dosage of drug administration and to reduce the stress that both the monkey and the researcher may experience. Taken together, this study showed that gastrostomy tube placement is a better alternative to oral drug administration in restraint for long‐term oral drug administration in rhesus monkeys who tend to refuse to eat the mixture of drug and fruit juice.
Transgenic expression of human leukocyte antigen‐E attenuates GalKO.hCD46 porcine lung xenograft injury
Authors: Laird Christopher T. , Burdorf Lars , French Beth M. , Kubicki Natalia , Cheng Xiangfei , Braileanu Gheorghe , Sun Wenji , O'Neill Natalie A. , Cimeno Arielle , Parsell Dawn , So Edward , Bähr Andrea , Klymiuk Nikolai , Phelps Carol J. , Ayares David , Azimzadeh Agnes M. , Pierson Richard N.
Published: March 2017

Background

Lung xenografts remain susceptible to loss of vascular barrier function within hours in spite of significant incremental advances based on genetic engineering to remove the Gal 1,3‐αGal antigen (GalTKO) and express human membrane cofactor protein (hCD46). Natural killer cells rapidly disappear from the blood during perfusion of GalTKO.hCD46 porcine lungs with human blood and presumably are sequestered within the lung vasculature. Here we asked whether porcine expression of the human NK cell inhibitory ligand HLA‐E and β2 microglobulin inhibits GalTKO.hCD46 pig cell injury or prolongs lung function in two preclinical perfusion models.

Methods

Lungs from pigs modified to express GalTKO.hCD46 (n=37) and GalTKO.hCD46.HLA‐E (n=5) were harvested and perfused with human blood until failure or elective termination at 4 hours. Airway pressures and pulmonary artery hemodynamics were recorded in real time. Blood samples were also collected throughout the experiment for analysis. Porcine aortic endothelial cells (PAECs) from each genotype were cultured in monolayers in microfluidic channels and used in fluorescent cytotoxicity assays using human NK cells.

Results

HLA‐E expression on GalTKO.hCD46 PAECs was associated with significantly decreased antibody‐dependent and antibody‐independent NK‐mediated cytotoxicity under in vitro conditions simulating physiologic shear stress. Relative to GalTKO.hCD46 pig lungs perfused with human blood on an ex vivo platform, additional expression of HLA‐E increased median lung survival (>4 hours, vs 162 minutes, P=.012), and was associated with attenuated rise in pulmonary vascular resistance, and decreased platelet activation and histamine elaboration. As expected, HLA‐E expression was not associated with a significant difference in NK cell adhesion to endothelial cells in vitro, or NK cell and neutrophil sequestration during organ perfusion.

Conclusions

We conclude human NK cell activation contributes significantly to GalTKO.hCD46 pig endothelial injury and lung inflammation and show that expression of HLA‐E is associated with physiologically meaningful protection of GalTKO.hCD46 cells and organs exposed to human blood.
Enhanced PEDOT adhesion on solid substrates with electrografted P(EDOT-NH
2
)
Authors: Ouyang Liangqi , Wei Bin , Kuo Chin-chen , Pathak Sheevangi , Farrell Brendan , Martin David C.
Published: March 2017

Electrografted films of amine-functionalized thiophenes significantly improve coating adhesion and maintain charge transport.
Extreme warmth and heat-stressed plankton in the tropics during the Paleocene-Eocene Thermal Maximum
Authors: Frieling Joost , Gebhardt Holger , Huber Matthew , Adekeye Olabisi A. , Akande Samuel O. , Reichart Gert-Jan , Middelburg Jack J. , Schouten Stefan , Sluijs Appy
Published: March 2017

During rapid global warming 56 million years ago, tropical sea surface temperatures exceeded 36°C and stressed eukaryotic plankton.
Three-dimensional microarchitected materials and devices using nanoparticle assembly by pointwise spatial printing
Authors: Saleh Mohammad Sadeq , Hu Chunshan , Panat Rahul
Published: March 2017

Nanoparticles can be assembled in space using additive printing to create complex hierarchical 3D microarchitected and nanoarchitected materials.
Decoupling biogeochemical records, extinction, and environmental change during the Cambrian SPICE event
Authors: Schiffbauer James D. , Huntley John Warren , Fike David A. , Jeffrey Matthew Jarrell , Gregg Jay M. , Shelton Kevin L.
Published: March 2017

Local depositional variation affects geological recording of globally recognized biogeochemical events such as the Cambrian SPICE.
Sequential self-folding of polymer sheets
Authors: Liu Ying , Shaw Brandi , Dickey Michael D. , Genzer Jan
Published: March 2017

We demonstrate an innovative strategy for sequentially self-folding 2D polymer sheets into 3D objects using light.
Long-range allosteric signaling in red light–regulated diguanylyl cyclases
Authors: Gourinchas Geoffrey , Etzl Stefan , Göbl Christoph , Vide Uršula , Madl Tobias , Winkler Andreas
Published: March 2017

Structural and dynamic properties of a full-length bacteriophytochrome reveal details of the molecular regulation mechanism.
Maintenance of macrophage transcriptional programs and intestinal homeostasis by epigenetic reader SP140
Authors: Mehta Stuti , Cronkite D. Alexander , Basavappa Megha , Saunders Tahnee L. , Adiliaghdam Fatemeh , Amatullah Hajera , Morrison Sara A. , Pagan Jose D. , Anthony Robert M. , Tonnerre Pierre , Lauer Georg M. , Lee James C. , Digumarthi Sreehaas , Pantano Lorena , Ho Sui Shannan J. , Ji Fei , Sadreyev Ruslan , Zhou Chan , Mullen Alan C. , Kumar Vinod , Li Yang , Wijmenga Cisca , Xavier Ramnik J. , Means Terry K. , Jeffrey Kate L.
Published: March 2017

The epigenetic reader SP140, which is polymorphic in Crohn’s disease patients, regulates transcriptional programs in macrophages.
Single-cell RNA-seq and computational analysis using temporal mixture modeling resolves T
H
1/T
FH
fate bifurcation in malaria
Authors: Lönnberg Tapio , Svensson Valentine , James Kylie R. , Fernandez-Ruiz Daniel , Sebina Ismail , Montandon Ruddy , Soon Megan S. F. , Fogg Lily G. , Nair Arya Sheela , Liligeto Urijah N. , Stubbington Michael J. T. , Ly Lam-Ha , Bagger Frederik Otzen , Zwiessele Max , Lawrence Neil D. , Souza-Fonseca-Guimaraes Fernando , Bunn Patrick T. , Engwerda Christian R. , Heath William R. , Billker Oliver , Stegle Oliver , Haque Ashraful , Teichmann Sarah A.
Published: March 2017

Computational modeling defines T helper cell differentiation toward multiple fates during experimental malaria.
Help not wanted in the joint
Authors: Lichtman Andrew H.
Published: March 2017

A newly discovered T cell subset that helps B cells is expanded in joints of rheumatoid arthritis patients.
It’s all in the family
Authors: Griffin Gabriel K.
Published: March 2017

CD70-deficiency causes primary immunodeficiency and susceptibility to EBV-driven lymphoma.
Biosynthesis of 2′-Chloropentostatin and 2′-Amino-2′-Deoxyadenosine Highlights a Single Gene Cluster Responsible for Two Independent Pathways in
Actinomadura
sp. Strain ATCC 39365
Authors: Gao Yaojie , Xu Gudan , Wu Pan , Liu Jin , Cai You-sheng , Deng Zixin , Chen Wenqing
Published: March 2017

2′-Chloropentostatin (2′-Cl PTN, 2′-chloro-2′-deoxycoformycin) and 2′-amino-2′-deoxyadenosine (2′-amino dA) are two adenosine-derived nucleoside antibiotics coproduced by
Actinomadura
sp. strain ATCC 39365. 2′-Cl PTN is a potent adenosine deaminase (ADA) inhibitor featuring an intriguing 1,3-diazepine ring, as well as a chlorination at C-2′ of ribose, and 2′-amino dA is an adenosine analog showing bioactivity against RNA-type virus infection. However, the biosynthetic logic of them has remained poorly understood. Here, we report the identification of a single gene cluster (
ada
) essential for the biosynthesis of 2′-Cl PTN and 2′-amino dA. Further systematic genetic investigations suggest that 2′-Cl PTN and 2′-amino dA are biosynthesized by independent pathways. Moreover, we provide evidence that a predicted cation/H
+
antiporter, AdaE, is involved in the chlorination step during 2′-Cl PTN biosynthesis. Notably, we demonstrate that 2′-amino dA biosynthesis is initiated by a Nudix hydrolase, AdaJ, catalyzing the hydrolysis of ATP. Finally, we reveal that the host ADA (designated ADA1), capable of converting adenosine/2′-amino dA to inosine/2′-amino dI, is not very sensitive to the powerful ADA inhibitor pentostatin. These findings provide a basis for the further rational pathway engineering of 2′-Cl PTN and 2′-amino dA production.

IMPORTANCE
2′-Cl PTN/PTN and 2′-amino dA have captivated the great interests of scientists, owing to their unusual chemical structures and remarkable bioactivities. However, the precise logic for their biosynthesis has been elusive for decades. Actually, the identification and elucidation of their biosynthetic pathways not only enrich the biochemical repertoire of novel enzymatic reactions but may also lay solid foundations for the pathway engineering and combinatorial biosynthesis of this family of purine nucleoside antibiotics to generate novel hybrid analogs with improved features.
Pseudomonas aeruginosa Aggregate Formation in an Alginate Bead Model System Exhibits
In Vivo
-Like Characteristics
Authors: Sønderholm Majken , Kragh Kasper Nørskov , Koren Klaus , Jakobsen Tim Holm , Darch Sophie E. , Alhede Maria , Jensen Peter Østrup , Whiteley Marvin , Kühl Michael , Bjarnsholt Thomas
Published: March 2017

Alginate beads represent a simple and highly reproducible
in vitro
model system for diffusion-limited bacterial growth. In this study, alginate beads were inoculated with
Pseudomonas aeruginosa
and followed for up to 72 h. Confocal microscopy revealed that
P. aeruginosa
formed dense clusters similar in size to
in vivo
aggregates observed
ex vivo
in cystic fibrosis lungs and chronic wounds. Bacterial aggregates primarily grew in the bead periphery and decreased in size and abundance toward the center of the bead. Microsensor measurements showed that the O
2
concentration decreased rapidly and reached anoxia ∼100 μm below the alginate bead surface. This gradient was relieved in beads supplemented with NO
3
−
as an alternative electron acceptor allowing for deeper growth into the beads. A comparison of gene expression profiles between planktonic and alginate-encapsulated
P. aeruginosa
confirmed that the bacteria experienced hypoxic and anoxic growth conditions. Furthermore, alginate-encapsulated
P. aeruginosa
exhibited a lower respiration rate than the planktonic counterpart and showed a high tolerance toward antibiotics. The inoculation and growth of
P. aeruginosa
in alginate beads represent a simple and flexible
in vivo
-like biofilm model system, wherein bacterial growth exhibits central features of
in vivo
biofilms. This was observed by the formation of small cell aggregates in a secondary matrix with O
2
-limited growth, which was alleviated by the addition of NO
3
−
as an alternative electron acceptor, and by reduced respiration rates, as well as an enhanced tolerance to antibiotic treatment.

IMPORTANCE
Pseudomonas aeruginosa
has been studied intensively for decades due to its involvement in chronic infections, such as cystic fibrosis and chronic wounds, where it forms biofilms. Much research has been dedicated to biofilm formation on surfaces; however, in chronic infections, most biofilms form small aggregates of cells not attached to a surface, but embedded in host material. In this study, bacteria were encapsulated in small alginate beads and formed aggregates similar to what is observed in chronic bacterial infections. Our findings show that aggregates are exposed to steep oxygen gradients, with zones of oxygen depletion, and that nitrate may serve as an alternative to oxygen, enabling growth in oxygen-depleted zones. This is important, as slow growth under low-oxygen conditions may render the bacteria tolerant toward antibiotics. This model provides an alternative to surface biofilm models and adds to the comprehension that biofilms do not depend on a surface for formation.
Construction of Bacillus thuringiensis Simulant Strains Suitable for Environmental Release
Authors: Park Sangjin , Kim Changhwan , Lee Daesang , Song Dong Hyun , Cheon Ki Cheol , Lee Hong Suk , Kim Seong Joo , Kim Jee Cheon , Lee Sang Yup
Published: March 2017

For a surrogate bacterium to be used in outdoor studies, it is important to consider environmental and human safety and ease of detection. Recently,
Bacillus thuringiensis
, a popular bioinsecticide bacterium, has been gaining attention as a surrogate bacterium for use in biodefense. In this study, we constructed simulant strains of
B. thuringiensis
with enhanced characteristics for environmental studies. Through transposon mutagenesis, pigment genes were inserted into the chromosome, producing yellow-colored colonies for easy detection. To prevent persistence of spores in the environment, a genetic circuit was designed to produce a spore without sporulation capability. Two
loxP
sites were inserted, one on each side of the
spo0A
gene, which encodes a sporulation master regulator, and a sporulation-dependent Cre expression cassette was inserted into the chromosome. This genetic circuit successfully deleted
spo0A
during sporulation, producing spores that lacked the
spo0A
gene. In addition, two major α/β-type small acid-soluble spore protein (SASP) genes, predicted by synteny analysis, were deleted. The spores of the mutant strain showed increased UV-C sensitivity and quickly lost viability when tested in a solar simulator. When the spores of the mutant strain were administered to the lungs of BALB/c mice, cells were quickly removed from the body, suggesting enhanced
in vivo
safety. All strains constructed in this study contain no antibiotic resistance markers and all heterologous genes were inserted into the chromosome, which are useful features for simulants to be released into the environment.

IMPORTANCE
B. thuringiensis
has recently been receiving increasing attention as a good spore simulant in biodefense research. However, few studies were done to properly address many important features of
B. thuringiensis
as a simulant in environmental studies. Since spores can persist in the environment for years after release, environmental contamination is a big problem, especially when genetically engineered strains are used. To solve these problems, we report here the development of
B. thuringiensis
simulant strains that are capable of forming yellow colonies for easy detection, incapable of forming spores more than once due to a genetic circuit, and lacking in two major SASP genes. The genetic circuit to produce a spore without sporulation capability, together with the deletion of SASP genes, ensures the environmental and human safety of the simulant strains developed in this study. All of these features will allow wider use of
B. thuringiensis
as a simulant for
Bacillus anthracis
in environmental release studies.
Use of Natural Transformation To Establish an Easy Knockout Method in Riemerella anatipestifer
Authors: Liu MaFeng , Zhang Li , Huang Li , Biville Francis , Zhu DeKang , Wang MingShu , Jia RenYong , Chen Shun , Sun KunFeng , Yang Qiao , Wu Ying , Chen XiaoYue , Cheng AnChun
Published: March 2017

Riemerella anatipestifer
is a member of the family
Flavobacteriaceae
and a major causative agent of duck serositis. Little is known about its genetics and pathogenesis. Several bacteria are competent for natural transformation; however, whether
R. anatipestifer
is also competent for natural transformation has not been investigated. Here, we showed that
R. anatipestifer
strain ATCC 11845 can uptake the chromosomal DNA of
R. anatipestifer
strain RA-CH-1 in all growth phases. Subsequently, a natural transformation-based knockout method was established for
R. anatipestifer
ATCC 11845. Targeted mutagenesis gave transformation frequencies of ∼10
−5
transformants. Competition assay experiments showed that
R. anatipestifer
ATCC 11845 preferentially took up its own DNA rather than heterogeneous DNA, such as
Escherichia coli
DNA. Transformation was less efficient with the shuttle plasmid pLMF03 (transformation frequencies of ∼10
−9
transformants). However, the efficiency of transformation was increased approximately 100-fold using pLMF03 derivatives containing
R. anatipestifer
DNA fragments (transformation frequencies of ∼10
−7
transformants). Finally, we found that the
R. anatipestifer
RA-CH-1 strain was also naturally transformable, suggesting that natural competence is widely applicable for this species. The findings described here provide important tools for the genetic manipulation of
R. anatipestifer
.

IMPORTANCE
Riemerella anatipestifer
is an important duck pathogen that belongs to the family
Flavobacteriaceae
. At least 21 different serotypes have been identified. Genetic diversity has been demonstrated among these serotypes. The genetic and pathogenic mechanisms of
R. anatipestifer
remain largely unknown because no genetic tools are available for this bacterium. At present, natural transformation has been found in some bacteria but not in
R. anatipestifer
. For the first time, we showed that natural transformation occurred in
R. anatipestifer
ATCC 11845 and
R. anatipestifer
RA-CH-1. Then, we established an easy gene knockout method in
R. anatipestifer
based on natural transformation. This information is important for further studies of the genetic diversity and pathogenesis in
R. anatipestifer
.
Prevalence, Genotype Richness, and Coinfection Patterns of Hemotropic Mycoplasmas in Raccoons (Procyon lotor) on Environmentally Protected and Urbanized Barrier Islands
Authors: Volokhov Dmitriy V. , Hwang Jusun , Chizhikov Vladimir E. , Danaceau Heather , Gottdenker Nicole L.
Published: March 2017

Raccoons (Procyon lotor) are successful urban adapters and hosts to a number of zoonotic and nonzoonotic pathogens, yet little is known about their hemoplasma infections and how prevalence varies across habitat types. This study identifies hemotropicMycoplasmaspecies infection in raccoons from urban and undisturbed habitats and compares hemoplasma infection in sympatric urban cats (Felis catus) from the same geographic region. We collected blood from raccoons (n= 95) on an urban coastal island (n= 37) and an undisturbed coastal island (n= 58) and from sympatric urban cats (n= 39) in Georgia, USA. Based on 16S rRNA gene amplification, 62.1% (59/95) of raccoons and 17.9% (7/39) of feral cats were positive for hemoplasma. There was a greater percentage of hemoplasma-infected raccoons on the undisturbed island (79.3% [46/58]) than on the urban island (35.1% [13/37]; χ2= 16.9,df= 1,P= 0.00004). Sequencing of the full-length 16S rRNA gene amplicons revealed six hemoplasma genotypes in raccoons, including five novel genotypes that were distinct from three known hemoplasma species identified in the sympatric cats. In addition, the hemoplasma genotypes detected in raccoons were not identified in sympatric cats or vice versa. Although all six hemoplasma genotypes were found in raccoons from urban and undisturbed islands, coinfection patterns differed between sites and among individuals, with the proportion of coinfected raccoons being greater in the undisturbed site. This study shows that raccoons are hosts for several novel hemoplasmas and that habitat type influences infection patterns.

IMPORTANCEThis study provides information about novel hemoplasmas identified in raccoons (Procyon lotor), which can be used for assessments of the prevalence of these hemoplasmas in raccoon populations and for future studies on the potential pathogenic impacts of these hemoplasmas on raccoon health. Raccoons from the undisturbed habitat had a higher prevalence of hemoplasma infection than urban raccoons. There does not appear to be cross-species transmission of hemotropic mycoplasmas between urban raccoons and feral cats. Raccoons appear to be hosts for several novel hemoplasmas, and habitat type influences infection patterns.