bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum testosterone and non‐alcoholic fatty liver disease in men and women in the US
Authors: Yim Jeong Yoon , Kim Jinju , Kim Donghee , Ahmed Aijaz
Published: March 2018

Background & Aims

Testosterone plays a role in predisposing individuals to cardiovascular and metabolic diseases, but its effects differ between men and women. We investigated the association between serum total testosterone and non‐alcoholic fatty liver disease in adults in the US.

Methods

A cross‐sectional analysis of data from participants in the 2011‐2012 National Health and Nutrition Examination Survey was performed. Subjects with significant alcohol consumption and those with viral hepatitis were excluded. We used the highest sex‐specific quartiles of serum total testosterone as references. Suspected non‐alcoholic fatty liver disease was diagnosed when serum alanine aminotransferase was >30 IU/L for men and >19 IU/L for women.

Results

Of the 4758 subjects (49.4% men), the prevalence of suspected non‐alcoholic fatty liver disease was inversely correlated with the sex‐specific quartiles of testosterone in men and women. In a multivariate model, low total testosterone levels were associated with progressively higher odds of suspected non‐alcoholic fatty liver disease in men after adjusting for age, obesity and other metabolic risk factors (P values for trends <.01). When the women were divided into 2 groups according to menopausal status, a significant correlation was observed only in the post‐menopausal women (P values for trends <.01). The adjusted odds ratios for suspected non‐alcoholic fatty liver disease were 1.72‐1.99 in men and 2.15‐2.26 in post‐menopausal women (lowest quartile vs highest quartile).

Conclusions

In this nationally representative sample of adults in the US, low total testosterone levels were associated with suspected non‐alcoholic fatty liver disease in men and post‐menopausal women independent of known risk factors.
A Bridge No Longer Too Far: A Case Study of One School's Exploration of the Promise and Possibilities of Mind, Brain, and Education Science for the Future of Education
Authors: Kelleher Ian , Whitman Glenn
Published: March 2018

Mind, brain, and education (MBE) science research continues to produce valuable results about brain development and the learning process—research that can and should inform education reform. Given the link between teacher efficacy and student learning outcomes, MBE is a discipline with considerable promise to help close gaps in school and teacher quality and student achievement. Yet, in our experience working with thousands of K‐12 teachers, very few have been trained to adapt their instructional strategies in ways that are informed by MBE research. Research on what helps and hinders learning exists, but, as yet, effective and efficient ways to translate it into classroom practice are rare. This article presents a case study of how one school is bridging the gap between MBE research and its integration into the classroom, a gap that was once deemed “a bridge too far” to cross. It also suggests a series of steps that form a possible translational pathway for teachers, school leaders, and policymakers.
Longitudinal Associations Among Executive Function, Visuomotor Integration, and Achievement in a High‐Risk Sample
Authors: Brock Laura L. , Kim Helyn , Grissmer David W.
Published: March 2018

The present study examines cross‐lagged associations among executive function, visuomotor skills, and math and reading achievement from kindergarten to second grade. Both executive function and visuomotor integration tend to be delayed in socioeconomically disadvantaged children and can explain nearly half the achievement gap at kindergarten entry. Participants were 259 students enrolled in elementary schools serving predominantly low‐income communities with multiple sociodemographic risk factors. Executive function at multiple time points predicted reading and math achievement. However, visuomotor integration in kindergarten alone predicted later reading and math. Initially, math predicts later reading. Subsequently, reading predicts later math.
Associations Between School Readiness and Obesity‐ and Inflammation‐Related Biomarkers in Low‐Income Preschoolers Within the Healthy Kids Study
Authors: Sutter Carolyn , Ontai Lenna L. , Shilts Mical K. , Lanoue Louise , Allen Lindsay H. , Townsend Marilyn S.
Published: March 2018

Previous research suggests obesity is negatively related to cognitive functioning and academic outcomes in addition to physical health. However, not much is known about this association in early childhood or potential physiological underpinnings. Biomarkers related to obesity have been associated with cognition, in particular the adipokine leptin, and pro‐inflammatory cytokines including interleukin‐6 (IL‐6), tumor necrosis factor‐alpha (TNF‐alpha) and C‐reactive protein (CRP). These associations may be further exacerbated for children who experience early life stress. With a sample of low‐income preschoolers, the current study examined associations between obesity‐related biomarkers and aspects of behavioral and cognitive school readiness. Partial correlations controlling for child age show hypothesized negative associations between pro‐inflammatory cytokines and school readiness, while leptin was positively associated with cognitive school readiness and body mass index (BMI) z‐score. Findings suggest connections between obesity, physiology, and school readiness need further examination, but may have implications for early childhood education and health interventions.
A dual role for proline iminopeptidase in the regulation of bacterial motility and host immunity
Authors: Kan Jinhong , An Lin , Wu Yao , Long Jia , Song Liyang , Fang Rongxiang , Jia Yantao
Published: March 2018

During plant–pathogen interactions, pathogenic bacteria have evolved multiple strategies to cope with the sophisticated defence systems of host plants. Proline iminopeptidase (PIP) is essential to Xanthomonas campestris pv. campestris (Xcc) virulence, and is conserved in many plant‐associated bacteria, but its pathogenic mechanism remains unclear. In this study, we found that disruption of pip in Xcc enhanced its flagella‐mediated bacterial motility by decreasing intracellular bis‐(3′,5′)‐cyclic dimeric guanosine monophosphate (c‐di‐GMP) levels, whereas overexpression of pip in Xcc restricted its bacterial motility by elevating c‐di‐GMP levels. We also found that PIP is a type III secretion system‐dependent effector capable of eliciting a hypersensitive response in non‐host, but not host plants. When we transformed pip into the host plant Arabidopsis, higher bacterial titres were observed in pip‐overexpressing plants relative to wild‐type plants after Xcc inoculation. The repressive function of PIP on plant immunity was dependent on PIP's enzymatic activity and acted through interference with the salicylic acid (SA) biosynthetic and regulatory genes. Thus, PIP simultaneously regulates two distinct regulatory networks during plant–microbe interactions, i.e. it affects intracellular c‐di‐GMP levels to coordinate bacterial behaviour, such as motility, and functions as a type III effector translocated into plant cells to suppress plant immunity. Both processes provide bacteria with the regulatory potential to rapidly adapt to complex environments, to utilize limited resources for growth and survival in a cost‐efficient manner and to improve the chances of bacterial survival by helping pathogens to inhabit the internal tissues of host plants.
Relative costs and benefits of clonal integration of Zoysia japonica under various N:P ratios
Authors: Jaafry Syed Wajahat Husain , Li Dezhi , Chen Huijuan , Niu Xiaoling , Li Bo
Published: March 2018

Clonal plants adaptively respond to abiotic stress, but to date little is known about under what circumstanses clonal integration is beneficial, or costly. To study the costs and benefits of clonal integration on clonal growth, we cultivated Zoysia japonica under three ratios of N:P (N:P ≈ 7, 14:1 and 21:1), and four types of stolon severing treatments (connected stolon CS, light severing LS, moderate severing MS, serious severing SS). The results showed that Z. japonica performed best at a low ratio of N:P (N:P ≈ 7:1). When the stolons were connected (CS), the growth of primary A‐ramets, multiple‐nodes and stolons benefited from clonal integration; however, the growth of primary B‐ramets on the primary stolons, A and B ramets was significantly reduced (p < 0.05). In the moderate stolon severing treatment MS7:1 (N:P ≈ 7:1), clonal integration appeared more cost effective than in all other treatments. On the whole, with increasing stolon severing intensity, the cost of clonal integration increased and the clonal growth of Z. japonica declined significantly. The pattern of biomass allocation may be useful for Z. japonica to adapt to the various environments, and clonal integration plays a significant role under adverse environmental conditions.
A nonlinear mathematical model investigating the sustainability of an urban system in the presence of haphazard urban development and excessive pollution
Authors: Jyotsna Kumari , Tandon Abhinav
Published: March 2018

The study investigates the sustainability of an urban system in the presence of haphazard urban development taking place in cities, through the use of nonlinear model system of differential equations. Here, the urban system comprises of urban forests and population, along with different development activities and associated pollution. In addition to equilibrium points and their stabilities, the qualitative behavior of the model system is also being established by determining the uniform persistence. However, quantitative behavior is being predicted through numerical solutions of the model system. The obtained behaviors demonstrate that unplanned development and its associated excessive pollution can disturb the stability of the urban system. It is also being revealed that overexploitation of forest resources by population and devastation of forest resources, as well as of population, through pollutants concentration may also pose a serious threat for a sustainable urban system in the long time.

Recommendations for Resource Managers

The sustainability of an urban system in the presence of haphazard development activities and excessive pollution is a matter of great concern as it may lead to extinction of urban forests as well as of urban population.

The admissible amount of control over urban development through government intervention is necessary for the orderly development of urban areas in harmony with natural environment. This would also help in protecting forest resources and, therefore, on the survival of its dependent population.

Urban forestry should be practiced, where emphasis should be on plantation of such vegetation, trees, and shrubs, etc., which have the pollution tolerating and mitigating abilities.

In order to establish sustainable urban system, urban development activities should harmonize the people and the environment, while taking proper advantage of abundant natural resources.
Ingestion of partially hydrolyzed whey protein suppresses epicutaneous sensitization to β‐lactoglobulin in mice
Authors: Matsubara Takeshi , Iwamoto Hiroshi , Nakazato Yuki , Okamoto Tomoyuki , Ehara Tatsuya , Izumi Hirohisa , Takeda Yasuhiro
Published: March 2018

Background

Epicutaneous sensitization to food allergens can occur through defective skin barriers. However, the relationship between oral tolerance and epicutaneous sensitization remains to be elucidated. We aimed to determine whether prior oral exposure to whey proteins or their hydrolysates prevents epicutaneous sensitization and subsequent food‐allergic reaction to the whey protein, β‐lactoglobulin (β‐LG), and investigated the underlying mechanisms.

Methods

BALB/c mice were given whey protein concentrate (WPC), two kinds of partial whey protein hydrolysate (PWH1 or PWH2), or extensive whey protein hydrolysate (EWH) in drinking water for 21 days. The mice were then epicutaneously sensitized with β‐LG on tape‐stripped skin. Sensitization was assessed by basophil activation tests and by measuring the level of serum β‐LG‐specific antibodies and cytokines secreted from β‐LG‐restimulated spleen and mesenteric lymph node (MLN) cells. Development of an allergic reaction was assessed by monitoring body temperature and by measuring mast cell protease‐1 level in plasma after the β‐LG oral challenge. Activated T‐cell population among β‐LG‐restimulated MLN cells was also analyzed.

Results

In mice fed with WPC, PWH1, or PWH2, sensitization and the development of an allergic reaction were totally reduced. The acceleration of cytokine release from the spleen and MLN cells or T‐cell activation was not evident after β‐LG restimulation. In EWH‐fed mice, a suppressive effect, though milder than that in WPC‐, PWH1‐, or PWH2‐fed mice, was observed during the development of the allergic reaction.

Conclusions

Prior oral exposure to partially hydrolyzed whey protein prevents epicutaneous sensitization and subsequent allergic response to β‐LG in mice.
Willful ignorance in law and morality
Authors: Sarch Alexander
Published: March 2018

This article introduces the main conceptual and normative questions about willful ignorance. The first section asks what willful ignorance is, while the second section asks why—and how much—it merits moral or legal condemnation. My approach is to critically examine the criminal law's view of willful ignorance. Doing so not only reveals the range of positions one might take about the phenomenon but also sheds light on foundational questions about the nature of culpability and the relation between law and morality.
The full life cycle of Leptosphaeria maculans completed on inoculated oilseed rape incubated under controlled conditions
Authors: Bousset L. , Ermel M. , Lebreton L.
Published: March 2018

Because epidemics of successive cropping seasons are not independent, epidemiological studies need to encompass the processes occurring during the transmission of epidemics from one season to the next. With Leptosphaeria maculans, infected stubble allows carry‐over of the fungus. Generation experiments using recurrent selection on field plots are a useful means of comparing the effects of selection pressures. However, the full life cycle of the fungus, from plant infection to the next generation of ascospores, has not yet been achieved under controlled conditions. Studies were undertaken to achieve an experimental set‐up with sexual reproduction under controlled conditions. Cankered oilseed rape stems were produced under controlled conditions, after inoculation with a mixture of 12 isolates across both mating types. Stems were cut longitudinally and attached to styropore plates. Stem halves were incubated outside or in climate chambers regularly soaked in tap water to ensure maturation. Incubation was stopped when mature pseudothecia were observed. In all three independent experiments, more stem halves had pseudothecia when incubated under controlled conditions (30–100%) than incubated outside (0–80%). To the authors’ knowledge, this is the first study achieving the full life cycle of the fungus under controlled conditions, from infection of the plant to mature pseudothecia. This opens up the prospect of running experiments year‐round to better understand inoculum production, to compare fungal fitness, or to run generation experiments with exotic pathogen populations.
Thyroid hormones and menstrual cycle function in a longitudinal cohort of premenopausal women
Authors: Jacobson Melanie H. , Howards Penelope P. , Darrow Lyndsey A. , Meadows Juliana W. , Kesner James S. , Spencer Jessica B. , Terrell Metrecia L. , Marcus Michele
Published: March 2018

Background

Previous studies have reported that hyperthyroid and hypothyroid women experience menstrual irregularities more often compared with euthyroid women, but reasons for this are not well‐understood and studies on thyroid hormones among euthyroid women are lacking. In a prospective cohort study of euthyroid women, this study characterised the relationship between thyroid hormone concentrations and prospectively collected menstrual function outcomes.

Methods

Between 2004‐2014, 86 euthyroid premenopausal women not lactating or taking hormonal medications participated in a study measuring menstrual function. Serum thyroid hormones were measured before the menstrual function study began. Women then collected first morning urine voids and completed daily bleeding diaries every day for three cycles. Urinary oestrogen and progesterone metabolites (estrone 3‐glucuronide (E13G) and pregnanediol 3‐glucuronide (Pd3G)) and follicle‐stimulating hormone were measured and adjusted for creatinine (Cr).

Results

Total thyroxine (T4) concentrations were positively associated with Pd3G and E13G. Women with higher (vs lower) T4 had greater luteal phase maximum Pd3G (Pd3G = 11.7 μg/mg Cr for women with high T4 vs Pd3G = 9.5 and 8.1 μg/mg Cr for women with medium and low T4, respectively) and greater follicular phase maximum E13G (E13G = 41.7 ng/mg Cr for women with high T4 vs E13G = 34.3 and 33.7 ng/mg Cr for women with medium and low T4, respectively).

Conclusions

Circulating thyroid hormone concentrations were associated with subtle differences in menstrual cycle function outcomes, particularly sex steroid hormone levels in healthy women. Results contribute to the understanding of the relationship between thyroid function and the menstrual cycle, and may have implications for fertility and chronic disease.
Actin as a cytoskeletal basis for cell architecture and a protein essential for ecdysis in Prorocentrum minimum (Dinophyceae, Prorocentrales)
Authors: Berdieva Mariia , Pozdnyakov Ilya , Matantseva Olga , Knyazev Nikolay , Skarlato Sergei
Published: March 2018

The specific cell architecture of prorocentroid dinoflagellates is reflected in the internal cell structure, particularly, in cytoskeleton organization. Cytoskeleton arrangement in a Prorocentrum minimum cell was investigated using fluorescent labeling approaches, electron‐microscopy and immunocytochemical methods. The absence of cortical microtubules was confirmed. Phalloidin – tetramethylrhodamine isothiocyanate conjugate staining demonstrated that F‐actin forms a dense layer in the cortical region of the cell; besides, it was detected in the ‘archoplasmic sphere’ adjacent to the nucleus. In some cells the rest of the cytoplasm and the nucleus were also slightly stained. In dividing cells, F‐actin was mainly distributed in the cortical region and in the cleavage furrow. Fluorescent deoxyribonuclease I staining demonstrated more evenly distributed cytoplasmic non‐polymerized actin; the basis of the nuclear actin pool is monomeric actin. It concentrates in the nucleoplasm and forms a meshwork around chromosomes. The significant amount of G‐actin is apparently localized in the P. minimum nucleolus. Assumed involvement of F‐actin in the process of stress‐induced ecdysis – cell cover shedding – was examined. A sharp decrease in the level of ecdysis was observed after treatment with actin‐depolymerizing agent latrunculin B. The fluorescent staining of treated cells demonstrated disturbance of the actin cytoskeleton and disappearance of the cortical F‐actin layer. Our results support the recent data on the actin involvement in fundamental nuclear processes: cytoplasmic F‐actin appears to participate in cell shape determination, cell cover rearrangement and development. Actin may play a substitute role in the absence of cortical microtubules, representing the cytoskeletal basis of P. minimum cell architecture.
Experiences of transgender individuals when accessing health care: a qualitative systematic review protocol
Authors: Valenta Tamera , Shade Kate , Lieggi Michelle
Published: March 2018

Review question/objective:

The objective is to synthesize existing qualitative literature examining the experiences of transgender individuals when accessing health care.
Morphological ontogeny of Ceratozetes shaldybinae (Acari, Oribatida, Ceratozetidae)
Authors: Seniczak Stanisław , Seniczak Anna , Kaczmarek Sławomir
Published: March 2018

The morphological ontogeny of Ceratozetes shaldybinae Seniczak et al., 2016c is described and illustrated. The adult of this species has a long lamellar cusp and 10 pairs of notogastral setae or alveolar vestiges, and is similar to that of C. helenae (Pavlichenko, 1993), but differs from the latter mainly by larger porose area A1 and longer seta v" on femur II. However, these species differ more distinctly from one another in the juveniles. The larva of C. shaldybinae has a pygidial shield bearing setal pair dp, whereas C. helenae lacks this shield and setae dp are placed on individual sclerites. In the tritonymph of C. shaldybinae, setae of p- and ad-series are inserted on unsclerotized cuticle, whereas in C. helenae they are placed on microsclerites. The tritonymphs of both species have the same number of setae on the gastronotal shield (five pairs), but in C. shaldybinae setae dm and dp are thicker than in C. helenae. The juveniles of these species differ also by the shape of some setae on the body and legs.
Fragile skin microbiomes in megacities are assembled by a predominantly niche-based process
Authors: Kim Hye-Jin , Kim Hanbyul , Kim Jin Ju , Myeong Nu Ri , Kim Taeyune , Park Taehun , Kim Eunjoo , Choi Ji-yei , Lee Johnhwan , An Susun , Sul Woo Jun
Published: March 2018

Predominant niche-based process assembly of megacity skin microbiomes results in a relatively fragile microbial network.
Global climate change and local land subsidence exacerbate inundation risk to the San Francisco Bay Area
Authors: Shirzaei Manoochehr , Bürgmann Roland
Published: March 2018

The risk of coastal flooding is likely exacerbated because of the concerted impact of sea level rise and local land subsidence.
Mapping metabolic changes by noninvasive, multiparametric, high-resolution imaging using endogenous contrast
Authors: Liu Zhiyi , Pouli Dimitra , Alonzo Carlo A. , Varone Antonio , Karaliota Sevasti , Quinn Kyle P. , Münger Karl , Karalis Katia P. , Georgakoudi Irene
Published: March 2018

Two-photon imaging provides noninvasive, label-free, quantitative assays of metabolic changes at the single-cell or tissue level.
Shark baselines and the conservation role of remote coral reef ecosystems
Authors: Ferretti Francesco , Curnick David , Liu Keli , Romanov Evgeny V. , Block Barbara A.
Published: March 2018

Integrative and historical approach redefines shark baselines in remote coral reef ecosystems.
Fluid pressure and shear zone development over the locked to slow slip region in Cascadia
Authors: Audet Pascal , Schaeffer Andrew J.
Published: March 2018

Seismic data collected at the Cascadia subduction zone illuminate seismic structure across the locked to slow slip transition.
Saildrone fleet could help replace aging buoys
Authors: Voosen Paul
Published: March 2018

Robotic test in Pacific Ocean heralds new way to monitor El Niño events.
China hones plans for ambitious x-ray probe
Authors: Normile Dennis
Published: March 2018

Mission would firm up China's status as a leader in x-ray astronomy.
Local transformations of the hippocampal cognitive map
Authors: Krupic Julija , Bauza Marius , Burton Stephen , O’Keefe John
Published: March 2018

The mechanisms behind grid cell changes

When grid cells were first discovered in the brain, the grids were considered to have rigid coordinates beyond the borders of the testing environments. However, recent findings suggest that the grid cell pattern can be altered easily by changing the space of the enclosure. But how? Krupic
et al.
discovered that local changes in the geometry of the environment shifted individual neighboring grid fields, while more distant fields remained unchanged. Thus, changes to the grid structure are localized. Stable landmarks continue to exert an effect on most grid cells, whereas the ones close to changed borders are modified.

Science
, this issue p.
1143
Sustained climate warming drives declining marine biological productivity
Authors: Moore J. Keith , Fu Weiwei , Primeau Francois , Britten Gregory L. , Lindsay Keith , Long Matthew , Doney Scott C. , Mahowald Natalie , Hoffman Forrest , Randerson James T.
Published: March 2018

Starving ocean productivity

Projected increases in greenhouse gas emissions could suppress marine biological productivity for a thousand years or more. As the climate warms, westerly winds in the Southern Hemisphere will strengthen and shift poleward, surface waters will warm, and sea ice will disappear. Moore
et al.
suggest that one effect of these changes will be a dramatic decrease in marine biological productivity (see the Perspective by Laufkötter and Gruber). This decrease will result from a global-scale redistribution of nutrients, with a net transfer to the deep ocean. By 2300, this could drive declines in fisheries yields by more than 20% globally and by nearly 60% in the North Atlantic.

Science
, this issue p.
1139
; see also p.
1103
Comment on “The growth pattern of Neandertals, reconstructed from a juvenile skeleton from El Sidrón (Spain)”
Authors: DeSilva Jeremy M.
Published: March 2018

Rosas
et al
. (Reports, 22 September 2017, p. 1282) calculate El Sidrón J1 to have reached only 87.5% of its adult brain size. This finding is based on an overestimation of Neandertal brain size. Pairwise comparisons with a larger sample of Neandertal fossils reveal that it is unlikely that the brain of El Sidrón would have grown appreciably larger.
Capturing dynamic protein interactions
Authors: Li Xiao-Han , Chavali Pavithra L. , Babu M. Madan
Published: March 2018

A method based on heat denaturation reveals how proteins interact in different cells
Increasing Resistance to Azithromycin in Neisseria gonorrhoeae in Eastern Chinese Cities: Resistance Mechanisms and Genetic Diversity among Isolates from Nanjing
Authors: Wan Chuan , Li Yang , Le Wen-Jing , Liu Yu-Rong , Li Sai , Wang Bao-Xi , Rice Peter A. , Su Xiao-Hong
Published: March 2018

Azithromycin resistance (AZM-R) of
Neisseria gonorrhoeae
is emerging as a clinical and public health challenge. We determined molecular characteristics of recent AZM-R Nanjing gonococcal isolates and tracked the emergence of AZM-R isolates in eastern Chinese cities in recent years. A total of 384
N. gonorrhoeae
isolates from Nanjing collected from 2013 to 2014 were tested for susceptibility to AZM and six additional antibiotics; all AZM-R strains were characterized genetically for resistance determinants by sequencing and were genotyped using
N. gonorrhoeae
multiantigen sequence typing (NG-MAST). Among the 384 isolates, 124 (32.3%) were AZM-R. High-level resistance (MIC, ≥256 mg/liter) was present in 10.4% (40/384) of isolates, all of which possessed the A2143G mutation in all four 23S rRNA alleles. Low- to mid-level resistance (MIC, 1 to 64 mg/liter) was present in 21.9% (84/384) of isolates, 59.5% of which possessed the C2599T mutation in all four 23S rRNA alleles. The 124 AZM-R isolates were distributed in 71 different NG-MAST sequence types (STs). ST1866 was the most prevalent type in high-level AZM-R (HL-AZM-R) isolates (45% [18/40]). This study, together with previous reports, revealed that the prevalence of AZM-R in
N. gonorrhoeae
isolates in certain eastern Chinese cities has risen >4-fold (7% to 32%) from 2008 to 2014. The principal mechanisms of AZM resistance in recent Nanjing isolates were A2143G mutations (high-level resistance) and C2599T mutations (low- to mid-level resistance) in the 23S rRNA alleles. Characterization of NG-MAST STs and phylogenetic analysis indicated the genetic diversity of
N. gonorrhoeae
in Nanjing; however, ST1866 was the dominant genotype associated with HL-AZM-R isolates.
Comprehensive Molecular Approach for Characterization of Hepatitis E Virus Genotype 3 Variants
Authors: Wang Bo , Harms Dominik , Papp C. Patrick , Niendorf Sandra , Jacobsen Sonja , Lütgehetmann Marc , Pischke Sven , Wedermeyer Heiner , Hofmann Jörg , Bock C.-Thomas
Published: March 2018

Autochthonous hepatitis E virus genotype 3 (HEV-3) infections in industrialized countries are more frequent than previously assumed. HEV-3 is zoonotic and the causal pathogen of chronic hepatitis E. According to the latest classification of the family
Hepeviridae
, 10 designated HEV-3 subtypes (HEV-3a to HEV-3j) and 7 unassigned HEV-3 subtypes are proposed. In order to identify and characterize the HEV-3 variants in circulation, we developed a molecular approach combining a sensitive HEV-specific real-time reverse transcription-PCR (RT-PCR) targeting the overlapping region of HEV ORF2 and ORF3 (the ORF2/3 region) and two newly designed consensus nested RT-PCRs targeting the HEV ORF1 and ORF2 genes, respectively. Since complete genome sequences are required for new HEV-3 subtype assignment, we implemented a straightforward approach for full-length HEV-3 genome amplification. Twenty-nine human serum samples and six human feces samples from chronic hepatitis E patients were selected for evaluation of the system. Viral loads ranged from 1 × 10
4
to 1.9 × 10
10
copies/ml of serum and from 1.8 × 10
4
to 1 × 10
12
copies/g of feces. Sequence and phylogenetic analyses of partial ORF1 and ORF2 sequences showed that HEV strains had considerable genetic diversity and clustered into the HEV-3c (29/35), HEV-3e (2/35), HEV-3f (2/35), and unassigned HEV-3 (2/35) subtypes. Moreover, from these strains, three full-length HEV-3 genome sequences were generated and characterized. DE/15-0030 represents a typical HEV-3c strain (95.7% nucleotide identity to wbGER27), while DE/15-0031 and SW/16-0282 have <89.2% homology to known HEV-3 strains and are phylogenetically divergent, indicating novel HEV-3 subtypes. In summary, our approach will significantly facilitate the detection, quantification, and determination of HEV-3 strains and will thus help to improve molecular diagnostics and our knowledge of HEV diversity and evolution.
Improved Discrimination of Bacillus anthracis from Closely Related Species in the
Bacillus cereus Sensu Lato
Group Based on Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry
Authors: Pauker Viktoria I. , Thoma Bryan R. , Grass Gregor , Bleichert Pauline , Hanczaruk Matthias , Zöller Lothar , Zange Sabine
Published: March 2018

Discrimination of highly pathogenic bacteria, such as
Bacillus anthracis
, from closely related species based on molecular biological methods is challenging. We applied matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) to a collection of
B. anthracis
strains and close relatives in order to significantly improve the statistical confidence of identification results for this group of bacteria. Protein mass spectra of 189 verified and diverse
Bacillus
strains of the
Bacillus cereus sensu lato
group were generated using MALDI-TOF MS and subsequently analyzed with supervised and unsupervised statistical methods, such as shrinkage discriminant analysis (SDA) and principal-component analysis (PCA). We aimed at identifying specific biomarkers in the protein spectra of
B. anthracis
not present in closely related
Bacillus
species. We could identify 7, 10, 18, and 14
B. anthracis
-specific biomarker candidates that were absent in
B. cereus
,
B. mycoides
,
B. thuringiensis
, and
B. weihenstephanensis
strains, respectively. Main spectra (MSP) of a defined collection of
Bacillus
strains were compiled using the Bruker Biotyper software and added to an in-house reference library. Reevaluation of this library with 15 hitherto untested strains of
B. anthracis
and
B. cereus
yielded improved score values. The
B. anthracis
strains were identified with score values between 2.33 and 2.55 using the in-house database, while the same strains were identified with scores between 1.94 and 2.37 using the commercial database, and no false-positive identifications occurred using the in-house database.
HIV-1 Nef Antagonizes SERINC5 Restriction by Downregulation of SERINC5 via the Endosome/Lysosome System
Authors: Shi Jing , Xiong Ran , Zhou Tao , Su Peiyi , Zhang Xihe , Qiu Xusheng , Li Hongmei , Li Sunan , Yu Changqing , Wang Bin , Ding Chan , Smithgall Thomas E. , Zheng Yong-Hui
Published: March 2018

The primate lentiviral accessory protein Nef downregulates CD4 and major histocompatibility complex class I (MHC-I) from the cell surface via independent endosomal trafficking pathways to promote viral pathogenesis. In addition, Nef antagonizes a novel restriction factor, SERINC5 (Ser5), to increase viral infectivity. To explore the molecular mechanism of Ser5 antagonism by Nef, we determined how Nef affects Ser5 expression and intracellular trafficking in comparison to CD4 and MHC-I. We confirm that Nef excludes Ser5 from human immunodeficiency virus type 1 (HIV-1) virions by downregulating its cell surface expression via similar functional motifs required for CD4 downregulation. We find that Nef decreases both Ser5 and CD4 expression at steady-state levels, which are rescued by NH
4
Cl or bafilomycin A1 treatment. Nef binding to Ser5 was detected in living cells using a bimolecular fluorescence complementation assay, where Nef membrane association is required for interaction. In addition, Nef triggers rapid Ser5 internalization via receptor-mediated endocytosis and relocalizes Ser5 to Rab5
+
early, Rab7
+
late, and Rab11
+
recycling endosomes. Manipulation of AP-2, Rab5, Rab7, and Rab11 expression levels affects the Nef-dependent Ser5 and CD4 downregulation. Moreover, although Nef does not promote Ser5 polyubiquitination, Ser5 downregulation relies on the ubiquitination pathway, and both K48- and K63-specific ubiquitin linkages are required for the downregulation. Finally, Nef promotes Ser5 colocalization with LAMP1, which is enhanced by bafilomycin A1 treatment, suggesting that Ser5 is targeted to lysosomes for destruction. We conclude that Nef uses a similar mechanism to downregulate Ser5 and CD4, which sorts Ser5 into a point-of-no-return degradative pathway to counteract its restriction.

IMPORTANCE
Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) express an accessory protein called Nef to promote viral pathogenesis. Nef drives immune escape
in vivo
through downregulation of CD4 and MHC-I from the host cell surface. Recently, Nef was reported to counteract a novel host restriction factor, Ser5, to increase viral infectivity. Nef downregulates cell surface Ser5, thus preventing its incorporation into virus particles, resulting in disruption of its antiviral activity. Here, we report mechanistic studies of Nef-mediated Ser5 downregulation in comparison to CD4 and MHC-I. We demonstrate that Nef binds directly to Ser5 in living cells and that Nef-Ser5 interaction requires Nef association with the plasma membrane. Subsequently, Nef internalizes Ser5 from the plasma membrane via receptor-mediated endocytosis, and targets ubiquitinated Ser5 to endosomes and lysosomes for destruction. Collectively, these results provide new insights into our ongoing understanding of the Nef-Ser5 arms race in HIV-1 infection.
What factors influence recruitment to a birth cohort of infants with Down’s syndrome?
Authors: Williams Georgina M , Neville Patricia , Gillespie Kathleen M , Leary Sam D , Hamilton-Shield Julian P , Searle Aidan J
Published: March 2018

Objective

To understand how to maximise recruitment of young infants with Down’s syndrome (DS) into research through qualitative interviews with parents and care providers. In complex neonatal and genetic conditions such as DS, frequently diagnosed after birth, parents may go through a period of adaptation. These factors need consideration when overcoming barriers to recruitment.

Participants and design

Participants, who were drawn from health professionals and volunteers working with families experiencing DS, were recruited using a purposive sampling strategy. Semistructured telephone interviews were completed with nine paediatricians, three research nurses and six family support workers. Five of those interviewed had a child with DS. The interviews were transcribed and analysed thematically.

Results

A positive decision to take part in a ‘from-birth’ cohort study depends on factors such as the child’s overall health, parent demographics (educational background and ethnicity), medical interactions that take place with the families (communication) and study logistics. The data suggest that recruitment methods need to take all these factors into consideration. Multiple recruitment methods should be considered including face to face, through parent and support groups, websites and social media. There also needs to be flexibility in the research timings to fit around the needs of the child and parents.

Conclusion

Researchers need to be aware of the variable responses elicited by families to a diagnosis of DS for their baby and be sensitive to the child’s current medical status. This does not preclude recruitment into studies, but to maximise uptake good communication and flexibility is essential.
ACL rupture is a single leg injury but a double leg problem: too much focus on ‘symmetry’ alone and that’s not enough!
Authors: Benjaminse Anne , Holden Sinead , Myer Gregory D
Published: March 2018

The authors present their thoughts on the focus on targeting asymmetry in rehabilitation after ACL reconstruction, which they think may not be rich enough to identify deficits.
Can child restraint product information developed using consumer testing sustain correct use 6 months after child restraint purchase? Study protocol for a cluster randomised controlled trial
Authors: Brown Julie , Elkington Jane , Hall Alexandra , Keay Lisa , Charlton Judith L , Hunter Kate , Koppel Sjaan , Hayen Andrew , Bilston Lynne E
Published: March 2018

Background

With long-standing and widespread high rates of errors in child restraint use, there is a need to identify effective methods to address this problem. Information supplied with products at the point of sale may be a potentially efficient delivery point for such a countermeasure. The aim of this study is to establish whether product materials developed using a consumer-driven approach reduce errors in restraint use among purchasers of new child restraint systems.

Methods

A cluster randomised controlled trial (cRCT) will be conducted. Retail stores (n=22) in the greater Sydney area will be randomised into intervention sites (n=11) and control sites (n=11), stratified by geographical and socioeconomic indicators. Participants (n=836) will enter the study on purchase of a restraint. Outcome measures are errors in installation of the restraint as observed by a trained researcher during a 6-month follow-up home assessment, and adjustment checks made by the parent when the child is placed into the restraint (observed using naturalistic methods). Process evaluation measures will also be collected during the home visit. An intention-to-treat approach will be used for all analyses. Correct use and adjustment checks made by the parent will be compared between control and intervention groups using a logistic regression model. The number of installation errors between groups will be compared using Poisson regression.

Discussion

This cRCT will determine the effectiveness of targeted, consumer-driven information on actual error rates in use of restraints. More broadly, it may provide a best practice model for developing safety product information.

Trial registration number

ACTRN12617001252303p; Pre-results.
Fourier supports of K-finite Bessel integrals on classical tube domains
Authors: Kobana Tetsuya , Kodaira Kaoru , Miyazaki Takuya
Published: March 2018

Let [Formula: see text] be the symmetric tube domain associated with the Jordan algebra [Formula: see text], [Formula: see text], [Formula: see text], or [Formula: see text], and [Formula: see text] be its Shilov boundary. Also, let [Formula: see text] be a degenerate principal series representation of [Formula: see text]. Then we investigate the Bessel integrals assigned to functions in general [Formula: see text]-types of [Formula: see text]. We give individual upper bounds of their supports, when [Formula: see text] is reducible. We also use the upper bounds to give a partition for the set of all [Formula: see text]-types in [Formula: see text], that turns out to explain the [Formula: see text]-module structure of [Formula: see text]. Thus, our results concretely realize a relationship observed by Kashiwara and Vergne [[Formula: see text]-types and singular spectrum, in Noncommutative Harmonic analysis, Lecture Notes in Mathematics, Vol. 728 (Springer, 1979), pp. 177–200] between the Fourier supports and the asymptotic [Formula: see text]-supports assigned to [Formula: see text]-submodules in [Formula: see text].
Identification of a mitochondria-targeting fluorescent small molecule for dual phototherapy
Authors: Chen Jie , Tan Xu , Luo Shenglin , Long Lei , Liu Lang , Liu Zujuan , Wang Yu , Shi Chunmeng
Published: March 2018

Phototherapy, mainly including photodynamic therapy (PDT) and photothermal therapy (PTT), is a noninvasive and effective approach for cancer treatment. Since integration of PDT and PTT for simultaneous synergistic PDT/PTT treatment enables us to improve phototherapeutic efficacy significantly, it has been attracting a lot of investigations in current days. Here, we introduce IR-52, a new mitochondria-targeting near infrared (NIR) fluorescent small molecule, which possesses structure-inherent PTT and PDT synergistic phototherapeutic effects without conjugation to specific ligands. After NIR light irradiation (808[Formula: see text]nm, 2[Formula: see text]W/cm2, 5[Formula: see text]min), both the hyperthermia and excessive singlet oxygen levels were determined when dissolving IR-52 in aqueous solutions. In vitro photoinduced cytotoxicity studies showed significant lower cell viabilities and higher necrotic/apoptotic rates when cancer cells were treated with IR-52 and irradiation, and its’ mitochondrial localization in cancer cells would partially explain its high cytotoxicity. Further in vivo synergetic PDT and PTT effects were demonstrated by high tumor surface temperature and significant inhibition of tumor growth. Our results strongly suggest that IR-52, which possesses excellent photosensitivity, may provide a promising strategy for tumor treatment with decreased side effects.
Heritability of proprioceptive senses
Authors: Missitzi Julia , Geladas Nickos , Misitzi Angelica , Misitzis Leonidas , Classen Joseph , Klissouras Vassilis
Published: March 2018

Heritability studies using the twin model have provided the basis to disentangle genetic and environmental factors that contribute to several complex human traits. However, the relative importance of these factors to individual differences in proprioception is largely unknown despite the fact that proprioceptive senses are of great importance, allowing us to respond to stimuli stemming from the space around us and react to altering circumstances. Hence, a total of 44 healthy male twins (11 MZ and 11 DZ pairs), 19–28 yr old, were examined for movement, position, and force sense at the elbow joint, and their heritability estimates were computed. Results showed that genetic factors explained 1) 72 and 76% of the total variance of movement sense at the start and the end of the movement, respectively, 2) 60 to 77% of the total variance of position sense, depending on the angle of elbow flexion and whether forearm positioning was active or passive, and 3) 73 and 70% of the total variance of the force sense at 90 and 60° of elbow flexion, respectively. It is concluded that proprioception assessed by these conscious sensations is to a substantial degree genetically dependent, with heritability indexes ranging from 0.60 to 0.77, depending on the task.

NEW & NOTEWORTHY Proprioceptive acuity varies among people, but it is not known how much of this variability is due to differences in their genes. This study is the first to report that proprioception, expressed as movement sense, position sense, and force sense, is substantially heritable, and it is conceivable that this may have implications for motor learning and control, neural development, and neurorehabilitation.
Identification and quantification of human microcirculatory leukocytes using handheld video microscopes at the bedside
Authors: Uz Zühre , van Gulik Thomas M. , Aydemirli Mehtap D. , Guerci Philippe , Ince Yasin , Cuppen Diede , Ergin Bulent , Aksu Ugur , de Mol Bas A. , Ince Can
Published: March 2018

Leukocyte recruitment and adhesion to the endothelium are hallmarks of systemic inflammation that manifest in a wide range of diseases. At present, no method is available to directly measure leukocyte kinetics at the bedside. In this study, we validate a new method to identify and quantify microcirculatory leukocytes observed by handheld vital microscopy (HVM) using space-time diagram (STD) analysis. Video clips ( n = 59) containing one capillary-postcapillary venule unit where leukocytes could be observed emanating from a capillary into a venule in cardiac surgery patients ( n = 20) were included. STD analysis and manual counting were used to quantify the number of leukocytes (total, rolling, and nonrolling). Pearson’s correlation and Bland-Altman analysis were used to determine agreement between the STDs and manual counting. For reproducibility, intra- and interobserver coefficients of variation (CVs) were assessed. Leukocyte (rolling and nonrolling) and red blood cell velocities were assessed. The STDs and manual counting procedures for the quantification of rolling leukocytes showed good agreement ( r = 0.8197, P < 0.0001), with a Bland-Altman analysis mean difference of −0.0 (−6.56; 6.56). The overall intraobserver CV for the STD method was 1.5%. The overall interobserver CVs for the STD and the manual method were 5.6% and 9.4%, respectively. The nonrolling velocity was significantly higher than the rolling velocity (812 ± 519 µm/s vs. 201 ± 149 µm/s, P = 0.001). STD results agreed with the manual counting procedure results, had a better reproducibility, and could assess the leukocyte velocity. STD analysis using bedside HVM imaging presented a new methodology for quantifying leukocyte kinetics and functions in the microcirculation.

NEW & NOTEWORTHY In this study, we introduce space-time diagram analysis of sublingual microcirculation imaging using handheld vital microscopy to identify and quantify the presence and kinetics of human microcirculatory leukocytes. We validated the methodology by choosing anatomical units consisting of a capillary connected to a venule, which allowed precise identification of leukocytes.
A Study of Chaos in Dynamical Systems
Authors: Effah-Poku S. , Obeng-Denteh W. , Dontwi I. K.
Published: March 2018

The behavior of systems such as periodicity, fixed points, and most importantly chaos has evolved as an integral part of mathematics, especially in dynamical system. This research presents a study on chaos as a property of nonlinear science. Systems with at least two of the following properties are considered to be chaotic in a certain sense: bifurcation and period doubling, period three, transitivity and dense orbit, sensitive dependence to initial conditions, and expansivity. These are termed as the routes to chaos.
Flexible Emergency Vehicle Network Design considering Stochastic Demands and Inverse-Direction Lanes
Authors: Wang Hua , Xiao Ling , Chen Zhang
Published: March 2018

We study transportation network design with stochastic demands and emergency vehicle (EV) lanes. Different from previous studies, this paper considers two groups of users, auto and EV travelers, whose road access rights are differentiated in the network, and addresses the value of incorporating inverse-direction lanes in network design. We formulate the problem as a bilevel optimization model, where the upper-level model aims to determine the optimal design of EV lanes and the lower-level model uses the user equilibrium principle to forecast the route choice of road users. A simulation-based genetic algorithm is proposed to solve the model. With numerical experiments, we demonstrate the value of deploying inverse-direction EV lanes and the computational efficiency of the proposed algorithm. We reach an intriguing finding that both regular and EV lane users can benefit from building EV lanes.