bluuebunny/crossref_metadata_2025 huggingface dataset:
Vertical transmission of sponge microbiota is inconsistent and unfaithful
Authors: Björk Johannes R. , Diéz-Vives Cristina , Astudillo-García Carmen , Archie Elizabeth A. , Montoya José M.
Published: September 2018

Classic coevolutionary theory predicts that if beneficial microbial symbionts improve host fitness, they should be faithfully transmitted to offspring. More recently, the hologenome theory of evolution predicts resemblance between parent and offspring microbiomes and high partner fidelity between host species and their vertically transmitted microbes. Here, we test these ideas for the first time in multiple coexisting host species with highly diverse microbiota, leveraging known parent-offspring pairs sampled from eight species of wild marine sponges (Porifera). We found that the processes governing vertical transmission were both neutral and selective. A neutral model explained 66% of the variance in larval microbiota, which was higher than the variance this model explained for adult sponge microbiota (R2= 27%). However, microbes that are enriched above neutral expectations in adults were disproportionately transferred to offspring. Patterns of vertical transmission were, however, incomplete: larval sponges shared, on average, 44.8% of microbes with their parents, which was not higher than the fraction they shared with nearby non-parental adults. Vertical transmission was also inconsistent across siblings, as larval sponges from the same parent only shared 17% of microbes. Finally, we found no evidence that vertically transmitted microbes are faithful to a single sponge host species. Surprisingly, larvae were just as likely to share vertically transmitted microbes with larvae from other sponge species as they were with their own species. Our study demonstrates that common predictions of vertical transmission that stem from species-poor systems are not necessarily true when scaling up to diverse and complex microbiomes.
Reinforcement targets sexual or postmating prezygotic reproductive barriers depending on species abundance and population history
Authors: Poikela Noora , Kinnunen Johanna , Wurdack Mareike , Kauranen Hannele , Schmitt Thomas , Kankare Maaria , Snook Rhonda R. , Hoikkala Anneli
Published: September 2018

The impact of different reproductive barriers on species or population isolation may vary in different stages of speciation depending on evolutionary forces acting within species and through species’ interactions. Genetic incompatibilities between interacting species are expected to reinforce prezygotic barriers in sympatric populations and create character displacement between conspecific populations living within and outside the area of sympatry. The outcome of reinforcement has been suggested to be affected by the strength of postzygotic barriers, the history of species coexistence, and the impact of species abundancies on females’ discrimination against heterospecific males. We tested these predictions inDrosophila montanaandDrosophila flavomontanapopulations from different geographic regimes. All barriers betweenD. montanafemales andD. flavomontanamales were extremely strong, while in the reciprocal cross postzygotic isolation was less effective and the target of reinforcement varied according to population type. In long-established sympatric populations, whereD. flavomontanais abundant, reinforcement targeted sexual isolation, and in populations, where this species is a new invader and rare, reinforcement targeted postmating prezygotic barriers. Reinforcement of these barriers also created respective barriers between differentD. flavomontanapopulations. These findings show that interspecies interactions have far-reaching effects on strengthening species barriers and promoting speciation.
Amygdala neuronal ensembles dynamically encode behavioral states
Authors: Gründemann Jan , Bitterman Yael , Lu Tingjia , Krabbe Sabine , Grewe Benjamin F. , Schnitzer Mark J. , Lüthi Andreas
Published: September 2018

Internal states, including affective or homeostatic states, are important behavioral motivators. The amygdala is a key brain region involved in the regulation of motivated behaviors, yet how distinct internal states are represented in amygdala circuits is unknown. Here, by imaging somatic neural calcium dynamics in freely moving mice, we identify changes in the relative activity levels of two major, non-overlapping populations of principal neurons in the basal nucleus of the amygdala (BA) that predict switches between exploratory and non-exploratory (defensive, anxiety-like) behavioral states across different environments. Moreover, the amygdala widely broadcasts internal state information via several output pathways to larger brain networks, and sensory responses in BA occur independently of behavioral state encoding. Thus, the brain processes external stimuli and internal states in an orthogonal manner, which may facilitate rapid and flexible selection of appropriate, state-dependent behavioral responses.
A screen for genes that regulate synaptic growth reveals mechanisms that stabilize synaptic strength
Authors: Goel Pragya , Khan Mehak , Howard Samantha , Kiragasi Beril , Kikuma Koto , Dickman Dion
Published: September 2018

Synapses grow, prune, and remodel throughout development, experience, and disease. This structural plasticity can destabilize information transfer in the nervous system. However, neural activity remains remarkably stable throughout life, implying that adaptive countermeasures exist to stabilize neurotransmission. Aberrant synaptic structure and function has been associated with a variety of neural diseases including Fragile X syndrome, autism, and intellectual disability. We have screened disruptions in over 300 genes in Drosophila for defects in synaptic growth at the neuromuscular junction. This effort identified 12 mutants with severe reductions or enhancements in synaptic growth. Remarkably, electrophysiological recordings revealed synaptic strength in all but one of these mutants was unchanged compared to wild type. We utilized a combination of genetic, anatomical, and electrophysiological analyses to illuminate three mechanisms that stabilize synaptic strength in the face of alterations in synaptic growth. These include compensatory changes in 1) postsynaptic receptor abundance; 2) presynaptic morphology; and 3) active zone structure. Together, this analysis identifies new genes that regulate synaptic growth and the adaptive strategies that synapses employ to homeostatically stabilize synaptic strength in response.

AUTHOR SUMMARY

Throughout development, maturation, experience, and disease, synapses undergo dramatic changes in growth and remodeling. Although these processes are necessary for learning and memory, they pose major challenges to stable function in the nervous system. However, neurotransmission is typically constrained within narrow physiological ranges, implying the existence of homeostatic mechanisms that maintain stable functionality despite drastic alterations in synapse number. In this study we investigate the relationship between synaptic growth and function across a variety of mutations in neural and synaptic genes in the fruitfly Drosophila melanogaster. Using the neuromuscular junction as a model system, we reveal three adaptive mechanisms that stabilize synaptic strength when synapses are dramatically under- or over-grown. Together, these findings provide insights into the strategies employed at both pre- and post-synaptic compartments to ensure stable functionality while allowing considerable flexibility in overall synapse number.
Repeated evolution of a morphological novelty: a phylogenetic analysis of the inflated fruiting calyx in the Physalideae tribe (Solanaceae)
Authors: Deanna Rocío , Larter Maximilien D. , Barboza Gloria E. , Smith Stacey D.
Published: September 2018

PREMISE OF THE STUDY

The evolution of novel fruit morphologies has been integral to the success of angiosperms. The inflated fruiting calyx, in which the balloon-like calyx swells to completely surround the fruit, has evolved repeatedly across angiosperms and is postulated to aid in protection and dispersal. Here we investigate the evolution of this trait in the tomatillos and their allies (Physalideae, Solanaceae), using a newly estimated phylogeny and a suite of comparative methods to infer evolutionary gains and losses.

METHODS

The Physalideae phylogeny was estimated using DNA sequences from four regions (ITS, LEAFY, trnL-F, waxy) using maximum likelihood and Bayesian Inference. Maximum likelihood model selection was used to determine the best fitting model of trait evolution. Using this model, we estimated ancestral states along with the numbers of gains and losses of fruiting calyx accrescence and inflation with Bayesian stochastic mapping. Also, phylogenetic signal in calyx morphology was examined with two metrics (parsimony score and Fritz and Purvis’ D).

KEY RESULTS

The well resolved phylogeny points to multiple taxa in need of revision, including the eight genera that are non-monophyletic as presently circumscribed. Model fitting indicated that calyx evolution has proceeded in stepwise fashion, from non-accrescent, to accrescent, to inflated. Moreover, these transitions appear to be largely irreversible. Among the 215 sampled Physalideae, we inferred 24 gains of fruiting calyx accrescence, 24 subsequent transitions to a fully inflated calyx and only two reversals. A median of 50 shifts were estimated in total across the clade from the ancestral non-accrescent calyx. Nonetheless, fruiting calyx accrescence and inflation show strong phylogenetic signal.

CONCLUSIONS

Our phylogeny greatly improves the resolution of Physalideae and highlights the need for taxonomic work. The analyses of trait evolution reveal that the inflated fruiting calyx has evolved many times and that the trajectory towards this phenotype is generally stepwise and directional. These results provide a strong foundation for studying the genetic and developmental mechanisms responsible for the repeated origins of this charismatic fruit trait.
Derivation of a simple postoperative delirium incidence and severity prediction model
Authors: H. Lindroth , L. Bratzke , S. Twadell , P. Rowley , J. Kildow , M. Danner , L. Turner , B. Hernandez , W. Chang , R. Brown , R.D. Sanders
Published: September 2018

Background

Delirium is an important postoperative complication, yet a simple and effective delirium prediction model remains elusive. We hypothesized that the combination of the National Surgical Quality Improvement Program (NSQIP) risk calculator for serious complications (NSQIP-SC) or risk of death (NSQIP-D), and cognitive tests of executive function (Trail Making Test A and B [TMTA, TMTB]), could provide a parsimonious model to predict postoperative delirium incidence or severity.

Methods

Data were collected from 100 adults (≥65yo) undergoing major non-cardiac surgery. In addition to NSQIP-SC, NSQIP-D, TMTA and TMTB, we collected participant age, sex, ASA score, tobacco use, type of surgery, depression, Framingham risk score, and preoperative blood pressure. Delirium was diagnosed with the Confusion Assessment Method (CAM), and the Delirium Rating Scale-R-98 (DRS) was used to assess symptom severity. LASSO and Best Subsets logistic and linear regression were employed in line with TRIPOD guidelines.

Results

Three participants were excluded due to intraoperative deaths (2) and alcohol withdrawal (1). Ninety-seven participants with a mean age of 71.68±4.55, 55% male (31/97 CAM+, 32%) and a mean Peak DRS of 21.5±6.40 were analyzed. Of the variables included, only NSQIP-SC and TMTB were identified to be predictors of postoperative delirium incidence (p<0.001, AUROC 0.81, 95% CI: 0.72, 0.90) and severity (p<0.001, Adj. R2: 0.30).

Conclusions

In this cohort, preoperative NSQIP-SC and TMTB were identified as predictors of postoperative delirium incidence and severity. Future studies should verify whether this two-factor model could be used for accurate delirium prediction.
Imaging tissues and cells beyond the diffraction limit with structured illumination microscopy and Bayesian image reconstruction
Authors: Pospíšil Jakub , Lukeš Tomáš , Bendesky Justin , Fliegel Karel , Spendier Kathrin , Hagen Guy M.
Published: September 2018

Background

Structured illumination microscopy (SIM) is a family of methods in optical fluorescence microscopy that can achieve both optical sectioning and super-resolution effects. SIM is a valuable method for high resolution imaging of fixed cells or tissues labeled with conventional fluorophores, as well as for imaging the dynamics of live cells expressing fluorescent protein constructs. In SIM, one acquires a set of images with shifting illumination patterns. This set of images is subsequently treated with image analysis algorithms to produce an image with reduced out-of-focus light (optical sectioning) and/or with improved resolution (super-resolution).

Findings

Five complete and freely available SIM datasets are presented including raw and analyzed data. We report methods for image acquisition and analysis using open source software along with examples of the resulting images when processed with different methods. We processed the data using established optical sectioning SIM and super-resolution SIM methods, and with newer Bayesian restoration approaches which we are developing.

Conclusion

Various methods for SIM data acquisition and processing are actively being developed, but complete raw data from SIM experiments is not typically published. Publicly available, high quality raw data with examples of processed results will aid researchers when developing new methods in SIM. Biologists will also find interest in the high-resolution images of animal tissues and cells we acquired. All of the data was processed with SIMToolbox, an open source and freely available software solution for SIM.
A cost effective high-resolution climbing assay applied to Drosophila Parkinson’s and proprioception mutants reveal novel behavioural phenotypes
Authors: Aggarwal Aman , Reichert Heinrich , VijayRaghavan K.
Published: September 2018

Severe locomotor impairment is a common phenotype of neurodegenerative disorders such as Parkinson’s disease (PD). Drosophila models of PD, studied from more than a decade, have helped in understanding the interaction between various genetic factors, such as parkin and PINK1, in this disease. To characterize locomotor behavioural phenotypes for these genes, fly climbing assays have been widely used. While these simple current assays for locomotor defects in Drosophila mutants measure some locomotor phenotypes well, it is possible that detection of subtle changes in behaviour is important to understand the early manifestation of locomotor disorders. We introduce a novel climbing behaviour assay which provides such fine-scale behavioural data and tests this proposition for the Drosophila model. We use this inexpensive, fully automated, high resolution assay to quantitatively characterize the parameters of climbing behaviour in three contexts. First, we characterize wild type flies and uncover a hitherto unknown sexual dimorphism in climbing behaviour. Second, we study climbing behaviour of heterozygous mutants of genes implicated in the fly PD model and reveal previously unreported prominent locomotor defects in some of these heterozygous fly lines. Finally, we study locomotor defects in a homozygous proprioceptory mutation (Trp-γ1) known to affect fine motor control in Drosophila. Moreover, we identify aberrant geotactic behaviour in Trp-γ1 mutants, thereby opening up a finer assay for geotaxis and its genetic basis. Our assay is therefore a cost-effective, general tool for measuring locomotor behaviours of wild type and mutant flies in fine detail and can reveal mild motor defects.

Significance statement

Fine control of neuronal activity is required for proper motor output. Severe locomotor impairment is a common result of neurodegenerative disorders such as Parkinson’s disease (PD). The fruitfly, Drosophila, has been widely used as a model system to study the genetics of these disorders and simple climbing assays have been used to study the behavioural phenotypes of mutations in these genes. Here we introduce a novel, fully automated, high resolution climbing behaviour assay and use this assay to characterize climbing behaviour in wild type flies and in various fly mutant lines related to PD and defects in proprioception. Our assay is a general tool for measuring locomotor behaviours of flies in fine detail and can reveal very mild motor defects.
Influence of Arm Swing on Cost of Transport during Walking
Authors: de Graaf Myriam L. , Hubert Juul , Houdijk Han , Bruijn Sjoerd M.
Published: September 2018

Normal arm swing plays a role in decreasing the cost of transport during walking. However, whether excessive arm swing can reduce the cost of transport even further is unknown. Therefore, we tested the effects of normal and exaggerated arm swing on the cost of transport in the current study. Healthy participants (n=12) walked on a treadmill (1.25 m/s) in seven trials with different arm swing amplitudes (in-phase, passive restricted, active restricted, normal, three gradations of extra arm swing), while metabolic energy cost and the vertical angular momentum (VAM) and ground reaction moment (GRM) were measured.

In general, VAM and GRM decreased as arm swing amplitude was increased, except for in the largest arm swing amplitude condition. The decreases in VAM and GRM were accompanied by a decrease in cost of transport from in-phase walking (negative amplitude) up to a slightly increased arm swing (non-significant difference compared to normal arm swing). The most excessive arm swings led to an increase in the cost of transport, most likely due to the cost of swinging the arms. In conclusion, increasing arm swing amplitude leads to a reduction in vertical angular moment and ground reaction moments, but it does not lead to a reduction in cost of transport for the most excessive arm swing amplitudes. Normal or slightly increased arm swing amplitude appears to be optimal in terms of cost of transport in young and healthy individuals.

SUMMARY STATEMENT

Excessive arm swing reduces the vertical angular momentum and ground reaction moment, but not necessarily the energetic cost of transport.
The spatial chronnectome reveals a dynamic interplay between functional segregation and integration
Authors: Iraji A. , DeRamus T.P. , Lewis N. , Yaesoubi M. , Stephen J.M. , Erhardt E. , Belger A. , Ford J.M. , McEwen S. , Mathalon D.H. , Mueller B.A. , Pearlson G.D. , Potkin S.G. , Preda A. , Turner J.A. , Vaidya J.G. , van Erp T.G.M. , Calhoun V.D.
Published: September 2018

The brain is highly dynamic, reorganizing its activity at different interacting spatial and temporal scales including variation within and between brain networks. The chronnectome is a model of the brain in which nodal activity and connectivity patterns are changing in fundamental and recurring ways through time. Most previous work has assumed fixed spatial nodes/networks, ignoring the possibility that spatial nodes or networks may vary in time, particularly at the level of the voxel. Here, we introduce an approach allowing for a spatially fluid chronnectome (called the spatial chronnectome for clarity), which focuses on the variation in spatiotemporal coupling at the voxel level within each network. We identify a novel set of spatially dynamic features which can be obtained and evaluated under different conditions. Results reveal transient spatially fluid interactions between intra- and inter-network relationships in which brain networks transiently merge and then separate again, emphasizing the dynamic interplay between segregation and integration. We also show that brain networks exhibit distinct spatial patterns with unique temporal characteristics, potentially explaining a broad spectrum of inconsistencies in previous studies which assumed static networks. Moreover, we show for the first time that anticorrelative connections to the default mode network, are transient as opposed to constant across the entire scan. Preliminary assessments of the approach using a multi-site dataset collected from 160 healthy subjects and 149 patients with schizophrenia (SZ) revealed the ability of the approach to obtain new information and nuanced alterations of brain networks that remain undetected during static analysis. For example, patients with SZ display transient decreases in voxel-wise network coupling including within visual and auditory networks that are not detectable in a spatially static analysis. Our approach also enabled calculation of a novel parameter, the intra-domain coupling variability which was higher within patients with SZ. The significant association between spatiotemporal uniformity and attention/vigilance cognitive domain highlights the cognitive relevance of the spatial chronnectome. In summary, the spatial chronnectome represents a new direction of research enabling the study of functional networks that are transient at the voxel level and identification of mechanisms for within and between-subject spatial variability to study functional brain homeostasis.
Elaborations on Mössbauer rotor experiments with synchrotron radiation and with usual resonant sources
Authors: Kholmetskii A. L. , Yarman T. , Yarman O. , Arik M.
Published: September 2018

A comparative analysis of Mössbauer experiments in a rotating system between a recent application using synchrotron radiation [Friedman et al. (2016). Eur. Phys. Lett.
114, 50010; Friedman et al. (2017). J. Synchrotron Rad.
24, 661–666] and usual sources of resonant radiation is carried out. The principal methodological difference between these experiments can be related to the fact that in the former set of experiments the source of the resonant radiation rests in a laboratory frame whereas for the latter set of experiments the source is attached to a rotating system. It is concluded that the utilization of ordinary Mössbauer sources remains the most promising path for further research appertaining to the Mössbauer effect in rotating systems.
When service providers fail: outsourcing help and consumer attitudes
Authors: Gazley Aaron , Simmonds Hamish
Published: September 2018

Purpose

The purpose of this paper is to investigate the effect of outsourcing and offshoring on brand loyalty in a service recovery context. In addition, the effect that consumer ethnocentrism has on these relationships is examined.

Design/methodology/approach

An experiment was designed using a series of service recovery scenarios that manipulated whether the recovery effort was conducted by an in-house/outsourced or local/offshored party.

Findings

The study shows that while outsourcing service recovery within the home country has no effect on loyalty, outsourcing to an offshore location does. In addition, the effect of offshoring of loyalty is greater for consumers who hold ethnocentric tendencies.

Practical implications

This research suggests the need to consider the delivery channel of service recovery to recover a service failure and retain customer loyalty. The results show that outsourcing within a local country may be effective, but the risks associated with offshoring are much greater.

Originality/value

Despite previous attempts to understand outsourcing and offshoring in a range of service scenarios, their role in service recovery is not well understood. Similarly, the impact that ethnocentrism might have on this process is overlooked. This paper therefore responds to calls within business theory, practice and consults for further study in this under-researched area.
Long-term consumption of capsicum annum (chilli pepper) and capsaicin diets suppresses pain perception and improves social behaviour of CD-1 mice
Authors: Nmaju Anyauba Uduka , Joshua Iwasam Ekom , Okon Udemeobong Edet , Nwankwo Azubuike Amakwe , Osim Eme Efiom
Published: September 2018

Purpose

Chilli pepper (Capsicum annum), an extensively cultivated vegetable, is commonly used to spice many dishes prepared in several parts of the world. It contains capsaicinoids. The most active amongst these capsaicinoids is capsaicin (8-methyl-N-vanillyl-6-nonenamide), which is neurogenic and so may affect nervous function. Therefore, the purpose of this paper is to investigate the effects of long-term consumption of chilli pepper and capsaicin diets on pain and social behaviour in CD-1 Swiss white mice.

Design/methodology/approach

In total, 30 male mice were randomly assigned into three groups of ten mice each, namely, control, pepper-diet (20 per cent w/w) and capsaicin-diet (10 per cent w/w) groups. Tail immersion, hot plate and formalin tests were conducted to assess pain perception, while nesting behaviour test was used to evaluate the social behaviour of the mice.

Findings

The latency of tail flick of both the pepper and capsaicin groups were significantly longer (p < 0.01 and p < 0.001, respectively) compared to control. The hind paw lick frequency, duration and flinching of both the pepper and capsaicin groups were also significantly reduced compared to control. The nesting score of the capsaicin group was significantly higher (p < 0.01) compared to control. However, the nesting score for pepper group was significantly lower (p < 0.05) compared to capsaicin group.

Originality/value

Long-term consumption of capsaicin and pepper diets suppressed pain and enhanced organized social behaviour in mice. One of the active principles responsible for the effects obtained with pepper on pain and social behaviour in mice may be capsaicin.
Epidemiology and bone‐related comorbidities of ingrown nail: A nationwide population‐based study
Authors: Cho Soo Yeon , Kim You Chan , Choi Jee Woong
Published: September 2018

Although ingrown nail (IN) is common, there is no large‐scale study regarding its epidemiology and risk factors, such as foot deformity. The purpose of this study is to determine the demographics of IN and clarify its association with bone‐related comorbidities of the ankle, foot and toe. Patients in a representative sample cohort of the National Health Information Database of South Korea from 2004 to 2013 who had IN were compared with a control group without IN. Ten‐year overall incidence was 307.5/100 000 person‐years (95% confidence interval, 304.1–310.9). IN incidence and prevalence showed an increasing trend, and IN was more common in women than in men. Incidence showed bimodal peaks, among teenagers and among participants in their 50s. The IN group showed more common valgus deformity (64.3%) than did the control group (61.6%), and flat foot was also a significant risk factor of IN. There were increasing tendencies of IN incidence and prevalence among females. Confirmed bone deformity, especially acquired valgus or varus deformity, and flat foot were associated with IN.
Update on pathophysiology and preventive strategies of anthracycline‐induced cardiotoxicity
Authors: Corremans Raphaëlle , Adão Rui , De Keulenaer Gilles W. , Leite‐Moreira Adelino F. , Brás‐Silva Carmen
Published: September 2018

Anthracycline chemotherapy has a prominent role in treating many forms of cancer. Unfortunately, cardiotoxic side effects represent a serious limitation to their use, with doxorubicin being the leading drug of the group. Indeed, anthracycline‐induced cardiomyopathy is an important public health concern because it may not be detected for many years and remains a lifelong threat. Even after decades of investigation, neither the exact mode of action of anthracyclines nor the pathways leading to their side effect are fully understood. It is increasingly important to establish collaboration between oncologists and cardiologists to improve the management of cancer patient receiving anthracyclines. This article reviews the clinical course, pathogenesis, cardiac monitoring and new concepts in diagnosing and preventing anthracycline‐induced cardiotoxicity.
Different‐shaped curves for serum uric acid with and without diabetes: Results from China Health and Retirement Longitudinal Study
Authors: Cheng Fang , Yin Xin , Duan Wenhou , Ye Runze , Zhu Yakun , Jia Chongqi
Published: September 2018

Background

Several studies have revealed conflicting results regarding the relationship between serum uric acid (SUA) and blood glucose concentrations. The aim of this study was to identify the shape of the curve between SUA and either fasting plasma glucose (FPG) or HbA1c in diabetic and non‐diabetic participants.

Methods

This cross‐sectional study of the relationship between SUA and diabetes and non‐diabetes was conducted in 10 266 participants. Data from the national baseline survey of the China Health and Retirement Longitudinal Study (CHARLS; 2011‐12) were used. Restrictive cubic spline regression and two piecewise linear regression models were used to detect non‐linear trends and calculate the slope of each segment.

Results

After adjusting for all confounding factors in all subjects, an L‐shaped relationship was found between FPG and SUA in males (β2 = 3.47, P < 0.01) and females (β2 = 5.84, P < 0.01), as well as between HbA1c and SUA in males (β2 = 0.10, P = 0.03) and females (β2 = 0.12, P = 0.02). In non‐diabetic individuals, there was a positive linear correlation between FPG and SUA in females (β = 0.62, P = 0.02). After a diagnosis of diabetes, a negative linear relationship was found between SUA and blood glucose in males, and a nearly L‐shaped curve was found in females.

Conclusions

An L‐shaped association was found between SUA and blood glucose in both genders. Stratified analysis revealed an L‐shaped curve only in diabetic females. Further studies are warranted to investigate the mechanisms of the association between uric acid and blood glucose levels.
Telomere dysfunction promotes transdifferentiation of human fibroblasts into myofibroblasts
Authors: Razdan Neetu , Vasilopoulos Themistoklis , Herbig Utz
Published: September 2018

Cells that had undergone telomere dysfunction‐induced senescence secrete numerous cytokines and other molecules, collectively called the senescence‐associated secretory phenotype (SASP). Although certain SASP factors have been demonstrated to promote cellular senescence in neighboring cells in a paracrine manner, the mechanisms leading to bystander senescence and the functional significance of these effects are currently unclear. Here, we demonstrate that TGF‐β1, a component of the SASP, causes telomere dysfunction in normal somatic human fibroblasts in a Smad3/NOX4/ROS‐dependent manner. Surprisingly, instead of activating cellular senescence, TGF‐β1‐induced telomere dysfunction caused fibroblasts to transdifferentiate into α‐SMA‐expressing myofibroblasts, a mesenchymal and contractile cell type that is critical for wound healing and tissue repair. Despite the presence of dysfunctional telomeres, transdifferentiated cells acquired the ability to contract collagen lattices and displayed a gene expression signature characteristic of functional myofibroblasts. Significantly, the formation of dysfunctional telomeres and downstream p53 signaling was necessary for myofibroblast transdifferentiation, as suppressing telomere dysfunction by expression of hTERT, inhibiting the signaling pathways that lead to stochastic telomere dysfunction, and suppressing p53 function prevented the generation of myofibroblasts in response to TGF‐β1 signaling. Furthermore, inducing telomere dysfunction using shRNA against TRF2 also caused cells to develop features that are characteristic of myofibroblasts, even in the absence of exogenous TGF‐β1. Overall, our data demonstrate that telomere dysfunction is not only compatible with cell functionality, but they also demonstrate that the generation of dysfunctional telomeres is an essential step for transdifferentiation of human fibroblasts into myofibroblasts.
Genetic characterization of Vietnamese Yellow cattle using mitochondrial DNA and Y‐chromosomal haplotypes and genes associated with economical traits
Authors: Le Thu N. A. , Vu Hai V. , Okuda Yu , Duong Huong T. , Nguyen Trung B. , Nguyen Van H. , Le Phung D. , Kunieda Tetsuo
Published: September 2018

Vietnamese Yellow cattle are native cattle well adapted to local tropical environment. The aim of this study was to investigate genetic characteristics of the Yellow cattle using molecular markers. We investigated the nucleotide sequences of mitochondrial DNA and SRY gene on Y chromosome, and genotyped SREBP‐1, SCD1, EDG1, NCAPG, DGAT1, MC1R, and HSP70 genes in the Yellow cattle population. The sequence analysis of the mitochondrial DNA showed that most of the cattle possesses zebu (Bos indicus) type I1 haplotype, suggesting relatively low genetic diversity in maternal lineage. The sequence analysis of the SRY gene indicates that while most of the males possess zebu type haplotype, taurine (Bos taurus) type haplotype was also observed, suggesting gene‐flow from taurine cattle. The results of the genotyping of the functional genes showed that the NCAPG, SCD, MC1R, and HsSP70 genes are polymorphic in the population, whereas the SREBP‐1, EDG1, and DGAT1 genes are monomorphic. Particularly, the presence of the desirable and undesirable alleles of the NCAPG and HSP70 genes, respectively, will be important for the selection of animals by potential performances in meat productivity and fertility. The present findings will be informative for future conservation and breeding of the Vietnamese Yellow cattle.
Solidarity and care as relational practices
Authors: Jennings Bruce
Published: September 2018

Many working in bioethics today are engaging in forms of normative interpretation concerning the meaningful contexts of relational agency and institutional structures of power. Using the framework of relational bioethics, this article focuses on two significant social practices that are significant for health policy and public health: the practices of solidarity and the practices of care. The main argument is that the affirming recognition of, and caring attention paid to, persons as moral subjects can politically motivate a society in three respects. The recognition of solidarity and the attention of care can prompt progressive change toward a democratic willingness: (a) to provide for equal respect for rights and dignity; (b) to provide the social resources and services needed for just health and well‐being; and (c) to focus its creativity and wealth on the actualization of potential flourishing of each and all. Solidarity is discussed as a morally developmental stance that moves from standing up for another, standing up with another, and standing up as another. Care is discussed as a morally developmental stance that moves from the attentive rehabilitation of another, attentive companionship with and for another, and attentive commitment to another.
Mechanism and prognostic value of indoleamine 2,3‐dioxygenase 1 expressed in hepatocellular carcinoma
Authors: Li Shaolong , Han Xue , Lyu Ning , Xie Qiankun , Deng Haijing , Mu Luwen , Pan Tao , Huang Xin , Wang Xia , Shi Yuanyuan , Zhao Ming
Published: September 2018

Indoleamine 2,3‐dioxygenase 1 (IDO1) is a tryptophan‐metabolizing enzyme that is widely distributed in normal or malignant tissues and contributes to immunologic tolerance and immune escape. However, in hepatocellular carcinoma (HCC), the characteristics and mechanism of IDO1 expression have not been well defined. In this study, IDO1 expression in tumor cells (T‐IDO1) was frequently detected (109/112) by immunohistochemistry in formalin‐fixed paraffin‐embedded specimens from HCC patients, and the expression patterns were mostly focal (102/109). Expression of T‐IDO1 was significantly associated with the infiltration of CD8+ T cells (P = .043), as well as younger age (<50 years old, P = .02). It was also found that IDO1 had diffuse expression in inflammatory cells in all specimens, which were defined as antigen‐presenting cells. Significant correlations among IDO1, IFNG, and CD8A transcriptional levels were observed in freshly resected HCC specimens; moreover, no constitutive IDO1 expression was detected in HCC cell lines until stimulated by interferon‐γ through the JAK2‐STAT1 signaling pathway, but not type I interferon. Survival analyses showed that increased T‐IDO1 and CD8+ T cell infiltration were significantly associated with superior overall survival (OS) (T‐IDO1, P = .003; CD8+ T cells, P = .004), and T‐IDO1 expression is an independent prognosis factor in both OS and disease‐free survival (OS, P = .007; disease‐free survival, P = .044). These findings indicated that T‐IDO1 expression in HCC is common and is dominantly driven by the host antitumor immune response, which is a favorable prognostic factor in HCC.
Bronchoscopic mucosal cryobiopsies as a method for studying airway disease
Authors: Hvidtfeldt Morten , Pulga Alexis , Hostrup Morten , Sanden Caroline , Mori Michiko , Bornesund Daisy , Larsen Klaus R. , Erjefält Jonas S. , Porsbjerg Celeste
Published: September 2018

Background

Investigating disease mechanisms and treatment responses in obstructive airway diseases with invasive sampling are hampered by the small size and mechanical artefacts that conventional forceps biopsies suffer from. Endoscopic cryobiopsies are larger and more intact and are being increasingly used. However, the technique has not yet been explored for obtaining mucosa biopsies.

Objective

To investigate differences in size and quality of endobronchial mucosal biopsies obtained with cryotechnique and forceps. Further, to check for eligibility of cryobiopsies to be evaluated with immunohistochemistry and in situ hybridization and to investigate tolerability and safety of the technique.

Methods

Endobronchial mucosal biopsies were obtained with cryotechnique and forceps from patients with haemoptysis undergoing bronchoscopy and evaluated by quantitative morphometry, automated immunohistochemistry and in situ hybridization.

Results

A total of 40 biopsies were obtained from 10 patients. Cross‐sectional areas were threefold larger in cryobiopsies (median: 3.08 mm2 (IQR: 1.79) vs 1.03 mm2 (IQR: 1.10), P < 0.001). Stretches of intact epithelium were 8‐fold longer (median: 4.61 mm (IQR: 4.50) vs 0.55 mm (IQR: 1.23), P = 0.001). Content of glands (median: 0.095 mm2 (IQR: 0.30) vs 0.00 mm2 (IQR: 0.01), P = 0.002) and airway smooth muscle (median: 0.25 mm2 (IQR: 0.30) vs 0.060 mm2 (IQR: 0.11), P = 0.02) was higher in the cryobiopsies compared with forceps biopsies. Further, the cryobiopsies had well‐preserved protein antigens and mRNA. Mild to moderate bleeding was the only complication observed.

Conclusion and clinical relevance

By yielding significantly larger and more intact biopsies, the cryotechnique represents a valuable new research tool to explore the bronchi in airway disease. Ultimately with the potential to create better understanding of underlying disease mechanisms and improvement of treatments.
Potential cofactors in accidental food allergic reactions are frequently present but may not influence severity and occurrence
Authors: Versluis Astrid , van Os‐Medendorp Harmieke , Blom W. Marty , Michelsen‐Huisman Anouska D. , Castenmiller Jacqueline J. M. , Noteborn Hubert P. J. M. , Houben Geert F. , Knulst André C.
Published: September 2018

Background

Cofactors, such as physical exercise and alcohol intake, might be associated with the severity or occurrence of food allergic reactions.

Objective

To gain insight into the frequency of presence of potential cofactors in accidental food allergic reactions in adults and to what extent these factors influence the severity and occurrence of allergic reactions.

Methods

A prospective cohort study was conducted, with a 1‐year follow‐up in adult patients with a physician‐diagnosed food allergy. Patients were required to fill in a questionnaire after every accidental allergic reactions to food over a 1‐year period. The primary outcome measure was the frequency that potential cofactors were present in these allergic reactions.

Results

A total of 157 patients were included, of which 46% reported a total of 153 reactions during a 1‐year follow‐up period. In 74% of the reactions, ≥1 potential cofactor was reported to be present: tiredness (38%), alcohol intake (16%), stress (14%), symptoms of pollinosis (16%), symptoms of asthma (9%), sickness/flu (3%), physical exercise (3%) and use of analgesics (2%). More than one potential cofactor was reported in almost half of all reactions (47%). There was no significant difference in the presence of these factors between mild, moderate and severe reactions (P = 0.522). In the total study population, 9% of the patients used medication that might act as cofactor (antacids, angiotensin receptor blockers [ARBs], beta blockers and angiotensin‐converting enzyme inhibitors [ACEIs]) on a daily basis, which however did not influence the occurrence of reactions. Furthermore, 38% daily used allergy‐suppressing medication.

Conclusions

Although factors suggested to be cofactors were frequently present during accidental food allergic reactions, we found no evidence for an association between the potential cofactors examined and reaction severity, in a population where most reactions were of mild to moderate severity.
In utero exposure to cigarette smoke and effects across generations: A conference of animals on asthma
Authors: Hammer Barbara , Wagner Christina , Divac Rankov Aleksandra , Reuter Sebastian , Bartel Sabine , Hylkema Machteld N. , Krüger Arne , Svanes Cecilie , Krauss‐Etschmann Susanne
Published: September 2018

Background

The prevalence of asthma and chronic obstructive pulmonary disease (COPD) has risen markedly over the last decades and is reaching epidemic proportions. However, underlying molecular mechanisms are not fully understood, hampering the urgently needed development of approaches to prevent these diseases. It is well established from epidemiological studies that prenatal exposure to cigarette smoke is one of the main risk factors for aberrant lung function development or reduced fetal growth, but also for the development of asthma and possibly COPD later in life. Of note, recent evidence suggests that the disease risk can be transferred across generations, that is, from grandparents to their grandchildren. While initial studies in mouse models on in utero smoke exposure have provided important mechanistic insights, there are still knowledge gaps that need to be filled.

Objective

Thus, in this review, we summarize current knowledge on this topic derived from mouse models, while also introducing two other relevant animal models: the fruit fly Drosophila melanogaster and the zebrafish Danio rerio.

Methods

This review is based on an intensive review of PubMed‐listed transgenerational animal studies from 1902 to 2018 and focuses in detail on selected literature due to space limitations.

Results

This review gives a comprehensive overview of mechanistic insights obtained in studies with the three species, while highlighting the remaining knowledge gaps. We will further discuss potential (dis)advantages of all three animal models.

Conclusion/Clinical Relevance

Many studies have already addressed transgenerational inheritance of disease risk in mouse, zebrafish or fly models. We here propose a novel strategy for how these three model organisms can be synergistically combined to achieve a more detailed understanding of in utero cigarette smoke‐induced transgenerational inheritance of disease risk.
Excision release of 5?hydroxycytosine oxidatively induced DNA base lesions from the lung genome by cat dander extract challenge stimulates allergic airway inflammation
Authors: Hosoki Koa , Jaruga Pawel , Itazawa Toshiko , Aguilera-Aguirre Leopoldo , Coskun Erdem , Hazra Tapas K. , Boldogh Istvan , Dizdaroglu Miral , Sur Sanjiv
Published: September 2018

Background

Ragweed pollen extract (RWPE) induces TLR4‐NFκB‐CXCL‐dependent recruitment of ROS‐generating neutrophils to the airway and OGG1 DNA glycosylase‐dependent excision of oxidatively induced 8‐OH‐Gua DNA base lesions from the airway epithelial cell genome. Administration of free 8‐OH‐Gua base stimulates RWPE‐induced allergic lung inflammation. These studies suggest that stimulation of innate receptors and their adaptor by allergenic extracts initiates excision of a set of DNA base lesions that facilitate innate/allergic lung inflammation.

Objective

To test the hypothesis that stimulation of a conserved innate receptor/adaptor pathway by allergenic extracts induces excision of a set of pro‐inflammatory oxidatively induced DNA base lesions from the lung genome that stimulate allergic airway inflammation.

Methods

Wild‐type (WT), Tlr4KO, Tlr2KO, Myd88KO, and TrifKO mice were intranasally challenged once or repeatedly with cat dander extract (CDE), and innate or allergic inflammation and gene expression were quantified. We utilized GC‐MS/MS to quantify a set of oxidatively induced DNA base lesions after challenge of naïve mice with CDE.

Results

A single CDE challenge stimulated innate neutrophil recruitment that was partially dependent on TLR4 and TLR2, and completely on Myd88, but not TRIF. A single CDE challenge stimulated MyD88‐dependent excision of DNA base lesions 5‐OH‐Cyt, FapyAde, and FapyGua from the lung genome. A single challenge of naïve WT mice with 5‐OH‐Cyt stimulated neutrophilic lung inflammation. Multiple CDE instillations stimulated MyD88‐dependent allergic airway inflammation. Multiple administrations of 5‐OH‐Cyt with CDE stimulated allergic sensitization and allergic airway inflammation.

Conclusions and Clinical Relevance

We show for the first time that CDE challenge stimulates MyD88‐dependent excision of DNA base lesions. Our data suggest that the resultant‐free base(s) contribute to CDE‐induced innate/allergic lung inflammation. We suggest that blocking the MyD88 pathway in the airways with specific inhibitors may be a novel targeted strategy of inhibiting amplification of innate and adaptive immune inflammation in allergic diseases by oxidatively induced DNA base lesions.
A single factor induces neuronal differentiation to suppress glioma cell growth
Authors: Fu Ji‐Qiang , Chen Zhen , Hu Yong‐Jia , Fan Zhao‐Huan , Guo Zhen‐Xing , Liang Jin‐Ye , Ryu Bo‐Mi , Ren Jian‐Lin , Shi Xiu‐Juan , Li Jiao , Jia Song , Wang Juan , Ke Xiao‐Si , Ma Xin , Tan Xiao , Zhang Ting , Chen Xian‐Zhen , Zhang Chen
Published: September 2018

Aim

Glioma, with fast growth and progression features, is the most common and aggressive tumor in the central nervous system and is essentially incurable. This study is aimed at inducing neuronal differentiation to suppress glioma cell growth with a single transcription factor.

Methods

Overexpression of transcription factor SRY (sex determining region Y)‐box 11 (SOX11) and Zic family member 1 (ZIC1) was, respectively, performed in glioma cells with lentivirus infection. CRISPR/Cas9 technology was used to knock out ZIC1 in U87 cells, and knockout efficiency was identified by Western blotting and Sanger sequencing. Cell cycle and apoptosis were detected by flow cytometry. The downstream targets of SOX11 were analyzed by Affymetrix GeneChip microarrays. qRT‐PCR and immunofluorescence technique were used to verify gene targets of genetically modified U87 cells. All the cells were imaged by a fluorescence microscope. Gene expression correlation analysis and overall survival analysis based on TCGA dataset are performed by GEPIA.

Results

We induced glioma cells into neuron‐like cells to suppress cell growth using a single transcription factor, SOX11 or ZIC1. Besides, we proved that there is a strong correlation between SOX11 and ZIC1. Our study revealed that SOX11 upregulates ZIC1 expression by binding with ZIC1 promoter, and ZIC1 partially mediates SOX11‐induced neuronal differentiation in U87 cells. However, SOX11 expression is not regulated by ZIC1. Moreover, high MAP2 expression means better overall survival in TCGA lower grade glioma.

Conclusion

This study revealed that glioma cells can be reprogrammed into neuron‐like cells using a single factor ZIC1, which may be a potential tumor suppressor gene for gliomas treatment.