bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences in morphological and physiological plasticity in two species of first-year conifer seedlings exposed to drought result in distinct survivorship patterns
Authors: Augustine Steven P , Reinhardt Keith
Published: April 2019

First-year tree seedlings represent a critical demographic life stage, functioning as a bottleneck to forest regeneration. Knowledge of how mortality is related to whole-seedling carbon and water relations is deficient and is required to understand how forest compositions will be altered in future climatic conditions. We performed a greenhouse drought experiment using first-year seedlings of two common pine species found in the Intermountain West, USA. Gas exchange, biomass gain, allometry and xylem water potentials were compared between well-watered and droughted seedlings from emergence until drought-induced mortality. In both species, morphological adjustments to confer drought tolerance, such as increased leaf mass per unit area, were not observed in seedlings exposed to drought, and droughted seedlings maintained photosynthesis and whole-seedling carbon gain well into the experiment. Yet, there were important differences between species in terms of carbon budgets, physiological responses and mortality patterns. In Pinus ponderosa P. & C. Lawson, physiological acclimation to drought was much greater, evident through stronger stomatal regulation and increased water-use efficiency. Photosynthesis and carbon budgets in P. ponderosa were greater than in Pinus contorta Dougl. ex. Loud., and survival was 100% until critical hydraulic thresholds in leaf water content and seedling water potentials were crossed. In P. contorta, physiological adjustments to drought were less, and mortality occurred much sooner and well before injurious hydraulic thresholds were approached. First-year conifer seedlings appear canalized for a suite of functional traits that prioritize short-term carbon gain over long-term drought tolerance, suggesting that conifer seedling survival is linked with carbon limitations, even during drought, with survival in species having narrower carbon survival margins being more hampered by carbon limitations.
Conservative management of endometrial intraepithelial neoplasia in a patient with cirrhosis undergoing orthotopic liver transplant
Authors: Morgan Jessica , Hinz Erica K.
Published: April 2019

Objective:

The aim of the study was to review the management of endometrial hyperplasia in a woman undergoing liver transplantation for alcoholic cirrhosis.

Methods:

This is a case presentation on a postmenopausal woman with a tissue diagnosis of endometrial intraepithelial neoplasia managed with a levonorgestrel intrauterine device, before and after liver transplantation. Full written informed consent was obtained from the patient to present her case.

Results:

The patient experienced resolution of her endometrial intraepithelial neoplasia with conversion to atrophic endometrium after management with levonorgestrel intrauterine device.

Conclusions:

A large percentage of women with cirrhosis experience abnormal uterine bleeding, which may be due to the coagulopathy that accompanies liver disease, or endometrial hyperplasia or carcinoma. Although hysterectomy is the criterion standard of treatment for atypical endometrial hyperplasia in a postmenopausal woman, patients with cirrhosis severe enough to require transplant are usually poor surgical candidates. Multiple studies have shown success with conservative management of atypical hyperplasia. There is a paucity of literature on managing patients undergoing transplant with abnormal uterine bleeding and it is therefore important to highlight conservative management options for this patient population.
The Effectiveness of an Intervention Program for Fathers of Hospitalized Preterm Infants on Paternal Support and Attachment 1 Month After Discharge
Authors: Chen Yi-Ling , Lee Tzu-Ying , Gau Meei-Ling , Lin Kuan-Chia
Published: April 2019

This aim of this study was to evaluate the effectiveness of an early intervention program to reduce paternal stress and increase fathering ability after a preterm infant's admission to the special care nursery and to influence paternal support for the mother and the father's attachment to the infant 1 month later. A historical comparison study was designed and an empowerment intervention strategy for the fathers of preterm infants was implemented. Forty-one fathers of preterm infants in the control group received routine care, and 41 fathers of preterm infants in the intervention group received an early fatherhood intervention program in the special care nursery. Both groups were followed 1 month after discharge. Fathers in the intervention group had significantly lower stress and higher fathering ability at their infant's discharge, provided better support to the mother in child-rearing, and had better father-infant attachment 1 month after discharge than fathers in the control group. Under cultural and hospitals' common practices, such an intervention can help the father to establish his fatherhood early and later enhance his supporting role to the mother and his relationship to the preterm infant. Nurses should include teaching childcare to fathers of preterm infants.
Extracorporeal Shock Wave Therapy Immediately Affects Achilles Tendon Structure and Widespread Pressure Pain Thresholds in Healthy People
Authors: Leong Hio Teng , Docking Sean , Girdwood Michael , Bonello Christian , Cook Jill , Rio Ebonie
Published: April 2019

Objective

Extracorporeal shockwave therapy is a common clinical treatment for tendinopathy, yet negative effects on tendon structure have been shown in animal studies. This study aimed to investigate the effect of extracorporeal shockwave therapy in healthy participants (i.e., no Achilles tendon pain or pathology).

Design

This study examined the effect of three bouts of weekly extracorporeal shockwave therapy for 3 wks in 13 healthy participants. Outcomes measures assessed were as follows: (a) Achilles tendon structure, quantified using ultrasound tissue characterization (before and 3 hrs after extracorporeal shockwave therapy), (b) pressure pain thresholds, over the Achilles tendon and common extensor tendon origin (before, immediately after, and 3 hrs after extracorporeal shockwave therapy), and (c) hop pain (before and immediately after extracorporeal shockwave therapy).

Results

There was a significant reduction in echo type I (P < 0.05) and increase in echo type II (P < 0.05) at 3 hrs after the first extracorporeal shockwave therapy session that recovered to baseline levels before week 2. There were no significant changes in ultrasound tissue characterization echo pattern observed in subsequent sessions. There were increased pressure pain thresholds immediately after extracorporeal shockwave therapy at the common extensor tendon origin but no significant change at the Achilles tendon. Pressure pain thresholds returned to baseline at 3 hrs after extracorporeal shockwave therapy. There were no significant changes in pressure pain threshold in subsequent sessions.

Conclusions

Extracorporeal shockwave therapy resulted in transient changes to tendon structure and widespread hyperalgesia.
Tendon Subluxation After Surgical Release of the First Dorsal Compartment in De Quervain Disease
Authors: Kim Ji-Hyo , Yang Seog-Won , Ham Hee-Jeong , Kim Jong-Pil
Published: April 2019

We aimed to determine whether dorsoulnar incision elevating radial flap and immobilization for the treatment of de Quervain disease have an advantage over simple midline incision and early mobilization, respectively, in terms of tendon subluxation and clinical outcomes. Forty-six patients with de Quervain disease were randomly divided into 2 groups (midline incision vs dorsoulnar incision) and 2 subgroups (immobilization vs early mobilization). Subluxation of intracompartmental tendons was measured in dynamic wrist positions at 12 and 24 weeks using ultrasonography. The DASH (Disabilities of the Arm, Shoulder, and Hand) and visual analog scale scores and grip and pinch strengths were evaluated. At 24 weeks, the tendons were displaced voloradially in wrist volar flexion (1.25 mm in midline incision vs 0.36 mm in dorsoulnar incision, P = 0.001), whereas the tendons were displaced dorsoulnarly in wrist extension (0.95 mm in midline incision vs 1.78 mm in dorsoulnar incision, P = 0.041). There were no significant differences in tendon displacement between early mobilization and immobilization groups. Clinical outcome measures showed no variation between the groups, and no significant correlation occurred with tendon subluxation. Dorsoulnar incision and postoperative immobilization do not have advantage over midline incision and early mobilization, respectively. However, tendon subluxation after release of the first dorsal compartment for de Quervain disease does not affect clinical outcomes.
IL-15 Improves Aging-Induced Persistent T Cell Exhaustion in Mouse Models of Repeated Sepsis
Authors: Saito Masafumi , Inoue Shigeaki , Yamashita Kimihiro , Kakeji Yoshihiro , Fukumoto Takumi , Kotani Joji
Published: April 2019

Aging is a grave problem in sepsis, and T cell exhaustion is the main cause of sepsis-induced immunosuppression. Sepsis- and aging-induced T cell exhaustion is related to secondary infection with a poor long-term outcome in the elderly. However, the trend, impact, and mechanism of T cell exhaustion are still unclear. Interleukin (IL)-15 improves survival rate of septic mice via its antiapoptotic effect on T cells; however, it is still unclear how IL-15 reverses prolonged T cell exhaustion in aged septic mice. The purpose of this study was to clarify the trend of sepsis-induced T cell exhaustion and whether IL-15 prevents aging-induced persistent T cell exhaustion in septic mice. Preserved cecal slurry was injected intraperitoneally into young (6-week-old) and aged mice (18–24-month-old) 4 times, to induce clinically relevant repeated sepsis. IL-15 (1.5 μg) or phosphate-buffered saline was injected subcutaneously 3 times, body weight was serially measured, and peripheral blood cells from their cheek were serially collected for 50 days. Sepsis-induced T cell exhaustion was significantly severe in aged mice than in young mice and was accompanied with decreased naive CD4+ and CD8+ T cells (P 
< 0.01) and increased expression of program death 1 on T cell (P 
< 0.01) and regulatory T cell population (P < 0.01). IL-15 significantly improved sepsis-induced T exhaustion, with significantly increased numbers of natural killer cells and macrophages, and significantly enhanced phagocytosis activity in aged septic mice (P < 0.05). It decreased the long-term mortality associated with sepsis survivors by improving T cell exhaustion over an extended duration and also ameliorated aging-induced persistent T cell exhaustion in septic mice.
Antibiotic susceptibility pattern of Salmonella isolates from enteric fever suspected patients
Authors: Shrestha Bijayata , Sayami Gita , Manandhar Sarita , Khanal Santosh
Published: April 2019

Background

Enteric fever is one of the most common diseases encountered worldwide and is endemic in Nepal. This study was conducted to access antibiotic susceptibility pattern of Salmonellaisolates from culture positive cases of enteric fever.

Methods

Altogether 505 blood samples were collected from patients clinically suspected of enteric fever attending HAMS Hospital. All blood samples were cultured by BACTEC method and sub cultured in blood agar and MacConkey agar plates. All isolates were identified by colony characteristics, biochemical tests and serotyping methods. Antibiotic susceptibility test was performed by modified Kirby Bauer disc diffusion method interpreted with CLSI guideline.

Result

Isolation rate of Salmonellaspecies was 3.6 %. Among 18 Salmonellaisolates, 10 were S. typhi, 8 were S. paratyphi A. The prevalence rate of infection was high among the age group 11–20  years (50 %) and among the male patients. However, there was no significant association of enteric fever with gender of patients (P=2.47). All 18 isolates were sensitive to Amoxycillin, Azithromycin, Ceftriaxone and Chloramphenicol, Ciprofloxacin and Ofloxacin. Majority of isolates were sensitive to Cefixime (94.4 %), Cotrimoxazole (94.4 %) and Cephotaxime (90 %). There were no any MDR isolates. Higher percentage of isolates was resistant to Nalidixic acid (87.5 %).

Conclusion

The decreased susceptibility to Fluroquinolones of S. typhi and S. Paratyphi A can be correlated with resistance to Nalidixic acid. Commonly used third generation Cephalosporins and rolled back first line drugs be the choice in case of NARS isolates.
Gut microbiota in Northern Thai populations
Authors: Popluechai Siam , Kullawong Niwed , Gentekaki Eleni
Published: April 2019

The human gastrointestinal tract represents a collection of prokaryotic and eukaryotic microorganisms. It has been reported that gut microbiota plays a role in health and disease. Imbalance of gut microbial communities has been implicated in several non-communicable diseases including inflammatory gastrointestinal diseases, Type 2 diabetes, and obesity. However, a role of gut microbiota in adult Southeast Asians remains largely unexplored. Herein, we present gut microbiota data obtained from Thai volunteers living in Chiang Rai Province, Thailand. We use a combination of quantitative PCR, Next Generation Sequencing (NGS), and gas chromatography-mass spectrometry (GC-MS) to investigate microbial communities, individual microbial taxa, and metabolites of NCDs volunteers. We consider prokaryotic taxa and their relationships with body mass index/waist to hip ratio and diet. We find that specific taxa of lower taxonomic levels are associated with the lean and overweight, but not the obese phenotype. We also find that microbial prokaryotic communities differ significantly amongst the different study groups.
Characterising the cell-mediated immune response to Lumpy skin disease virus
Authors: Wijesiriwardana Najith , Haga Ismar , Sanz-Bernardo Beatriz , Graham Simon , Beard Pip
Published: April 2019

Lumpy skin disease (LSD), a high-impact disease of cattle and water buffalo, is a direct threat to the European cattle industry. The causative agent is the lumpy skin disease virus (LSDV), an enveloped dsDNA virus which belongs to the family Poxviridae. Affected cattle present multiple cutaneous nodules that are characteristic of a LSDV infection. The case fatality rate of LSD is low, however affected animals suffer substantial production losses including weight loss and reduced milk production. On a wider scale, LSD is a high consequence transboundary disease with mandated export restrictions imposed on affected countries leading to substantial economic costs. Currently, there is no cure for LSDV infected cattle. Hence, mass vaccination is an important component in minimizing the spread of LSDV. There are only a handful of commercially available live attenuated vaccines in the current market. These vaccines vary in efficacy, quality, and safety, which leaves some scope for further development. This improvement is hampered by a poor understanding of the immunology of LSDV, particularly the protective immune mechanisms. In this project, we are investigating the immune response to LSDV with a focus on characterising the cell-mediated immune response. Peripheral blood mononuclear cells from LSDV immunised/infected cattle and flow cytometry assays are used to detect the production of IFN-γ by CD4+T-helper cells and CD8+cytotoxic T cells in response to live LSDV stimulation. Our goal is to improve understanding of the immune response to LSDV in order to develop effective vaccines and control programs in the future.
MICROALARM: “a new system for rapid quantification of the total bacteria in water samples”
Authors: Ángel Fernández-Fuentes Miguel , Soria Elena , Yáñez Adela , Jofre Marc , Hurth Cedric , Martínez Pedro , Pruneri Valerio , Catalán Vicente
Published: April 2019

Background

Analytical methods applied in diagnostic microbiology laboratories are usually performed manually and have several drawbacks, the long time-to-results (48–72 h) being the major one. Rapid detection methods may overcome the disadvantages of traditional microbiological methods and achieve fast detection, which will help preventing the spread of waterborne pathogens and outbreaks of waterborne diseases. The objective of the MICROALARM project is to validate a platform for monitoring the quantification of the total bacteria present in water samples.

Methods

The MICROALARM system integrates a microfluidic cartridge where the microorganisms from the sample are labelled to facilitate the detection and measurement by a fluorescence sensor. The prototype system has been validated according to ISO 16140-2 : 2016 in the laboratory through the comparison with conventional (culture isolation) and alternative methods (flow cytometry) to determine whether the method is suitable for quantifying microorganisms in water samples.

Results

The system will be capable of processing, labelling and quantifying automatically the total bacteria of the water sample using a membrane-permeable fluorescence marker. The system has been validated at the laboratory scale using a wide range of water matrices, then installed and validated in different facilities with satisfactory results.

Conclusion

The MICROALARM system is designed to be portable, thus suitable for on-site applications. It will be a low-cost solution for rapid microbiological analysis. The system will avoid water sampling and transport to the laboratory while enabling on-site quantification of the total bacteria in a reduced timeframe for early decision-making.
Viable metabolisms in a simulated martian chemical environment
Authors: Macey Michael , Ramkissoon Nisha K. , Pearson Victoria K. , Schwenzer Susanne P , Olsson-Francis Karen
Published: April 2019

There is evidence that water may exist on Mars as brines in the subsurface. The chemistries of these brines will be greatly influenced by the local lithologies, which would impact on the organisms that could potentially live within them. There are multiple metabolisms that are theoretically viable under martian chemical conditions. In order to better establish which of these are capable of supporting persistent growth under martian conditions, we performed a series of enrichments using four geological simulants for Mars: a global composition, an early and unaltered basaltic composition, a sulfur-rich composition, and a haematite-rich composition. Enrichments were inoculated with sediment from Pyefleet mudflats in the Colne estuary (Essex, UK). Mudflat sediment was added to the simulant materials and a brine based on the chemistry of Rocknest. Enrichments were supplied with a H2/CO2 headspace at 1 bar pressure and incubated for 20 days. The enrichments were repeatedly subcultured into fresh simulant material and brines in order to effectively select for a community actively growing in this chemical environment. The enriched community was characterised through the isolation and identification of microbes, microscopy and the amplicon sequencing of 16S rRNA genes amplified from DNA extracted from each stage of the enrichment. Biotic and abiotic experiments were conducted to identify geochemical changes that occur due to the presence of microbial activity. We will present details on the communities enriched on the different martian simulants, metabolisms identified as present within the actively growing community and geochemical changes that were identified.
The co-occurrence and co-exclusion of evolving objects in prokaryotes
Authors: Whelan Fiona J , Rusilowicz Martin , McInerney James O
Published: April 2019

Throughout evolution, evolving objects (domains, genes, operons etc.) have continuously combined, forming new proteins, gene clusters, and genomes. Horizontal gene transfer, particularly among prokaryotes, has facilitated this combinatorial process. Thus, evolving objects that interact positively or synergistically with each other are expected to co-occur more often than by chance; conversely, evolving objects may avoid co-occurrence, indicating an antagonistic or redundant functionality between objects. In this work, we use methods adapted from graph theory to understand patterns of co-occurrence and exclusion in prokaryotes. We have implemented multi-level graph models in which each node (vertex) is a gene or species connected by an edge (relationship) to another node to display these coincidence relationships. Our method incorporates the phylogenetic distribution and synthenic distances of these genes, and we demonstrate how these concepts can be used to identify conserved clusters of vertical and horizontally inherited units of selection. We apply these multi-level graph models to a variety of datasets including prokaryotic pangenomes, and metagenomic sequencing datasets from human-associated microbial communities. We find evidence for genes that significantly co-occur with each other within each of these datasets; these genetic clusters include objects from characterized biological pathways but also include genes with unknown functions. Further, we identify genes that exclude each other, indicating evolving objects with antagonistic or redundant biological functions. This work represents a different approach to understanding the evolution of prokaryotes and allows us to draw novel hypotheses as to the potential role of these genetic clusters in prokaryote biology.
BTV-GLUE: a new bioinformatic resource for genomic studies of Bluetongue virus
Authors: Singer Joshua B. , Nomikou Kyriaki , Hughes Joseph , Mertens Peter , Gifford Robert , Palmarini Massimo
Published: April 2019

Bluetongue virus (BTV) is an arbovirus transmitted by biting midges (Culicoides pp.). BTV causes a severe disease (bluetongue) in domestic and wild ruminant species with high levels of morbidity and mortality. Bluetongue has emerged as an important disease in sheep and cattle worldwide. The BTV genome is composed by ten linear dsRNA segments, packaged within a triple-layered icosahedral protein-capsid, and encode 7 structural and 4/5 non-structural proteins. To date, there are at least 27 BTV serotypes (mainly determined by the VP2 outer capsid protein) circulating worldwide. In addition, high rates of reassortment involving all genome segments have been documented, complicating epidemiological studies and vaccination programmes. We have developed BTV-GLUE (http://btv.glue.cvr.ac.uk), a new bioinformatics sequence data resource for bluetongue virus. Sequences from the NCBI nucleotide database are curated along with complementary sequence metadata and are integrated together inside GLUE (http://tools.glue.cvr.ac.uk), a data-centric software package for capturing virus sequence data and organising it along evolutionary lines. The dataset also contains reference sequences with genome feature annotations, multiple sequence alignments, defined clades and phylogenetic trees, for each BTV segment and clade. A new automated genotyping tool for all segments has been developed. The resource may also be used as an offline bioinformatics toolkit. BTV-GLUE will help the BTV community to study varying aspects of BTV biology and evolution and will facilitate the adoption of a nomenclature that more easily distinguishes the properties of BTV strains circulating worldwide.
Large-scale generation of mutant strains in Candida parapsilosis using CRISPR-Cas9
Authors: Lombardi Lisa , Salzberg Letal I. , Cinnéide Eoin Ó , O’Brien Caoimhe , Butler Geraldine
Published: April 2019

In order to streamline the study of the pathogenic yeast Candida parapsilosis, we developed a plasmid-based CRISPR-Cas9 system (pRIBO) for gene editing in this species. However, pRIBO was not feasible for large-scale generation of mutant strains. We recently addressed this bottleneck by generating pCP-tRNA, an improved version of pRIBO in which the guide sequence can be easily cloned into the SapI-digested plasmid, and the release of the mature sgRNA is mediated by endogenous RNase cleavage of the C. parapsilosis tRNAAla, and by self-cleavage of the HDV ribozyme. We are currently using pCP-tRNA for the systematic generation of mutant strains. Suitable guides were computationally designed to induce Cas9 cleavage within the first 25 % of each ORF in the genome, which is then repaired by recombination with a repair template (RT) containing 30 bp homology arms, 11 bp to introduce a stop codon in the functional reading frame, and a unique tag. In 4 months, 288 plasmids targeting genes encoding transcription factors, phosphokinases, or unknown functions, were transformed into C. parapsilosis with the corresponding RTs. The system resulted in gene editing of 62 % of the 288 genes at high efficiency (80–100 % of the colonies tested were positive); 16 % of the genes in the panel may be essential based on homology with related species, and we believe that the remaining 22 % may be successfully edited by selecting a different guide. In conclusion, we demonstrate that pCP-tRNA is a valuable tool for high throughput generation of mutants in C. parapsilosis.
MicroED with the Falcon III direct electron detector
Authors: Hattne Johan , Martynowycz Michael W. , Gonen Tamir
Published: April 2019

Microcrystal electron diffraction (MicroED) combines crystallography and electron cryomicroscopy (cryo-EM) into a method that can be used for high-resolution structure determination. In MicroED nanosized crystals, often intractable by other techniques, are probed by high-energy electrons in a transmission electron microscope and the diffracted signal is recorded on an electron detector. Since only a small number of different detectors have been used for MicroED measurements in the past, their impact on data quality has not been investigated. Here we evaluate two different cameras using crystals of the well-characterized serine protease proteinase K. Compared to previously used equipment, the Falcon III direct electron detector and the CMOS-based CetaD camera can collect complete datasets both faster and using lower total exposure. As an effect of the lower dose, radiation damage is reduced, which is confirmed in both real and reciprocal space. The increased speed and lower exposure requirements have implications on model quality and the prospects for further automation of MicroED.
AtetRA-based promoter system for the generation of conditional knockouts inCampylobacter jejuni
Authors: Cohen Eli J. , Quek Rui Tong , Beeby Morgan
Published: April 2019

Campylobacter jejuniis responsible for tens of millions of cases of gastroenteritis each year. Despite its prevalence and impact on human health, the repertoire of genetic tools available for researchers to studyC. jejuniremains limited. In order to expand upon the genetic toolkit in this species, we have engineered a system for generating conditional knockouts based on thetetRAtetracycline-resistance cassette. This system exhibits tight repressibility and titratability of target-gene expression and will be useful for future research on this important human pathogen.
Lowe Syndrome-linked endocytic adaptors direct membrane cycling kinetics with OCRL inDictyostelium discoideum
Authors: Luscher Alexandre , Fröhlich Florian , Barisch Caroline , Littlewood Clare , Metcalfe Joe , Leuba Florence , Palma Anita , Pirruccello Michelle , Cesareni Gianni , Stagi Massimiliano , Walther Tobias C. , Soldati Thierry , De Camilli Pietro , Swan Laura E.
Published: April 2019

Mutations of the inositol 5-phosphatase OCRL cause Lowe Syndrome (LS), characterized by congenital cataract, low IQ and defective kidney proximal tubule resorption. A key subset of LS mutants abolishes OCRL’s interactions with endocytic adaptors containing F&H peptide motifs. Converging unbiased methods examining human peptides and the unicellular phagocytic organismDictyostelium discoideum, reveal that, like OCRL, theDictyosteliumOCRL orthologue Dd5P4 binds two proteins closely related to the F&H proteins APPL1 and Ses1/2 (also referred to as IPIP27A/B). In addition, a novel conserved F&H interactor was identified, GxcU (inDictyostelium)and the Cdc42-GEF Frabin (in human cells). Examining these proteins inDictyostelium discoideum, we find that, like OCRL, Dd5P4 acts at well-conserved and physically distinct endocytic stations. Dd5P4 functions in coordination with F&H proteins to control membrane deformation at multiple stages of endocytosis, and suppresses GxcU-mediated activity during fluid-phase micropinocytosis. We also reveal that OCRL/Dd5P4 acts at the contractile vacuole, an exocytic osmoregulatory organelle. We propose F&H peptide-containing proteins may be key modifiers of LS phenotypes.
PSC-RED, an Albumin-Free Robust Erythroid Differentiation Method to Produce Enucleated Red Blood Cells from Human Pluripotent Stem Cells
Authors: Olivier Emmanuel N , Zhang Shouping , Yan Zi , Suzuka Sandra , Roberts Karl , Wang Kai , Bouhassira Eric E
Published: April 2019

Cultured red blood cells (cRBCs) have many potential applications in transfusion medicine and drug delivery. We report that we have developed chemically defined, albumin-free Robust Erythroid Differentiation (RED) methods to produce enucleated cRBCs from human induced pluripotent stem cells (iPSCs). Human iPSC-derived cRBCs produced with either the short or long variation of the RED protocol respectively express embryonic/fetal or a mixture of fetal and adult hemoglobins. The long version of the protocol produces up to 50% of enucleated cells at an unprecedented yield. RED is scalable and relies on inexpensive components and therefore dramatically increases the feasibility and economic viability of all translational applications of cRBCs.

Highlights

PSC-RED: A chemically-defined, albumin-free Robust Erythroid Differentiation (RED) methods to produce cRBCs from human induced pluripotent stem cells.

PSC-RED produces up to 50% enucleated cells at an unprecedented yield.

PSC-RED is scalable and relies on inexpensive components and therefore increases the feasibility and economic viability of translational applications of cRBCs.
Increasing growth rate slows adaptation when genotypes compete for diffusing resources
Authors: Chacón Jeremy M. , Harcombe William R.
Published: April 2019

The rate at which a species responds to natural selection is a central predictor of the species’ ability to adapt to environmental change. It is well-known that spatially-structured environments slow the rate of adaptation due to increased intra-genotype competition. Here, we show that this effect magnifies over time as a species becomes better adapted and grows faster. Using a reaction-diffusion model, we demonstrate that growth rates are inextricably coupled with effective spatial scales, such that higher growth rates cause more localized competition. This has two effects: selection requires more generations for beneficial mutations to fix, and spatially-caused genetic drift increases. Together, these effects diminish the value of additional growth rate mutations in structured environments.

Author Summary

What determines how quickly a beneficial mutation will spread through a population? The intuitive answer is that mutations that confer faster growth rates will spread at a rate that is relative to the size of the growth-rate benefit. Indeed, this is true in a well-mixed environment where all genotypes compete globally. But most organisms don’t live in a simple well-mixed environment. Many organisms, like bacteria, live in a structured environment, such as on the surface of a solid substrate. Does life on a surface change the expectation about the spread of faster-growing mutants? We developed a mathematical model to answer this question, and found that on a surface, the actual growth rates—not just the relative growth rates—were critical to determining how fast a faster-growing mutant spread through a population. When the simulated organisms grew slowly, competition was basically global and a faster-growing mutant could pre-empt resources from far-away competitors. In contrast, when organisms grew more quickly, competition became much more localized, and the faster-growing mutant could only steal resources from neighboring competitors. This result means that there are diminishing returns to series of mutations which confer growth-rate benefits. This idea will help us predict and understand future and past evolutionary trajectories.
Laminin N-terminus α31 regulates keratinocyte adhesion and migration through modifying the organisation and proteolytic processing of laminin 332
Authors: Troughton Lee D. , Iorio Valentina , Shaw Liam , Sugden Conor J , Yamamoto Kazuhiro , Hamill Kevin J.
Published: April 2019

Laminin N-terminus α31 (LaNt α31), a member of the laminin superfamily, expressed at low levels in intact epithelium but upregulated during wound repair. Increased expression of LaNt α31 reduced migration rate of corneal keratinocytes through an unknown mechanism. Here, we investigated whether LaNt α31 influences cell behaviour through modulating laminin-mediated processes. Adenoviral delivery of LaNt α31 into corneal epithelial cells led to reduced migration speed and increased cell spreading and changed laminin 332 organisation from diffuse arcs to tight clusters. Enhanced recruitment of collagen XVII and bullous pemphigoid antigen 1e to β4 integrin, indicating early maturation of hemidesmosomes, and changed focal adhesion distribution were also identified. LaNt α31 and laminin β3 co-immunoprecipitated from doubly transduced cells and were deposited together in live imaging experiment. Moreover, LaNt α31 expression led to increased matrix metalloproteinase (MMP) activity and proteolytic processing of laminin α3, and the inhibition of MMP activity rescued the laminin and hemidesmosome phenotypes. Provision of cell-derived extracellular matrix rescued the cell spreading and motility effects. These findings reveal LaNt α31 as a new player in regulating cell-to-matrix adhesion through its ability to influence laminin organisation and proteolytic processing.
Best-compromise nutritional menus for childhood obesity
Authors: Bello Paul , Gallardo Pedro , Pradenas Lorena , Ferland Jacques A. , Parada Victor
Published: April 2019

Childhood obesity is an undeniable reality and has shown a rapid growth in many countries. Obesity at an early age not only increases the risks of chronic diseases but also produces a problem for the whole healthcare system. One way to alleviate this problem is to provide each patient with an appropriate menu that can be defined with a mathematical model. Existing mathematical models only partially address the objective and constraints of childhood obesity; therefore, the solutions provided are insufficient for health specialists to prepare nutritional menus for individual patients. This manuscript proposes a multiobjective mathematical programming model to aid healthy nutritional menu planning to prevent childhood obesity. This model enables a plan for combinations and amounts of food across different schedules and daily meals. This approach minimizes the major risk factors of childhood obesity (i.e., glycemic load and cholesterol intake). In addition, it considers the minimization of nutritional mismatch and total cost. The model is solved using a deterministic method and two metaheuristic methods. To complete this numerical study, test instances associated with children aged 4-18 years old were created. The quality of the solutions generated using the three methods was similar, but the metaheuristic methods provided solutions in less computational time. The numerical results indicate proper guidelines for personalized plans for individual children.
Triggers and motivators of privacy protection behavior on Facebook
Authors: Alkire Linda , Pohlmann Johannes , Barnett Willy
Published: April 2019

Purpose

Internet user privacy risks have been a topical subject with respect to consumers, corporations and governments. In line with the recent privacy scandals linked to social media, the aim of this study is to explore users’ privacy protection behaviors (PPB) on Facebook through the actions they take to protect their privacy, their underlying motives and the values behind these protective actions. Moreover, this study aims to address an unintended consequence of Facebook usage. Despite Facebook’s positive and uplifting goal of connecting people, consumers are forced to resort to specific behaviors to protect their privacy and well-being.

Design/methodology/approach

This study adopts an exploratory research approach by using a well-established qualitative technique: structured laddering interviews. In total, 20 in-depth personal interviews were conducted with the Millennials.

Findings

Results show that the process of privacy protection is initiated by experiences, uncertainty and literacy, rather than threats, which leads to concerns that trigger PPBs. The most common PPBs include: “Reflection,” “Avoidance,” “Intervention,” “Restriction,” “Control,” and “Restraint.” The underlying motives for the adoption of these strategies include: “Success,” “Security,” “Social Recognition,” “A World of Peace,” “Exclusivity of Self,” “Being in Control,” “Meaning” and “True Friendship”.

Originality/value

The present research adopts a transdisciplinary framework to help fill the gap regarding the interplay of PPBs on Facebook, the triggers of those behaviors and their underlying motives. It contributes to the service literature and practice as it provides insights into a growing area of interest, whereas more social media channels are being created and more services are using social media strategies to engage and interact with their customers. Finally, it addresses the growing need to consider the impact of technological services, including internet and social media, on consumers’ and societies’ well-being.
Design of biomimetic human-skin-like tactile flexible sensor
Authors: Lu Xiaozhou , Xie Xi , Gao Qiaobo , Hu Hanlun , Yang Jiayi , Wang Hui , Wang Songlin , Chen Renjie
Published: April 2019

Purpose

The hands of intelligent robots perceive external stimuli and respond effectively according to tactile or pressure sensors. However, the traditional tactile and pressure sensors cannot perform human-skin-like intelligent properties of high sensitivity, large measurement range, multi-function and flexibility simultaneously. The purpose of this paper is to present a flexible tactile-pressure sensor based on hyper-elastics polydimethylsiloxane and plate capacitance.

Design/methodology/approach

With regard to this problem, this paper presents a flexible tactile-pressure sensor based on hyper-elastics PDMS and plate capacitance. The sensor has a size of 10 mm × 10 mm × 1.3 mm and is composed of four upper electrodes, one middle driving electrode and one lower electrode. The authors first analyzed the structure and the tactile-pressure sensing principle of human skin to obtain the design parameters of the sensor. Then they presented the working principle, material selection and mechanical structure design and fabrication process of the sensor. The authors also fabricated several sample devices of the sensor and carried out experiments to establish the relationship between the sensor output and the pressure.

Findings

The results show that the tactile part of the sensor can measure a range of 0.05-1N/mm2 micro pressure with a sensitivity of 2.93 per cent/N and a linearity of 0.03 per cent. The pressure part of the sensor can measure a range of 1-30N/mm2 pressure with a sensitivity of 0.08 per cent/N and a linearity of 0.07 per cent.

Originality/value

This paper analyzes the tactile and pressure sensing principles of human skin and develop an intelligent sensitive human-skin-like tactile-pressure sensor for intelligent robot perception systems. The sensor can achieve to imitate the tactile and pressure function simultaneously with a measurement resolution of 0.01 N and a spatial resolution of 2 mm.
The Logic of the Survival of North Korea
Authors: Hirose Kentaro , Kurizaki Shuhei
Published: April 2019

Why has North Korea been able to survive up to now, while other rogue states such as Afghanistan and Iraq have suffered military intervention by the USA? To solve this puzzle, we present a simple two‐level game model that takes into account strategic interdependence between intrastate and interstate wars. Using the two‐level game framework, we show that the ethnic homogeneity of North Korea helps defend itself from US armed intervention, whereas a rogue state with a relatively heterogeneous society is expected to experience international insecurity by providing the USA with an opportunity to find domestic allies that help it win an interstate war against the rogue state. As a policy implication, we discuss the possibility that the recent development of a market economy in North Korea might destabilize the peace between the USA and North Korea.
Letter: dietary fibre benefits for the oesophagus—physical rather than metabolic action?
Authors: Morozov Sergey
Published: April 2019

Linked Content

This article is linked to O’Grady et al and O’Grady and Shanahan papers. To view these articles, visit https://doi.org/10.1111/apt.15129 and https://doi.org/10.1111/apt.15238.
Letter: nonselective beta‐blockers, endoscopic therapy and portal vein thrombosis in cirrhosis
Authors: Bosch Jaume , Berzigotti Annalisa
Published: April 2019

Linked Content

This article is linked to Nery et al and Nery and Valla papers. To view these articles, visit https://doi.org/10.1111/apt.15137 and https://doi.org/10.1111/apt.15262.
How to reject Benatar's asymmetry argument
Authors: Magnusson Erik
Published: April 2019

In this article I reconsider David Benatar's primary argument for anti‐natalism—the asymmetry argument—and outline a three‐step process for rejecting it. I begin in Part 2 by reconstructing the asymmetry argument into three main premises. I then turn in Parts 3–5 to explain how each of these premises is in fact false. Finally, I conclude in Part 6 by considering the relationship between the asymmetry argument and the quality of life argument in Benatar's overall case for anti‐natalism and argue that it is the latter argument that is actually doing the work. In this sense, the asymmetry argument is not only unsuccessful in generating Benatar's anti‐natalist conclusion, it is also unnecessary as well.
Hydrogen sulfide inhibits calcification of heart valves; implications for calcific aortic valve disease
Authors: Sikura Katalin Éva , Potor László , Szerafin Tamás , Oros Melinda , Nagy Péter , Méhes Gábor , Hendrik Zoltán , Zarjou Abolfazl , Agarwal Anupam , Posta Niké , Torregrossa Roberta , Whiteman Matthew , Fürtös Ibolya , Balla György , Balla József
Published: April 2019

Background and Purpose

Calcification of heart valves is a frequent pathological finding in chronic kidney disease and in elderly patients. Hydrogen sulfide (H2S) may exert anti‐calcific actions. Here we investigated H2S as an inhibitor of valvular calcification and to identify its targets in the pathogenesis.

Experimental Approach

Effects of H2S on osteoblastic transdifferentiation of valvular interstitial cells (VIC) isolated from samples of human aortic valves were studied using immunohistochemistry and western blots. We also assessed H2S on valvular calcification in apolipoprotein E‐deficient (ApoE−/−) mice.

Key Results

In human VIC, H2S from donor compounds (NaSH, Na2S, GYY4137, AP67, and AP72) inhibited mineralization/osteoblastic transdifferentiation, dose‐dependently in response to phosphate. Accumulation of calcium in the extracellular matrix and expression of osteocalcin and alkaline phosphatase was also inhibited. RUNX2 was not translocated to the nucleus and phosphate uptake was decreased. Pyrophosphate generation was increased via up‐regulating ENPP2 and ANK1. Lowering endogenous production of H2S by concomitant silencing of cystathionine γ‐lyase (CSE) and cystathionine β‐synthase (CBS) favoured VIC calcification. analysis of human specimens revealed higher Expression of CSE in aorta stenosis valves with calcification (AS) was higher than in valves of aortic insufficiency (AI). In contrast, tissue H2S generation was lower in AS valves compared to AI valves. Valvular calcification in ApoE−/− mice on a high‐fat diet was inhibited by H2S.

Conclusions and Implications

The endogenous CSE‐CBS/H2S system exerts anti‐calcification effects in heart valves providing a novel therapeutic approach to prevent hardening of valves.

Linked Articles

This article is part of a themed section on Hydrogen Sulfide in Biology & Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.4/issuetoc
Care in crisis—Is there a solution? Reflections on the Care Crisis Review 2018
Authors: Holt Kim , Kelly Nancy
Published: April 2019

In 2017, the number of applications for care orders in England and Wales was the highest ever recorded at 14,207. This is a significant factor, contributing to the rise in the number of children who are looked after, which is at the highest level since 1985.

The authors reflect on the recently published Care Crisis Review 2018, a sector‐led review, which examines the reasons for the rise in care proceedings and the number of children in care. The review sought to identify changes to policy and practice within local authorities and the family justice system, in an attempt to divert cases away from the family courts and to reduce the number of children in care, where it is safe to do so.

Whilst the legislative framework is largely effective and the system generally works well, there is insufficient funding and resources to meet the needs of children and their families when they seek help, regardless of whether this is at an early stage or when they are in crisis and most in need of care and protection.
AFCC Think Tanks: Promoting Dialogue on Difficult Issues in Family Law*
Authors: Salem Peter
Published: April 2019

This article examines three think tanks sponsored by the Association of Family and Conciliation Courts, which convened representatives of different disciplines, often with differing perspectives, to address policy and practice dilemmas in family law and dispute resolution. This essay was initially commissioned by the Nuffield Foundation, London, UK, as an Insight Article for its Family Justice Observatory, which aims to improve the use of data and research evidence in the family justice system in England and Wales. The think tank process is described and analyzed, identifying factors that created challenges and those that led to success.
Slash, Shoot, Kill: Gang Recruitment of Children and the Penalties Gangs Face
Authors: Finelli Giuseppe A.
Published: April 2019

Criminal street gang recruitment of minors has proliferated through countless communities in the United States as tensions continue to rise between gangs, communities, and the police. In response, many state legislatures have proposed legislation to combat such influence. However, not only are the proposed penalties too lenient, but some states do not even have laws that prosecute criminal street gang recruitment of minors. This note proposes that all 50 states enact an anti–gang recruitment statute specifically targeting recruiters of criminal street gangs by criminalizing gang recruitment of a minor.
Cash cycle: A cross‐country analysis
Authors: Jalal Abu , Khaksari Shahriar
Published: April 2019

We study the cross‐country differences in the cash cycles of companies and find a negative relation between a country's development and the cash cycles of its corporations. The ability of companies to obtain raw materials on credit and to better manage inventory plays significant roles in shortening the cash cycle. Various country‐specific factors affect cash cycles. Firms with shorter cash cycles invest more in R&D and participate in more acquisitions. They also have a higher valuation and lower leverage. Overall, our findings indicate a close relation between a company's working capital management, its valuation, and the country's level of development.