bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential diagnostic significance of epithelial and stromal CD10 expression in tumors of trichogenic origin
Authors: Kneitz Hermann , Fetzer Stefanie , Goebeler Matthias , Bröcker Eva‐Bettina
Published: June 2018

Background and objectives

The histological differential diagnosis between benign trichogenic skin tumors and basal cell carcinoma may be challenging. We therefore set out to investigate whether expression of CD10, a cell surface protein with neutral endopeptidase activity, might be a suitable marker for the histological differential diagnosis of trichogenic skin tumors.

Patients and methods

We immunohistochemically analyzed 119 cases of benign trichogenic skin tumors and basal cell carcinoma. These included 28 nodular and 15 sclerosing basal cell carcinomas, 21 Pinkus tumors, 20 trichoblastomas, nine trichofolliculomas, eleven trichoepitheliomas, five desmoplastic trichoepitheliomas, and ten seborrheic keratoses.

Results

The majority of nodular basal cell carcinomas expressed CD10 in tumor cells at the peripheral (22/28 [75 %]). On the other hand, trichoblastomas revealed peripheral CD10 expression in only 10 % (2/20) of cases, whereas 50 % showed central expression (10/20). Peripheral epithelial expression of CD10 was also found in Pinkus tumors (9/21 [42.9 %]) and trichoepithelioma (4/11 [36.4 %]). Desmoplastic trichoepithelioma showed no tumoral CD10 expression at all (0/5 [0 %]), while the majority of sclerosing basal cell carcinomas was positive for CD10 (13/15 [86.7 %]).

Conclusions

Our findings suggest that epithelial expression of CD10 – and not peritumoral stromal CD10 expression, as has been postulated – may well be of differential diagnostic significance. The pattern of distribution of CD10‐positive neoplastic cells in particular can be useful in the diagnosis of trichogenic tumors.
Differenzialdiagnostische Bedeutung epithelialer und stromaler CD10‐Expression in Tumoren trichogenen Ursprungs
Authors: Kneitz Hermann , Fetzer Stefanie , Goebeler Matthias , Bröcker Eva‐Bettina
Published: June 2018

Hintergrund und Ziele

Die histologische Differenzialdiagnose zwischen benignen trichogenen Hauttumoren und dem Basalzellkarzinom ist mitunter schwierig. Wir untersuchten in der vorliegenden Arbeit, ob CD10, ein Zelloberflächenprotein mit neutraler Endopeptidaseaktivität, ein geeigneter Marker für die histologische Differenzialdiagnose trichogener Hauttumoren sein könnte.

Patienten und Methodik

119 trichogene Hauttumoren und Basalzellkarzinome wurden immunhistologisch analysiert. Im Einzelnen handelte es sich um 28 solide und 15 sklerodermiforme Basalzellkarzinome, 21 Pinkus‐Tumoren, 20 Trichoblastome, neun Trichofollikulome, elf Trichoepitheliome, fünf desmoplastische Trichoepitheliome und zehn seborrhoische Keratosen.

Ergebnisse

Das solide Basalzellkarzinom exprimierte in den randständigen Zellen CD10 (22/28 [75 %]), während Trichoblastome nur in 10 % der Fälle (2/20) eine randständige Expression von CD10 aufwiesen und häufiger eine zentrale Expression zeigten (10/20 [50 %]). Eine randständige epitheliale Expression von CD10 war auch in Pinkus‐Tumoren (9/21 [42,9 %]) und Trichoepitheliomen (4/11 [36,4 %]) zu finden. Im desmoplastischen Trichoepitheliom war keine CD10‐Expression in den Tumorzellen zu erkennen (0/5 [0 %]), während die meisten sklerodermiformen Basalzellkarzinome CD10‐positiv waren.

Schlussfolgerungen

Die Befunde zeigen, dass eine epitheliale CD10–Expression durchaus eine differenzialdiagnostische Bedeutung hat, nicht aber, wie in der Literatur postuliert, die peritumorale, stromale Immunreaktivität. Besonders das Verteilungsmuster der CD10‐positiven Tumorzellen in trichogenen Tumoren kann eine diagnostische Hilfe sein.
A randomized comparison of three prandial insulin dosing algorithms for children and adolescents with Type 1 diabetes
Authors: Lopez P. E. , Evans M. , King B. R. , Jones T. W. , Bell K. , McElduff P. , Davis E. A. , Smart C. E.
Published: June 2018

Aim

To compare systematically the impact of two novel insulin‐dosing algorithms (the Pankowska Equation and the Food Insulin Index) with carbohydrate counting on postprandial glucose excursions following a high fat and a high protein meal.

Methods

A randomized, crossover trial at two Paediatric Diabetes centres was conducted. On each day, participants consumed a high protein or high fat meal with similar carbohydrate amounts. Insulin was delivered according to carbohydrate counting, the Pankowska Equation or the Food Insulin Index. Subjects fasted for 5 h following the test meal and physical activity was standardized. Postprandial glycaemia was measured for 300 min using continuous glucose monitoring.

Results

33 children participated in the study. When compared to carbohydrate counting, the Pankowska Equation resulted in lower glycaemic excursion for 90–240 min after the high protein meal (p < 0.05) and lower peak glycaemic excursion (p < 0.05). The risk of hypoglycaemia was significantly lower for carbohydrate counting and the Food Insulin Index compared to the Pankowska Equation (OR 0.76 carbohydrate counting vs. the Pankowska Equation and 0.81 the Food Insulin Index vs. the Pankowska Equation). There was no significant difference in glycaemic excursions when carbohydrate counting was compared to the Food Insulin Index.

Conclusion

The Pankowska Equation resulted in reduced postprandial hyperglycaemia at the expense of an increase in hypoglycaemia. There were no significant differences when carbohydrate counting was compared to the Food Insulin Index. Further research is required to optimize prandial insulin dosing.
Protecting the economic health of the poor in India: Are health mutuals the right medicine?
Authors: Madhur Sunit Kumar , Saha Somen
Published: June 2018

In addition to government‐sponsored health insurance schemes (GSHIS), many microfinance institutions (MFIs) and community‐based organizations (CBOs) in India have started microinsurance health insurance schemes. These include health mutuals for the benefit of their members. This article explores these as an alternative health‐financing model in India. A literature search produced 926 relevant publications. After applying advanced search options and removing duplicates, abstracts of 324 papers were read and then 47 papers reviewed, and finally 29 were included in this review. Five key themes emerged: (1) “Health for all” arguments and opportunities in favour of micro health insurance schemes; (2) micro health insurance products; (3) impact of micro health insurance schemes; (4) systematic irregularities and regulatory framework; and (5) innovation. We also look at the emerging market patterns that will define micro health insurance products. Health mutuals can effectively provide mass health protection to the poor and not so poor through efficient business models, bespoke benefit packages and multiple payment plans. They can reduce financial vulnerability and improve health outcomes. While GSHIS can cover a substantial tranche of expected health‐related costs, the balance can be supplemented through innovative financial products that reduce financial risk.
Constructing New Representations and the Implications for Decision Making Theory: Learning from Archimedes
Authors: Giacomoni Gilbert
Published: June 2018

In general decision making theory modeling inferential reasoning, there is an information asymmetry that arises from the fact that the universe of possibles, which is assumed to be stable, is not formalized as conditional in operative rules. Standing as a classic counter‐example is an innovational model (the Archimedes thought experiment) in which the universe of discourse, that is, the reference universe, must be reframed and extended. Here, new theoretical foundations are put forth: (1) a formalized concept of a reference universe; (2) a two‐fold rationality, with or without an excluded middle, to operate within a reference universe; or (3) a non‐reflexive identity entailed in a reframing process, adding a new dimension to the existing knowledge base. This opens outlooks for modeling a process whereby new representations for decision making can be constructed. Moreover, it is a process that constitutes a unique vantage point from which to observe innovative situations and to contemplate the link to paradox theory in management research.
Be global or be gone: Global mindset as a source of division in an international business community
Authors: Goxe François , Belhoste Nathalie
Published: June 2018

Global mindset is usually considered as a positive skill or resource that helps individuals and companies succeed internationally. We argue that it is also a collective scheme of thought that brings some actors together and sets others apart. We investigate this perspective through a qualitative study of French MNC managers, internationalisation support providers, and SME owners and managers attempting to create or grow their business in China. We reveal that global mindset is a double‐edged concept: it is not solely an instrument for integration, but also a doxa, a particular viewpoint imposed to identify and reject outsiders through symbolic struggles. This alternative conceptualisation is necessary to rethink the social forces at work in the field of international business. It is also necessary to encourage educators and practitioners to acknowledge the struggles that result from the imposition of certain views and behaviours and to adapt education, support and training programs accordingly.
Multimodal seizure detection: A review
Authors: Leijten Frans S. S. ,   the Dutch TeleEpilepsy Consortium
Published: June 2018

A review is given on the combined use of multiple modalities in non electroencephalography (EEG)‐based detection of motor seizures in children and adults. A literature search of papers was done on multimodal seizure detection with extraction of data on type of modalities, study design and algorithm, sensitivity, false detection rate, and seizure types. Evidence of superiority was sought for using multiple instead of single modalities. Seven papers were found from 2010 to 2017, mostly using contact sensors such as accelerometers (n = 5), electromyography (n = 2), heart rate (n = 2), electrodermal activity (n = 1), and oximetry (n = 1). Remote sensors included video, radar, movement, and sound. All studies but one were in‐hospital, with video‐EEG as a gold standard. Algorithms were based on physiology and supervised machine learning, but did not always include a separate test dataset. Sensitivity ranged from 4% to 100% and false detection rate from 0.25 to 20 per 8 hours. Tonic–clonic seizure detection performed best. False detections tended to be restricted to a minority (16%‐30%) of patients. Use of multiple sensors increased sensitivity; false detections decreased in one study, but increased in another.

These preliminary studies suggest that detection of tonic–clonic seizures might be feasible, but larger field studies are required under more rigorous design that precludes bias. Generic algorithms probably suffice for the majority of patients.
Standards for testing and clinical validation of seizure detection devices
Authors: Beniczky Sándor , Ryvlin Philippe
Published: June 2018

To increase the quality of studies on seizure detection devices, we propose standards for testing and clinical validation of such devices. We identified 4 key features that are important for studies on seizure detection devices: subjects, recordings, data analysis and alarms, and reference standard. For each of these features, we list the specific aspects that need to be addressed in the studies, and depending on these, studies are classified into 5 phases (0‐4). We propose a set of outcome measures that need to be reported, and we propose standards for reporting the results. These standards will help in designing and reporting studies on seizure detection devices, they will give readers clear information on the level of evidence provided by the studies, and they will help regulatory bodies in assessing the quality of the validation studies. These standards are flexible, allowing classification of the studies into one of the 5 phases. We propose actions that can facilitate development of novel methods and devices.
The lived experiences of foreign women: Influences on their international working lives
Authors: Kemp Linzi J. , Rickett Bridgette
Published: June 2018

The lived experiences of foreign women were explored to discover influences on their international working lives. Life history narratives were collected in interviews with 12 participants who were female, foreign (nationality differs from their country of employment) and employed or a business owner in the United Arab Emirates. A phenomenological framework of analysis resulted in identification of three emergent themes around life experiences that had shaped participants' working lives: becoming a new generation of expatriates; adjustment to sociocultural change; and centrality of womanhood. The implication of these themes was the influence from lived experiences on the development and professional identity of foreign working‐women. Findings offer insight about influences on the actual and potential economic participation of foreign women for business practitioners and policymakers. A new classification of foreign worker, the ‘foreign working‐woman’ (FW‐W), extends the body of academic knowledge. A research direction is proposed for further international study about influences from life experiences on the FW‐W.
Resisting sexism and speciesism in the social sciences: Using feminist, species‐inclusive, visual methods to value the work of women and (other) animals
Authors: Taylor Nik , Fraser Heather
Published: June 2018

Visual methods offer social scientists some promising possibilities for valuing the work of women and animals in domestic homes and formal organizations, such as schools, hospitals, residential care facilities and other workplaces. In this article, we consider how visual methods might be used to ‘put women and animals in the frame’. We draw data and inspiration from our What is it About Animals study [2015–2016], which involved an online call for people over 16 years of age, to post pictures, poems, stories and videos depicting what animals mean to them. We pay attention to attempts to resist sexism and speciesism in the valuing of work, including emotional labour. We consider the possibility of post‐humanist methods for animal subject‐hood, and a sociology of animals, emotions and work. We end with a discussion of possible future visual methods projects to value the work of women and (other) animals.
JAK‐STAT signaling pathway inhibition: a role for treatment of discoid lupus erythematosus and dermatomyositis
Authors: Kahn Jared S. , Deverapalli Sandhya Chowdary , Rosmarin David M.
Published: June 2018

Background

Discoid lupus erythematosus (DLE) and dermatomyositis (DM) are inflammatory autoimmune diseases that manifest primarily in the skin but can be linked to systemic complications. Although there is an in‐depth understanding of the clinical presentation of these two diseases, much less is known regarding the pathophysiology. This has limited the effective treatment options for patients.

Objective

An understanding of the pathogenesis of each disease in greater detail will lead to newer targeted medications with less morbidity. This review article endeavors to substantiate the use of new treatments which target the JAK‐STAT pathway while elaborating on the immunopathology as well.

Methods

PubMed was searched for relevant review articles, case reports, case series reports, randomized clinical trials (RCTs), basic science articles. Appropriate key terms and MeSH terms were utilized in the search. Clinicaltrials.gov was used to find relevant and current clinical trials being conducted in DLE and DM patients.

Results

A review of the literature supports the proposal that though there are likely many components and pathways involved in the destruction of keratinocytes, the Th1 cell immune response and specifically the JAK‐STAT signaling pathway is common to both DLE and DM.

Conclusion

Although further study is needed to determine the efficacy and benefits of JAK inhibitors over conventional therapy, these medications should be considered in refractory cases.
Identification of antioxidant and anti‐inflammatory peptides obtained by simulated gastrointestinal digestion of three edible insects species (Gryllodes sigillatus, Tenebrio molitor, Schistocerca gragaria)
Authors: Zielińska Ewelina , Baraniak Barbara , Karaś Monika
Published: June 2018

The aim of this study was to determine the effect of heat treatment of edible insects on antioxidant and anti‐inflammatory activities of peptide fractions from hydrolysates obtained by in vitro gastrointestinal digestion thereof. Identification of bioactive peptides from the edible insects and their chemical synthesis were carried out as well. The highest antiradical activity against ABTS•+ and DPPH• was noted for the peptide fraction from the Gryllodes sigillatus protein preparation (EC50 value 2.75 and 6.91 μg mL−1, respectively). This fraction exhibited the strongest LOX and COX‐2 inhibitory activity (IC50 value 0.13 and 0.26 μg mL−1, respectively). The peptide fraction from the Tenebrio molitor protein preparation showed the highest Fe2+ chelating ability (EC50 value 2.21 μg mL−1) and the highest reducing power (0.198). The heat treatment process has a positive effect on the antioxidant and anti‐inflammatory properties of peptides. All identified and synthesised peptides from insect protein showed antioxidant and anti‐inflammatory activity.
In situ enzymatic synthesis and purification of theaflavin‐3,3′‐digallate monomer and incorporation into nanoliposome
Authors: Ding Yangping , Zou Liqiang , Lu Changqi , Tong Huarong , Chen Bingcan
Published: June 2018

The aim of this study was to develop a novel ethanol‐water based enzymatic synthesis coupled with column chromatography purification technique to synthesise theaflavin‐3,3′‐digallate (TFDG) using underutilised summer and autumn fresh tea leaves. Enzymatic synthesised TFDG was incorporated into nanoliposome using ethanol injection combined with dynamic high‐pressure microfluidisation technique at pH 5.5. TFDG with a purity of 90.5% at the gram level was achieved by applying ethanol with different concentrations as eluent, and the yield of TFDG was 36.00%. TFDG nanoliposome showed the great in vitro digestion stability, with the particle size, polydispersity, zeta potential being 59.43 ± 5.67 nm, 0.31 ± 0.025 and ‐8.28 ± 0.24 mV, respectively. Nanoliposome encapsulation can significantly improve the stability of TFDG as indicated by the greater resistance upon in vitro digestion studies under both the mild alkaline pH and simulated intestinal fluid. The current research laid a foundation for the further application of TFDG as functional ingredients in food industry.
A Proposed Timescale for the Evolution of Armophorean Ciliates: Clevelandellids Diversify More Rapidly Than Metopids
Authors: Vďačný Peter , Rajter Ľubomír , Stoeck Thorsten , Foissner Wilhelm
Published: June 2018

Members of the class Armophorea occur in microaerophilic and anaerobic habitats, including the digestive tract of invertebrates and vertebrates. Phylogenetic kinships of metopid and clevelandellid armophoreans conflict with traditional morphology‐based classifications. To reconcile their relationships and understand their morphological evolution and diversification, we utilized the molecular clock theory as well as information contained in the estimated time trees and morphology of extant taxa. The radiation of the last common ancestor of metopids and clevelandellids very likely occurred during the Paleozoic and crown diversification of the endosymbiotic clevelandellids dates back to the Mesozoic. According to diversification analyses, endosymbiotic clevelandellids have higher net diversification rates than predominantly free‐living metopids. Their cladogenic success was very likely associated with sharply isolated ecological niches constituted by their hosts. Conflicts between traditional classifications and molecular phylogenies of metopids and clevelandellids very likely come from processes, leading to further diversification without extinction of ancestral lineages as well as from morphological plesiomorphies incorrectly classified as apomorphies. Our study thus suggests that diversification processes and reconstruction of ancestral morphologies improve the understanding of paraphyly which occurs in groups of organisms with an apparently long evolutionary history and when speciation prevails over extinction.
DO ANALYSTS WHO MOVE MARKETS HAVE BETTER CAREERS?
Authors: Balashov Vadim S.
Published: June 2018

In this article I investigate the association between analysts’ ability to issue influential recommendations and their career outcomes. The fraction of recommendations that are defined as influential are linked to a higher probability of an analyst moving to a higher status brokerage house, and a lower probability of either being demoted to a lower status brokerage house or leaving the profession. Analysts who more often issue influential recommendations also have a higher chance of being ranked by Institutional Investor All‐America, having longer careers, and experiencing lower job turnover compared to peers.
Out of the outhouse: The impact of place‐based policies on dwelling characteristics in Appalachia
Authors: Grossman Daniel S. , Humphreys Brad R. , Ruseski Jane E.
Published: June 2018

The Appalachian Regional Commission (ARC) administers and partially funds investment projects designed to improve economic conditions in the Appalachian region, an area of persistent poverty and reduced economic opportunity in the eastern United States in and around the Appalachian mountains. Previous research on the effectiveness of ARC programs is mixed. We analyze the impact of ARC investment projects related to expanding sewerage and waste water treatment on dwelling characteristics. Results from a difference‐in‐differences model using a quasi‐experimental approach show that ARC investment projects improved access to running water, and increased sewer hookups and indoor bathrooms in dwellings.
Respiratory virus detection and co‐infection in children and adults in a large Australian hospital in 2009–2015
Authors: Ching Natasha S , Kotsanas Despina , Easton Mee L , Francis Michelle J , Korman Tony M , Buttery Jim P
Published: June 2018

Aim

This hospital network‐based retrospective observational study aimed to describe the prevalence and seasonality of paediatric and adult viral respiratory pathogens and their rates of co‐infections, following the introduction of a rapid multiplex molecular diagnostic assay.

Methods

All nasopharyngeal samples tested in patients presenting to Monash Health, Melbourne, Australia, from August 2009 to July 2015 by means of multiplex tandem polymerase chain reaction using the Respiratory Pathogen 12Plex kit (AusDiagnostics) were included in the analysis.

Results

There were 28 729 patient samples analysed after duplicate samples were excluded. Positive results were twice as likely in paediatrics, 7573/11 491 (65.9%), compared to adults, 5410/17 238 (31.4%). Co‐infection was more frequent in paediatrics, 1642/7573 (21.7% of positives), compared to adults 299/5410 (5.5%). Adenovirus had a high prevalence as a co‐infection, 639/990 (64.5%), in paediatrics. Testing frequency increased by 179% in the paediatric group and by 949% for adults over the 6 years of observation.

Conclusions

This study demonstrated a significant difference in the positive detection rate of pathogens and co‐infections between the population groups. Adenovirus had a surprisingly high prevalence as a co‐infection, especially in paediatric patients. Over the study period, rapid uptake of the test was observed, especially in adults. This raises concerns about how we can ensure that testing remains rational and is able to be provided in a cost‐effective manner in the future.
First fossil record of Cedrelospermum (Ulmaceae) from the Qinghai–Tibetan Plateau: Implications for morphological evolution and biogeography
Authors: Jia Lin‐Bo , Su Tao , Huang Yong‐Jiang , Wu Fei‐Xiang , Deng Tao , Zhou Zhe‐Kun
Published: June 2018

Cedrelospermum Saporta is an extinct genus in the Ulmaceae with abundant fossil records in North America and Europe. However, so far, fossil records of this genus from Asia are sparse, which limits the interpretations of the morphological evolution and biogeographical history of the genus. Here we report well‐preserved fruits (Cedrelospermum tibeticum sp. nov.) and a leaf (Cedrelospermum sp.) of Cedrelospermum from the upper Oligocene Lunpola and Nyima basins in the Qinghai–Tibetan Plateau (QTP). This is the first fossil record of Cedrelospermum in the QTP, showing that this genus grew in this region during the late Oligocene. Cedrelospermum tibeticum fruits are double‐winged, morphologically similar to the Eocene and Oligocene double‐winged Cedrelospermum species from North America. This supports the hypothesis that Cedrelospermum migrated to Asia from North America by way of the Bering Land Bridge. Given that Cedrelospermum was a typical element of Northern Hemispheric flora in the Paleogene and Neogene, the presence of this genus indicates that the central region of the QTP was phytogeographically linked with other parts of the Northern Hemisphere during the late Oligocene. The morphological observations of C. tibeticum fruits and other double‐winged Cedrelospermum fruits suggest an evolutionary trend from obtuse to acute apex for the primary wing. Cedrelospermum tibeticum likely had warm and wet climatic requirements. This type of an environment possibly existed in the central QTP in the late Oligocene, thereby supporting the survival of C. tibeticum.
Blood parasites prevalence of migrating passerines increases over the spring passage period
Authors: Emmenegger T. , Bauer S. , Hahn S. , Müller S. B. , Spina F. , Jenni L.
Published: June 2018

Whether long‐distance animal migration facilitates or hampers pathogen transmission depends on how infections affect the routes and timing of migrating hosts. If an infection directly or indirectly impedes migratory flight capacity, infected individuals lag behind their uninfected conspecifics. Although such temporal segregation can limit parasite transmission and thus play an important role for host–parasite interactions, empirical evidence remains scarce. Here, we investigated haemosporidians – blood parasites commonly infecting birds – in four passerine species on spring passage and linked infection status to passage date. As a step towards identifying the mechanisms behind infection‐related delays, we incorporated sets of individual, energetic, haematological and biometric variables into the analysis. Haemosporidian prevalence virtually doubled between birds sampled at the beginning of the passage period with those sampled 1 month later. This indicates that infected individuals arrived later than uninfected individuals. Both the average prevalence and its increase over time varied among host species. In addition, the leucocyte counts of infected birds were elevated, suggesting that immune response may require resources which could otherwise be allocated to migratory flights. However, infection status was not related to any other variable such as body mass, energy stores, sex, age and feather length. Yet regardless of the underlying mechanisms, infection‐related differential timing might influence transmission and affect pathogen prevalence in wildlife populations year‐round.
Plasmodium falciparum subtilisin‐like ookinete protein SOPT plays an important and conserved role during ookinete infection of the Anopheles stephensi midgut
Authors: Armistead Jennifer S. , Jennison Charlie , O'Neill Matthew T. , Lopaticki Sash , Liehl Peter , Hanson Kirsten K. , Annoura Takeshi , Rajasekaran Pravin , Erickson Sara M. , Tonkin Christopher J. , Khan Shahid M. , Mota Maria M. , Boddey Justin A.
Published: June 2018

Transmission of the malaria parasite Plasmodium falciparum involves infection of Anopheles mosquitoes. Here we characterize SOPT, a protein expressed in P. falciparum ookinetes that facilitates infection of the mosquito midgut. SOPT was identified on the basis that it contains a signal peptide, a PEXEL‐like sequence and is expressed in asexual, ookinete and sporozoite stages, suggesting it is involved in infecting the human or mosquito host. SOPT is predicted to contain a subtilisin‐like fold with a non‐canonical catalytic triad and is orthologous to P. berghei PIMMS2. Localization studies reveal that SOPT is not exported to the erythrocyte but is expressed in ookinetes at the parasite periphery. SOPT‐deficient parasites develop normally through the asexual and sexual stages and produce equivalent numbers of ookinetes to NF54 controls, however, they form fewer oocysts and sporozoites in mosquitoes. SOPT‐deficient parasites were also unable to activate the immune‐responsive midgut invasion marker SRPN6 after mosquito ingestion, suggesting they are defective for entry into the midgut. Disruption of SOPT in P. berghei (PIMMS2) did not affect other lifecycle stages or ookinete development but again resulted in fewer oocysts and sporozoites in mosquitoes. Collectively, this study shows that SOPT/PIMMS2 plays a conserved role in ookinetes of different Plasmodium species.
Abnormal gene methylation during embryonic development after preimplantation genetic testing increases risk of liver‐derived insulin resistance
Authors: Zheng Mei Mei , Cao Hua Rong , Zhang Wu Yue , Yan Pei Pei , Xu Jing Yi , Zhao Heng Li , Zhu Feng , Zhang Jing Jing , Li Yan , Zhu Hui
Published: June 2018

The operations involved in preimplantation genetic testing (PGT) occur during the key stages of gametogenesis and early embryonic development, and the health of progeny following PGT (PGT‐born) is worthy of attention. In order to fully assess the potential risk of abnormal glucose metabolism in adult PGT‐born offspring and to evaluate possible mechanisms, we compared a mouse model of PGT (in vitro cultured embryos with biopsy, hereafter “PTG‐born mice”), an in vitro embryo manipulation mouse model (in vitro cultured embryos without biopsy), and normal mice. PGT‐born mice displayed increased fasting glucose, and decreased glycogen synthesis and glucose oxidative utilization in the liver. Moreover, PGT‐born mice also displayed reduced expression of insulin receptor, AKT, and insulin‐stimulated Akt phosphorylation (pAkt) in the liver. These results suggest a potential risk of insulin resistance in adult PGT‐born mice. By analyzing the DNA methylation profiles of 7.5 days postconception (dpc) embryos, we identified differentially methylated genes associated with liver development between PGT‐born and control groups; some of these genes are associated with glucose homeostasis and insulin response. These results suggest that abnormal methylation in embryos that develop after PGT may be a potential mechanism occurring during embryonic development that can influence the risk of liver‐derived insulin resistance in adulthood.
Is there a will to meaning?
Authors: Pigliucci Massimo
Published: June 2018

All thinking human beings seek an answer to the question, What is the meaning of life? Herein are discussed answers to this question, drawing on various traditions, but especially from Stoicism.
Physiological pacing in young patients with complex congenital heart defects
Authors: Silvetti Massimo Stefano , Pazzano Vincenzo , Battipaglia Irma , Di Mambro Corrado , Calvieri Camilla , Saputo Fabio Anselmo , Verticelli Letizia , Carotti Adriano , Torcinaro Sergio , Drago Fabrizio
Published: June 2018

Aim

Young patients with operated complex congenital heart defects (CHD) often develop sinus node dysfunction (SND) requiring permanent pacing with rate‐responsive function. Activity‐driven sensors cannot account for nonmovement stress and cannot modulate heart rate physiologically. Closed Loop Stimulation (CLS, Biotronik, Berlin, Germany) is a physiological rate‐responsive pacemaker based on the indirect measure of ventricular contractility. No data are available on the effects of such pacing strategy in young patients.

Methods

We report a series of nine patients with CHD and SND who underwent single‐chamber CLS‐atrial pacing with endocardial or epicardial lead. During the first 30 days, the pacemaker was programmed in AAI pacing mode and then was switched to CLS‐atrial pacing mode. An in‐hospital control was scheduled 1–2 months later to evaluate the CLS response to neurovegetative stresses (i.e., nonmovement stress [Stroop color test, handgrip] and exercise stress test) and Holter monitor. CLS pacing was compared with rate‐responsive accelerometer‐driven pacing (AAIR).

Results

At telemetric interrogation, CLS pacing showed a more physiological pattern of 24‐h heart rate trends than accelerometer sensors. The data obtained during nonmovement/exercise stress demonstrated a physiological increase in the pacing rate with CLS, in synergy with spontaneous events. The accelerometer sensor histogram, during nonmovement stress, showed a “nonresponse” behavior (only lower rate events), and during exercise test showed most events in lower rate range. Holter monitoring showed increase of average and maximum heart rate compared with AAIR.

Conclusion

In young CHD patients, endocardial/epicardial CLS‐atrial pacing demonstrated a physiological response of heart rate to neurovegetative and physical stresses.
Up‐regulation of lipid biosynthesis increases the oil content in leaves of Sorghum bicolor
Authors: Vanhercke Thomas , Belide Srinivas , Taylor Matthew C. , El Tahchy Anna , Okada Shoko , Rolland Vivien , Liu Qing , Mitchell Madeline , Shrestha Pushkar , Venables Ingrid , Ma Lina , Blundell Cheryl , Mathew Anu , Ziolkowski Lisa , Niesner Nathalie , Hussain Dawar , Dong Bei , Liu Guoquan , Godwin Ian D. , Lee Jiwon , Rug Melanie , Zhou Xue‐Rong , Singh Surinder P. , Petrie James R.
Published: June 2018

Synthesis and accumulation of the storage lipid triacylglycerol in vegetative plant tissues has emerged as a promising strategy to meet the world's future need for vegetable oil. Sorghum (Sorghum bicolor) is a particularly attractive target crop given its high biomass, drought resistance and C4 photosynthesis. While oilseed‐like triacylglycerol levels have been engineered in the C3 model plant tobacco, progress in C4 monocot crops has been lagging behind. In this study, we report the accumulation of triacylglycerol in sorghum leaf tissues to levels between 3 and 8.4% on a dry weight basis depending on leaf and plant developmental stage. This was achieved by the combined overexpression of genes encoding the Zea mays WRI1 transcription factor, Umbelopsis ramanniana UrDGAT2a acyltransferase and Sesamum indicum Oleosin‐L oil body protein. Increased oil content was visible as lipid droplets, primarily in the leaf mesophyll cells. A comparison between a constitutive and mesophyll‐specific promoter driving WRI1 expression revealed distinct changes in the overall leaf lipidome as well as transitory starch and soluble sugar levels. Metabolome profiling uncovered changes in the abundance of various amino acids and dicarboxylic acids. The results presented here are a first step forward towards the development of sorghum as a dedicated biomass oil crop and provide a basis for further combinatorial metabolic engineering.
Transgenic creeping bentgrass overexpressing Osa‐miR393a exhibits altered plant development and improved multiple stress tolerance
Authors: Zhao Junming , Yuan Shuangrong , Zhou Man , Yuan Ning , Li Zhigang , Hu Qian , Bethea Frank G. , Liu Haibo , Li Shigui , Luo Hong
Published: June 2018

MicroRNA393 (miR393) has been implicated in plant growth, development and multiple stress responses in annual species such as Arabidopsis and rice. However, the role of miR393 in perennial grasses remains unexplored. Creeping bentgrass (Agrostis stolonifera L.) is an environmentally and economically important C3 cool‐season perennial turfgrass. Understanding how miR393 functions in this representative turf species would allow the development of novel strategies in genetically engineering grass species for improved abiotic stress tolerance. We have generated and characterized transgenic creeping bentgrass plants overexpressing rice pri‐miR393a (Osa‐miR393a). We found that Osa‐miR393a transgenics had fewer, but longer tillers, enhanced drought stress tolerance associated with reduced stomata density and denser cuticles, improved salt stress tolerance associated with increased uptake of potassium and enhanced heat stress tolerance associated with induced expression of small heat‐shock protein in comparison with wild‐type controls. We also identified two targets of miR393, AsAFB2 and AsTIR1, whose expression is repressed in transgenics. Taken together, our results revealed the distinctive roles of miR393/target module in plant development and stress responses between creeping bentgrass and other annual species, suggesting that miR393 would be a promising candidate for generating superior crop cultivars with enhanced multiple stress tolerance, thus contributing to agricultural productivity.
A Meta‐Analysis of Newsvendor Experiments: Revisiting the Pull‐to‐Center Asymmetry
Authors: Zhang Yinghao , Siemsen Enno
Published: June 2018

The field of behavioral operations has produced a rich tradition of experiments in newsvendor decision‐making. Our study provides a meta‐analysis of 24 papers in this research area; we confirm that the pull‐to‐center (PtC) effect, where average order quantities in a sample lie in between average demand and optimal order quantities, is a very stable observable phenomenon across studies. However, we also show that the asymmetry in the PtC effect between high‐margin and low‐margin conditions varies significantly from study to study; factors that allow predicting the extent and direction of the PtC asymmetry include the likelihood of obtaining losses, the way underage costs are presented to subjects, and the existence of a decision support system. We validate these factors using a controlled experiment. In conclusion, the PtC asymmetry appears less as a fundamental attribute of human behavior, but rather as a function of the design aspects of the experiment.
More than Pathological Formalization: Understanding Organizational Structure and Red Tape
Authors: Kaufmann Wesley , Borry Erin L. , DeHart‐Davis Leisha
Published: June 2018

Most research has conceptualized red tape as being a pathological subset of organizational formalization. This article argues that focusing on a single dimension of organizational structure as a red tape driver is unrealistically narrow. Specifically, the article advances hypotheses as to how organizational centralization and hierarchy affect perceived red tape, in addition to formalization. This reasoning is tested using survey data from employees of three local government organizations in the southeastern United States. All three hypotheses are supported: higher levels of organizational formalization, centralization, and hierarchy are associated with more red tape. Open‐ended comments also indicate that red tape is not solely perceived as related to formalization. The findings imply that red tape is a multifaceted perception of organizational structure rather than perceived pathological formalization.
The Birth of Being and Time: Heidegger's Pivotal 1921 Reading of Aristotle's On the Soul
Authors: Gonzalez Francisco J.
Published: June 2018

During the 1920s Heidegger gave no less than twelve seminars and lecture courses devoted either exclusively or in large part to the reading of Aristotle's texts. Seven of these, especially the smaller seminars for advanced students, have not been published and apparently will never be included in the Gesamtausgabe. My focus here is on the very first of these. Billed as a reading of Aristotle's De Anima, much of it was devoted to Aristotle's Metaphysics. This decision not to separate Aristotle's “psychology” from his “ontology” is a key move of the seminar that anticipates the project of Being and Time. This and many other ways in which Heidegger's early reading of De Anima anticipates the key moves of the later book constitute one of the reasons for its importance. Another is that the seminar allows us to see what gets suppressed in Heidegger's reading of Aristotle, most significantly, the phenomenon of life itself in favor of an eventual focus on the being of human life or Dasein. This early seminar thus enables us not only to better understand Heidegger's project, but also to raise some fundamental questions concerning it.
Are All Primitives Created Equal?
Authors: Miller J. T. M.
Published: June 2018

Primitives are both important and unavoidable, and which set of primitives we endorse will greatly shape our theories and how those theories provide solutions to the problems that we take to be important. After introducing the notion of a primitive posit, I discuss the different kinds of primitives that we might posit. Following Cowling (), I distinguish between ontological and ideological primitives, and, following Benovsky (), between functional and content views of primitives. I then propose that these two distinctions cut across each other leading to four types of primitive posits. I then argue that theoretical virtues should be taken to be metatheoretical ideological primitives. I close with some reflections on the global nature of comparing sets of primitives.
Extracellular signal‐regulated kinase 2 has duality in function between neuronal and astrocyte expression following neonatal hypoxic–ischaemic cerebral injury
Authors: Thei Laura , Rocha‐Ferreira Eridan , Peebles Donald , Raivich Gennadij , Hristova Mariya
Published: June 2018

Key points

This study identifies phosphorylated extracellular signal‐regulated kinase (ERK) to be immediately diminished followed by a rapid if transient increase for up to 4 h following hypoxic–ischaemic insult (HI) in the neonatal mouse.

Phosphorylated ERK up‐regulation was prevented with systemic injection of the mitogen‐activated protein kinase kinase (MEK) inhibitor SL327. Treatment with SL327 both pre‐ and post‐HI gave a strong reduction in the number of dying cells and microgliosis.

By utilising transgenic mouse mutations, we observe that neuronal ERK2 significantly contributes to tissue damage, while ERK1 and astrocytic ERK2 are neuroprotective.

Compared to global inactivation, selective cell‐specific interference with ERK activity could result in stronger neuroprotection.

Hypoxia–ischaemia (HI) is a major cause of neonatal brain injury resulting in cerebral palsy, epilepsy, cognitive impairment and other neurological disabilities. The role of extracellular signal‐regulated kinase (ERK) isoforms and their mitogen‐activated protein kinase kinase (MEK)‐dependent phosphorylation in HI has previously been explored but remains unresolved at cellular level. This is pertinent given the growing awareness of the role of non‐neuronal cells in neuroprotection. Using a modified Rice–Vannucci model of HI in the neonatal mouse we observed time‐ and cell‐dependent ERK phosphorylation (pERK), with strongly up‐regulated pERK immunoreactivity first in periventricular white matter axons within 15–45 min of HI, followed by forebrain astrocytes and neurons (1–4 h post‐HI), and return to baseline by 16 h. We explored the effects of pharmacological ERK blockade through the MEK inhibitor SL327 on neonatal HI‐brain damage following HI alone (30 or 60 min) or lipopolysaccharide (LPS)‐sensitised HI insult (30 min). Global inhibition of ERK phosphorylation with systemically applied SL327 abolished forebrain pERK immunoreactivity, and significantly reduced cell death and associated microglial activation at 48 h post‐HI. We then explored the effects of cell‐specific ERK2 deletion alone or in combination with global ERK1 knockout under the same conditions of HI insult. Neuronal ERK2 deletion strongly decreased infarct size, neuronal cell death and microglial activation in grey matter following both HI alone or LPS‐sensitised HI. ERK1 deletion attenuated the protective effect of neuronal ERK2 deletion. Removal of astroglial ERK2 produced a reverse response, with a 3‐ to 4‐fold increase in microglial activation and cell death. Our data suggest a cell‐specific and time‐dependent role of ERK in neonatal HI, with a predominant, neurotoxic effect of neuronal ERK2, which is counteracted by neuroprotection by ERK1 and astrocytic ERK2. Overall, global pharmacological inhibition of ERK phosphorylation is strongly neuroprotective.
Bicarbonate directly modulates activity of chemosensitive neurons in the retrotrapezoid nucleus
Authors: Gonçalves Christopher M. , Mulkey Daniel K.
Published: June 2018

Key Points

Changes in CO2 result in corresponding changes in both H+ and HCO3− and despite evidence that HCO3− can function as an independent signalling molecule, there is little evidence suggesting HCO3− contributes to respiratory chemoreception.

We show that HCO3− directly activates chemosensitive retrotrapezoid nucleus (RTN) neurons.

Identifying all relevant signalling molecules is essential for understanding how chemoreceptors function, and because HCO3− and H+ are buffered by separate cellular mechanisms, having the ability to sense both modalities adds additional information regarding changes in CO2 that are not necessarily reflected by pH alone.

HCO3− may be particularly important for regulating activity of RTN chemoreceptors during sustained intracellular acidifications when TASK‐2 channels, which appear to be the sole intracellular pH sensor, are minimally active.

Central chemoreception is the mechanism by which the brain regulates breathing in response to changes in tissue CO2/H+. The retrotrapezoid nucleus (RTN) is an important site of respiratory chemoreception. Mechanisms underlying RTN chemoreception involve H+‐mediated activation of chemosensitive neurons and CO2/H+‐evoked ATP‐purinergic signalling by local astrocytes, which activates chemosensitive neurons directly and indirectly by maintaining vascular tone when CO2/H+ levels are high. Although changes in CO2 result in corresponding changes in both H+ and HCO3− and despite evidence that HCO3− can function as an independent signalling molecule, there is little evidence suggesting HCO3− contributes to respiratory chemoreception. Therefore, the goal of this study was to determine whether HCO3− regulates activity of chemosensitive RTN neurons independent of pH. Cell‐attached recordings were used to monitor activity of chemosensitive RTN neurons in brainstem slices (300 μm thick) isolated from rat pups (postnatal days 7–11) during exposure to low or high concentrations of HCO3−. In a subset of experiments, we also included 2′,7′‐bis(2carboxyethyl)‐5‐(and 6)‐carboxyfluorescein (BCECF) in the internal solution to measure pHi under each experimental condition. We found that HCO3− activates chemosensitive RTN neurons by mechanisms independent of intracellular or extracellular pH, glutamate, GABA, glycine or purinergic signalling, soluble adenylyl cyclase activity, nitric oxide or KCNQ channels. These results establish HCO3− as a novel independent modulator of chemoreceptor activity, and because the levels of HCO3− along with H+ are buffered by independent cellular mechanisms, these results suggest HCO3− chemoreception adds additional information regarding changes in CO2 that are not necessarily reflected by pH.