bluuebunny/crossref_metadata_2025 huggingface dataset:
C. elegansgenetic background modifies the core transcriptional response in an α-synuclein model of Parkinson’s disease
Authors: Wang Yiru A. , Snoek Basten L. , Sterken Mark G. , Riksen Joost A.G. , Stastna Jana J. , Kammenga Jan E. , Harvey Simon C.
Published: June 2018

Accumulation of protein aggregates is a major cause of Parkinson’s disease (PD), a progressive neurodegenerative condition that is one of the most common causes of dementia. TransgenicCaenorhabditis elegansworms expressing the human synaptic protein α-synuclein show inclusions of aggregated protein and replicate the defining pathological hallmarks of PD. It is however not known how PD progression and pathology differs among individual genetic backgrounds. Here, we compared gene expression patterns, and investigated the phenotypic consequences of transgenic α-synuclein expression in five differentC. elegansgenetic backgrounds. Transcriptome analysis indicates that the effects of -synuclein expression on pathways associated with nutrient storage, lipid transportation and ion exchange depend on the genetic background. The gene expression changes we observe suggest that a range of phenotypes will be affected by α-synuclein expression. We experimentally confirm this, showing that the transgenic lines generally show delayed development, reduced lifespan, and an increased rate of matricidal hatching. These phenotypic effects coincide with the core changes in gene expression, linking developmental arrest, mobility, metabolic and cellular repair mechanisms to α-synuclein expression. Together, our results show both genotype-specific effects and core alterations in global gene expression and in phenotype in response to -synuclein. We conclude that the PD effects are substantially modified by the genetic background, illustrating that genetic background mechanisms should be elucidated to understand individual variation in PD.
Neural gain control measured through cortical gamma oscillations is associated with individual variations in sensory sensitivity
Authors: Orekhova EV , Stroganova TA , Schneiderman JF , Lundström S , Riaz B , Sarovic D , Sysoeva OV , Gillberg C , Hadjikhani N
Published: June 2018

Gamma oscillations facilitate information processing by shaping the excitatory input/output of neuronal populations, and their suppression by strong excitatory drive may stem from inhibitory-based gain control of network excitation. Individual variations in the gamma suppression may therefore reflect efficiency of gain control and subjective sensitivity to everyday sensory events. To test this prediction, we assessed the link between self-reported sensory sensitivity and changes in magneto-encephalographic gamma oscillations as a function of motion velocity of high-contrast visual gratings. The induced gamma oscillations increased in frequency and decreased in power with increasing stimulation intensity. As expected, weaker suppression of the gamma response correlated with sensory hypersensitivity. Robustness of this result was confirmed by its replication in the two samples: neurotypical subjects and people with autism, who had generally higher sensory sensitivity. We conclude that intensity-related suppression of gamma response is a promising biomarker of homeostatic control of the excitation-inhibition balance in the visual cortex.
Palbociclib and fulvestrant act in synergy to modulate central carbon metabolism in breast cancer cells
Authors: Warth Benedikt , Palermo Amelia , Rattray Nicholas J.W. , Lee Nathan V , Zhu Zhou , Hoang Linh T. , Mazurek Anthony , Dann Stephen , VanArsdale Todd , Fantin Valeria , Shields David , Siuzdak Gary , Johnson Caroline H.
Published: June 2018

Palbociclib, is a selective inhibitor of cyclin-dependent kinases 4 and 6 and used as a first-line treatment for patients with estrogen receptor positive breast cancer. It has been shown that patients have improved progression-free survival when treated in combination with fulvestrant, an estrogen receptor antagonist. However, the mechanisms for this survival advantage are not known. We sought to analyze metabolic and transcriptomic changes in MCF-7 adenocarcinoma breast cancer cells following single and combined treatments to determine if selective metabolic pathways are targeted during combination therapy. Our results showed that individually, the drugs caused metabolic disruption to the same metabolic pathways, however fulvestrant additionally attenuated the pentose phosphate pathway and the production of important coenzymes. A comprehensive effect was observed when the drugs were applied together, confirming the combinatory therapy′s synergism in the cell model. This study highlights the power of merging high-dimensional datasets to unravel mechanisms involved in cancer metabolism and therapy.

Highlights

○

First study employing multi-omics to investigate combined therapy on breast cancer cells

○

Fulvestrant attenuates the pentose phosphate pathway and coenzyme production

○

Synergism of palbociclib and fulvestrant was confirmed in vitro

○

Altered key pathways have been identified

eTOC Blurb

Johnson et al. applied an innovative multi-omics approach to decipher metabolic pathways affected by single versus combination dosing of palbociclib and fulvestrant in estrogen receptor positive breast cancer. Key metabolites and genes were correlated within metabolic pathways and shown to be involved in the drugs′ synergism.
Nitrative signaling into cardiac lactate dehydrogenase Trp324 modulates active site loop mobility and activity under metabolic stress
Authors: Nogales Cristian , Frijhoff Jeroen , Thoenges Detlef , Sessions Richard B. , Sickmann Albert , Nedvetskaya Tatiana , Ibarra-Alvarado Cesar , Schmitz Vera , Rösen Peter , Goedecke Axel , Jovanović Aleksandar , Perlman David H. , Klinke Anna , Baldus Stephan , Casas Ana I. , Bai Péter , Szabo Csaba , Feelisch Martin , Schmidt Harald H.H.W.
Published: June 2018

Protein tyrosine nitration is a hallmark of oxidative stress related disease states, commonly detected as anti-nitrotyrosine immunoreactivity. The precise reactive oxygen sources, mechanisms of nitration as well as the modified target proteins and functional consequences, however, remain often unclear. Here we explore protein tyrosine nitration under basal conditions and find surprisingly physiologically nitrated proteins. Upon purifying a prominent physiologically nitrotyrosine immunopositive in hearts from mouse, rat and pig, we identify it as lactate dehydrogenase (LDH). Mechanistically, LDH’s degree of basal nitration depended on two canonical sources, NO synthase (NOS) and myeloperoxidase (MPO), respectively. When validating the nitrated amino acid by MALDI-TOF mass spectrometry, we, surprisingly, located LDH nitration not to a tyrosine but the C-terminal tryptophan, Trp324. Molecular dynamics simulations suggested that Trp324 nitration restricts the interaction of the active site loop with the C-terminal α-helix essential for activity. This prediction was confirmed by enzyme kinetics revealing an apparent lower Vmax of nitrated LDH, although yet unidentified concurrent oxidative modifications may contribute. Protein nitration is, thus, not a by definition disease marker but reflects also physiological signaling by eNOS/NO, MPO/nitrite and possibly other pathways. The commonly used assay of anti-nitrotyrosine immunoreactivity is apparently cross-reactive to nitrotryptophan requiring a reevaluation of the protein nitration literature. In the case of LDH, nitration of Trp324 is aggravated under cardiac metabolic stress conditions and functionally limits maximal enzyme activity. Trp324-nitrated LDH may serve both as a previously not recognized disease biomarker and possibly mechanistic lead to understand the metabolic changes under these conditions.
Notch3 Promotes Prostate Cancer-Induced Bone Lesion Development via MMP-3
Authors: Ganguly Sourik S. , Hostetter Galen , Tang Lin , Frank Sander B. , Saboda Kathylynn , Mehra Rohit , Wang Lisha , Li Xiaohong , Keller Evan T. , Miranti Cindy K.
Published: June 2018

Prostate cancer metastases primarily localize in the bone where they induce a unique osteoblastic response. Elevated Notch activity is associated with high-grade disease and metastasis. To address how Notch affects prostate cancer bone lesions, we manipulated Notch expression in mouse tibia xenografts and monitored tumor growth, lesion phenotype, and the bone microenvironment. Prostate cancer cell lines that induce mixed osteoblastic lesions in bone expressed 5-6 times more Notch3, than tumor cells that produce osteolytic lesions. Expression of active Notch3 (NICD3) in osteolytic tumors reduced osteolytic lesion area and enhanced osteoblastogenesis, while loss of Notch3 in osteoblastic tumors enhanced osteolytic lesion area and decreased osteoblastogensis. This was accompanied by a respective decrease and increase in the number of active osteoclasts and osteoblasts at the tumor-bone interface, without any effect on tumor proliferation. Conditioned medium from NICD3-expressing cells enhanced osteoblast differentiation and proliferation in vitro, while simultaneously inhibiting osteoclastogenesis. MMP-3 was specifically elevated and secreted by NICD3-expressing tumors, and inhibition of MMP-3 rescued the NICD3-induced osteoblastic phenotypes. Clinical osteoblastic bone metastasis samples had higher levels of Notch3 and MMP-3 compared to patient matched visceral metastases or osteolytic metastasis samples. We identified a Notch3-MMP-3 axis in human prostate cancer bone metastases that contributes to osteoblastic lesion formation by blocking osteoclast differentiation, while also contributing to osteoblastogenesis. These studies define a new role for Notch3 in manipulating the tumor microenvironment in bone metastases.
Losing maternal care: Neotenic gene expression in the preoptic area of avian brood parasites
Authors: Lynch Kathleen S. , O’Connell Lauren A. , Louder Matthew I. M. , Pellicano Anthony , Gaglio Annmarie , Xiang Angell , Balakrishnan Christopher N. , Fischer Eva K.
Published: June 2018

Parental care for is critical for offspring survival in many species. However, parental behaviors have been lost in roughly 1% of avian species known as the obligate brood parasites. To shed light on molecular and neurobiological mechanisms mediating brood parasitic behavior, brain gene expression patterns between two brood parasitic species and one closely related non-parasitic Icterid (blackbird) species were compared. Our analyses focused on gene expression changes specifically in the preoptic area (POA), a brain region known to play a critical role in maternal behavior across vertebrates. Using comparative transcriptomic approaches, we identified gene expression patterns associated with brood parasitism and evaluated two alternative explanations for the evolution of brood parasitism: reduced expression of parental-related genes in the POA versus retention of juvenile (neotenic) gene expression. While we did not find evidence for large scale gene downregulation, expression patterns did reflect substantial evidence for neotenic POA gene expression in parasitic birds. Differentially expressed genes with previously established roles in parental care were identified. Targeted examination of these selected candidate genes in additional hypothalamic regions revealed species differences in gene expression patterns is not POA-specific. Together, these results provide new insights into neurogenomics underlying maternal behavior loss in avian brood parasites.
Relationships between meconium concentrations of acute phase proteins
Authors: Lisowska‐Myjak Barbara , Skarżyńska Ewa , Płazińska Maria , Jakimiuk Artur
Published: June 2018

Meconium concentrations of naturally accumulated ceruloplasmin (CER), lactoferrin (LF), and neutrophil gelatinase‐associated lipocalin (NGAL) and their relationships considered as a panel of acute phase proteins could be used for the assessment of fetal homeostasis. CER, LF and NGAL concentrations were measured using enzyme‐linked immunosorbent assay kits in meconium portions (n = 80) collected from 19 healthy neonates. The coefficients of variation (CV) of the meconium LF (1.77) and NGAL (1.26) were about two‐fold higher than that of CER (0.73) with significant (P < 0.05) correlations between all three parameters. The LF to NGAL ratio (CV = 0.67) correlated strongly with the CER concentrations (r = 0.39, P < 0.01). These correlations between CER, LF and NGAL concentrations suggest their combined involvement in the metabolic processes in the developing fetus.
Total flucloxacillin plasma concentrations poorly reflect unbound concentrations in hospitalized patients with Staphylococcus aureus bacteraemia
Authors: Chin Paul Ken Leong , Drennan Philip George , Gardiner Sharon Jane , Zhang Mei , Dalton Simon Charles , Chambers Stephen Thomas , Begg Evan James
Published: June 2018

Aims

Flucloxacillin dosing may be guided by measurement of its total plasma concentrations. Flucloxacillin is highly protein bound with fraction unbound in plasma (fu) of around 0.04 in healthy individuals. The utility of measuring unbound flucloxacillin concentrations for patients outside the intensive care unit (ICU) is not established. We aimed to compare flucloxacillin fu in non‐ICU hospitalised patients against healthy volunteers, and to examine the performance of a published model for predicting unbound concentrations, using total flucloxacillin and plasma albumin concentrations.

Methods

Data from 12 healthy volunteers (248 samples) and 47 hospitalized patients (61 samples) were examined. Plasma flucloxacillin concentrations were measured using a validated liquid chromatography–tandem mass spectrometry method. Flucloxacillin fu for the two groups was compared using a generalized estimating equation model to account for clustered observations. The performance of the single protein binding site prediction model in hospitalized patients was compared with measured unbound concentrations using Bland–Altman plots.

Results

The median (range) flucloxacillin fu for healthy (median albumin 45 g l–1) and hospitalized individuals (median albumin 30 g l–1) were 0.04 (0.02–0.07) and 0.10 (0.05–0.37), respectively (P < 0.0001). The prediction model underpredicted unbound flucloxacillin concentrations with a mean bias (95% limits of agreement) of –54% (–137%, +30%).

Conclusions

The flucloxacillin fu values observed in our cohort of hospitalized patients had a wide range and were greater than those of healthy individuals. Unbound flucloxacillin plasma concentrations were predicted poorly by the model. Instead, unbound concentrations should be measured to guide dosing.
α‐blockers as medical expulsive therapy for ureteric stones: a Cochrane systematic review
Authors: Campschroer Thijs , Zhu Xiaoye , Vernooij Robin W.M. , Lock Tycho M.T.W.
Published: June 2018

Objective

To assess the effects of α‐blockers compared to standard therapy or placebo for ureteric stones of ≤10 mm confirmed by imaging in adult patients presenting with symptoms of ureteric stone disease.

Patients and Methods

We performed a systematic search in multiple databases and grey literature with no restrictions on the language of publication or publication status, up until November 2017. We included randomised controlled trials evaluating ureteric stone passage in adult patients that compared α‐blockers with standard therapy or placebo. Two review authors were independently responsible for study selection, data extraction, and risk‐of‐bias assessment. We performed a meta‐analysis using a random‐effect model. The quality of evidence was assessed on outcome basis according to Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach.

Results

We included 67 studies, with 10 509 participants overall. Of these, 15 studies with 5 787 participants used a placebo. Stone clearance: treatment with an α‐blocker may result in a large increase in stone clearance (risk ratio [RR] 1.45, 95% confidence interval [CI] 1.36–1.55; low‐quality evidence), corresponding to 278 more (95% CI: 223–340 more) stone clearances per 1 000 participants. For major adverse events, treatment with an α‐blocker may have little effect (RR 1.25, 95% CI: 0.80–1.96; low‐quality evidence), which corresponds to five more (95% CI four fewer to 19 more) major adverse events per 1 000 participants. Patients treated with α‐blockers may also experience shorter stone expulsion times (mean difference [MD] −3.40 days, 95% CI: −4.17 to −2.63; low‐quality evidence), use less diclofenac (MD −82.41 mg, 95% CI: −122.51 to −42.31; low‐quality evidence) and likely require fewer hospitalisations (RR 0.51, 95% CI: 0.34–0.77; moderate‐quality evidence). Meanwhile, the need for surgical intervention appears similar (RR 0.74, 95% CI: 0.53–1.02; low‐quality evidence). Based on a pre‐defined subgroup analysis (test for subgroup difference, P = 0.002), there may be a different effect of α‐blockers based on stone size with RRs of 1.06 (95% CI: 0.98–1.15; P = 0.16; I² = 62%) for stones of ≤5 mm vs 1.45 (95% CI: 1.22–1.72; P < 0.0001; I² = 59%) for stones of >5 mm. We did not find evidence for possible subgroup effects based on stone location or α‐blocker type.

Conclusions

In patients with ureteric stones, α‐blockers likely increase stone clearance but probably also slightly increase the risk of major adverse events. Subgroup analyses suggest that α‐blockers may be less effective in smaller (≤5 mm) than larger stones (>5 mm).
Late‐season snowfall is associated with decreased offspring survival in two migratory arctic‐breeding songbird species
Authors: Chmura H. E. , Krause J. S. , Pérez J. H. , Asmus A. , Sweet S. K. , Hunt K. E. , Meddle S. L. , McElreath R. , Boelman N. T. , Gough L. , Wingfield J. C.
Published: June 2018

While the effect of weather on reproduction has been studied for many years in avian taxa, the rapid pace of climate change in arctic regions has added urgency to this question by changing the weather conditions species experience during breeding. Given this, it is important to understand how factors such as temperature, rain, snowfall, and wind affect reproduction both directly and indirectly (e.g. through their effects on food availability). In this study, we ask how weather factors and food availability influence daily survival rates of clutches in two arctic‐breeding migratory songbirds: the Lapland longspur Calcarius lapponicus, a circumpolar breeder, and Gambel's white‐crowned sparrow Zonotrichia leucophrys gambelii, which breeds in shrubby habitats across tundra, boreal and continental climates. To do this, we monitored clutch survival in these two species from egg‐lay through fledge at field sites located near Toolik Field Station (North Slope, Alaska) across 5 yr (2012–2016). Our results indicate that snowfall and cold temperatures decreased offspring survival rates in both species; although Lapland longspurs were more susceptible to snowfall. Food availability, quantified by pitfall sampling and sweep‐net sampling methods, had minimal effects on offspring survival. Some climate models predict increased precipitation for the Arctic with global warming, and in the Toolik region, total snow accumulation may be increasing. Placed in this context, our results suggest that changes in snow storms with climate change could have substantial consequences for reproduction in migratory songbirds breeding in the North American Arctic.
Disruptive Innovation: An Intellectual History and Directions for Future Research
Authors: Christensen Clayton M. , McDonald Rory , Altman Elizabeth J. , Palmer Jonathan E.
Published: June 2018

The concept of disruptive innovation has gained considerable currency among practitioners despite widespread misunderstanding of its core principles. Similarly, foundational research on disruption has elicited frequent citation and vibrant debate in academic circles, but subsequent empirical research has rarely engaged with its key theoretical arguments. This inconsistent reception warrants a thoughtful evaluation of research on disruptive innovation within management and strategy. We trace the theory’s intellectual history, noting how its core principles have been clarified by anomaly‐seeking research. We also trace the theory’s evolution from a technology‐change framework—essentially descriptive and relatively limited in scope—to a more broadly explanatory causal theory of innovation and competitive response. This assessment reveals that our understanding of the phenomenon of disruption has changed as the theory has developed. To reinvigorate academic interest in disruptive innovation, we propose several underexplored topics—response strategies, performance trajectories, and innovation metrics—to guide future research.
Morphology and molecular phylogeny of epizoic araphid diatoms on marine zooplankton, including Pseudofalcula hyalina gen. & comb. nov. (Fragilariophyceae, Bacillariophyta)
Authors: Gómez Fernando , Wang Lu , Lin Senjie
Published: June 2018

Some diatoms are able to colonize as epibionts on their potential zooplankton predators. Here, we report Pseudohimantidium pacificum living on the copepod Corycaeus giesbrechti and as a new finding on Oithona nana, Protoraphis atlantica living on the copepod Pontellopsis brevis, Protoraphis hustedtiana on the cypris larvae of barnacles, and Falcula hyalina on the copepod Acartia lilljeborgii. The epizoic diatoms were able to grow as free‐living forms under culture conditions. Pseudohimantidium pacificum and P. atlantica appeared as the most derived species from their benthic diatom ancestors. The mucilage pad or stalk of the strains of these species showed important morphological distinction when compared with their epizoic forms. Barnacle larvae explore benthic habitats before settlement, and epibiosis on them is an example where P. hustedtiana profits from the host behavior for dispersal of its benthic populations. Molecular phylogenies based on the SSU rRNA and RuBisCO large subunit (rbcL) gene sequences revealed F. hyalina as an independent lineage within the Fragilariales (Tabularia, Catacombas, and others), consistent with its morphological distinction in the low number of rows (≤6) in the ocellulimbus, among other features. We propose the transfer of F. hyalina to the genus Pseudofalcula gen. nov. Molecular phylogeny suggests a single order for the members of the Cyclophorales and the Protoraphidales, and that the epibioses of araphid diatoms on marine zooplankton have been independently acquired several times. These clades are constituted of both epizoic and epiphytic/epilithic forms that evidence a recent acquisition of the epizoic modus vivendi.
Status and future of disease protection and grape berry quality alteration by micro-organisms in viticulture
Authors: Otoguro M. , Suzuki S.
Published: June 2018

Grapevine is one of the most widely grown fruit crops in the world. At present, however, there is much concern regarding chemical pollution in viticulture due to the application of chemical fungicides and fertilizers. One viticultural practice to resolve this issue is the application of micro-organisms to grapevine as a substitute for chemicals. Some micro-organisms act as an enhancer of grape berry quality as well as a suppresser of disease in grapevine through their antagonistic ability and/or systemic resistance inducing ability. Herein, we review current and prospective applications of micro-organisms in viticulture.

Significance and Impact of the Study

In this review, we evaluate the applicability of micro-organisms in viticulture. Micro-organisms can improve grape berry quality through grapevine disease protection and grape berry quality alteration. Because the use of micro-organisms to protect grapevine from plant diseases is safer than the use of chemical fungicides, the use of biofungicides in viticulture is expected to be enhanced by the increasing consumer concern towards chemical fungicides. Micro-organisms also modify plant secondary metabolites for use as flavours, pharmaceuticals and food additives. Studies of micro-organisms that promote polyphenol, anthocyanin and aroma compound biosynthesis are in progress with an eye to improving grape berry quality.
Sepsis‐induced acute kidney injury: A disease of the microcirculation
Authors: Ma Shuai , Evans Roger G. , Iguchi Naoya , Tare Marianne , Parkington Helena C. , Bellomo Rinaldo , May Clive N. , Lankadeva Yugeesh R.
Published: June 2018

AKI is a common complication of sepsis and is significantly associated with mortality. Sepsis accounts for more than 50% of the cases of AKI, with a mortality rate of up to 40%. The pathogenesis of septic AKI is complex, but there is emerging evidence that, at least in the first 48 hours, the defects may be functional rather than structural in nature. For example, septic AKI is associated with an absence of histopathological changes, but with microvascular abnormalities and tubular stress. In this context, renal medullary hypoxia due to redistribution of intra‐renal perfusion is emerging as a critical mediator of septic AKI. Clinically, vasopressor drugs remain the cornerstone of therapy for maintenance of blood pressure and organ perfusion. However, in septic AKI, there is insensitivity to vasopressors such as norepinephrine, leading to persistent hypotension and organ failure. Vasopressin, angiotensin II, and, paradoxically, α2‐adrenergic receptor agonists (clonidine and dexmedetomidine) may be feasible adjunct therapies for catecholamine‐resistant vasodilatory shock. In this review, we outline the recent progress made in understanding how these drugs may influence the renal microcirculation, which represents a crucial step toward developing better approaches for the circulatory management of patients with septic AKI.
Complementarity of gymnosperms and angiosperms along an altitudinal temperature gradient
Authors: Caspersen John P. , Thürig Esther , Rigling Andreas , Zimmermann Niklaus E.
Published: June 2018

In seasonal tropical forests, evergreen–deciduous mixtures are more productive than monocultures because they intercept more light throughout the year, reflecting complementary resource use by functional groups possessing different traits. This suggests that temperate and boreal forests may also exhibit overyielding, due to the difference in phenology between gymnosperms and angiosperms. However, complementarity could also arise from differences in morphology between needle leaves and broad leaves, or facilitation by N‐fixing species. Alternatively, mixtures may be more productive simply because interspecific competition is less intense than intraspecific competition. We used forest inventory data to assess the complementarity of the main functional groups in Switzerland. We employed a trait‐based analysis of competition to determine whether: 1) trait differences reduce the intensity of competition between complementary functional groups, 2) complementarity is observed along a broad altitudinal temperature gradient. N‐fixing species facilitated the growth of non‐fixing species, such that 50/50 mixtures were 50% more productive than monocultures, though half the overyielding was due to the alleviation of intraspecific competition. In contrast, we found no evidence of complementarity between evergreen and deciduous species. For example, in stands where larch was mixed with other gymnosperms, there was no reduction in heterospecific competition among evergreen species, even though evergreens cast shade on one another throughout the year. In cold montane forests, broadleaf species reduced the suppression of needleleaf species, and vice versa. Thus, 50/50 mixtures of needleleaf and broadleaf species were 15% more productive than needleleaf monocultures. However, in warm lowland forests, broadleaf species exacerbated the suppression of needleleaf species, completely offsetting the positive effect that needleleaf species had on broadleaf species. In summary, we found no evidence of complementarity between evergreen and deciduous species, but needleleaf–broadleaf mixtures exhibited overyielding in cold montane forests, which is consistent with the stress gradient hypothesis, though the underlying mechanisms remain uncertain.
Comparison of Histidine‐Tryptophan‐Ketoglutarate and University of Wisconsin preservation solutions in pediatric liver transplantation
Authors: Mangus Richard S. , Schroering Joel R. , Hathaway Taylor J. , Kubal Chandrashekhar A. , Fridell Jonathan A.
Published: June 2018

UW and HTK solutions are the two primary organ preservation solutions most used in the United States. This study analyzes use of the two solutions in all pediatric liver transplants performed at a single center between 2001and 2017. Outcome measures included early graft function, as well as graft and patient survival. Bile duct complications were reviewed. Operative technique, immunosuppressive protocols, and donor acceptance criteria remained uniform among participating surgeons throughout the study period. There were 104 pediatric liver transplants with complete data during the study period, 75 preserved with HTK (68%) and 29 with UW (26%). Demographics were similar. Cold and warm ischemia times were similar. Peak ALT post‐transplant was higher in the UW group at both peak and post‐transplant day 3. The peak TB levels were similar. Bile duct strictures were more common in the UW group (44% vs 16%, P < .01). Early graft survival was statistically similar at 7‐, 90‐ and 365‐days post‐transplant. Cox regression graft survival was similar at 10‐years. This study suggests that use of HTK in pediatric liver transplantation is safe with outcomes similar to UW, though bile duct stricture rates may be lower with HTK.
On Partial Agreement and Oblique Case
Authors: Atlamaz Ümit , Baker Mark
Published: June 2018

In many languages, overt case marking hidesϕ‐features from agreement probes. In some languages, such as Hindi, this effect is absolute. But in Adıyaman Kurmanji, our focus here, the effect is partial: the number feature of third‐person oblique subjects can be registered on the verb. We account for the difference by saying that overtly case‐marked nominals are in fact agreed with in the syntax, but the actual transfer ofϕ‐feature values happens at PF, where it is sensitive to postsyntactic operations like Fusion. All and only heads that fuse with case (a K head) can feed valuation and thus be realized on the agreement probe. Adıyaman Kurmanji is a language where number fuses with K and this feeds agreement, resulting in partial agreement with overtly case‐marked nominals (in number but not person), whereas Hindi is not. The possibility of object agreement in these languages is, we claim, the result of Multiple Agree, which creates complex feature bundles on agreement probes that are only partially realized morphologically at PF. We further support our theory by applying it to Icelandic and Faroese, languages that are often thought not to have agreement with oblique subjects but that may allow agreement in very specific situations, which our theory elucidates.
Long weekly working hours and ischaemic heart disease: a follow-up study among 145 861 randomly selected workers in Denmark
Authors: Hannerz Harald , Larsen Ann Dyreborg , Garde Anne Helene
Published: June 2018

Objectives

The aim of the present study was to test if incidences of ischaemic heart disease (IHD) and usage of antihypertensive drugs are independent of weekly working hours (WWH) among full-time employees in Denmark.

Design and participants

Data on WWH from participants of the Danish labour force surveys, 1999–2013, were linked on an individual level to national registers with data on socioeconomic status (SES), industry, emigrations, redeemed prescriptions, hospital contacts and deaths. Participants were followed until the end of 2014 (on average 7.7 years). Poisson regression was used to model incidence rates as a function of WWH. The analyses were controlled for calendar time, time passed since start of follow-up, employment in the healthcare industry, age, sex, SES and night work.

Results

In total, we found 3635 cases of IHD and 20 648 cases of antihypertensive drug usage. The rate ratio of IHD was 0.95 (95% CI 0.85 to 1.06) for 41–48 compared with 32–40 WWH and 1.07 (0.94 to 1.21) for >48 compared with 32–40 WWH. The corresponding rate ratios for antihypertensive drug usage were 0.99 (0.95 to 1.04) and 1.02 (0.97 to 1.08). No statistically significant interactions between WWH and sex, SES and night work, respectively, were found.

Conclusion

In this Danish sample, we did not find any statistically significant association between WWH and IHD or antihypertensive drug usage.
Changes in the rate of publicly financed knee arthroscopies: an analysis of data from the Norwegian patient registry from 2012 to 2016
Authors: Holtedahl Robin , Brox Jens Ivar , Aune Arne Kristian , Nguyen Daniel , Risberg May Arna , Tjomsland Ole
Published: June 2018

Objective

To examine rates of publicly financed knee arthroscopic surgery in Norway between 2012 and 2016.

Design

Analysis of anonymised data from the National Patient Registry.

Interventions

Beginning in 2012, South-Eastern Norway Regional Health Authority implemented administrative measures to bring down rates of knee arthroscopy. Similar measures were not introduced in the other three Regional Health Authorities.

Main outcome measures

We analysed annual national rates of publicly financed knee arthroscopies in 2012 and 2016. We compared the rates in South-Eastern Norway Regional Health Authority with corresponding rates in the rest of the country. Variations by county, public hospital versus publicly reimbursed private hospital, gender and age were also assessed.

Results

The overall annual rate of arthroscopic procedures declined by 33% from 2012 to 2016, from 310 to 207 per 100 000 inhabitants, respectively. Hospitals in South-Eastern Norway Regional Health Authority reported a 48% reduction, compared with mean 13% in the other three Regional Health Authorities. In public hospitals, rates decreased nationally by 42%, while rates in publicly reimbursed private hospitals increased by 12%. Rates in publicly reimbursed private hospitals decreased by 30% in South-Eastern Norway Regional Health Authority but increased by 63% in the other Regional Health Authorities. The proportion of patients ≥50 years (excluding meniscal repairs) in Norway was 54% in 2012 and fell to 46% in 2016. Average rates per county varied by a factor of 3:1.

Conclusion

We report a marked overall reduction of knee arthroscopic procedures from 2012 to 2016 in publicly funded hospitals. The largest decrease was reported in South-Eastern Norway Regional Health Authority, and this coincides in time with implemented administrative measures. The results suggest that the trend of increasing rates of knee arthroscopies can be reversed through purposeful professional and administrative interventions.
Impact of Exercise Restriction on Arrhythmic Risk Among Patients With Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Wang Weijia , Orgeron Gabriela , Tichnell Crystal , Murray Brittney , Crosson Jane , Monfredi Oliver , Cadrin‐Tourigny Julia , Tandri Harikrishna , Calkins Hugh , James Cynthia A.
Published: June 2018

Background

Prior studies have shown a close link between exercise and development of arrhythmogenic right ventricular cardiomyopathy. How much exercise restriction reduces ventricular arrhythmia (VA), how genotype modifies its benefit, and whether it reduces risk sufficiently to defer implantable cardioverter‐defibrillator (
ICD
) placement in arrhythmogenic right ventricular cardiomyopathy are unknown.

Methods and Results

We interviewed 129 arrhythmogenic right ventricular cardiomyopathy patients (age: 34.0±14.8 years; male: 60%) with
ICD
s (36% primary prevention) about exercise participation. Exercise change was defined as annual exercise duration and dose in the 3 years before clinical presentation minus that after presentation. The primary outcome was appropriate
ICD
therapy for VA. During the 5.1 years (interquartile range: 2.7–10.8 years) after presentation, 74% (95/129) patients reduced exercise dose and 85 (66%) patients experienced the primary outcome. In multivariate analyses, top tertile reduction in exercise duration and dose were both associated with less
VA
(duration: hazard ratio: 0.23 [95% confidence interval, 0.07–0.81]; dose: hazard ratio: 0.14 [95% confidence interval, 0.04–0.44]). Greater reduction in exercise dose conferred greater reduction in
VA
(
P
=0.01 for trend). Patients without desmosomal mutations and those with primary‐prevention
ICD
s benefited more from exercise reduction (
P
=0.16 and
P
=0.06 for interaction); however, 58% (18/31) of athletes who reduced exercise dose by >80% still experienced
VA
.

Conclusions

Exercise restriction should be recommended to all arrhythmogenic right ventricular cardiomyopathy patients with
ICD
s. Patients who are “gene‐elusive” and those with primary‐prevention devices may particularly benefit. Exercise reduction is unlikely to reduce arrhythmia sufficiently in high‐risk patients to alter decision‐making regarding
ICD
implantation.
The Good, the Bad, and the Indifferent: Physical Disability, Social Role Configurations, and Changes in Loneliness Among Married and Unmarried Older Adults
Authors: Warner David F. , Adams Scott A. , Anderson Raeda K.
Published: June 2018

Objectives: To examine how social role configurations (SRCs)—combinations of the quality of spousal, family, and friend relationships—moderate the association between functional limitations (FLs) and loneliness among married and unmarried older adults and whether this differs by gender. Method: Longitudinal data from the National Social Life, Health, and Aging Project on married ( n = 945) and unmarried ( n = 443) older adults (aged 57-85 years). Latent class analysis was used to identify SRCs. Tobit regression models examined the associations between FLs, SRCs, and loneliness. Results: Nine SRCs were identified. The effectiveness of SRCs for coping with FLs did not differ by marital status despite higher loneliness among the unmarried. Only for women with FLs did SRCs characterized by negativity/strain exacerbate loneliness. For men with FLs, SRCs characterized by excess positivity/support were problematic. Discussion: These findings underscore the importance of considering how SRCs provide resources for coping with FLs that have gendered implications.
How Voters Punish and Donors Protect Legislators Embroiled in Scandal
Authors: Hamel Brian T. , Miller Michael G.
Published: June 2018

Previous studies have largely overlooked three key components of a scandal that could determine how it shapes election outcomes: the extent to which it is covered in the media, the potential that donors respond differently than voters, and the likelihood that the impact of scandals have changed over time. Examining U.S. House scandals between 1980 and 2010, we find that while scandal-tainted politicians receive fewer votes and are less likely to win than otherwise similar legislators not embroiled in scandal, donors actually contribute more money to their campaigns after the scandal’s revelation. Both of these effects, however, are limited to financial and sex scandals that garnered national media attention. Moreover, we find that voters are less punitive and donors are even more supportive in the post-1994 period of nationalized electoral politics.
Leitbilder einer Verkehrswende
Authors: Uhle Christian
Published: June 2018

Eine Verkehrswende weg vom Automobil wäre ein zutiefst visionärer und politischer Akt.Dafür sind Zukunftsvisionen und Leitbilder notwendig. Nur so kann eine Mobilitätsrevolutionauch Treiber für eine umfassende Transformation werden.
The effects of parent-involved science activities on basic science process skills of the children in the age group of 5-6
Authors: Yılmaz Gül , İlkörücü Şirin , Çepni Salih
Published: June 2018

This study aims to examine the effects in science activities including parent involvement activities, concerning the science process skills of children aged 5-6, attending pre-school, and analyses the obtained information regarding the views of the parents involved in the program. The study group consisted of 30 children in the 5-6 age group, and 15 parents who were attending lessons. The embedded mixed method design was used in the study. Quantitative data was collected by a pre-school science process skills scale for children aged 60-72 months, and the qualitative data was collected through a semi-structured interview form with the parents. At the end of the study, the quantitative data showed that the experimental groups' children’s' science process skills, especially predicting-inferring-communicating sub-scale skills, were found to be more developed than what the control group's children. The qualitative data leads us to an understanding that the parents had a positive view of parent involvement activities and that communication with their children increased, was derived from the qualitative data, as well. It was noted that the parents raised their children's motivation towards science and tended to support them more in terms of science. It is suggested that pre-school education programs ought to include more science process-based activities with parent involvement.
Double Bubbles on the Real Line with Log-Convex Density
Authors: Bongiovanni Eliot , Di Giosia Leonardo , Diaz Alejandro , Habib Jahangir , Kakkar Arjun , Kenigsberg Lea , Pittman Dylanger , Sothanaphan Nat , Zhu Weitao
Published: June 2018

The classic double bubble theorem says that the least-perimeter way to enclose and separate two prescribed volumes in ℝN is the standard double bubble. We seek the optimal double bubble in ℝN with density, which we assume to be strictly log-convex. For N = 1 we show that the solution is sometimes two contiguous intervals and sometimes three contiguous intervals. In higher dimensions we think that the solution is sometimes a standard double bubble and sometimes concentric spheres (e.g. for one volume small and the other large).
Cultural Intolerance and Aversion to Foreign Judgments in the American States
Authors: Efrat Asif , Newman Abraham L.
Published: June 2018

Is there hostility toward things foreign in the US legal system? Existing work examines the success of foreign litigants in American courts and fails to find clear evidence for the existence of xenophobia. We propose to shift the debate toward the legislative framework underlying transnational litigation. Specifically, this study examines the willingness to facilitate the enforcement of foreign judgments through state legislation. Our statistical analysis finds that cultural attitudes do matter: where society exhibits intolerance and xenophobia, foreign judgments are less welcome. By demonstrating how cultural attitudes shape the law, this study contributes to the debate on the social origins of legal norms, and also advances the analysis of legal-system interaction in the age of globalization.
On the constancy of signs and order of magnitude of Fourier–Haar coefficients
Authors: Gogoladze Larry , Tsagareishvili Vakhtang
Published: June 2018

In the paper, we investigate the relation between the properties of functions and their Fourier–Haar coefficients. We show that for some classes of functions Fourier–Haar coefficients have constant signs and order of magnitude.
In 1964, Golubov proved in [B. I. Golubov,
On Fourier series of continuous functions with respect to a Haar system (in Russian),
Izv. Akad. Nauk SSSR Ser. Mat. 28 1964, 1271–1296] that if

f
⁢

(
x
)

∈

C
⁢

(
0
,
1
)

{f(x)\in C(0,1)}

, then its Fourier–Haar coefficients have constant signs when

f
⁢

(
x
)

{f(x)}

is a nonincreasing function on

[
0
,
1
]

{[0,1]}

, and in some cases those coefficients have a certain order of magnitude.
In the present paper, we continue to investigate the properties of functions which follow from the behavior of their Fourier–Haar coefficients.
Upregulation of Twist is involved in Gli1 induced migration and invasion of hepatocarcinoma cells
Authors: Li Juan , He Yuting , Cao Yuan , Yu Yan , Chen Xiaolong , Gao Xiaojuan , Hu Qiuyue
Published: June 2018

Hedgehog (Hh) signaling is involved in the progression of hepatocellular carcinoma (HCC), while its detailed mechanisms are not well illustrated. Our present study revealed that the expression of Gli1, while not Gli2 or Gli3, is significantly increased in HCC cell lines and 20/28 (71.4%) HCC tissues as compared with their corresponding controls. Over expression of Gli1 can promote the migration, invasion and epithelial-mesenchymal transition (EMT) of HCC cells. Gli1 can increase the expression of Twist, while not other EMT transcription factors such as Snail, ZEB1 or Slug. Gli1 increases the transcription of Twist while it has no significant effect on the protein or mRNA stability. Chromatin immunoprecipitation-polymerase chain reaction confirms that Gli1 can directly bind to the promoter of Twist, in which the third binding site is essential for Gli1 induced transcription. Collectively, our data suggest that upregulation of Twist is involved in Gli1 induced migration and invasion of HCC cells.
Cold atmospheric plasma treatment inhibits growth in colorectal cancer cells
Authors: Schneider Christin , Arndt Stephanie , Zimmermann Julia L. , Li Yangfang , Karrer Sigrid , Bosserhoff Anja K.
Published: June 2018

Plasma oncology is a relatively new field of research. Recent developments have indicated that cold atmospheric plasma (CAP) technology is an interesting new therapeutic approach to cancer treatment. In this study, p53 wildtype (LoVo) and human p53 mutated (HT29 and SW480) colorectal cancer cells were treated with the miniFlatPlaSter – a device particularly developed for the treatment of tumor cells – that uses the Surface Micro Discharge (SMD) technology for plasma production in air. The present study analyzed the effects of plasma on colorectal cancer cells in vitro and on normal colon tissue ex vivo. Plasma treatment had strong effects on colon cancer cells, such as inhibition of cell proliferation, induction of cell death and modulation of p21 expression. In contrast, CAP treatment of murine colon tissue ex vivo for up to 2 min did not show any toxic effect on normal colon cells compared to H2O2 positive control. In summary, these results suggest that the miniFlatPlaSter plasma device is able to kill colorectal cancer cells independent of their p53 mutation status. Thus, this device presents a promising new approach in colon cancer therapy.
Modifications in small nuclear RNAs and their roles in spliceosome assembly and function
Authors: Bohnsack Markus T. , Sloan Katherine E.
Published: June 2018

Modifications in cellular RNAs have emerged as key regulators of all aspects of gene expression, including pre-mRNA splicing. During spliceosome assembly and function, the small nuclear RNAs (snRNAs) form numerous dynamic RNA-RNA and RNA-protein interactions, which are required for spliceosome assembly, correct positioning of the spliceosome on substrate pre-mRNAs and catalysis. The human snRNAs contain several base methylations as well as a myriad of pseudouridines and 2′-O-methylated nucleotides, which are largely introduced by small Cajal body-specific ribonucleoproteins (scaRNPs). Modified nucleotides typically cluster in functionally important regions of the snRNAs, suggesting that their presence could optimise the interactions of snRNAs with each other or with pre-mRNAs, or may affect the binding of spliceosomal proteins. snRNA modifications appear to play important roles in snRNP biogenesis and spliceosome assembly, and have also been proposed to influence the efficiency and fidelity of pre-mRNA splicing. Interestingly, alterations in the modification status of snRNAs have recently been observed in different cellular conditions, implying that some snRNA modifications are dynamic and raising the possibility that these modifications may fine-tune the spliceosome for particular functions. Here, we review the current knowledge on the snRNA modification machinery and discuss the timing, functions and dynamics of modifications in snRNAs.