bluuebunny/crossref_metadata_2025 huggingface dataset:
The development and validation of a multivariable prognostic model to predict foot ulceration in diabetes using a systematic review and individual patient data meta‐analyses
Authors: Crawford F. , Cezard G. , Chappell F. M. ,   the PODUS Group
Published: August 2018

Aims

Diabetes guidelines recommend screening for the risk of foot ulceration but vary substantially in the underlying evidence base. Our purpose was to derive and validate a prognostic model of independent risk factors for foot ulceration in diabetes using all available individual patient data from cohort studies conducted worldwide.

Methods

We conducted a systematic review and meta‐analysis of individual patient data from 10 cohort studies of risk factors in the prediction of foot ulceration in diabetes. Predictors were selected for plausibility, availability and low heterogeneity. Logistic regression produced adjusted odds ratios (ORs) for foot ulceration by ulceration history, monofilament insensitivity, any absent pedal pulse, age, sex and diabetes duration.

Results

The 10 studies contained data from 16 385 participants. A history of foot ulceration produced the largest OR [6.59 (95% CI 2.49 to 17.45)], insensitivity to a 10 g monofilament [3.18 (95% CI 2.65 to 3.82)] and any absent pedal pulse [1.97 (95% CI 1.62 to 2.39)] were consistently, independently predictive. Combining three predictors produced sensitivities between 90.0% (95% CI 69.9% to 97.2%) and 95.3% (95% CI 84.5% to 98.7%); the corresponding specificities were between 12.1% (95% CI 8.2% to 17.3%) and 63.9% (95% CI 61.1% to 66.6%).

Conclusions

This prognostic model of only three risk factors, a history of foot ulceration, an inability to feel a 10 g monofilament and the absence of any pedal pulse, compares favourably with more complex approaches to foot risk assessment recommended in clinical diabetes guidelines.
Reduced vitamin D levels in painful diabetic peripheral neuropathy
Authors: Shillo P. , Selvarajah D. , Greig M. , Gandhi R. , Rao G. , Wilkinson I. D. , Anand P. , Tesfaye S.
Published: August 2018

Aim

Recent studies have reported an association between low vitamin D levels and diabetic peripheral neuropathy. However, many of these did not differentiate between people with painful diabetic peripheral neuropathy and those with painless diabetic peripheral neuropathy, or assess major confounding factors including sunlight exposure and daily activity. Our study addressed these limitations and evaluated vitamin D levels in people with carefully phenotyped diabetic peripheral neuropathy and controls.

Methods

Forty‐five white Europeans with Type 2 diabetes and 14 healthy volunteers underwent clinical and neurophysiological assessments. People with Type 2 diabetes were then divided into three groups (17 with painful diabetic peripheral neuropathy, 14 with painless diabetic peripheral neuropathy and 14 with no diabetic peripheral neuropathy). All had seasonal sunlight exposure and daily activity measured, underwent a lower limb skin biopsy and had 25‐hydroxyvitamin D measured during the summer months, July to September.

Results

After adjusting for age, BMI, activity score and sunlight exposure, 25‐hydroxyvitamin D levels (nmol/l) (se) were significantly lower in people with painful diabetic peripheral neuropathy [painful diabetic peripheral neuropathy 34.9 (5.8), healthy volunteers 62.05 (6.7), no diabetic peripheral neuropathy 49.6 (6.1), painless diabetic peripheral neuropathy 53.1 (6.2); ANCOVAP = 0.03]. Direct logistic regression was used to assess the impact of seven independent variables on painful diabetic peripheral neuropathy. Vitamin D was the only independent variable to make a statistically significant contribution to the model with an inverted odds ratio of 1.11. Lower 25‐hydroxyvitamin D levels also correlated with lower cold detection thresholds (r = 0.39, P = 0.02) and subepidermal nerve fibre densities (r = 0.42, P = 0.01).

Conclusions

We have demonstrated a significant difference in 25‐hydroxyvitamin D levels in well‐characterized people with painful diabetic peripheral neuropathy, while accounting for the main confounding factors. This suggests a possible role for vitamin D in the pathogenesis of painful diabetic peripheral neuropathy. Further prospective and intervention trials are required to prove causality between low vitamin D levels and painful diabetic peripheral neuropathy.
Towards new learning environments—Collective civic actions as learning interventions in post‐Communist Belgrade
Authors: Popović Katarina , Maksimović Maja , Jovanović Aleksa
Published: August 2018

This article focuses on the social dimension of well‐being, based on a critical analysis of the way it is conceptualised in late capitalism: As the dimensions of individual state of mind and body, something that evolves in the individual realm, stressing personal responsibility and achievement of well‐being as a solitary act. Then, the contemporary conceptualisation and approaches to policy making for well‐being are compared with the policy of adult and youth education and learning. The perspective of a strong individual orientation, detachment from the social, community and collective aspects and efforts seem to be a common denominator. Agency is considered not only as a possibility for individuals to create and change the environment, but also as a process of active co‐construction of social reality. This includes (re)connection with a community, very often through new ways of community learning, civic actions and civic activities. An analysis of how these perspectives converge in civic interventions in urban areas of Belgrade places togetherness at the core of the broader approach to well‐being and learning. This article presents several examples of civic activities in urban spaces whose learning character is interpreted within the concept of public pedagogy. The examples presented prevail in the post‐Communist countries because public spaces as zones of civic interventions can oppose the controlling authority and through the fight for human and civil rights represent the bottom line of togetherness and collective agency. Learning through collective civic actions thus provides new ways of understanding well‐being.
The Economics of Fortune in Schiller's “Der Ring des Polykrates”
Authors: Hutchinson Christopher
Published: August 2018

This article discusses the reappearance of fortune as a literary motif at the turn of the nineteenth century in the context of the growing influence of Adam Smith's economic thought in Germany by looking at Schiller's 1797 ballad “Der Ring des Polykrates” as an example. The article's main argument is that fortune, long associated with incalculable fate, could find expression in this work as a herald of the uncontrollable regulatory forces and in‐built crises of economic liberalism. “Der Ring des Polykrates” is a poem – in true ballad tradition – of the border. This border is one between cameralist economic orthodoxy and the new, liberal model of Smith and Malthus. It is this intersection that allows for the centrality of fortune in the poem and also for its reappearance on the literary scene.
Vivisections: Scripting Life in Hölderlin's “Das Belebende”
Authors: Mendicino Kristina
Published: August 2018

In “Das Belebende,” the last of his “Pindar‐Fragmente,” Friedrich Hölderlin retraces a scene of genesis without generation, in an unheard of combination of verse and prose, which may initially appear to be written in German, but which, upon closer examination, shows itself to be composed in multiple languages at once. Throughout his text, the limits of a national language, as well as nature, as they may conventionally be understood, are broken through, revealing instead a force of language that belongs to none, but opens new possibilities for the articulation of life, one of the most prevalent topoi of Romantic poetics and science. Against the sedimentation of sense that one might call “semantics,” drawing upon the etymological derivation of the word from “σῆμα,” or “burial mound,” the course that “Das Belebende” cuts through an originally pathless earth opens insights into the life that may be at stake in writing per se.
Nesting ecology of a naturalized population of MallardsAnas platyrhynchosin New Zealand
Authors: Sheppard Jennifer L. , Amundson Courtney L. , Arnold Todd W. , Klee David
Published: August 2018

Investigating the reproductive ecology of naturalized species provides insights into the role of the source population's characteristics vs. post‐release adaptation that influence the success of introduction programmes. Introduced and naturalized MallardsAnas platyrhynchosare widely established in New Zealand (NZ), but little is known regarding their reproductive ecology. We evaluated the nesting ecology of female Mallards at two study sites inNZ(Southland and Waikato) in 2014–15. We radiotagged 241 pre‐breeding females with abdominal‐implant transmitters and measured breeding incidence, nesting chronology and re‐nesting propensity. We monitored 271 nests to evaluate nest survival, clutch and egg size, egg hatchability and partial clutch depredation. Breeding incidence averaged (mean ± se) 0.91 ± 0.03, clutch size averaged 9.9 ± 0.1 eggs, 94 ± 2% of eggs hatched in successful nests, partial depredation affected 6 ± 1% of eggs in clutches that were not fully destroyed by predators, and re‐nesting propensity following failure of nests or broods was 0.50 ± 0.003. Nesting season (first nest initiated to last nest hatched) lasted 4.5 months and mean initiation date of first detected nest attempts was 28 August ± 3.3 days. Smaller females were less likely to nest, but older, larger or better condition females nested earlier, re‐nested more often and laid larger clutches than did younger, smaller or poorer condition females. Younger females in Southland had higher nest survival; cumulative nest survival ranged from 0.25 ± 0.007 for adult females in Waikato to 0.50 ± 0.007 for yearling females in Southland. Compared with Mallards in their native range, the nesting season inNZwas longer, clutches and eggs were larger, and nest survival was generally greater. Different predators and climate, introgression with native heterospecifics and/or the sedentary nature of Mallards inNZmay have contributed to these differences.
Sensory mechanisms of natal stream imprinting and homing in Oncorhynchus spp.
Authors: Ueda Hiroshi
Published: August 2018

Juvenile Oncorhynchus spp. can memorise their natal stream during downstream migration; juveniles migrate to feed during their growth phase and then they migrate long distances from their feeding habitat to their natal stream to reproduce as adults. Two different sensory mechanisms, olfaction and navigation, are involved in the imprinting and homing processes during short‐distance migration within the natal stream and long‐distance migration in open water, respectively. Here, olfactory functions are reviewed from both neurophysiological studies on the olfactory discrimination ability of natal stream odours and neuroendocrinological studies on the hormonal controlling mechanisms of olfactory memory formation and retrieval in the brain. These studies revealed that the long‐term stability of dissolved free amino‐acid composition in the natal stream is crucial for olfactory imprinting and homing. Additionally, the brain–pituitary–thyroid and brain–pituitary–gonadal hormones play important roles in olfactory memory formation and retrieval, respectively. Navigation functions were reviewed from physiological biotelemetry techniques with sensory interference experiments during the homing migration of anadromous and lacustrine Oncorhynchus spp. The experiments demonstrated that Oncorhynchus spp. used compass navigation mechanisms in the open water. These findings are discussed in relation to the sensory mechanisms involved in natal stream imprinting and homing in Oncorhynchus spp.
Phylogeography of the widespread creek chub Semotilus atromaculatus (Cypriniformes: Leuciscidae)
Authors: Schönhuth Susana , Gagne Roderick B. , Alda Fernando , Neely David A. , Mayden Richard L. , Blum Michael J.
Published: August 2018

The extent and nature of genetic differentiation in Semotilus atromaculatus, one of the most abundant and widespread leuciscids in North America, were evaluated based on mitochondrial (mt) and nuclear DNA sequence variation. Phylogenetic relationships were first inferred based on a fragment of the cytochrome b (cytb) region and the nuclear intron s7 gene for S. atromaculatus and all other congeners as well as representative species from all other genera in the creek chub–plagopterin clade. The phylogeography of major haplogroups of S. atromaculatus was also assessed according to variation in a fragment of the mitochondrial cytb region from 567 individuals across its range. All analyses identified S. thoreauianus, S. lumbee and S. corporalis as reciprocally monophyletic groups. Analyses of nuclear sequence variation resolved S. atromaculatus as a single clade, where S. thoreauianus and S. lumbee were recovered as the sister group to S. atromaculatus, and S. corporalis was resolved as sister to all other species in the genus. Analyses of mtDNA sequence variation recovered S. atromaculatus as three well supported and differentiated monophyletic groups, with a widespread genetically homogeneous lineage extending across most of the current range of the species; a more geographically restricted and geographically structured lineage in the southern Appalachians, sister group to S. lumbee; and a geographically restricted lineage was identified from two Gulf Slope basins. Evidence of complex mito‐nuclear discordance and phylogeographic differentiation within S. atromaculatus illustrates that further analysis of widespread species is warranted to understand North American freshwater fish diversity and distributions.
Orexins increase the firing activity of nigral dopaminergic neurons and participate in motor control in rats
Authors: Liu Cui , Xue Yan , Liu Mei‐Fang , Wang Ying , Liu Zi‐Ran , Diao Hui‐Ling , Chen Lei
Published: August 2018

Orexin is a member of neuropeptides which is involved in the central motor control. The substantia nigra pars compacta (SNc) is an important nucleus participating in motor control under both physiological and pathological conditions. Morphological studies reveal that orexinergic neurons located in lateral hypothalamus innervate the SNc. Both orexin‐1 receptors (OX1R) and orexin‐2 receptors (OX2R) are expressed in the SNc. To investigate the effects of orexins on SNc, single unit in vivo extracellular recordings and behavioral tests were performed in this study. Micro‐pressure administration of orexin A and orexin B significantly increased the spontaneous firing rate of nigral DAergic neurons by 65.87 ± 7.73% and 90.49 ± 17.83%, respectively. The excitatory effects of orexin A on nigral DAergic neurons were mainly mediated by OX1R, while OX2R were involved in the increase in firing rate induced by orexin B. Selectively blocking OX1R and OX2R significantly decreased the firing rate of nigral DAergic neurons by 36.77 ± 6.26% and 32.04 ± 6.12%, respectively, which suggested that endogenous orexins modulated the spontaneous firing activity of nigral DAergic neurons. Finally, both elevated body swing test and haloperidol‐induced postural behavioral test showed that unilateral microinjection of orexin A and orexin B induced significantly contralateral‐biased swing and deflection behavior. Meanwhile, the specific OX1R and OX2R antagonists produced opposite effects. The present electrophysiological and behavioral studies suggested that orexins increased the firing activity of nigral DAergic neurons and participated in central motor control.

Open Practices

Open Science: This manuscript was awarded with the Open Materials Badge.

For more information see: https://cos.io/our-services/open-science-badges/

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Clinical relevance of serum antibodies to GD1b in immune‐mediated neuropathies
Authors: Taams Noor E. , Notermans Nicolette C. , Fokkink Willem‐Jan R. , Tio‐Gillen Anne P. , Huizinga Ruth , Schreurs Marco W. J. , Jacobs Bart C.
Published: August 2018

Antibodies to the ganglioside GD1b have been reported in various forms of immune‐mediated neuropathy, but their clinical relevance for diagnosis and prognosis is unknown. We investigated the prevalence of anti‐GD1b antibodies in acute and chronic immune‐mediated neuropathies, and the clinical presentation and outcome in Guillain‐Barré syndrome (GBS) and Miller Fisher‐GBS overlap syndrome (MF‐GBS). Anti‐GD1b, anti‐GM1 and anti‐GQ1b antibodies were tested in serum of patients with GBS (N = 165), Miller Fisher syndrome (N = 10), MF‐GBS (N = 28), monoclonal gammopathy of unknown significance neuropathy (MGUS; N = 101), chronic inflammatory demyelinating polyneuropathy (N = 29), paraneoplastic syndrome with anti‐Hu‐associated neuropathy (PNS; N = 11), other auto‐immune diseases (AID; N = 60), and healthy controls (HC; N = 60). All samples were tested by enzyme‐linked immunosorbent assay according to the Inflammatory Neuropathy Cause and Treatment protocol. IgM anti‐GD1b antibodies were found in GBS (N = 4; 2.4%), MGUS (N = 3; 3.0%), and PNS patients (N = 1; 9.1%). IgG anti‐GD1b antibodies were found in GBS (N = 20; 12.1%) and MF‐GBS (N = 4; 14.3%) patients, but not in the AID and HC group. In the combined group of MF‐GBS and GBS patients ((MF‐)GBS), 14/36 (38.9%) patients with IgG anti‐GD1b antibodies also had IgG anti‐GM1 antibodies, and IgG anti‐GD1b and IgG anti‐GQ1b antibodies were found in 3/29 (10.3%) patients. Patients with (MF‐)GBS and anti‐GD1b without anti‐GM1 antibodies did not differ regarding sensory disturbances or disease severity but recovered faster regarding the ability to walk independently compared with patients without anti‐GD1b antibodies (P = 0.031) and with patients with both anti‐GD1b and anti‐GM1 antibodies (P = 0.034). In conclusion, testing for anti‐GD1b antibodies may identify a specific group of immune‐mediated neuropathies and (MF‐)GBS patients with only anti‐GD1b antibodies tend to recover faster.
Spinal Cord Atrophy in Multiple Sclerosis: A Systematic Review and Meta‐Analysis
Authors: Casserly Courtney , Seyman Estelle E. , Alcaide‐Leon Paula , Guenette Melanie , Lyons Carrie , Sankar Stephanie , Svendrovski Anton , Baral Stefan , Oh Jiwon
Published: August 2018

BACKGROUND AND PURPOSE

Spinal cord atrophy (SCA) is an important emerging outcome measure in multiple sclerosis (MS); however, there is limited consensus on the magnitude and rate of atrophy. The objective of this study was to synthesize the available data on measures of SCA in MS.

METHODS

Using published guidelines, relevant literature databases were searched between 1977 and 2017 for case‐control or cohort studies reporting a quantitative measure of SCA in MS patients. Random‐effects models pooled cross‐sectional measures and longitudinal rates of SCA in MS and healthy controls (HCs). Student's t‐test assessed differences between pooled measures in patient subgroups. Heterogeneity was assessed using DerSimonian and Laird's Q‐test and the I 2‐index.

RESULTS

A total of 1,465 studies were retrieved including 94 that met inclusion and exclusion criteria. Pooled estimates of mean cervical spinal cord (SC) cross‐sectional area (CSA) in all MS patients, relapsing‐remitting MS (RRMS), all progressive MS, secondary progressive MS (SPMS), primary‐progressive MS (PPMS), and HC were: 73.07 mm2 (95% CI [71.52‐74.62]), 78.88 mm2 (95% CI [76.92‐80.85]), 69.72 mm2 (95% CI [67.96‐71.48]), 68.55 mm2 (95% CI [65.43‐71.66]), 70.98 mm2 (95% CI [68.78‐73.19]), and 80.87 mm2 (95% C I [78.70‐83.04]), respectively. Pooled SC‐CSA was greater in HC versus MS (P < .001) and RRMS versus progressive MS (P < .001). SCA showed moderate correlations with global disability in cross‐sectional studies (r‐value with disability score range [−.75 to −.22]). In longitudinal studies, the pooled annual rate of SCA was 1.78%/year (95%CI [1.28‐2.27]).

CONCLUSIONS

The SC is atrophied in MS. The magnitude of SCA is greater in progressive versus relapsing forms and correlates with clinical disability. The pooled estimate of annual rate of SCA is greater than reported rates of brain atrophy in MS. These results demonstrate that SCA is highly relevant as an imaging outcome in MS clinical trials.
Long‐term effects of nutrient enrichment controlling plant species and functional composition in a boreal rich fen
Authors: Øien Dag‐Inge , Pedersen Bård , Kozub Łukasz , Goldstein Klara , Wilk Mateusz
Published: August 2018

Questions

How does long‐term increase in nutrient availability affect species composition, species diversity and functional composition in boreal rich fens, and how does this differ from short‐term effects? What are the possible mechanisms behind the observed changes, and how does nutrient limitation influence species diversity in these communities?

Location

Sølendet Nature Reserve, central Norway.

Methods

A full‐factorial field experiment. Plots in two localities received one of following treatments (n = 3): no nutrient addition (control), N, P, K, NP, NK, PK and NPK addition. Cover of plant species was recorded before treatment, and after two and 15 years of treatment.

Results

Two years of nutrient addition caused small changes in species composition, but addition of NP led to large increase in abundance of species with high ability to exploit the added nutrients—a direct result of the elimination of nutrient limitation in the communities. After 15 years of nutrient addition there were significant changes following three different pathways, one for each of N, P and NP addition. The addition of NP led to large community shifts, considerable species turnover and reduced species and functional richness, mainly caused by increase in cover of highly competitive and tussock‐forming grasses like Deschampsia cespitosa, Festuca ovina and Molinia caerulea, out‐competing other species, especially bryophytes. Addition of N led to smaller changes in species turnover, and without clear dominant species. Addition of P led to considerable species turnover, but no reduction in species or functional richness, and the bryophyte diversity increased. This is explained by the bryophytes’ association with N‐fixing cyanobacteria, suggesting less N limitation and a greater ability to utilize the added P when vascular plants suffer from N shortage. In addition, bryophytes are more sensitive to low P availability, due to larger P requirements compared to vascular plants. There was no effect of K addition.

Conclusions

Both N and P limitation is essential for the maintenance of high species diversity in boreal rich fens, and P limitation controls bryophyte diversity. From a management perspective, N and P limitation is vital in the conservation of boreal rich fens or when a functional fen system is reestablished through restoration measures.
X‐ray computed tomography of extraterrestrial rocks eradicates their natural radiation record and the information it contains
Authors: Sears Derek W. G. , Sehlke Alexander , Friedrich Jon M. , Rivers Mark L. , Ebel Denton S.
Published: August 2018

The radiation record of extraterrestrial rocks provides important insights into their thermal and radiation history. For meteorites this relates to their orbits, thermal history, terrestrial age, preatmospheric size and shape, and possibly cosmic ray exposure age. For meteorites from the Moon and Mars, the radiation record allows insights into transit times. For Martian surface samples, the radiation record enables estimates of their sedimentary age. Despite this, there is a growing tendency to artificially expose these samples to large radiation doses by the use of X‐ray computed tomography (CT) imaging, often as part of their initial examination. In order to understand the effect of synchrotron microCTon meteorites, we placed samples of the Bruderheim L6 chondrite in theCTimaging port of the Advanced Photon Source at the Argonne National Laboratory, Argonne, Illinois. Monoenergetic X‐ray beams of 25 and 46 keV and a high flux broad spectrum beam were used. The synchrotronCTprocedure exposed the samples to radiation doses significantly higher than the natural doses observed for meteorites (1670 to ~10,000 Gyr, compared to ~1000 Gyr for natural samples). It is clear thatCTimaging, whether using a laboratory system as in our previous report or using the synchrotron source, makes measurement of the natural radiation record of the samples impossible. Samples should not be placed in aCTscanner without due consideration of the loss of unique information for these valuable extraterrestrial samples.
Metabolomic signature of the postprandial experience
Authors: Malagelada Carolina , Pribic Teodora , Ciccantelli Barbara , Cañellas Nicolau , Gomez Josep , Amigo Nuria , Accarino Anna , Correig Xavier , Azpiroz Fernando
Published: August 2018

Background

Ingestion of a meal up to maximal tolerance induces unpleasant fullness sensation and changes in circulating metabolites. Our aim was to evaluate the relation between postprandial sensations and the metabolomic responses to a comfort meal.

Methods

In 32 non‐obese healthy men, homeostatic sensations (hunger/satiety, fullness), hedonic sensations (digestive well‐being, mood), and the metabolomic profile in plasma (low‐molecular weight metabolites and lipoprotein profiles) were measured before and 20 minutes after a comfort meal (warm ham and cheese sandwich and juice; total 300 mL; 425 kcal). Perception was measured on 10 cm scales and the metabolomic response by nuclear magnetic resonance spectroscopy.

Key Results

The comfort meal induced homeostatic sensations (satiety and fullness) associated with a positive hedonic reward (enhanced digestive well‐being and mood) and a clear change in the metabolomic profile with a sharp discrimination between the pre and postprandial state by a non‐supervised principal component analysis. The change in circulating metabolites correlated with the postprandial sensations: the increase in alanine correlated with the increase in fullness (R = 0.50; P = 0.004) and well‐being (R = 0.50; P = 0.004); the increase in glucose correlated with the sensation of fullness (R = 0.40; P = 0.023) and enhanced mood (R = 0.41; P = 0.020).

Conclusion and inferences

Metabolomic changes in the response to a meal may provide an objective index of the postprandial experience, which may have clinical implications in the management of patients with poor meal tolerance or meal‐related symptoms.
Are language features and emotion regulation related to maternal depression in autism and language delay?
Authors: Özyurt Gonca , Dinsever Eliküçük Çağla , Tufan Ali Evren , Baykara Burak
Published: August 2018

Background

Language and communication are very important in child social, emotional and cognitive development. Delay in language is usually the first complaint for children diagnosed with autism spectrum disorder (ASD) or developmental language delay (DLD). This study evaluated language features and emotion regulation skills in children diagnosed withASDandDLDand their association with maternal depression.

Method

The sample consisted of children aged 24–54 months diagnosed withASD(n= 31), or withDLD(n= 45), and 52 healthy controls. The Test of Early Language Development (TELD‐3) was used to evaluate language profiles, and the beck depression inventory (BDI) was used to examine maternal depression. Children's emotion regulation skills were evaluated using the emotion regulation checklist.

Results

Children withDLDhad a significantly higher developmental age, were linguistically more developed and had better emotion regulation than theASDgroup. All domains of language onTELD‐3 except expressive syntax were more developed inDLD. MaternalBDIscore did not differ significantly betweenDLDandASD. Both of these disorders were not associated with maternal depression.

Conclusion

Children withDLDwere less impaired than children withASD, both in terms of language and in emotion regulation.
Steric Demand and Rate‐determining Step for Photoenolization of Di‐ortho‐substituted Acetophenone Derivatives
Authors: Das Anushree , Thomas Suma S. , Garofoli August A. , Chavez Kevin A. , Krause Jeanette A. , Bohne Cornelia , Gudmundsdottir Anna D.
Published: August 2018

Laser flash photolysis of ketone 1 in argon‐saturated methanol yields triplet biradical 1BR (τ = 63 ns) that intersystem crosses to form photoenols Z‐1P (λmax = 350 nm, τ ~ 10 μs) and E‐1P (λmax = 350 nm, τ > 6 ms). The activation barrier for Z‐1P re‐forming ketone 1 through a 1,5‐H shift was determined as 7.7 ± 0.3 kcal mol−1. In contrast, for ketone 2, which has a less sterically hindered carbonyl moiety, laser flash photolysis in argon‐saturated methanol revealed the formation of biradical 2BR (λmax = 330 nm, τ ~ 303 ns) that intersystem crosses to form photoenol E‐2P (λmax = 350 nm, τ > 42 μs), but photoenol Z‐2P was not detected. However, in more viscous basic H‐bond acceptor (BHA) solvent, such as hexamethylphosphoramide, triplet 2BR intersystem crosses to form both Z‐2P (λmax = 370 nm, τ ~ 1.5 μs) and E‐2P. Thus, laser flash photolysis of ketone 2 in methanol reveals that intersystem crossing from 2BR to form Z‐2P is slower than the 1,5‐H shift of Z‐2P, whereas in viscous BHA solvents, the 1,5‐H shift becomes slower than the intersystem crossing from 2BR to Z‐2P. Density functional theory and coupled cluster calculations were performed to support the reaction mechanisms for photoenolization of ketones 1 and 2.
Temperature‐sensitive wheat stem rust resistance gene Sr15 is effective against Puccinia graminis f. sp. tritici race TTKSK
Authors: Gao L. , Babiker E. M. , Nava I. C. , Nirmala J. , Bedo Z. , Lang L. , Chao S. , Gale S. , Jin Y. , Anderson J. A. , Bansal U. , Park R. F. , Rouse M. N. , Bonman J. M. , Bariana H.
Published: August 2018

The wheat stem rust fungus, Puccinia graminis f. sp. tritici (Pgt), race TTKSK and related races pose a serious threat to world wheat production. Knowing the effectiveness of wheat stem rust resistance (Sr) genes against Pgt race TTKSK is fundamental in mitigating this threat through resistance breeding. Sr15 was previously identified as being ineffective against Pgt race TTKSK. Here, multirace disease phenotyping data, linkage analyses, allelism testing and haplotype analyses are presented to support the conclusion that Sr15 is effective against Pgt race TTKSK. Resistance to race TTKSK was mapped to Sr15 in a biparental population. Thirty‐two accessions with Sr15 displayed seedling resistance phenotypes against race TTKSK. However, these accessions were susceptible as seedlings at high temperatures (22–25 °C), consistent with previous reports that the interaction between avirulent Pgt isolates and Sr15 is temperature‐sensitive. Markers STS638, wri4 and KASP_IWB30995 were found to predict the presence of Sr15, suggesting the utility of these assays for marker‐assisted selection in breeding programmes. The effectiveness of Sr15 to specific Pgt races and temperatures makes it a less‐desirable TTKSK‐effective gene. Wheat lines assayed as resistant to race TTKSK at the seedling stage may possess Sr15 and breeders should be aware of the limitations of Sr15 for conferring stem rust resistance.
Physical abuse of the elderly: a 4‐year retrospective evaluation in the emergency department
Authors: Altintop Ismail , Tatli Mehmet
Published: August 2018

Aim

Elderly physical abuse (EPA) is defined as injury or assault to or the restriction of an elderly person. Although EPA is an important social problem, its diagnosis is difficult because of tendency to cover up the event. In this study, patients aged 65 years and over who presented at the emergency department (ED) for forensic reasons and in whom physical abuse was suspected were examined. The aim of this study was to raise ED awareness of EPA and thereby to contribute to treatment plans for these patients in the ED.

Methods

The study was conducted over a 4‐year period between January 2013 and January 2017. Patients were selected retrospectively from the hospital information system according to the following criteria: (i) admission to ED with trauma; (ii) aged 65 and older; and (iii) evaluated as having forensic trauma by an ED specialist based on either the patient's history or the specialist's observations and suspicions.

Results

The patients included 80 men (69%) and 36 women (31%), with a mean age of 73.92 ± 7.08 years. The length of ED stay was 0–1 h in 27.6% of patients and 1–6 h in 46.6%. When the causes of physical trauma were examined, general assault was seen as the most prevalent, occurring in nearly 63% of the patients.

Conclusions

There may be three conclusions for the current study: First, although EPA is a rare problem for patients referred to emergency services, health professionals should be suspicious when examining patients 65 years or older because of the difficulties of diagnosing EPA. Second, in patients with no history of suspicious trauma or suspicious radiological imaging results, EPA is also common. Third, because of the undetected EPA mechanism, patients should be examined forensically in suspicious cases and deaths.
Cortisol response to awakening in prepubertal children and adults: Magnitude and variability
Authors: Bernsdorf Manja , Schwabe Lars
Published: August 2018

Within the first 30–45 min after awakening, there is a characteristic rise in cortisol that is referred to as cortisol awakening response (CAR). Over the past decades, the CAR has become an important biomarker, mainly because of its reported association with health and disease. Previous research showed that the CAR can already be reliably assessed in infants and children. Yet, earlier findings on the influence of age have been inconsistent, and limited attention has been devoted to prepubertal children. Here, we aimed to contrast the magnitude and stability of the CAR in prepubertal children and adults. To this end, 24 healthy adults between 35 and 50 years of age and 24 healthy children between 6 and 9 years of age collected four salivary cortisol samples within 45 min after awakening on 4 separate days, 2 weekdays, and 2 weekend days. Our results showed that there was a marked CAR on weekdays and weekend days in both adults and children. In children, however, the CAR was overall significantly attenuated relative to adults. Moreover, while the cortisol increases after awakening were, both on weekdays and weekend days, highly correlated in adults, there were no such associations in children. Together, these data suggest that the CAR is less pronounced and less stable in prepubertal children compared to adults. Such age differences need to be taken into account when using the CAR as a biomarker in clinical settings.
The RAF‐like mitogen‐activated protein kinase kinase kinases RAF22 and RAF28 are required for the regulation of embryogenesis in Arabidopsis
Authors: Wang Bo , Liu Guting , Zhang Jing , Li Yuan , Yang Hailian , Ren Dongtao
Published: August 2018

In Arabidopsis, embryonic development follows a stereotypical pattern of cell division. Although many factors have been reported to participate in establishment of the proper embryonic pattern, the molecular mechanisms underlying pattern formation are unclear. In this study we showed that RAF22 and RAF28, two RAF‐like mitogen‐activated protein kinase kinase kinases (MAPKKKs) in Arabidopsis, are involved in the regulation of embryogenesis. The double knockout mutant of RAF22 and RAF28 was embryo lethal. A large proportion of the raf22−/−raf28+/− mutant embryos exhibited various defects, including disordered proembryo cell divisions, disruption of the bilaterally symmetrical structure, abnormally formative divisions of hypophysis and exaggerated suspensor growth. Whereas the kinase active form of RAF22 could complement these embryonic aberrant phenotypes, the kinase inactive form could not. The restrictive expression of the basal cell fate marker WOX8 in the abnormally dividing suspensor cells and the apical cell linage marker WOX2 in the abnormal proembryos indicated that apical and basal cell fates were unchanged in the abnormal embryos. The polar distribution of the auxin maxima and the PIN1 and PIN7 auxin transporters was markedly altered in the abnormal embryos. Our results suggest that RAF22 and RAF28 are important components of embryogenesis and that auxin polar transport may be involved in this regulation.
Hybridization‐facilitated genome merger and repeated chromosome fusion after 8 million years
Authors: Mandáková Terezie , Guo Xinyi , Özüdoğru Barış , Mummenhoff Klaus , Lysak Martin A.
Published: August 2018

The small genus Ricotia (nine species, Brassicaceae) is confined to the eastern Mediterranean. By comparative chromosome painting and a dated multi‐gene chloroplast phylogeny, we reconstructed the origin and subsequent evolution of Ricotia. The ancestral Ricotia genome originated through hybridization between two older genomes with n = 7 and n = 8 chromosomes, respectively, on the Turkish mainland during the Early Miocene (c. 17.8 million years ago, Ma). Since then, the allotetraploid (n = 15) genome has been altered by two independent descending dysploidies (DD) to n = 14 in Ricotia aucheri and the Tenuifolia clade (2 spp.). By the Late Miocene (c. 10 Ma), the latter clade started to evolve in the most diverse Ricotia core clade (6 spp.), the process preceded by a DD event to n = 13. It is noteworthy that this dysploidy was mediated by a unique chromosomal rearrangement, merging together the same two chromosomes as were merged during the origin of a fusion chromosome within the paternal n = 7 genome c. 20 Ma. This shows that within a time period of c. 8 Myr genome evolution can repeat itself and that structurally very similar chromosomes may originate repeatedly from the same ancestral chromosomes by different pathways (end‐to‐end translocation versus nested chromosome insertion).
Citizen science, public policy
Authors: Guerrini Christi J. , Majumder Mary A. , Lewellyn Meaganne J. , McGuire Amy L.
Published: August 2018

New research models may benefit from policy modifications
Evolutionary history and adaptation of a human pygmy population of Flores Island, Indonesia
Authors: Tucci Serena , Vohr Samuel H. , McCoy Rajiv C. , Vernot Benjamin , Robinson Matthew R. , Barbieri Chiara , Nelson Brad J. , Fu Wenqing , Purnomo Gludhug A. , Sudoyo Herawati , Eichler Evan E. , Barbujani Guido , Visscher Peter M. , Akey Joshua M. , Green Richard E.
Published: August 2018

The genetics of human short stature

Flores Island in Indonesia has a long history of hominin occupation, including by the extinct
Homo floresiensis
and a more recent settlement by modern humans. Furthermore, Flores has an extant population of pygmy humans, and
H. floresiensis
exhibited a diminutive adult size relative to other hominins. Tucci
et al.
examined genetic variation among 32 individuals, including 10 sequenced genomes, from a population of pygmies living close to the cave where
H. floresiensis
remains were discovered. These individuals exhibit signatures of polygenic selection explaining the short stature and have genomic content from both Neanderthals and Denisovans, but no additional archaic lineages. Thus, restricted height is under selection at this location and has evolved independently at least twice in hominins.

Science
, this issue p.
511
Emergent simplicity in microbial community assembly
Authors: Goldford Joshua E. , Lu Nanxi , Bajić Djordje , Estrela Sylvie , Tikhonov Mikhail , Sanchez-Gorostiaga Alicia , Segrè Daniel , Mehta Pankaj , Sanchez Alvaro
Published: August 2018

Interchanging species of similar function

Under natural conditions, bacteria form mixed, interacting communities. Understanding how such communities assemble and stabilize is important in a range of contexts, from biotechnological applications to what happens in our guts. Goldford
et al.
sampled the microbial communities from soil and plants containing hundreds to thousands of sequence variants. The organisms were passaged after culture in low concentrations of single carbon sources and were cross-fed with each other's metabolites; then, the resulting communities were sequenced using 16S ribosomal RNA, and the outcomes were modeled mathematically. The mix of species that survived under steady conditions converged reproducibly to reflect the experimentally imposed conditions rather than the mix of species initially inoculated—although at coarse phylogenetic levels, taxonomic patterns persisted.

Science
, this issue p.
469
Single-cell transcriptomes from human kidneys reveal the cellular identity of renal tumors
Authors: Young Matthew D. , Mitchell Thomas J. , Vieira Braga Felipe A. , Tran Maxine G. B. , Stewart Benjamin J. , Ferdinand John R. , Collord Grace , Botting Rachel A. , Popescu Dorin-Mirel , Loudon Kevin W. , Vento-Tormo Roser , Stephenson Emily , Cagan Alex , Farndon Sarah J. , Del Castillo Velasco-Herrera Martin , Guzzo Charlotte , Richoz Nathan , Mamanova Lira , Aho Tevita , Armitage James N. , Riddick Antony C. P. , Mushtaq Imran , Farrell Stephen , Rampling Dyanne , Nicholson James , Filby Andrew , Burge Johanna , Lisgo Steven , Maxwell Patrick H. , Lindsay Susan , Warren Anne Y. , Stewart Grant D. , Sebire Neil , Coleman Nicholas , Haniffa Muzlifah , Teichmann Sarah A. , Clatworthy Menna , Behjati Sam
Published: August 2018

Pediatric and adult kidney tumors differ

Understanding tumor origins and the similarities and differences between organ-specific cancers is important for determining treatment options. Young
et al.
generated more than 72,000 single-cell transcriptomes from healthy and cancerous human kidneys. From these data, they determined that Wilms tumor, a pediatric kidney cancer, originates from aberrant fetal cells, whereas adult kidney cancers are likely derived from a specific subtype of proximal convoluted tubular cell.

Science
, this issue p.
594
Nitazoxanide Inhibits Human Norovirus Replication and Synergizes with Ribavirin by Activation of Cellular Antiviral Response
Authors: Dang Wen , Xu Lei , Ma Buyun , Chen Sunrui , Yin Yuebang , Chang Kyeong-Ok , Peppelenbosch Maikel P. , Pan Qiuwei
Published: August 2018

Norovirus is the main cause of viral gastroenteritis worldwide. Although norovirus gastroenteritis is self-limiting in immunocompetent individuals, chronic infections with debilitating and life-threatening complications occur in immunocompromised patients.
The Vibrio H-Ring Facilitates the Outer Membrane Penetration of the Polar Sheathed Flagellum
Authors: Zhu Shiwei , Nishikino Tatsuro , Kojima Seiji , Homma Michio , Liu Jun
Published: August 2018

Flagellum is the major organelle for motility in many bacterial species. While most bacteria possess external flagella, such as the multiple peritrichous flagella found in
Escherichia coli
and
Salmonella enterica
or the single polar sheathed flagellum in
Vibrio
spp., spirochetes uniquely assemble periplasmic flagella, which are embedded between their inner and outer membranes. Here, we show for the first time that the external flagella in
Vibrio alginolyticus
can be changed as periplasmic flagella by deleting two flagellar genes. The discovery here may provide new insights into the molecular basis underlying assembly, diversity, and evolution of flagella.
The Human Cytomegalovirus Trimer and Pentamer Promote Sequential Steps in Entry into Epithelial and Endothelial Cells at Cell Surfaces and Endosomes
Authors: Liu Jing , Jardetzky Ted S. , Chin Andrea L. , Johnson David C. , Vanarsdall Adam L.
Published: August 2018

HCMV infects nearly 80% of the world's population and causes significant morbidity and mortality. The current antiviral agents used to treat HCMV infections are prone to resistance and can be toxic to patients, and there is no current vaccine against HCMV available. The data in this report will lead to a better understanding of how essential HCMV envelope glycoproteins function during infection of biologically important cell types and will have significant implications for understanding HCMV pathogenesis for developing new therapeutics.
Nitric Oxide Disrupts Zinc Homeostasis in Salmonella enterica Serovar Typhimurium
Authors: Frawley Elaine R. , Karlinsey Joyce E. , Singhal Anshika , Libby Stephen J. , Doulias Paschalis-Thomas , Ischiropoulos Harry , Fang Ferric C.
Published: August 2018

Nitric oxide (NO·) produced by mammalian cells exerts antimicrobial actions that result primarily from the modification of protein thiols (
S
-nitrosylation) and metal centers. A comprehensive approach was used to identify novel targets of NO· in
Salmonella enterica
serovar Typhimurium (
S.
 Typhimurium). Newly identified targets include zinc metalloproteins required for DNA replication and repair (DnaG, PriA, and TopA), protein synthesis (AlaS and RpmE), and various metabolic activities (ClpX, GloB, MetE, PepA, and QueC). The cytotoxic actions of free zinc are mitigated by the ZntA and ZitB zinc efflux transporters, which are required for
S.
 Typhimurium resistance to zinc overload and nitrosative stress
in vitro
. Zinc efflux also ameliorates NO·-dependent zinc mobilization following internalization by activated macrophages and is required for virulence in NO·-producing mice, demonstrating that host-derived NO· causes zinc stress in intracellular bacteria.

IMPORTANCE
Nitric oxide (NO·) is produced by macrophages in response to inflammatory stimuli and restricts the growth of intracellular bacteria. Mechanisms of NO·-dependent antimicrobial actions are incompletely understood. Here, we show that zinc metalloproteins are important targets of NO· in
Salmonella
, including the DNA replication proteins DnaG and PriA, which were hypothesized to be NO· targets in earlier studies. Like iron, zinc is a cofactor for several essential proteins but is toxic at elevated concentrations. This study demonstrates that NO· mobilizes free zinc in
Salmonella
and that specific efflux transporters ameliorate the cytotoxic effects of free zinc during infection.
Adhesion of Staphylococcus aureus to Corneocytes from Atopic Dermatitis Patients Is Controlled by Natural Moisturizing Factor Levels
Authors: Feuillie Cécile , Vitry Pauline , McAleer Maeve A. , Kezic Sanja , Irvine Alan D. , Geoghegan Joan A. , Dufrêne Yves F.
Published: August 2018

The bacterial pathogen
Staphylococcus aureus
plays an important role in atopic dermatitis (AD), a chronic disorder that mostly affects children. Colonization of the skin of AD patients by
S. aureus
exacerbates the disease, but the molecular determinants of the bacterium-skin adhesive interactions are poorly understood. Specifically, reduced levels of natural moisturizing factor (NMF) in the stratum corneum have been shown to be associated with more severe AD symptoms, but whether this is directly related to
S. aureus
adhesion is still an open question. Here, we demonstrate a novel relationship between NMF expression in AD skin and strength of bacterial adhesion. Low-NMF corneocytes, unlike high-NMF ones, are covered by a dense layer of nanoscale villus protrusions.
S. aureus
bacteria isolated from AD skin bind much more strongly to corneocytes when the NMF level is reduced. Strong binding forces originate from a specific interaction between the bacterial adhesion clumping factor B (ClfB) and skin ligands. Remarkably, mechanical tension dramatically strengthens ClfB-mediated adhesion, as observed with catch bonds, demonstrating that physical stress plays a role in promoting colonization of AD skin by
S. aureus
. Collectively, our findings demonstrate that patient NMF levels regulate the strength of
S. aureus
-corneocyte adhesion, the first step in skin colonization, and suggest that the ClfB binding mechanism could represent a potential target for new therapeutic treatments.

IMPORTANCE
Bacterium-skin interactions play important roles in skin disorders, yet their molecular details are poorly understood. In this study, we decipher the molecular forces at play during adhesion of
Staphylococcus aureus
to skin corneocytes in the clinically important context of atopic dermatitis (AD), also known as eczema. We identify a unique relationship between the level of natural moisturizing factor (NMF) in the skin and the strength of bacterium-corneocyte adhesion. Bacterial adhesion is primarily mediated by the surface protein clumping factor B (ClfB) and is enhanced by physical stress, highlighting the role of protein mechanobiology in skin colonization. Similar to a catch bond behavior, this mechanism represents a promising target for the development of novel antistaphylococcal agents.