bluuebunny/crossref_metadata_2025 huggingface dataset:
Veterans’ Reliance on VA Care by Type of Service and Distance to VA for Nonelderly VA-Medicaid Dual Enrollees
Authors: Yoon Jean , Vanneman Megan E. , Dally Sharon K. , Trivedi Amal N. , Phibbs Ciaran S.
Published: February 2019

Background:

Not much is known about nonelderly veterans and their reliance on care from the Veterans Affairs (VA) health care system when they have access to non-VA care.

Objectives:

To estimate VA reliance for nonelderly veterans enrolled in VA and Medicaid.

Research Design:

Retrospective, longitudinal analysis of Medicaid claims data and VA administrative data to compare patients’ utilization of VA and Medicaid services 12 months before and for up to 12 months after Medicaid enrollment began.

Subjects:

Nonelderly veterans (below 65 y) receiving VA care and newly enrolled in Medicaid, calendar years 2006–2010 (N=19,890).

Measures:

VA reliance (proportion of care received in VA) for major categories of outpatient and inpatient care.

Results:

Patients used VA outpatient care at similar levels after enrolling in Medicaid with the exceptions of emergency department (ED) and obstetrics/gynecology care, which decreased. VA inpatient utilization was similar after Medicaid enrollment for most types of care. VA-adjusted outpatient reliance was highest for mental health care (0.99) and lowest for ED care (0.02). VA-adjusted inpatient reliance was highest for respiratory (0.80) and cancer stays (0.80) and lowest for musculoskeletal stays (0.20). Associations between VA reliance and distance to VA providers varied by type of care.

Conclusions:

Veterans dually enrolled in Medicaid received most of their outpatient care from the VA except ED, obstetrics/gynecology, and dental care. Patients received most of their inpatient care from Medicaid except mental health, respiratory, and cancer care. Sensitivity to travel distance to VA providers explained some of these differences.
Physiologic diagnosis of congenital heart disease in cyanotic neonates
Authors: Desai Kinjal , Rabinowitz Edon J. , Epstein Shilpi
Published: February 2019

Purpose of review

We aim to improve diagnosis of congenital heart disease (CHD) with cyanosis by physiology for general practitioners to reduce time to appropriate treatment.

Recent findings

New implementation of the critical congenital heart disease (CCHD) pulse oximetry screen has improved rate of diagnosis of CHD in recent years. However, many infants with cyanotic heart lesions often decompensate before screening in the newborn nursery, or have lesions that are not amenable to pulse oximetry screening and that present later in the emergency room. Recent literature has shown preoperative acidosis because of delayed diagnosis of cyanotic CHD worsens outcomes postoperatively. Wide availability of prostaglandin therapy and catheter procedures help to preoperatively stabilize critical cardiac patients. With a firm grasp of the underlying physiology of neonatal cyanotic CHD, practitioners can appropriately implement these therapies more judiciously. This early recognition will subsequently improve overall outcomes.

Physiologic diagnosis of CHD with cyanosis by general practitioners will allow initiation of appropriate management more quickly and effectively. This may avoid progressive clinical decompensation and acidosis until cardiology consultation and potential intervention are available.
Hepatosplenic Fungal Infections in Children With Leukemia—Risk Factors and Outcome: A Multicentric Study
Authors: Celkan Tiraje , Kizilocak Hande , Evim Melike , Meral Güneş Adalet , Özbek Namik Y. , Yarali Neşe , Ünal Ekrem , Patiroğlu Türkan , Yilmaz Karapinar Deniz , Sarper Nazan , Zengin Emine , Karaman Serap , Koçak Ülker , Kürekçi Emin , Özdemir Canan , Tuğcu Deniz , Uysalol Ezgi , Dikme Gürcan , Adaletli İbrahim , Kuruoğlu Sebuh , Kebudi Rejin
Published: February 2019

Background:

Invasive fungal infections, including hepatosplenic fungal infections (HSFI), cause significant morbidity and mortality in children with leukemia. There are not enough data to support for the best approach to diagnosis of HSFI in children, nor for the best treatment.

Procedure:

In this multicentric study, we assessed the demographic data, clinical and radiologic features, treatment, and outcome of 40 children with leukemia and HSFI from 12 centers.

Results:

All cases were radiologically diagnosed with abdominal ultrasound, which was performed at a median of 7 days, of the febrile neutropenic episode. Mucor was identified by histopathology in 1, and Candida was identified in blood cultures in 8 patients. Twenty-two had fungal infection in additional sites, mostly lungs. Nine patients died. Four received a single agent, and 36 a combination of antifungals.

Conclusions:

Early diagnosis of HSFI is challenging because signs and symptoms are usually nonspecific. In neutropenic children, persistent fever, back pain extending to the shoulder, widespread muscle pain, and increased serum galactomannan levels should alert clinicians. Abdominal imaging, particularly an abdominal ultrasound, which is easy to perform and available even in most resource-limited countries, should be recommended in children with prolonged neutropenic fever, even in the absence of localizing signs and symptoms.
Cognitive rehabilitation is advantageous in terms of fatigue and independence in pediatric cancer treatment: a randomized-controlled study
Authors: Akel Burcu S. , Şahin Sedef , Huri Meral , Akyüz Canan
Published: February 2019

This study aimed to investigate the effect of task-oriented inpatient cognitive rehabilitation on fatigue perception and independence in daily activities. Forty (22 males, 18 females) children with pediatric cancer were randomized to either study [n = 22; 10.81 (1.33) years] or control [n = 18; 10.16 (1.24) years] groups. The study group received a cognitive rehabilitation intervention in addition to a routine therapy program, and the control group received a routine therapy program for 15 sessions. Cognitive status, fatigue, and daily life activity outcomes were assessed by blinded assessors in before and after interventions in the hospital setting. The study group showed a significant decrease in fatigue (P values for fatigue before, during, and after activity: P < 0.001) and in the control group (P values for fatigue only in during and post activity: P < 0.05). A statistically significant improvement was found in functional independence for the study group in all activities of daily living areas areas (P < 0.001), whereas no differences were found in the control group. Cognitive rehabilitation appears to provide beneficial effects in decreasing fatigue, improving functional status in activities of daily living, and increasing cognitive skills at the early stages in inpatient rehabilitation of pediatric cancer.
Targeted Education and Trends in Pediatric Nurses Perceptions of Barriers, Facilitators, Confidence, and Attitudes Toward Research and Evidence-Based Practice Over Time
Authors: Cline Genieveve J. , Burger Kristina J. , Amankwah Ernest K. , Goldenberg Neil A. , Ghazarian Sharon R.
Published: February 2019

The purpose of this repeated cross-sectional study was to periodically assess perceptions of pediatric nurses’ confidence, attitudes, barriers, and facilitators to research utilization and evidence-based practice as changes to the nursing research environment and a targeted curriculum were implemented. The study results were used by the nursing professional development specialist to further customize the nursing research curriculum to better meet the self-reported education and mentorship needs of the nurses.
Headaches in Idiopathic Intracranial Hypertension
Authors: Friedman Deborah I.
Published: February 2019

Background:

Headache is the most common symptom of idiopathic intracranial hypertension (IIH) and may not resolve with intracranial pressure–lowering treatments. Many patients with IIH have a pre-existing history of migraine. Approximately two-thirds of patients with IIH continue to experience headaches after the other manifestations of the disorder resolve. There are no evidence-based guidelines for treating IIH-related headaches.

Evidence Acquisition:

This review proposes mechanisms by which IIH produces both acute and ongoing headache. The article analyzes the literature regarding medical and procedural therapies for IIH, apropos to their effectiveness for treating headaches. It then proposes strategies to use in clinical practice, incorporating treatments used for the primary headache disorders of migraine and tension-type headache, the most common phenotypes of IIH-associated headache.

Conclusions:

Treatments used to manage primary headache disorders may be effective in the management of IIH-associated headache, although none have been specifically studied in this condition.

Results:

Recommendations provided consider a holistic approach to the problem based on existing guidelines and clinical experience.
Tuning turbine rotor design for very large wind farms
Authors: Nishino Takafumi , Hunter William
Published: February 2019

A new theoretical method is presented for future multi-scale aerodynamic optimization of very large wind farms. The new method combines a recent two-scale coupled momentum analysis of ideal wind turbine arrays with the classical blade-element-momentum (BEM) theory for turbine rotor design, making it possible to explore some potentially important relationships between the design of rotors and their performance in a very large wind farm. The details of the original two-scale momentum model are described first, followed by the new coupling procedure with the classical BEM theory and some example solutions. The example solutions, obtained using a simplified but still realistic NREL S809 aerofoil performance curve, illustrate how the aerodynamically optimal rotor design may change depending on the farm density. It is also shown that the peak power of the rotors designed optimally for a given farm (i.e. ‘tuned' rotors) could be noticeably higher than that of the rotors designed for a different farm (i.e. ‘untuned' rotors) even if the blade pitch angle is allowed to be adjusted optimally during the operation. The results presented are for ideal very large wind farms and a possible future extension of the present work for real large wind farms is also discussed briefly.
Nonlinear rotating viscoelastic jets during forcespinning process
Authors: Riahi Daniel N.
Published: February 2019

In the usual forcespinning (FS) process, a fluid jet is forced through an orifice of a rotating spinneret leading to the formation of a jet with curved centreline. In this paper, we investigate the properties of nonlinear viscoelastic jets during the FS process. We apply scaling and perturbation techniques to determine the modelling system for the viscoelastic jets, subjected to the Giesekus constitutive equations for the stress tensor. We calculate numerically the expressions for the nonlinear steady solutions for the jet quantities such as radius, speed, stretching rate, strain rate, tensile force and trajectory. We determine these quantities for different values of the parameters such as those representing the effects due to rotation, surface tension, viscosity, jet drag and viscoelasticity. We find, in particular, that the fibre jet radius decreases and the tensile force increases with the jet arc length as well as with increasing the effects of rotation and viscoelasticity. Both viscosity and surface tension indicate stabilizing effect on the viscoelastic jet. In addition, strain rate, stretching rate and the jet speed increase with the arc length, viscoelasticity and rotation rate.
Acoustic scattering from a fluid cylinder with Willis constitutive properties
Authors: Muhlestein Michael B. , Goldsberry Benjamin M. , Norris Andrew N. , Haberman Michael R.
Published: February 2019

A material that exhibits Willis coupling has constitutive equations that couple the pressure–strain and momentum–velocity relationships. This coupling arises from subwavelength asymmetry and non-locality in heterogeneous media. This paper considers the problem of the scattering of a plane wave by a cylinder exhibiting Willis coupling using both analytical and numerical approaches. First, a perturbation method is used to describe the influence of Willis coupling on the scattered field to a first-order approximation. A higher order analysis of the scattering based on generalized impedances is then derived. Finally, a finite-element method-based numerical scheme for calculating the scattered field is presented. These three analyses are compared and show strong agreement for low to moderate levels of Willis coupling.
Analytical mechanics of asteroid disassembly using the Orbital Siphon effect
Authors: Viale Andrea , McInnes Colin , Ceriotti Matteo
Published: February 2019

A chain of tether-connected payload masses assembled from the surface material of a spherical rotating asteroid is envisaged as a means of delivering a fraction of the asteroid mass into orbit, without the need of external work to be done. Under conditions to be discussed, a net radial force is established on the chain which can be exploited to initialize an
orbital siphon
effect: new payloads are connected to the chain while top payloads are removed and released into orbit. Adopting simplifying assumptions, the underlying dynamics of the problem is entirely analytical and is investigated in detail. The amount of mass extractable from the asteroid is then discussed, according to a range of strategies. It is proposed that the scheme could in future provide an efficient means of extracting material resources from rotating Near Earth Asteroids.
Aromatoleum gen. nov., a novel genus accommodating the phylogenetic lineage including Azoarcus evansii and related species, and proposal of Aromatoleum aromaticum sp. nov., Aromatoleum petrolei sp. nov., Aromatoleum bremense sp. nov., Aromatoleum toluolicum sp. nov. and Aromatoleum diolicum sp. nov.
Authors: Rabus Ralf , Wöhlbrand Lars , Thies Daniela , Meyer Markus , Reinhold-Hurek Barbara , Kämpfer Peter
Published: February 2019

Comparative 16S rRNA gene sequence analysis and major physiological differences indicate two distinct sublineages within the genus

Azoarcus

: the

Azoarcus evansii

lineage, comprising

Azoarcus

evansii

(type strain KB740T=DSM 6898T=CIP 109473T=NBRC 107771T),

Azoarcus

buckelii

(type strain U120T=DSM 14744T=LMG 26916T),

Azoarcus

anaerobius

(type strain LuFRes1T=DSM 12081T=LMG 30943T),

Azoarcus

tolulyticus

(type strain Tol-4T=ATCC 51758T=CIP 109470T),

Azoarcus

toluvorans

(type strain Td21T=ATCC 700604T=DSM 15124T) and

Azoarcus

toluclasticus

(type strain MF63T=ATCC 700605T), and the

Azoarcus indigens

lineage, comprising

Azoarcus

indigens

(type strain VB32T=ATCC 51398T=LMG 9092T),

Azoarcus communis

(type strain SWub3T=ATCC 51397T=LMG 9095T) and

Azoarcus

olearius

(type strain DQS-4T=BCRC 80407T=KCTC 23918T=LMG 26893T).

Az. evansii

lineage members have remarkable anaerobic degradation capacities encompassing a multitude of alkylbenzenes, aromatic compounds and monoterpenes, often involving novel biochemical reactions. In contrast,

Az. indigens

lineage members are diazotrophic endophytes lacking these catabolic capacities. It is proposed that species of the

Az. evansii

lineage should be classified in a novel genus, Aromatoleum gen. nov. Finally, based on the literature and new growth, DNA–DNA hybridization and proteomic data, the following five new species are proposed: Aromatoleum aromaticum sp. nov. (type strain EbN1T=DSM 19018T=LMG 30748T and strain pCyN1=DSM 19016=LMG 31004), Aromatoleum petrolei sp. nov. (type strain ToN1T=DSM 19019T=LMG 30746T), Aromatoleumbremense sp. nov. (type strain PbN1T=DSM 19017T=LMG 31005T), Aromatoleum toluolicum sp. nov. (type strain TT=DSM 19020T=LMG 30751T) and Aromatoleum diolicum sp. nov. (type strain 22LinT=DSM 15408T=LMG 30750T).
Sweet revenge -Streptococcus pyogenesshowcases first example of immune evasion through specific IgG glycan hydrolysis
Authors: Naegeli Andreas , Bratanis Eleni , Karlsson Christofer , Shannon Oonagh , Kalluru Raja , Linder Adam , Malmström Johan , Collin Mattias
Published: February 2019

Streptococcus pyogenes(Group A streptococcus, GAS) is an important human pathogen responsible for a wide variety of diseases from uncomplicated tonsillitis to life-threatening invasive infections. GAS secretes EndoS, an endoglycosidase able to specifically cleave the conservedN-glycan on human IgG antibodies.In vitro, removal of this glycan impairs IgG effector functions but its relevance to GAS infectionin vivois unclear. Using targeted mass spectrometry, we were able to characterize the effects of EndoS on host IgG glycosylation during the course of natural infections in human patients. We found substantial IgG glycan hydrolysis locally at site of infection as well as systemically in the most severe cases. Using these findings we were able to set up appropriate model systems to demonstrate decreased resistance to phagocytic killing of GAS lacking EndoSin vitro, as well as decreased virulence in a mouse model of invasive infection. This study represents the first described example of specific bacterial IgG glycan hydrolysis during infection and highlights the importance of IgG glycan hydrolysis for streptococcal pathogenesis. We thereby offer new insights into the mechanism of immune evasion employed by this pathogen with clear implications for treatment of severe GAS infections and future efforts at vaccine development.
The Telomerase Reverse Transcriptase (TERT) and p53 Regulate Mammalian PNS and CNS Axon Regeneration downstream of c-Myc
Authors: Ma Jin-Jin , Xu Ren-Jie , Ju Xin , Wang Wei-Hua , Luo Zong-Ping , Liu Chang-Mei , Yang Lei , Li Bin , Chen Jian-Quan , Meng Bin , Yang Hui-Lin , Zhou Feng-Quan , Saijilafu
Published: February 2019

Although several genes have been identified to promote axon regeneration in the central nervous system, our understanding of the molecular mechanisms by which mammalian axon regeneration is regulated is still limited and fragmented. Here by using sensory axon and optic nerve regeneration as model systems, we revealed an unexpected role of telomerase reverse transcriptase (TERT) in regulation of axon regeneration. We also provided strong evidence that TERT and p53 acted downstream of c-Myc to control sensory axon regeneration. More importantly, overexpression of p53 in sensory neurons and retinal ganglion cells (RGCs) was sufficient to promote sensory axon and optic never regeneration, respectively. The study revealed a novel c-Myc-TERT-p53 signaling pathway, expanding horizons for novel approaches promoting CNS axon regeneration.
Clonal Architecture of the Epidermis: Homeostasis Limits Keratinocyte Evolution
Authors: Schenck Ryan O. , Kim Eunjung , Bravo Rafael R. , West Jeffrey , Leedham Simon , Shibata Darryl , Anderson Alexander R.A.
Published: February 2019

The skin is the largest human organ, functioning to serve as the protective barrier to the harsh, outside world. Recent studies have revealed that large numbers of somatic mutations accumulate in normal tissue, which can be used to infer skin cell dynamics1-5. Here we present the first realistic, cell-genome mechanistic epidermal model that shows homeostasis imposes a characteristic log-linear subclone size distribution for both neutral and oncogenic driver mutations, where the largest skin subclones are the oldest subclones. Because homeostasis inherently limits proliferation and therefore clonal sweeps, selection for driver mutations (NOTCH1 and TP53) in normal epidermis is instead conferred by greater persistence, which leads to larger subclone sizes. These results highlight how the integration of mechanistic modeling with genomic data provide novel insights into the evolutionary cell dynamics of normal human homeostatic tissues.
Dynamic interactions of lymphatic vessels at the hair follicle stem cell niche during hair regeneration
Authors: Peña-Jimenez Daniel , Fontenete Silvia , Megias Diego , Fustero-Torre Coral , Graña-Castro Osvaldo , Castellana Donatello , Loewe Robert , Perez-Moreno Mirna
Published: February 2019

Lymphatic vessels (LV) are essential for skin fluid homeostasis and immune cell trafficking, but whether LV are associated with hair follicle (HF) regeneration is not known. Here, by using steady and live imaging approaches in mouse skin, we show that lymphatic capillaries distribute to the anterior permanent region of individual HF and interconnect neighboring HF at the level of the HF bulge, in a hair follicle stem cell (HFSC)-dependent manner. LV further connect individual HF in triads and dynamically flow across the skin. Interestingly, at the onset of the physiological HFSC activation, or upon pharmacological or genetic induction of HF growth, LV transiently expand their caliber suggesting an increased tissue drainage capacity. Interestingly, the physiological LV caliber increase is associated with a distinct gene expression correlated to ECM and cytoskeletal reorganization. Using mouse genetics, we show that the depletion of LV blocks the pharmacological induction of HF growth. Our findings define LV as components of the HFSC niche, coordinating HF connections at tissue-level, and provide insight into their functional contribution to HF regeneration.
Blood and Brain Gene Expression Trajectories Underlying Neuropathology and Cognitive Impairment in Neurodegeneration
Authors: Iturria-Medina Yasser , Khan Ahmed F. , Adewale Quadri ,   Alzheimer’s Disease Neuroimaging Initiative
Published: February 2019

Neurodegenerative disorders take decades to develop and their early detection is challenged by confounding non-pathological aging processes. For all neurodegenerative conditions, we lack longitudinal gene expression (GE) data covering their large temporal evolution, which hinders the fully understanding of the underlying dynamic molecular mechanisms. Here, we aimed to overcome this limitation by introducing a novel GE contrastive trajectory inference (GE-cTI) method that reveals enriched temporal patterns in a diseased population. Evaluated on 1969 subjects in the spectrum of late-onset Alzheimer’s and Huntington’s diseases (from ROSMAP, HBTRC and ADNI studies), this unsupervised machine learning algorithm strongly predicts neuropathological severity (e.g. Braak, Amyloid and Vonsattel stages). Furthermore, when applied to in-vivo blood samples (ADNI), it predicts 97% of the variance in memory deterioration and its future declining rate, supporting the identification of a powerful and minimally invasive (blood-based) tool for early clinical screening and disease prevention. This technique also allows the discovery of genes and molecular pathways, in both peripheral and brain tissues, that are highly predictive of disease evolution. Eighty percent of the most predictive molecular pathways identified in the brain were also top predictors in the blood. The GE-cTI is a promising tool for revealing complex neuropathological mechanisms, with direct implications for implementing personalized dynamic treatments in neurology.

HIGHLIGHTS

- Unsupervised learning detects enriched gene expression (GE) trajectories in disease

- These plasma and brain GE trajectories predict neuropathology and future cognitive impairment

- Most predictive molecular functions/pathways in the brain are also top predictors in the plasma

- By identifying plasma GE trajectories, patients can be easily screened and follow dynamic treatments
N-cadherin-Presented Slit Repulsive-Cues Direct Collective Schwann cell Migration
Authors: Hoving Julian J.A , Harford-Wright Elizabeth , Wingfield-Digby Patrick , Cattin Anne-Laure , Campana Mariana , Morgan Toby , Quereda Victor , Torchiaro Erica , Lloyd Alison C.
Published: February 2019

Collective cell migration is fundamental for the development of organisms and in the adult, for tissue regeneration and in pathological conditions such as cancer. Migration as a coherent group requires the maintenance of cell-cell interactions, while contact-inhibition-of-locomotion (CIL), a local repulsive force, propels the group forward. Here we show that the cell-cell interaction molecule, N-cadherin, regulates both adhesion and repulsion processes during Schwann cell collective migration, which is required for peripheral nerve regeneration. However, distinct from its role in cell-cell adhesion, the repulsion process is independent of N-cadherin trans-homodimerisation and the associated adherens junction complex. Rather, the extracellular domain of N-cadherin acts to traffic a repulsive Slit2/Slit3 signal to the cell-surface. Inhibiting Slit2/Slit3 signalling inhibits CIL and subsequently collective SC migration, resulting in adherent, non-migratory cell clusters. These findings provide insight into how opposing signals can mediate collective cell migration and how CIL pathways are promising targets for inhibiting pathological cell migration.
Isolation of cardiomyocytes undergoing mitosis with complete cytokinesis
Authors: Milliron Hsiao-yun Y. , Weiland Matthew J. , Kort Eric J. , Jovinge Stefan
Published: February 2019

Rationale-Adult human cardiomyocytes (CMs) do not complete cytokinesis despite passing through the S-phase of the cell cycle. As a result polyploidization and multinucleation occur. In order to get a deeper understanding of the mechanisms surrounding division of CMs there is a crucial need for a technique to isolate CMs that complete cell division/cytokinesis.

Objective-Markers of cell cycle progression based on DNA content cannot distinguish between mitotic CMs that fail to complete cytokinesis from those cells that undergo true cell division. With the use of molecular beacons (MB) targeting specific mRNAs we aimed to identify truly proliferative CMs derived from hiPSCs.

Methods and Results-Fluorescence activated cell-sorting combined with molecular beacons was performed to sort CM populations enriched for mitotic cells. Expressions of cell-cycle specific genes were confirmed by means of RT-qPCR, single-cell RNA sequencing (scRNA-seq). We further characterized the sorted groups by proliferation assays and time-lapse microscopy which confirmed the proliferative advantage of MB-positive cell populations relative to MB-negative and G2/M populations. Gene expression analysis revealed that the MB-positive CM subpopulation exhibited patterns consistent with the biological processes of nuclear division, chromosome segregation, and transition from M to G1 phase. The use of dual-MBs targeting CDC20 and SPG20 mRNAs (CDC20+SPG20+) enabled the enrichment of cytokinetic events. Interestingly, cells that did not complete cytokinesis and remained binucleated were found to be CDC20−SPG20+ while polyploid CMs that replicated DNA but failed to complete karyokinesis were found to be CDC20−SPG20−.

Conclusions-This study demonstrates a novel alternative to existing DNA content-based approaches for sorting CMs with true mitotic potential that can be used to study in detail the unique dynamics of CM nuclei during mitosis. Together with high-throughput scRNA-seq, our technique for sorting live CMs undergoing cytokinesis would provide a basis for future studies to uncover mechanisms underlying the development and regeneration of heart tissue.
Unpacking conditional neutrality: genomic signatures of selection on conditionally beneficial and conditionally deleterious mutations
Authors: Mee Jonathan A. , Yeaman Samuel
Published: February 2019

It is common to look for signatures of local adaptation in genomes by identifying loci with extreme levels of allele frequency divergence among populations. This approach to finding genes associated with local adaptation often assumes antagonistic pleiotropy, wherein alternative alleles are strongly favoured in alternative environments. Conditional neutrality has been proposed as an alternative to antagonistic pleiotropy, but conditionally neutral polymorphisms are transient and it is unclear how much outlier signal would be maintained under different forms of conditional neutrality. Here, we use individual-based simulations and a simple analytical heuristic to show that a pattern that mimics local adaptation at the phenotypic level, where each genotype has the highest fitness in its home environment, can be produced by the accumulation of mutations that are neutral in their home environment and deleterious in non-local environments. Because conditionally deleterious mutations likely arise at a rate many times higher than conditionally beneficial mutations, they can have a significant cumulative effect on fitness even when individual effect sizes are small. We show that conditionally deleterious mutations driving non-local maladaptation may be undetectable by even the most powerful genome scans, as differences in allele frequency between populations are typically small. We also explore the evolutionary effects of conditionally-beneficial mutations and find that they can maintain significant signals of local adaptation, and they would be more readily detectable than conditionally deleterious mutations using conventional genome scan approaches. We discuss implications for interpreting outcomes of transplant experiments and genome scans that are used to study the genetic basis of local adaptation.
Linear Input as a Fundamental Motif of Brain Connectivity Organization
Authors: O’Rawe Jonathan F. , Leung Hoi-Chung
Published: February 2019

Describing the pattern of region-to-region functional connectivity is an important step towards understanding information transfer and transformation between brain regions. Although fMRI data are limited in spatial resolution, recent advances in technology afford more precise mapping. Here, we extended previous methods, connective field mapping, to 3 dimensions to provide a more concise estimate of the organization and potential information transformation from one region to another. We first replicated previous work with the 3 dimensional model by showing that the topology of functional connectivity between early visual regions maintained along their eccentricity axis or the anterior-posterior dimension. We then examined higher order visual regions (e,g, fusiform face area) and showed that their pattern of connectivity, the convergence and biased sampling, seem to contribute to some of their core receptive field properties. We further demonstrated that linearity of input is a fundamental aspect of functional connectivity of the whole brain, with higher linearity between regions within a network than across networks; that is, high connective linearity was evident between early visual areas, and between prefrontal areas, but less evident between them. By decomposing the whole brain linearity matrix with manifold learning techniques, we found that the principle mode of the linearity maps onto decompositions in both functional connectivity and genetic expression reported in previous studies. The current work provides evidence supporting that linearity of input is likely a fundamental motif of functional connectivity between regions for information processing across the brain, with high linearity preserving the integrity of information from one region to another within a network.
Urinary glucocorticoids in harbour seal (Phoca vitulina) pups during rehabilitation
Authors: Wilson Susan C. , Villanueva Stella , Jones Kayleigh A. , Hayes William , Dmitrieva Lilia , Smyth Wesley
Published: February 2019

The glucocorticoid (GC) hormone cortisol is often measured in animals to indicate their welfare and stress levels. However, the levels of other naturally occurring GCs are usually overlooked. We aimed to investigate whether aspects of the care and conditions of harbour seal (Phoca vitulina) pups in rehabilitation centres are reflected in urinary concentrations of four endogenous GCs. Urine samples were collected non-invasively from pups taken in as “orphans” at five different rehabilitation centres: three on the Irish Sea and two in the southern North Sea. Concentrations of urinary cortisol, cortisone, prednisolone and prednisone were analysed by mass spectrometry. Urinary concentrations of endogenous prednisolone and prednisone occurred in similar magnitude to cortisol, for the first time in any mammal species. The levels of all GC concentrations decreased as pups gained mass, but the most significant effect was for prednisone. Pups with mass less than 11kg, i.e. healthy average birth mass, had significantly higher levels of prednisone (but not of the other GCs) than pups of 11kg or more. Cortisol, cortisone and prednisolone concentrations were slightly higher for pups without access to water than those with water; however, we found no significant effect of social group on GC levels. Based on these findings, we tentatively suggest that the GCs may be elevated in harbour seal pups during rehabilitation in response to some physiological factors deviating from the norm of free-living pups. Our findings highlight the importance of measuring other GCs, in addition to cortisol, for understanding stressors affecting the welfare of seal pup in rehabilitation.
Propagating patterns of activity across motor cortex facilitate movement initiation
Authors: Balasubramanian Karthikeyan , Papadourakis Vasileios , Liang Wei , Takahashi Kazutaka , Best Matt , Suminski Aaron J. , Hatsopoulos Nicholas G.
Published: February 2019

Voluntary movement initiation involves the modulation of neurons in the primary motor cortex (M1) around movement onset. Yet, similar modulations of M1 activity occur during movement planning when no movement occurs. Here, we show that a sequential spatio-temporal pattern of excitability based on beta oscillation amplitude attenuation propagates across M1 prior to the initiation of reaching movements in one of two oppositely oriented directions along the rostro-caudal axis. Using spatiotemporal patterns of intracortical microstimulation, we find that reaction time increases significantly when stimulation is delivered against but not with the natural propagation orientation suggesting that movement initiation requires a precise recruitment pattern in M1. Functional connections among M1 units emerge at movement onset that are oriented along the same rostro-caudal axis but not during movement planning. Finally, we show that beta amplitude profiles can more accurately decode muscle activity when these patterns conform to the natural propagating patterns. These findings provide the first causal evidence that large-scale, spatially organized propagating patterns of cortical excitability and activity are behaviorally relevant and may be a necessary component of movement initiation.
Single cell profiling of the VMH reveals a sexually dimorphic regulatory node of energy expenditure
Authors: van Veen J. Edward , Kammel Laura G. , Bunda Patricia C. , Shum Michael , Reid Michelle S. , Park Jae W. , Zhang Zhi , Massa Megan G. , Arneson Douglas , Hrncir Haley , Liesa Marc , Arnold Arthur P. , Yang Xia , Correa Stephanie M.
Published: February 2019

Estrogen signaling in the central nervous system promotes weight loss by increasing thermogenesis and physical activity in the ventromedial hypothalamus (VMH), but the precise neuronal populations regulating these aspects of energy expenditure remain unclear. Here we define the molecular and functional heterogeneity of the VMH using single cell RNA sequencing, in situ hybridization, chemogenetic activation, and targeted gene knockdown. We describe six molecularly distinct neuron clusters in the VMH. In females, estrogen receptor alpha (ERα) is restricted to neurons expressing tachykinin-1 (Tac1) or reprimo (Rprm). Further, Tac1 and Rprm expression is enriched in females, a sex difference that is established by permanent effects of gonadal hormones early in life. Finally, while Tac1 ablation selectively impairs movement, here we show that silencing Rprm selectively dysregulates temperature without affecting physical activity. Together this work provides a novel architectural framework whereby distinct and sexually differentiated neuron populations within the VMH mediate sex-specific aspects of metabolic homeostasis.
Unmatched level of molecular convergence among deeply divergent complex multicellular fungi
Authors: Merényi Zsolt , Prasanna Arun N. , Zheng Wang , Kovács Károly , Hegedüs Botond , Bálint Balázs , Papp Balázs , Townsend Jeffrey P. , Nagy László G.
Published: February 2019

Convergent evolution is pervasive in nature, but it is poorly understood how various constraints and natural selection limit the diversity of evolvable phenotypes. Here, we report that, despite >650 million years of divergence, the same genes have repeatedly been co-opted for the development of complex multicellularity in the two largest clades of fungi—the Ascomycota and Basidiomycota. Co-opted genes have undergone duplications in both clades, resulting in >81% convergence across shared multicellularity-related families. This convergence is coupled with a rich repertoire of multicellularity-related genes in ancestors that predate complex multicellular fungi, suggesting that the coding capacity of early fungal genomes was well suited for the repeated evolution of complex multicellularity. Our work suggests that evolution may be predictable not only when organisms are closely related or are under similar selection pressures, but also if the genome biases the potential evolutionary trajectories organisms can take, even across large phylogenetic distances.
Visible light-triggered NO generation from Naphthalimide-based probe for photoreceptor-mediated plant root growth regulation
Authors: Biswas Suprakash , Upadhyay Neha , Kar Debojyoti , Datta Sourav , Koner Apurba Lal
Published: February 2019

An efficient visible light-triggered nitric oxide (NO) releasing fluorescent molecule is designed and synthesized by coupling 2,6-dimethyl nitrobenzene moiety at the peri-position of 1, 8-naphthalimide through an alkene bond. The NO-releasing ability is investigated in details using various spectroscopic techniques, and the photoproduct was also characterized. Further, the photo-generated NO has been employed to examine the effect of photoreceptor-mediated NO uptake on plant root growth regulation.
Spatio-temporal dynamics of face perception
Authors: Muukkonen I. , Ölander K. , Numminen J. , Salmela V.R.
Published: February 2019

The temporal and spatial neural processing of faces have been studied rigorously, but few studies have unified these dimensions to reveal the spatio-temporal dynamics postulated by the models of face processing. We used support vector machine decoding and representational similarity analysis to combine information from different locations (fMRI), timepoints (EEG), and theoretical models. By correlating information matrices derived from pair-wise decodings of neural responses to different facial expressions (neutral, happy, fearful, angry), we found early EEG timepoints (110-150 ms) to match fMRI data from early visual cortex (EVC), and later timepoints (170 – 250 ms) to match data from occipital and fusiform face areas (OFA/FFA) and posterior superior temporal sulcus (pSTS). The earliest correlations were driven by information from happy faces, and the later by more accurate decoding of fearful and angry faces. Model comparisons revealed systematic changes along the processing hierarchy, from emotional distance and visual feature coding in EVC to coding of intensity of expressions in right pSTS. The results highlight the importance of multimodal approach for understanding functional roles of different brain regions.
An orthogonal c-Cbl recognition mode targets LynA for rapid degradation and builds specificity into the LynA checkpoint
Authors: Brian Ben F. , Nunez Myra G. , Schwertfeger Kathryn L. , Freedman Tanya S.
Published: February 2019

The activity of Src-family kinases (SFKs), which phosphorylate immunoreceptor tyrosine-based activation motifs (ITAMs), is critical factor regulating myeloid-cell activation. In a previous paper (Freedman et al., 2015) we showed in macrophages that the SFK LynA is uniquely susceptible to rapid ubiquitin-mediated degradation, functioning as a rheostat regulating ITAM signaling. We now report the mechanism by which LynA is preferentially targeted for degradation and how cell specificity is built into the LynA rheostat. Using genetic and biochemical analysis, we found that the E3 ubiquitin ligase c-Cbl preferentially targets LynA via tyrosine 32 in its unique insert region. This orthogonal mode of c-Cbl recognition depresses the steady-state level of macrophage LynA. Mast cells, however, express little c-Cbl and have correspondingly high steady-state levels of LynA. Upon activation, mast-cell LynA is not rapidly degraded, and SFK-mediated signaling is amplified relative to macrophages. Cell-specific c-Cbl expression therefore builds cell specificity into the LynA checkpoint.
Social Instability is an Effective Chronic Stress Paradigm for both Male and Female Mice
Authors: Yohn Christine N. , Ashamalla Sandra A. , Bokka Leshya , Gergues Mark M. , Garino Alexander , Samuels Benjamin A.
Published: February 2019

Despite stress-associated disorders having a higher incidence rate in females, preclinical research mainly focuses on males. Chronic stress paradigms, such as chronic social defeat and chronic corticosterone administration, were mainly designed and validated in males and subsequent attempts to use these paradigms in females has demonstrated sex differences in the behavioral and HPA axis response to stress. Here, we developed a social stress paradigm, social instability stress (SIS), which exposes adult mice to unstable social hierarchies for 7 weeks. SIS effectively induces negative valence behaviors and hypothalamus-pituitary-adrenal (HPA) axis activation in both males and females. Importantly, while there were effects of estrous cycle on behavior, this variability did not impact the overall effects of SIS on behavior, suggesting estrous does not need to be tracked while utilizing SIS. Furthermore, the effects of SIS on negative valence behaviors were also reversed following chronic antidepressant treatment with fluoxetine (FLX) in both males and females. SIS also reduced adult hippocampal neurogenesis in female mice, while chronic FLX treatment increased adult hippocampal neurogenesis in both males and females. Overall, these data demonstrate that the SIS paradigm is an ethologically valid approach that effectively induces chronic stress in both adult male and adult female mice.
The influence of X-ray diffraction pattern angular range on Rietveld refinement results used for quantitative analysis, crystallite size calculation and unit-cell parameter refinement
Authors: Uvarov Vladimir
Published: February 2019

This article reports a detailed examination of the effect of the magnitude of the angular range of an X-ray diffraction (XRD) pattern on the Rietveld refinement results used in quantitative phase analysis and quality assurance/quality control applications. XRD patterns from 14 different samples (artificial mixtures, and inorganic and organic materials with nano- and submicrometre crystallite sizes) were recorded in 2θ interval from 5–10 to 120°. All XRD patterns were processed using Rietveld refinement. The magnitude of the workable angular range was gradually increased, and thereby the number of peaks used in Rietveld refinement was also increased, step by step. Three XRD patterns simulated using CIFs were processed in the same way. Analysis of the results obtained indicated that the magnitude of the angular range chosen for Rietveld refinement does not significantly affect the calculated values of unit-cell parameters, crystallite sizes and percentage of phases. The values of unit-cell parameters obtained for different angular ranges diverge by 10−4 Å (rarely by 10−3 Å), that is about 10−2% in relative numbers. The average difference between the calculated and actual phase percentage in artificial mixtures was 1.2%. The maximal difference for the crystallite size did not exceed 0.47, 5.2 and 7.7 nm at crystallite sizes lower than 20, 50 and 120 nm, respectively. It has been established that these differences are statistically insignificant.
Structural studies and antileishmanial activity of 2-acetylpyridine and 2-benzoylpyridine nitroimidazole-derived hydrazones
Authors: Oliveira Ana P. A. , Ferreira Isabella P. , Despaigne Angel A. Recio , Silva Jeferson G. da , Vieira Ana Carolina S. , Santos Mariana S , Alexandre-Moreira Magna S. , Diniz Renata , Beraldo Heloisa
Published: February 2019

Three imidazole hydrazone compounds, namely 2-(4-nitro-1H-imidazol-1-yl)-N′-[1-(pyridin-2-yl)ethylidene]acetohydrazide, C12H12N6O3, (1), 2-(2-nitro-1H-imidazol-1-yl)-N′-[1-(pyridin-2-yl)ethylidene]acetohydrazide, C12H12N6O3, (2), and 2-(2-nitro-1H-imidazol-1-yl)-N′-[(phenyl)(pyridin-2-yl)methylidene]acetohydrazide, C17H14N6O3, (3), were obtained and fully characterized, including their crystal structure determinations. While all the compounds proved not to be cytotoxic to J774.A1 macrophage cells, (1) and (3) exhibited activity against Leishmania chagasi, whereas (2) was revealed to be inactive. Since both (1) and (3) exhibited antileishmanial effects, while (2) was devoid of activity, the presence of the acetyl or benzoyl groups was possibly not a determining factor in the observed antiprotozoal activity. In contrast, since (1) and (3) are 4-nitroimidazole derivatives and (2) is a 2-nitroimidazole-derived compound, the presence of the 4-nitro group probably favours antileishmanial activity over the 2-nitro group. The results suggested that further investigations on compounds (1) and (3) as bioreducible antileishmanial prodrug candidates are called for.
Preparation and corrosion resistance of titanium-zirconium/nickel-coated carbon nanotubes chemical nano-composite conversion coatings
Authors: Wang Xiaobo , Li Zhipeng , Zhan Wen , Tu Jesong , Zuo Xiaohua , Deng Xiangyi , Gui Boyi
Published: February 2019

Purpose

This study aims to expand the reliability and special functions of lightweight materials for high-end equipment and green manufacturing, so that it is the first such research to carry out nano-composite technology of nickel-coated carbon nanotubes (Ni-CNTs)-based titanium-zirconium chemical conversion on aluminum alloy substrate.

Design/methodology/approach

Corrosion behavior of various coatings was investigated using dropping corrosion test, linear polarization and electrochemical impedance spectroscopy. The results showed that the corrosion resistance of the nano-composite conversion coatings was significantly improved to compare with the conventional titanium-zirconium conversion coating. The morphology and microdomain characteristics of the nano-composite conversion coatings were characterized by SEM/eds/EPMA, which indicated that the CNT or Ni-CNTs addition promoting the integrity coverage of coatings in a short time.

Findings

Surface morphology of titanium-zirconium (Ti-Zr)/Ni-CNT specimens exhibited smooth, compact and little pores. The nano-composite conversion coatings are mainly composed of Al, O, C and Ti elements and contain a small amount of F and Zr elements, which illuminated that CNT or Ni-CNT addition could co-deposit with aluminum and titanium metal oxides.

Originality/value

The study of corrosion resistance of nano-composite conversion coatings and the micro-zone film-formation characteristics would be provided theoretical support for the development of basic research on surface treatment of aluminum alloys.