bluuebunny/crossref_metadata_2025 huggingface dataset:
On the opening angle of magnetized jets from neutron-star mergers: the case of GRB170817A
Authors: Nathanail Antonios , Gill Ramandeep , Porth Oliver , Fromm Christian M , Rezzolla Luciano
Published: May 2020

The observations of GW170817/GRB170817A have confirmed that the coalescence of a neutron-star binary is the progenitor of a short gamma-ray burst (GRB). In the standard picture of a short GRB, a collimated highly relativistic outflow is launched after merger and it successfully breaks out from the surrounding ejected matter. Using initial conditions inspired from numerical-relativity binary neutron-star merger simulations, we have performed general-relativistic hydrodynamic (HD) and magnetohydrodynamic (MHD) simulations in which the jet is launched and propagates self-consistently. The complete set of simulations suggests that: (i) MHD jets have an intrinsic energy and velocity polar structure with a ‘hollow core’ subtending an angle θcore ≈ 4°–5° and an opening angle of θjet > ≳ 10°; (ii) MHD jets eject significant amounts of matter and two orders of magnitude more than HD jets; (iii) the energy stratification in MHD jets naturally yields the power-law energy scaling E(> Γβ) ∝ (Γβ)−4.5; (iv) MHD jets provide fits to the afterglow data from GRB170817A that are comparatively better than those of the HD jets and without free parameters; and (v) finally, both of the best-fitting HD/MHD models suggest an observation angle θobs ≃ 21° for GRB170817A.
H i gas content of SDSS galaxies revealed by ALFALFA: implications for the mass–metallicity relation and the environmental dependence of H i in the local Universe
Authors: Zu Ying
Published: May 2020

The neutral hydrogen (H i) gas is an important barometer of recent star formation and metal enrichment activities in galaxies. I develop a novel statistical method for predicting the H i-to-stellar mass ratio, $f_{\mathrm{H\,{\small I}}}$, of galaxies from their stellar mass and optical colour, and apply it to a volume-limited galaxy sample jointly observed by the Sloan Digital Sky Survey and the Arecibo Legacy Fast ALFA survey. I eliminate the impact of the Malmquist bias against H i-deficient systems on the $f_{\mathrm{H\,{\small I}}}$ predictor by properly accounting for the H i detection probability of each galaxy in the analysis. The best-fitting $f_{\mathrm{H\,{\small I}}}$ predictor, with an estimated scatter of 0.272 dex, provides excellent description to the observed H i mass function. After defining an H i excess parameter as the deviation of the observed $f_{\mathrm{H\,{\small I}}}$ from the expected value, I confirm that there exists a strong secondary dependence of the mass–metallicity relation on H i excess. By further examining the 2D metallicity distribution on the specific star formation rate (sSFR) versus H i excess plane, I show that the metallicity dependence on H i is likely more fundamental than that on sSFR. In addition, I find that the environmental dependence of H i in the local Universe can be effectively described by the cross-correlation coefficient between H i excess and the red galaxy overdensity ρcc = − 0.18. This weak anticorrelation also successfully explains the observed dependence of H i clustering on $f_{\mathrm{H\,{\small I}}}$. My method provides a useful framework for learning H i gas evolution from the synergy between future H i and optical galaxy surveys.
Wavelet analysis of the long-term activity of V833 Tau
Authors: Stepanov R , Bondar’ N I , Katsova M M , Sokoloff D , Frick P
Published: May 2020

The bulk of available stellar activity observations is frequently checked for the manifestation of signs in comparison with the known characteristic of solar magnetic modulation. The problem is that stellar activity records are usually an order of magnitude shorter than available observations of solar activity variation. Therefore, the resolved time-scales of stellar activity are insufficient to decide reliably that a cyclic variation for a particular star is similar to the well-known 11-yr sunspot cycles. As a result, recent studies report several stars with double or multiple cycles which serve to challenge the underlying theoretical understanding. This is why a consistent method to separate ‘true’ cycles from stochastic variations is required. In this paper, we suggest that a conservative method, based on the best practice of wavelet analysis previously applied to the study of solar activity, for studying and interpreting the longest available stellar activity record – photometric monitoring of V833 Tau for more than 100 yr. We find that the observed variations of V833 Tau with time-scales of 2–50 yr should be comparable with the known quasi-periodic solar mid-term variations, whereas the true cycle of V833 Tau, if it exists, should be of about a century or even longer. We argue that this conclusion does not contradict the expectations from the stellar dynamo theory.
Platelet-derived growth factor B restores vascular barrier integrity and diminishes permeability in ovarian hyperstimulation syndrome
Authors: Pascuali Natalia , Scotti Leopoldina , Oubiña Gonzalo , de Zúñiga Ignacio , Gomez Peña Mariana , Pomilio Carlos , Saravia Flavia , Tesone Marta , Abramovich Dalhia , Parborell Fernanda
Published: May 2020

Although advances in the prediction and management of ovarian hyperstimulation syndrome (OHSS) have been introduced, complete prevention is not yet possible. Previously, we and other authors have shown that vascular endothelial growth factor, angiopoietins (ANGPTs) and sphingosine-1-phosphate are involved in OHSS etiology. In addition, we have demonstrated that ovarian protein levels of platelet-derived growth factor (PDGF) ligands -B and -D decrease in an OHSS rat model, whilst PDGFR-β and ANGPT2 remain unchanged. In the present work, we investigated the role of PDGF-B in OHSS by evaluating ligand protein levels in follicular fluid (FF) from women at risk of developing OHSS and by using an immature rat model of OHSS. We demonstrated that PDGF-B and PDGF-D are lower in FF from women at risk of developing OHSS compared to control patients (P < 0.05). In the OHSS rat model, PDGF-B (0.5 µg/ovary) administration decreased ovarian weight (P < 0.05), reduced serum progesterone (P < 0.05) and lowered the percentage of cysts (P < 0.05), compared to untreated OHSS rats, but had no effect on the proportion of follicles or corpora lutea (CL). PDGF-B treatment also restored the expression of steroidogenic acute regulatory protein (P < 0.05) and P450 cholesterol side-chain cleavage enzyme (P < 0.01) to control levels. In addition, PDGF-B increased the peri-endothelial cell area in CL and cystic structures, and reduced vascular permeability compared to untreated OHSS ovaries. Lastly, PDGF-B increased the levels of junction proteins claudin-5 (P < 0.05), occludin (P < 0.05) and β-catenin (P < 0.05), while boosting the extracellular deposition of collagen IV surrounding the ovarian vasculature (PP < 0.01), compared to OHSS alone. In conclusion, our findings indicate that PDGF-B could be another crucial mediator in the onset and development of OHSS, which may lead to the development of novel prediction markers and therapeutic strategies.
Nick-seq for single-nucleotide resolution genomic maps of DNA modifications and damage
Authors: Cao Bo , Wu Xiaolin , Zhou Jieliang , Wu Hang , Liu Lili , Zhang Qinghua , DeMott Michael S , Gu Chen , Wang Lianrong , You Delin , Dedon Peter C
Published: May 2020

DNA damage and epigenetic marks are well established to have profound influences on genome stability and cell phenotype, yet there are few technologies to obtain high-resolution genomic maps of the many types of chemical modifications of DNA. Here we present Nick-seq for quantitative, sensitive, and accurate mapping of DNA modifications at single-nucleotide resolution across genomes. Pre-existing breaks are first blocked and DNA modifications are then converted enzymatically or chemically to strand-breaks for both 3′-extension by nick-translation to produce nuclease-resistant oligonucleotides and 3′-terminal transferase tailing. Following library preparation and next generation sequencing, the complementary datasets are mined with a custom workflow to increase sensitivity, specificity and accuracy of the map. The utility of Nick-seq is demonstrated with genomic maps of site-specific endonuclease strand-breaks in purified DNA from Eschericia coli, phosphorothioate epigenetics in Salmonella enterica Cerro 87, and oxidation-induced abasic sites in DNA from E. coli treated with a sublethal dose of hydrogen peroxide. Nick-seq applicability is demonstrated with strategies for >25 types of DNA modification and damage.
Allograft Nerve Repair Reduces Postoperative Neuropathic Pain Following Nerve Biopsy
Authors: Sakamuri Sarada , Wilson Thomas J
Published: May 2020

BACKGROUND

New or worsened neuropathic pain is common following nerve biopsy and significantly impacts quality of life.

OBJECTIVE

To examine the impact of allograft nerve repair on the likelihood of postoperative worsened neuropathic pain following nerve biopsy.

METHODS

A retrospective cohort study was performed comparing standard nerve biopsy to nerve biopsy with allograft repair. Consecutive patients (N = 51) who underwent whole nerve biopsy between August 1, 2017, and August 1, 2019, by a single surgeon were evaluated for inclusion. The primary outcome was significant worsening of visual analog scale (VAS) score in the nerve distribution 6-mo postbiopsy. Secondary outcomes included significant worsening of VAS in the nerve distribution 3-wk postbiopsy and significant change in Zung Self-Rating Depression Scale 6-mo postbiopsy.

RESULTS

In a multivariate model, allograft nerve repair significantly reduced the likelihood of increased neuropathic pain at 6-mo postbiopsy (odds ratio 0.02, P = .03). Worsened neuropathic pain occurred in 28% of the standard nerve biopsy cohort compared to 4% of the allograft nerve repair cohort. In a multivariate model, an increase in neuropathic pain was strongly associated with an increased likelihood of self-reported depression (odds ratio 57.4, P = .01)

CONCLUSION

Allograft nerve repair significantly reduces the likelihood of postbiopsy worsened neuropathic pain compared to standard techniques. Neuropathic pain significantly impacts quality of life after nerve biopsy, and this is the first technique to demonstrate a significant reduction in neuropathic pain while maintaining the ability to harvest an adequate nerve specimen.
Histological conversion from adenocarcinoma to small cell carcinoma of the lung after treatment with an immune checkpoint inhibitor: a case report
Authors: Miura Naoko , Matsubara Taichi , Takamori Shinkichi , Haratake Naoki , Toyozawa Ryo , Yamaguchi Masafumi , Seto Takashi , Taguchi Kenichi , Takenoyama Mitsuhiro
Published: May 2020

The transformation of adenocarcinoma to small cell lung cancer has been reported as acquisition of resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors. We here report a patient who presented histologically confirmed transformation of adenocarcinoma to small cell lung cancer after treatment with immune checkpoint inhibitor. A 65-year-old man was treated with pembrolizumab as first-line therapy and achieved temporarily a stable disease with progression after six cycles of this agent. At that stage, a transbronchial biopsy showed small cell lung cancer, and he was found to have high serum concentrations of neuron-specific enolase despite concentrations of numerous tumor markers, including neuron-specific enolase, having been within normal limits at the time of presentation. The patient thereafter was treated as a small cell carcinoma patient using cisplatin plus irinotecan and amrubicin.
Hypoglossal-Facial Side-to-End Neurorrhaphy With Concomitant Masseteric-Zygomatic Nerve Branch Coaptation and Muscle Transfer for Facial Reanimation: Technique and Case Report
Authors: Yoshioka Nobutaka
Published: May 2020

BACKGROUND

Hypoglossal-facial direct side-to-end neurorrhaphy has become widely used for facial reanimation in patients with irreversible facial nerve damage. Although this procedure achieves good restoration of facial function, it has disadvantages such as mass movement and lack of spontaneity.

OBJECTIVE

To present a new facial reanimation technique using hypoglossal-facial direct side-to-end neurorrhaphy with concomitant masseteric-zygomatic nerve branch coaptation and secondary muscle transfer to reduce mass movement and achieve a spontaneous smile in patients with facial paralysis.

METHODS

This article describes a novel facial reanimation technique that employs hypoglossal and masseteric nerve transfer combined with secondary vascularized functional gracilis muscle transfer.

RESULTS

Details of the technique are reported in a patient with complete facial paralysis after brain surgery. The hypoglossal nerve was partially served and connected to the mastoid segment of the facial nerve by side-to-end anastomosis to restore facial symmetry. A nerve supplying the masseter muscle was coapted with a zygomatic branch by end-to-end anastomosis to restore voluntary movement of the oral commissure, as well as to assist with eye closure. A cross face sural nerve graft was connected to zygomatic branches on the healthy side. In the second stage, a vascularized functional gracilis muscle graft was transplanted using the cross face nerve graft as the donor nerve to restore a natural smile.

CONCLUSION

Hypoglossal-facial neurorrhaphy with concomitant masseteric-zygomatic nerve branch coaptation and muscle transfer is an alternative facial reanimation technique that reduces mass movement and achieves a natural smile.
Lumbar Lateral Recess Decompression: 2-Dimensional Operative Video
Authors: Khalsa Siri Sahib S , Saadeh Yamaan S , Yee Timothy J , Strong Michael J , Smith Brandon W , Oppenlander Mark E
Published: May 2020

Lateral recess stenosis is a common cause of lumbar radiculopathy in adults. A lumbar nerve root travels in the lateral recess prior to exiting the spinal canal via the neural foramen. In the lateral recess, the traversing nerve root is susceptible to compression by the degenerative hypertrophy of the medial facet in addition to hypertrophied ligamentum flavum and herniated intervertebral disc.
1
These degenerative changes are also typically associated with neural foraminal stenosis. Surgical treatment in unilateral cases consists of hemilaminectomy, medial facetectomy, foraminotomy, and, if applicable, microdiscectomy. In this video, we present a case of a 64-yr-old male presenting with progressive left L5 radiculopathy refractory to conservative management, with magnetic resonance imaging (MRI) findings of left L4-5 foraminal and lateral recess stenosis. We demonstrate the operative steps to complete a left L4-5 hemilaminectomy, medial facetectomy, foraminotomy, and microdiscectomy. Appropriate patient consent was obtained.
Microsurgical Resection of a C1-C2 Dumbbell and Ventral Cervical Schwannoma: 2-Dimensional Operative Video
Authors: Nguyen Vincent N , Khan Nickalus R , Arnautović Kenan I
Published: May 2020

Dumbbell schwannoma of the cervical spine is a known entity,
1-5
and should be radically resected with the preservation or improvement of neurological function. However, to our knowledge, an operative video of a C1-C2 cervical dumbbell schwannoma with ventral extension and dorsal spinal cord compression has not been reported previously. This tumor resection video performed by the senior author (KIA) includes details of dural opening, and techniques for microsurgical resection and for postoperative closure to avoid cerebrospinal fluid (CSF) leak and pseudomeningocele formation.

Fat grafting was performed through a small paraumbilical incision. The patient was prone in MAYFIELD 3-point pin fixation (Integra LifeSciences, Plainsboro Township, New Jersey). Intraoperative neurophysiological electrodes were placed for somatosensory evoked potential (SSEP) and motor evoked potential (MEP) monitoring. Stealth neuronavigation was used to aid in tumor localization. A small suboccipital craniectomy and C1 laminectomy were performed before opening the dura. Using a microsurgical technique, the dura was opened in the form of the letter “Y.” The right-sided dentate ligament was cut to aid in the mobilization of the tumor away from the spinal cord. After dividing the tumor at the dumbbell isthmus, the ventral tumor component was removed, with attention paid to the division of a perforator coming from the vertebral artery. Intraforaminal tumor debulking was performed with a cavitron ultrasonic surgical aspirator (CUSA) and resected.

High cervical dumbbell schwannoma should be radically resected while preserving and improving preoperative neurological function. Avoidance of CSF leak and formation of pseudomeningocele should be planned at the beginning, utilizing fascia and fat graft to avoid this feared complication.

The patient provided written consent and permission to publish her image.
Supraclavicular Resection of a Cervical Rib Causing Thoracic Outlet Syndrome: 2-Dimensional Operative Video
Authors: Burks Stephen Shelby , Wolfe Erin M , Yoon Jang Won , Levi Allan D
Published: May 2020

Presence of a cervical rib results from overdevelopment of the seventh cervical vertebrae.
1-3
The cervical rib along with scalene muscles can cause neurogenic thoracic outlet syndrome.
4,5
Rib resection is typically done via anterior approach, using either supraclavicular or transaxillary route.
6,7
We present an operative video detailing supraclavicular resection of a cervical rib causing neurogenic thoracic outlet syndrome with direct decompression of the lower trunk of the brachial plexus. The patient presented with severe symptoms including hand atrophy. We were able to directly visualize the rib and resect it, along with scalene musculature. We present 3-mo follow-up data noting clinical improvement in neuropathic symptoms.
The paediatric developmental toolkit: Facilitating learning of child development
Authors: Young Elizabeth , Jegathesan Thivia , Park Hyeji , Zubairi Mohammad Samad
Published: May 2020

Background

Recent paediatric and family medicine graduates report feeling unprepared to identify and address children and youth with developmental disorders. Developmental history taking and physical examination alone limit engagement with children and youth in an interactive manner to assess development. The paediatric developmental toolkit (PDT) was developed to provide trainees with the opportunity to interact with a child in a play-based manner.

Objectives

The primary objective of this study was to determine the feasibility of PDT within clinical settings, and qualitatively explore how the PDT can be used by teachers and trainees.

Methods

Trainees and their clinical teachers participated in a qualitative study. Trainees used the PDT in clinical settings and were interviewed following their clinical encounters. Interactions between clinical teachers and trainees following the use of the PDT were also recorded. Teachers were interviewed following the trainees’ case presentations and closures of clinic visits. Trainee interviews, teacher and trainee interactions, and teacher interviews were audiotaped, transcribed, and analyzed thematically.

Results

Nine trainees (six paediatric residents, two family medicine residents, and one clinical clerk medical student) and four developmental paediatricians participated in the study. Each trainee used the PDT twice in two different clinical encounters. All residents agreed the PDT enabled them to observe a child’s developmental skills in a short period of time. Clinical teachers all felt the toolkit allowed trainees to more holistically consider a child’s development and diagnosis.

Conclusions

As medical education shifts to a competency-based education curriculum, the PDT is an innovative tool that can be used to enhance paediatric and family medicine residents’ learning of child development by enabling opportunities for interaction with children.
Arabidopsis SMN2/HEN2, Encoding DEAD-Box RNA Helicase, Governs Proper Expression of the Resistance Gene SMN1/RPS6 and Is Involved in Dwarf, Autoimmune Phenotypes of mekk1 and mpk4 Mutants
Authors: Takagi Momoko , Iwamoto Naoki , Kubo Yuta , Morimoto Takayuki , Takagi Hiroki , Takahashi Fuminori , Nishiuchi Takumi , Tanaka Keisuke , Taji Teruaki , Kaminaka Hironori , Shinozaki Kazuo , Akimitsu Kazuya , Terauchi Ryohei , Shirasu Ken , Ichimura Kazuya
Published: May 2020

In Arabidopsis thaliana, a mitogen-activated protein kinase pathway, MEKK1–MKK1/MKK2–MPK4, is important for basal resistance and disruption of this pathway results in dwarf, autoimmune phenotypes. To elucidate the complex mechanisms activated by the disruption of this pathway, we have previously developed a mutant screening system based on a dwarf autoimmune line that overexpressed the N-terminal regulatory domain of MEKK1. Here, we report that the second group of mutants, smn2, had defects in the SMN2 gene, encoding a DEAD-box RNA helicase. SMN2 is identical to HEN2, whose function is vital for the nuclear RNA exosome because it provides non-ribosomal RNA specificity for RNA turnover, RNA quality control and RNA processing. Aberrant SMN1/RPS6 transcripts were detected in smn2 and hen2 mutants. Disease resistance against Pseudomonas syringae pv. tomato DC3000 (hopA1), which is conferred by SMN1/RPS6, was decreased in smn2 mutants, suggesting a functional connection between SMN1/RPS6 and SMN2/HEN2. We produced double mutants mekk1smn2 and mpk4smn2 to determine whether the smn2 mutations suppress the dwarf, autoimmune phenotypes of the mekk1 and mpk4 mutants, as the smn1 mutations do. As expected, the mekk1 and mpk4 phenotypes were suppressed by the smn2 mutations. These results suggested that SMN2 is involved in the proper function of SMN1/RPS6. The Gene Ontology enrichment analysis using RNA-seq data showed that defense genes were downregulated in smn2, suggesting a positive contribution of SMN2 to the genome-wide expression of defense genes. In conclusion, this study provides novel insight into plant immunity via SMN2/HEN2, an essential component of the nuclear RNA exosome.
Validation of the Safer Opioid Prescribing Evaluation Tool (SOPET) for Assessing Adherence to the Centers for Disease Control Opioid Prescribing Guidelines
Authors: Navis Allison , George Mary-Catherine , Nmashie Alexandra , Hoang Ethan , Cedillo Gabriela , Robinson-Papp Jessica
Published: May 2020

Objective

In response to the opioid epidemic, the Centers for Disease Control and Prevention issued guidelines (CDCG) in 2016 for the prescription of opioids for chronic pain. To facilitate research into whether CDCG implementation will lead to reductions in opioid prescribing and improved patient safety, we sought to validate a tool that quantifies CDCG adherence based on clinical documentation.

Design

The Safe Opioid Prescribing Evaluation Tool (SOPET) was developed in four phases as part of a study to improve the implementation of the CDCG in the clinical setting. Four raters with varying levels of clinical experience and expertise were trained to use the SOPET and then used it to evaluate 21 baseline patient encounters. Intraclass correlation coefficient (ICC) estimates and their 95% confident intervals (CIs) were calculated for the total SOPET score based on a mean-rating (k = 4), absolute-agreement, two-way random-effects model. For intrarater reliability, two-way mixed-effect models were used.

Results

Inter-rater reliability was good, with an average-measures ICC of 0.82 (95% CI = 0.63–0.92). Intrarater reliability was excellent for the three raters, who were MDs, with average-measures ICCs as follows: 0.92 (95% CI = 0.81–0.97), 0.97 (95% CI = 0.92–0.99), 0.99 (95% CI = 0.99–0.99). However, the intrarater reliability for the non-MD rater was lower 0.69 (95% CI = 0.22–0.88).

Conclusions

Overall, the SOPET is useful for evaluating implementation of the CDCG in clinical documentation. It is an important first step in the design of future studies assessing whether adherence to the CDCG improves patient safety outcomes.
RADIOECOLOGICAL IMPACT AND THE ASSOCIATED HAZARDS DUE TO NORM FROM OIL AND GAS PRODUCTION FACILITY IN THE WESTERN DESERT OF EGYPT
Authors: Ebaid Yasser Y , Hassan Yasser , Elshemey Wael M
Published: May 2020

An oil and gas production facility in the western desert of Egypt was investigated for possible radiation risks due to the routine operation. Radium-226, Radium-228 and Potassium-40 were assessed in the soil samples collected from the adjacent soakaway pond. The average 226Ra, 228Ra and 40K activity concentrations were 881.0 ± 42.0, 966.0 ± 43.0 and 143.0 ± 8.0 Bq kg−1, respectively. Both 226Ra and 228Ra were above the world ranges, while 40K was within the world range. Water samples from the facilities effluent’s produced water showed elevated levels of both radium isotopes. The effective doses at three different points on the separator outer surfaces over the period between 1995 and 2014 were assessed. The maximum reading was 5.4 μSv h−1 on 2014. The time has significantly contributed to the enhancement of the effective dose readings. However, they are still within the expected range encountered in similar studies reported by International Atomic Energy Agency (IAEA).
The Trace Kynurenine, Cinnabarinic Acid, Displays Potent Antipsychotic-Like Activity in Mice and Its Levels Are Reduced in the Prefrontal Cortex of Individuals Affected by Schizophrenia
Authors: Ulivieri Martina , Wierońska Joanna Monika , Lionetto Luana , Martinello Katiuscia , Cieslik Paulina , Chocyk Agnieszka , Curto Martina , Di Menna Luisa , Iacovelli Luisa , Traficante Anna , Liberatore Francesca , Mascio Giada , Antenucci Nico , Giannino Giuseppe , Vergassola Matteo , Pittaluga Anna , Bruno Valeria , Battaglia Giuseppe , Fucile Sergio , Simmaco Maurizio , Nicoletti Ferdinando , Pilc Andrzej , Fazio Francesco
Published: May 2020

Cinnabarinic acid (CA) is a kynurenine metabolite that activates mGlu4 metabotropic glutamate receptors. Using a highly sensitive ultra-performance liquid chromatography/tandem mass spectrometry (UPLC/MS-MS) method, we found that CA is present in trace amounts in human brain tissue. CA levels were largely reduced in the prefrontal cortex (PFC) of individuals affected by schizophrenia. This reduction did not correlate with age, sex, duration of the disease, and duration and type of antipsychotic medication and might, therefore, represent a trait of schizophrenia. Interestingly, systemic treatment with low doses of CA (<1 mg/kg, i.p.) showed robust efficacy in several behavioral tests useful to study antipsychotic-like activity in mice and rats and attenuated MK-801-evoked glutamate release. CA failed to display antipsychotic-like activity and inhibit excitatory synaptic transmission in mice lacking mGlu4 receptors. These findings suggest that CA is a potent endogenous antipsychotic-like molecule and reduced CA levels in the PFC might contribute to the pathophysiology of schizophrenia.
The Sustainable Development Goals and Building a Culture of Health
Authors: Rosa William E. , Hassmiller Susan B.
Published: May 2020

This article is one in a series in which contributing authors discuss how the United Nations (UN) Sustainable Development Goals (SDGs) are linked to everyday clinical issues; national public health emergencies; and other nursing issues, such as leadership, shared governance, and advocacy. The 2030 Agenda for Sustainable Development, a 15-year plan of action to achieve the goals, was unanimously adopted by all UN member states in September 2015 and took effect on January 1, 2016. The Agenda consists of 17 SDGs addressing social, economic, and environmental determinants of health and 169 associated targets focused on five themes: people, planet, peace, prosperity, and partnership. The SDGs build on the work of the UN's Millennium Development Goals, which were in effect from 2000 to 2015.
Hypothetical control of postural sway
Authors: Mangalam Madhur , Kelty-Stephen Damian G.
Published: May 2020

Quiet standing exhibits strongly intermittent variability that has inspired at least two interpretations. First, variability can be intermittent through the alternating engagement and disengagement of complementary control processes at distinct scales. A second and perhaps deeper way to interpret this intermittency is through the possibility that postural control depends on cascade-like interactions across many timescales at once, suggesting specific non-Gaussian distributional properties at different timescales. Multiscale probability density function (PDF) analysis shows that quiet standing on a stable surface exhibits a crossover from low, increasing non-Gaussianity (consistent with exponential distributions) at shorter timescales, reflecting inertial control, towards higher non-Gaussianity. Feedback-based control at medium to longer timescales yields a linear decrease characteristic of cascade dynamics. Destabilizing quiet standing with unstable surface or closed eyes serves to attenuate inertial control and to elicit more of the feedback-based control over progressively shorter timescales. The result was to strengthen the appearance of the linear decay indicating cascade dynamics. Finally, both linear and nonlinear indices of postural sway also govern the relative strength of crossover or of linear decay, suggesting that tempering of non-Gaussianity across log-timescale is a function of both extrinsic constraints and endogenous postural control. These results provide new evidence that cascading interactions across longer-timescales supporting postural corrections can even recruit shorter-timescale processes with novel task constraints that can destabilize posture.
The genetic architecture of post-zygotic reproductive isolation betweenAnopheles coluzziiandAn. quadriannulatus
Authors: Deitz Kevin C. , Takken Willem , Slotman Michel A.
Published: May 2020

Abstract

TheAnopheles gambiaecomplex is comprised of eight morphologically indistinguishable species and has emerged as a model system for the study of speciation genetics due to the rapid radiation of its member species over the past two million years. Male hybrids between mostAn. gambiaecomplex species pairs are sterile, and some genotype combinations in hybrid males cause inviability. We investigated the genetic basis of hybrid male inviability and sterility betweenAn. coluzziiandAn. quadriannulatusby measuring segregation distortion and performing a QTL analysis of sterility in a backcross population. Hybrid males were inviable if they inherited theAn. coluzziiX chromosome and were homozygous at one or more loci in 18.9 Mb region of chromosome 3. TheAn. coluzziiX chromosome has a disproportionately large effect on hybrid sterility when introgressed into anAn. quadriannulatusgenetic background. Additionally, an epistatic interaction between theAn. coluzziiX and a 1.12 Mb, pericentric region of theAn. quadriannulatus3L chromosome arm has a statistically significant contribution to the hybrid sterility phenotype. This same epistatic interaction occurs when theAn. coluzziiX is introgressed into the genetic background ofAn. arabiensis,the sister species ofAn. quadriannulatus, suggesting that this may represent one of the first Dobzhansky–Muller incompatibilities to evolve early in the radiation of theAnopheles gambiaespecies complex. We describe the additive effects of each sterility QTL, epistatic interactions between them, and genes within QTL with protein functions related to mating behavior, reproduction, spermatogenesis, and microtubule morphogenesis, whose divergence may contribute to post-zygotic reproductive isolation betweenAn. coluzziiandAn. quadriannulatus.
Estimating colocalization probability from limited summary statistics
Authors: King Emily A. , Dunbar Fengjiao , Davis Justin Wade , Degner Jacob F.
Published: May 2020

1

1.1

Motivation

A common approach to understanding the mechanisms of noncoding GWAS associations is to test the GWAS variant for association with lower level cellular phenotypes such as gene expression. However, significant association to gene expression will often arise from linkage disequilibrium to a separate causal variant and be unrelated to the mechanism underlying the GWAS association. Colocalization is a statistical genetic method used to determine whether the same variant is causal for multiple phenotypes and is stronger evidence for understanding mechanism than shared significance. Current colocalization methods require full summary statistics for both traits, limiting their use with the majority of reported GWAS associations (e.g. GWAS Catalog). We propose a new approximation to the popular coloc method [1] that can be applied when limited summary statistics are available, as in the common scenario where a GWAS catalog hit would be tested for colocalization with a GTEx eQTL. Our method (POint EstiMation of Colocalization - POEMColoc) imputes missing summary statistics using LD structure in a reference panel, and performs colocalization between the imputed statistics and full summary statistics for a second trait.

1.2

Results

As a test of whether we are able to approximate the posterior probability of colocalization, we apply our method to colocalization of UK Biobank phenotypes and GTEx eQTL. We show good correlation between posterior probabilities of colocalization computed from imputed and observed UK Biobank summary statistics. We perform simulations and show that the POEMColoc method can identify shared causality with similar accuracy to the coloc method. We evaluate scenarios that might reduce POEMColoc performance and show that multiple independent causal variants in a region and imputation from a limited subset of typed variants have a larger effect while mismatched ancestry in the reference panel has a modest effect.

We apply POEMColoc to estimate colocalization of GWAS Catalog entries and GTEx eQTL. We find evidence for colocalization of ~ 150,000 trait-gene-tissue triplets. We find that colocalized trait-gene pairs are enriched in tissues relevant to the etiology of the disease (e.g., thyroid eQTLs are enriched in colocalized hypothyroidism GWAS signals). Further, we find that colocalized trait-gene pairs are enriched in approved drug target - indication pairs.

1.3

Availability

POEMColoc is freely available as an R package athttps://github.com/AbbVie-ComputationalGenomics/POEMColoc
Co-expression signatures of combinatorial gene regulation
Authors: Gomez-Cano Fabio , Xu Qian , Shiu Shin-Han , Krishnan Arjun , Grotewold Erich
Published: May 2020

Gene co-expression analyses provide a powerful tool to determine gene associations. The interaction of transcription factors (TFs) with their target genes is an essential step in gene regulation, yet to what extent TFs-target gene associations are recovered in co-expression studies remains unclear. Using the wealth of data available for Arabidopsis, we show here that protein-DNA interactions are overall poor indicators of TF-target co-expression, yet the inclusion of TF-TF interaction information significantly enhance co-expression signals. These results highlight the impact of combinatorial gene control on such gene association networks. We integrated this information to predict higher-order regulatory complexes, which are difficult to identify experimentally. We demonstrate that genes strongly co-expressed with a TF are also enriched in indirect targets. Our results have significant implications on the empirical understanding of complex gene regulatory networks and transcription factor function, and the significance of co-expression from the perspective of protein-protein and protein-DNA interactions.
Native perennial and non-native annual grasses shape pathogen community composition and disease severity in a California grassland
Authors: Kendig Amy E. , Spear Erin R. , Daws S. Caroline , Flory S. Luke , Mordecai Erin A.
Published: May 2020

The densities of highly competent plant hosts may shape pathogen community composition and disease severity, altering disease risk and impacts. Life history and evolutionary history influence host competence: longer-lived species tend to be better defended than shorter-lived species and pathogens adapt to infect species with which they have longer evolutionary histories. It is unclear, however, how the densities of species that differ in competence due to life and evolutionary histories affect plant pathogen community composition and disease severity.

We examined foliar fungal pathogens on two host groups in a California grassland: native perennial and non-native annual grasses. We first characterized pathogen community composition and disease severity on the two host groups to approximate differences in competence. We then used observational and manipulated gradients of native perennial and non-native annual grass densities to assess the effects of each host group on pathogen community composition and disease severity in 1-m2plots.

Native perennial and non-native annual grasses hosted distinct pathogen communities but shared generalist pathogens. Native perennial grasses hosted pathogens with larger host ranges and experienced greater disease severity (75% higher proportions of leaves with lesions) than non-native annuals. While the relative abundances of three common pathogens tended to shift, and disease severity of native perennial grasses tended to increase with increasing densities of both host groups, these changes were not statistically significant.

Synthesis.The life and evolutionary histories of grasses likely influence their competence for different pathogen species, leading to distinct pathogen communities and differences in disease severity. However, there was no evidence that the density of either host group significantly affected pathogen community composition or disease severity. Therefore, variation in competence for different pathogens likely shapes pathogen community composition and disease severity but may not interact with host density to alter disease risk and impacts at small scales.
PDIP38 is a novel adaptor-like modulator of the mitochondrial AAA+ protease CLPXP
Authors: Strack Philip R. , Brodie Erica J. , Zhan Hanmiao , Schuenemann Verena J. , Valente Liz J. , Saiyed Tamanna , Zeth Kornelius , Truscott Kaye N. , Dougan David A.
Published: May 2020

Polymerase δ interacting protein of 38 kDa (PDIP38) was originally identified in a yeast two hybrid screen as an interacting protein of DNA polymerase delta, more than a decade ago. Since this time several subcellular locations have been reported and hence its function remains controversial. Our current understanding of PDIP38 function has also been hampered by a lack of detailed biochemical or structural analysis of this protein. Here we show, that human PDIP38 is directed to the mitochondrion, where it resides in the matrix compartment, together with its partner protein CLPX. PDIP38 is a bifunctional protein, composed of two conserved domains separated by an α-helical hinge region (or middle domain). The N-terminal (YccV-like) domain of PDIP38 forms an SH3-like β-barrel, which interacts specifically with CLPX, via the adaptor docking loop within the N-terminal Zinc binding domain (ZBD) of CLPX. In contrast, the C-terminal (DUF525) domain forms an Immunoglobin-like β-sandwich fold, which contains a highly conserved hydrophobic groove. Based on the physicochemical properties of this groove, we propose that PDIP38 is required for the recognition (and delivery to CLPXP) of proteins bearing specific hydrophobic degrons, potentially located at the termini of the target protein. Significantly, interaction with PDIP38 stabilizes the steady state levels of CLPXin vivo. Consistent with these data, PDIP38 inhibits the LONM-mediated turnover of CLPXin vitro.Collectively, our findings shed new light on the mechanistic and functional significance of PDIP38, indicating that in contrast to its initial identification as a nuclear protein, PIDP38 is abona fidemitochondrial adaptor protein for the CLPXP protease.
Sampling strategies for modelling above ground biomass using optimal imagery and LiDAR metrics
Authors: Murphy Seamus
Published: May 2020

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“The author has withdrawn their manuscript due to improper referencing of validation and LiDAR datasets. The author has withdrawn the work while they perform additional analysis to explore their conclusions further. Therefore, the authors do not wish this work to be cited as reference for their project. If you have any questions, please contact the corresponding author.”
Seasonal variation in brain mu-opioid receptor availability
Authors: Sun Lihua , Tang Jing , Liljenbäck Heidi , Honkaniemi Aake , Virta Jenni , Isojärvi Janne , Karjalainen Tomi , Kantonen Tatu , Nuutila Pirjo , Hietala Jarmo , Kaasinen Valtteri , Kalliokoski Kari , Hirvonen Jussi , Scheinin Harry , Helin Semi , Eerola Kim , Savontaus Eriika , Yatkin Emrah , Rinne Juha O. , Roivainen Anne , Nummenmaa Lauri
Published: May 2020

Seasonal rhythms influence mood and sociability. The brain μ-opioid receptor (MOR) system modulates a multitude of seasonally varying socioemotional functions, but its seasonal variation remains elusive with no previously reportedin vivoevidence. Here, we studied the seasonal effects on brain MOR availability via analysing a dataset (n=204) of [11C]carfentanil positron emission tomography (PET) scans of healthy volunteers. We found that seasonally varying daylength had an inverted U-shaped functional relationship with brain MOR availability. Brain regions sensitive to daylength spanned the socio-emotional brain circuits, where MOR availability formed a spring-like peak. Causal effect of daylength on brain MOR availability was further verified by apost hocexperiment with repeated PET imaging of rats (n=9) under seasonal photoperiodic simulation. Therefore, thein vivobrain MOR availability in normal humans shows significant seasonal variation, which aligns with expected seasonal variation in mood and suicidality.
Transcriptional Profiling Reveals the Transcription Factor Networks Regulating the Survival of Striatal Neurons
Authors: Yang Lin , Su Zihao , Wang Ziwu , Li Zhenmeiyu , Shang Zicong , Du Heng , Liu Guoping , Qi Dashi , Yang Zhengang , Xu Zhejun , Zhang Zhuangzhi
Published: May 2020

The striatum is structurally highly diverse, and its organ functionality critically depends on normal embryonic development. Although several studies have been conducted on the gene functional changes that occur during striatal development, a system-wide analysis of the underlying molecular changes is lacking. Here, we present a comprehensive transcriptome profile that allowed us to explore the trajectory of striatal development and identify the correlation between the striatal development and Huntington’s disease (HD). Furthermore, we applied an integrative transcriptomic profiling approach based on machine learning to systematically map a global landscape of 277 transcription factor (TF) networks. Most of these TF networks are linked to biological processes, and some unannotated genes provide information about the corresponding mechanisms. For example, we found that the Meis2 and Six3 were crucial for the survival of striatal neurons, which was verified using conditional knockout (CKO) mice. Finally, we used RNA-Seq to speculate their downstream targets.
How to quantitatively measure, assess and correct the fluorescence crosstalk in the wide-field microscopy
Authors: Tie Hieng Chiong , Lu Lei
Published: May 2020

During the multi-color fluorescence imaging, a fluorophore can be detected in the non-corresponding channel due to the broad spectra of the fluorophore and filters, resulting in the artefact called the crosstalk (crossover or bleed-through). Unfortunately, the fluorescence crosstalk is ubiquitous for the conventional fluorescence microscopy. Significant crosstalk can distort the image and lead to incorrect interpretation. Here, we introduce a simple quantitative metric, the crosstalk factor, to measure the crosstalk effect of a fluorophore on a channel in the wide-field fluorescence microscopy. We describe a cell biologist friendly protocol which should be easily implemented by cell biologists using commonly available image processing software such as ImageJ.
An anatomically accurate and personalizable head injury model: Significance of brain and white matter tract morphological variability on strain
Authors: Li Xiaogai , Zhou Zhou , Kleiven Svein
Published: May 2020

Finite element head (FE) models are important numerical tools to study head injuries and develop protection systems. The generation of anatomically accurate and subject-specific head models with conforming hexahedral meshes remains a significant challenge. The focus of this study is to present two developmental work: First, an anatomically detailed FE head model with conforming hexahedral meshes that has smooth interfaces between the brain and the cerebrospinal fluid, embedded with white matter (WM) fiber tracts; Second, a morphing approach for subject-specific head model generation via a new hierarchical image registration pipeline integrating Demons and Dramms deformable registration algorithms. The performance of the head model is evaluated by comparing model predictions with experimental data of brain-skull relative motion, brain strain, and intracranial pressure. To demonstrate the applicability of the head model and the pipeline, six subject-specific head models of largely varying intracranial volume and shape are generated, incorporated with subject-specific WM fiber tracts. DICE similarity coefficients for cranial, brain mask, local brain regions, and lateral ventricles are calculated to evaluate personalization accuracy, demonstrating the efficiency of the pipeline in generating detailed subject-specific head models achieving satisfactory element quality without further mesh repairing. The six head models are then subjected to the same concussive loading to study sensitivity of brain strain to inter-subject variability of the brain and WM fiber morphology. The simulation results show significant differences in maximum principal strain (MPS) and axonal strain (MAS) in local brain regions (one-way ANOVA test, p<0.001), as well as their locations also vary among the subjects, demonstrating the need to further investigate the significance of subject-specific models. The techniques developed in this study may contribute to better evaluation of individual brain injury and development of individualized head protection systems in the future. This study also contains general aspects the research community may find useful: on the use of experimental brain strain close to or at injury level for head model validation; the hierarchical image registration pipeline can be used to morph other head models, such as smoothed-voxel models.