bluuebunny/crossref_metadata_2025 huggingface dataset:
Pandora is on Earth: new species of Eukoenenia (Palpigradi) emerging at risk of extinction
Authors: Souza Maysa F. V. R. , Ferreira Rodrigo L.
Published: May 2018

In 2008 the change to the Brazilian legislation regarding the use of natural caves has caused an increase in the number of studies on environmental impacts involving caves. The legislation requires the classification of such environments according to their importance, and caves that are not classified highly may be irreversibly impacted. Thus, caves in rocks of high economic interest have been intensively sampled, which has resulted in the collection of several specimens of Palpigradi in them. The Iron Quadrangle (in Minas Gerais state) stands out among these areas as one the most important sources of iron ore in Brazil. Several palpigrades from this region are housed in collections: most of them belong to the edaphic species Eukoenenia ferratilis, and a small portion belong to new species that are morphologically quite distinct from E. ferratilis, with longer bodies and more elongated appendages, indicating the presence of troglomorphisms. Therefore, the present study aimed to describe three new troglobitic species of Eukoenenia, which can be distinguished morphometrically and by means of some qualitative characters. These descriptions are important for the preservation of the caves where they occur, since the presence of troglobitic species increases the relevance of the caves, which have been severely threatened by mining activities.
On the genus Spirobranchus (Annelida, Serpulidae) from the northern Red Sea, and a description of a new species
Authors: Perry Orly , Bronstein Omri , Simon-Blecher Noa , Atkins Ayelet , Kupriyanova Elena , ten Hove Harry , Levy Oren , Fine Maoz
Published: May 2018

Species of the genus Spirobranchus, commonly known as Christmas tree worms, are abundant throughout tropical Indo-Pacific and Atlantic Oceans. Information on the species inhabiting the Red Sea in general and the Gulf of Eilat (Gulf of Aqaba) in particular, has so far been very limited. Here we present a multigene phylogenetic analysis, examining both mitochondrial (Cyt-b) and nuclear (ITS2 and 18S) markers, to support the presence of four distinct Spirobranchus species in the Gulf of Eilat: S. corniculatus (including three taxa previously regarded as full species: S. gaymardi, S. cruciger, and S. corniculatus), S. cf. tetraceros, S. gardineri and a new species Spirobranchus aloni, likely endemic to the Red Sea (including two morphotypes with slightly different opercular morphology). The results presented here emphasise that the combination of molecular and in-depth morphological evaluation holds great prospects for a better understanding of species divergence and relationships.
ALMA deep field in SSA22: Survey design and source catalog of a 20 arcmin2 survey at 1.1 mm
Authors: Umehata Hideki , Hatsukade Bunyo , Smail Ian , Alexander David M , Ivison Rob J , Matsuda Yuichi , Tamura Yoichi , Kohno Kotaro , Kato Yuta , Hayatsu Natsuki H , Kubo Mariko , Ikarashi Soh
Published: May 2018

To search for dust-obscured star-formation activity in the early Universe, it is essential to obtain a deep and wide submillimeter/millimeter map. The advent of the Atacama Large Millimeter/submillimeter Array (ALMA) has enabled us to obtain such maps with sufficiently high spatial resolution to be free from source confusion. We present a new 1.1 mm-wave map obtained by ALMA in the SSA22 field. The field contains a remarkable proto-cluster at z = 3.09; therefore, it is an ideal region to investigate the role of a large-scale cosmic web on dust-obscured star formation. The typical 1σ depth of our map is 73 μJy beam−1 with a ${0^{^{\prime\prime}_{.}}5}$ resolution. Combining the present survey with earlier, archived observations, we map an area of 20 arcmin2 (71 comoving Mpc2 at z = 3.09). Within the combined survey area we have detected 35 sources at a signal-to-noise ratio (S/N) >5, with flux densities of S1.1mm = 0.43–5.6 mJy, equivalent to star-formation rates of ≳100–1000 M⊙ yr−1 at z = 3.09, for a Chabrier initial mass function: 17 sources out of 35 are new detections. The cumulative number counts show an excess by a factor of three to five compared to blank fields. The excess suggests enhanced, dust-enshrouded star-formation activity in the proto-cluster on a 10 comoving Mpc scale, indicating accelerated galaxy evolution in this overdense region.
Functional Neuroanatomy of Emotion and Its Regulation in PTSD
Authors: Fitzgerald Jacklynn M. , DiGangi Julia A. , Phan K. Luan
Published: May 2018

Posttraumatic stress disorder (PTSD) is a devastating disorder, linked to profound mental, physical, occupational, and functional impairment. In addition, it is a highly complex disorder, characterized by symptom heterogeneity across multiple domains. Nevertheless, emotion dysregulation arising from the exaggerated response to threat or from the inability to regulate negative emotional states plays a defining role in the pathophysiology of PTSD. In order to improve our understanding of how emotion dysregulation manifests in this illness, functional neuroimaging research over the past 20 years provides great insight into underlying neuroanatomy of each component of emotion dysregulation in the context of PTSD. While prior reviews exist on the topic of neuroimaging findings in PTSD, the present review synthesizes that work through the lens of emotion and its regulation. Studies that employed tasks of emotional responding and symptom provocation, implicit regulation (e.g., emotional Stroop and interference), explicit regulation (e.g., cognitive reappraisal), and fear conditioning/extinction were reviewed. Findings demonstrate that emotion dysregulation in PTSD arises from complications within a large neurocircuitry involving the amygdala, insula, hippocampus, anterior cingulate cortex, and prefrontal cortex. Although an exaggerated response in the amygdala and insula to negative emotional triggers is pervasive, PTSD is also marked by deficient appraisal, resolution, and management of negative emotional states subserved by the anterior cingulate cortex and prefrontal cortex during regulation. These findings further support the importance of studying emotion-regulation deficits in tandem with exaggerated symptom provocation in order to better understand the constellation of symptoms present in those with PTSD.
Evidenced-Based Treatment of Posttraumatic Stress Disorder: An Updated Review of Validated Psychotherapeutic and Pharmacological Approaches
Authors: Charney Meredith E. , Hellberg Samantha N. , Bui Eric , Simon Naomi M.
Published: May 2018

Learning objectives

After participating in this activity, learners should be better able to:

• Evaluate psychotherapeutic and pharmacologic approaches to treating patients with posttraumatic stress disorder.

A strong evidence base exists for psychological and pharmacological interventions for the treatment of posttraumatic stress disorder (PTSD). The published literature investigating the effectiveness of these treatments in reducing the symptoms and impairments associated with PTSD has expanded substantially in recent years. This review provides a concise overview of the empirical literature examining these treatment approaches. Evidence-based, trauma-focused therapies are recommended as first-line interventions, with the most support for cognitive- and exposure-based approaches. Prolonged exposure and cognitive processing therapy are the two most cited and rigorously investigated. Various other evidence-supported protocols are discussed. Pharmacotherapies can be used when evidence-based psychotherapies are not available or are ineffective, or on the basis of patient preference. Pharmacotherapy with the most support for PTSD includes selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. Evidence supports the implementation of these interventions across genders, populations, and settings. Given that little research directly compares the effectiveness of different PTSD interventions and their mechanisms of action, it remains uncertain how to best select and tailor treatments to optimize individual outcomes. Future directions and novel, ongoing research are discussed.
Glucocorticoids and Hippocampal Structure and Function in PTSD
Authors: Szeszko Philip R. , Lehrner Amy , Yehuda Rachel
Published: May 2018

This review examines the putative link between glucocorticoid and hippocampal abnormalities in posttraumatic stress disorder (PTSD). Increased glucocorticoid receptor (GR) sensitivity in PTSD may permit enhanced negative feedback inhibition of cortisol at the pituitary, hypothalamus, or other brain regions comprising the hypothalamic-pituitary-adrenal (HPA) axis and would be expected to affect other physiological systems that are regulated by glucocorticoids. Molecular and transcriptional studies of cortisol are consistent with the hypothesis that cortisol actions may be amplified in PTSD as a result of enhanced GR sensitivity in monocytes and some brain regions, although cortisol levels themselves are unchanged and oftentimes lower than normal. Concurrently, magnetic resonance imaging studies have demonstrated that individuals with PTSD have smaller hippocampal volume than individuals without PTSD. Initial hypotheses regarding the mechanism underlying hippocampal alterations in PTSD focused on elevated glucocorticoid levels in combination with extreme stress as the primary cause, but this explanation has not been well supported in human studies. Lack of data from neuroimaging studies preclude a firm link between PTSD onset and hippocampal volume changes. Rather, the available evidence is consistent with the possibility that smaller hippocampal volume (like reduced cortisol levels and enhanced GR sensitivity) may be a vulnerability factor for developing the disorder; limitations of hippocampal-based models of PTSD are described. We further review neuroimaging studies examining hippocampal structure and function following manipulation of glucocorticoid levels and also examining changes in the hippocampus in relationship to other brain regions. Evidence that the GR may be an important therapeutic target for the treatment of PTSD, especially for functions subserved by the hippocampus, is discussed. Implications of the current review for future research are described, with an emphasis on the need to integrate findings of glucocorticoid abnormalities with functional-imaging paradigms to formulate a comprehensive model of HPA-axis functioning in PTSD.
Fear Processing, Psychophysiology, and PTSD
Authors: Norrholm Seth Davin , Jovanovic Tanja
Published: May 2018

The processing and regulation of fear is one of the key components of posttraumatic stress disorder (PTSD). Fear can involve both acute and potential threats that can manifest in different behaviors and result from activity within different neural nodes and networks. Fear circuits have been studied extensively in animal models for several decades and in human neuroimaging research for almost 20 years. Therefore, the centrality of fear processing to PTSD lends the disorder to be more tractable to investigation at the level of brain and behavior, and provides several observable phenotypes that can be linked to PTSD symptoms. Moreover, psychophysiological metrics of fear conditioning offer tools that can be used to shift diagnostic paradigms in psychiatry toward neurobiology—consistent with a Research Domain Criteria approach to PTSD. In general, mammalian fear processing can be divided into fear learning (or acquisition), during which an association develops between previously neutral stimuli and aversive outcomes, and fear extinction, in which the latter associations are suppressed by a new form of learning. This review describes translational research in both fear acquisition and extinction, along with their relevance to PTSD and PTSD treatment, focusing specifically on the empirical value and potential clinical utility of psychophysiological methods.
Understanding Resilience and Preventing and Treating PTSD
Authors: Horn Sarah R. , Feder Adriana
Published: May 2018

Resilience is defined as the dynamic ability to adapt successfully in the face of adversity, trauma, or significant threat. Some of the key early studies of resilience were observational studies in children. They were followed by research in adults, studies testing interventions to promote resilience in different populations, and a recent upsurge of studies on the underlying genomic and neurobiological mechanisms. Neural and molecular studies in preclinical models of resilience are also increasingly identifying active stress adaptations in resilient animals. Knowledge gained from animal and human studies of resilience can be harnessed to develop new preventive interventions to enhance resilience in at-risk populations. Further, treatment interventions focused on enhancing potentially modifiable protective factors that are consistently linked to psychological resilience can enrich currently available treatment interventions for individuals with posttraumatic stress disorder (PTSD). Translating our expanding knowledge of the neurobiology of resilience additionally promises to yield novel therapeutic strategies for treating this disabling condition. This review summarizes the vast field of resilience research spanning genomic, psychosocial, and neurobiological levels, and discusses how findings have led and can lead to new preventive and treatment interventions for PTSD.
Experience and Prognosis of Systemic Neonatal Thrombosis at a Level III NICU
Authors: Unal Sevim , Gönülal Deniz , Siyah Bilgin Betül , Koşan Çulha Vildan , Yarali Neşe
Published: May 2018

Objective:

The objective of this article was to evaluate neonates diagnosed systemic thrombosis and their outcomes.

Methods:

We retrospectively evaluated data of neonatal systemic thrombosis between January 2011 and December 2016.

Results:

Among 4376 hospitalized, 30 neonates (0.69%) were diagnosed systemic thrombosis. Their mean birth weight was 2422±1152 g (680 to 4750 g), gestational age was 35±5.4 weeks (25 to 41 wk). There were 25 neonates (83.3%) with venous, 5 patients (16.7%) with arterial thrombosis. The most common sites that thrombi localized were major vessels (n=11) and central nervous system (n=8). Central catheter insertion (76.7%) and prematurity (46.7%) were the most common risk factors. Congenital prothrombotic risk factors included G1691A mutation in factor V Leiden (n=1), mutation in factor XIII (n=1), C677T mutation in methylenetetrahydrofolate reductase (n=6). More than 1 congenital risk factor was identified in 5 patients. The patients were treated with low-molecular weight heparin. The mortality rate was 13.3% (n=4). Two patients required amputation (left foot, left upper extremity). Unilateral renal atrophy (n=1), cerebral palsy (n=2), hemiparesis (n=1) were identified among followed 24 patients.

Conclusions:

Critically ill neonates are at risk for thrombosis, and devastating consequences can result. As indwelling catheters and prematurity are important, careful monitorization, early diagnosis and therapy, cautious care of central catheter might reduce the incidence and adverse outcome.
Incidental Metastatic Melanoma Identified on 68Ga–Prostate-Specific Membrane Antigen PET/CT for Metastatic Prostate Cancer
Authors: Snow Hayden A. , Hofman Michael S. , Mitchell Catherine A. , Gyorki David E. , Smith Myles J.F.
Published: May 2018

A 78-year-old man with a history of surgically treated prostate cancer and melanoma underwent 68Ga-prostate-specific membrane antigen (PSMA) PET/CT for biochemical recurrence of his prostate cancer. This revealed locoregionally recurrent prostate cancer and a separate PSMA-avid nodule in his left arm. Subsequent 18F-FDG PET/CT and excision confirmed this to be an in-transit melanoma metastasis. Prostate-specific membrane antigen PET/CT has become a widely used and valuable tool in the assessment of prostate cancer, particularly biochemically recurrent. Uptake of PSMA has been described in a multitude of different benign and malignant conditions, but it has only rarely been documented in melanoma.
Monitoring of Conjunctival Microcirculation Reflects Sublingual Microcirculation in Ovine Septic and Hemorrhagic Shock
Authors: Hessler Michael , Arnemann Philip-Helge , Zamit Frédéric , Seidel Laura , Kampmeier Tim-Gerald , Kathöfer Ulrich , Alnawaiseh Maged , Tchaichian Saman , Rehberg Sebastian , Ertmer Christian
Published: May 2018

Introduction:

The conjunctival region may serve as an alternative site for microcirculatory measurements. The present study was performed to investigate the correlation of sublingual and conjunctival microcirculation in ovine models of septic and hemorrhagic shock.

Methods:

Septic shock was induced in 10 sheep by inoculation of feces into the peritoneal cavity until mean arterial pressure (MAP) was <60 mm Hg and arterial lactate level was ≥1.8 mmol· L−1. In another 10 sheep, hemorrhagic shock was induced by stepwise blood withdrawal of 3×10 mL·kg−1. Systemic hemodynamics and parameters of blood gas analysis were analyzed. Conjunctival and sublingual microcirculation were monitored and analyzed according to current recommendations. Parameters were measured at baseline and at shock time.

Results:

Septic shock resulted in a significant drop in MAP and cardiac index (CI), and an increase in arterial lactate levels. While the total vessel density (TVD) in the sublingual microcirculation was relatively well maintained, the perfused vessel density (PVD) and the microvascular flow index (MFI) were significantly reduced in septic shock. Hemorrhagic shock reduced MAP and CI, and increased arterial lactate levels. TVD was relatively unchanged in hemorrhagic shock, while PVD and MFI were significantly decreased. The conjunctival microcirculation showed similar changes to the sublingual microcirculation in both models.

Conclusions:

The findings of the current study support the proposed use of the conjunctiva as an alternative site for microcirculatory monitoring in hemorrhagic and septic shock. Further studies should focus on the impact of therapy and the loss of correlation between the different microcirculatory regions in advanced shock.
Total Pharyngo-esophageal Stenosis: A New Surgical Procedure Using Modified Retrograde Transillumination Approach
Authors: Lechien Jerome R. , Dapri Giovanni , Saussez Sven
Published: May 2018

We performed a modified combined anterograde-retrograde dilatation in a 60-year-old woman with complete pharyngo-esophageal stricture (PES). With a large endoscopic view from the upper (laryngoscope) and lower (pediatric gastroscope introduced via gastrostomy tube) parts of the PES, the approach consisted of a retrograde puncture of the complete PES by transillumination to take the guide coming from the pediatric endoscope. The guide was pulled through the mouth and the PES dilatation was made using successive boogies of various diameters through the guide. Finally, a salivary bypass was placed to maintain the diameter of the pharyngo-esophageal way. The surgical approach was performed in 25 minutes without short, medium, and long-term complications. The patient started oral alimentation the day after the surgery, and the salivary bypass was removed after 6 months. The subject had no recurrence of the PES at 5 years.
Sensory prediction errors, not performance errors, update memories in visuomotor adaptation
Authors: Lee Kangwoo , Oh Youngmin , Izawa Jun , Schweighofer Nicolas
Published: May 2018

Sensory prediction errors are thought to update memories in motor 1 adaptation, but the role of performance errors is largely unknown. To dissociate these errors, we manipulated visual feedback during fast shooting movements under visuomotor rotation. Participants were instructed to strategically correct for performance errors by shooting to a neighboring target in one of four conditions: following the movement onset, the main target, the neighboring target, both targets, or none of the targets disappeared. Participants in all conditions experienced a drift away from the main target following the strategy. In conditions where the main target was shown, participants often tried to minimize performance errors caused by the drift by generating corrective movements. However, despite differences in performance during adaptation between conditions, memory decay in a delayed washout block was indistinguishable between conditions. Our results thus suggest that, in visuomotor adaptation, sensory predictions errors, but not performance errors, update the slow, temporally stable, component of motor memory.
Early transcriptional responses after dengue vaccination mirror the response to natural infection and predict neutralizing antibody titers
Authors: Popper Stephen J. , Strouts Fiona R. , Lindow Janet C. , Cheng Henry K. , Montoya Magelda , Balmaseda Angel , Durbin Anna P. , Whitehead Stephen S. , Harris Eva , Kirkpatrick Beth D. , Relman David A.
Published: May 2018

Background: Several promising live attenuated virus (LAV) dengue vaccines are in development, but information about innate immune responses and early correlates of protection are lacking. Methods: We characterized human genome-wide transcripts in whole blood from 10 volunteers at 11 time-points after immunization with the dengue virus type 3 (DENV-3) component of the NIH dengue vaccine candidate TV003 and from 30 hospitalized children with acute primary DENV-3 infection. We compared day-specific gene expression patterns with subsequent neutralizing antibody (NAb) titers. Results: The transcriptional response to vaccination was largely confined to days 5-20 and was dominated by an interferon-associated signature and a cell cycle signature that peaked on days 8 and 14, respectively. Changes in transcript abundance were much greater in magnitude and scope in symptomatic natural infection than following vaccination (maximum fold-change >200 versus 21 post-vaccination; 3,210 versus 286 transcripts with significant fold-change), but shared gene modules were induced in the same sequence. The abundance of 131 transcripts on days 8 and 9 post-vaccination was strongly correlated with NAb titers measured 6 weeks post-vaccination. Conclusions: LAV dengue vaccination elicits early transcriptional responses that mirror those found in symptomatic natural infection and provide candidate early markers of protection against DENV infection.
Non-mydriatic chorioretinal imaging in a transmission geometry and application to retinal oximetry
Authors: Weber Timothy D. , Mertz Jerome
Published: May 2018

The human retina is typically imaged in a reflection geometry, where light is delivered through the pupil and images are formed from the light reflected back from the retina. In this configuration, artifacts caused by retinal surface reflex are often encountered, which complicate quantitative interpretation of the reflection images. We present an alternative illumination method, which avoids these artifacts. The method uses deeply penetrating near-infrared (NIR) light delivered transcranially from the side of the head, and exploits multiple scattering to redirect a portion of the light towards the posterior eye. This unique transmission geometry simplifies absorption measurements and enables flash-free, non-mydriatic imaging as deep as the choroid. Images taken with this new transillumination approach are applied to retinal oximetry.

OCIS codes: (170.4460) Ophthalmic optics and devices; (170.2945) Illumination design; (170.1470) Blood or tissue constituent monitoring.
Drug Target Identification and Virtual Screening in Pursuit of Phytochemical Intervention ofMycobacterium chelonae
Authors: Basharat Zarrin , Zaib Shumaila , Yasmin Azra , Tong Yigang
Published: May 2018

Mycobacterium chelonaeis a rapidly growing mycobacterium present in the environment. It is associated with skin and soft tissue infections including abscess, cellulitis and osteomyelitis. Other infections by this bacterium are post-operative/transplant-associated, catheter, prostheses and even concomitant to haemodialytic procedures. In this study, we employ a subtractive genomics approach to predict the potential therapeutic candidates, intended for experimental research against this bacterium. A computational workflow was devised and executed to procure core proteome targets essential to the pathogen but with no similarity to the human host. Initially, essentialMycobacterium chelonaeproteins were predicted through homology searching of core proteome content from 19 different bacteria. Druggable proteins were then identified and N-acetylglucosamine-1-phosphate uridyltransferase (GlmU) was chosen as a case study from identified therapeutic targets, based on its important bifunctional role. Structure modeling was followed by virtual screening of phytochemicals (N > 10,000) against it. 4,4’-[(1E)-5-hydroxy-4-(methoxymethyl)-1-pentene-1,5-diyl]diphenol, apigenin-7-O-beta-gluconopyranoside and methyl rosmarinate were screened as compounds having best potential for binding GlmU. Phytotherapy helps curb the menace of antibiotic resistance so treatment ofMycobacterium chelonaeinfection through this method is recommended.
Gap perception in bumblebees
Authors: Ravi Sridhar , Bertrand Olivier , Siesenop Tim , Manz Lea-Sophie , Doussot Charlotte , Fisher Alex , Egelhaaf Martin
Published: May 2018

A number of insects fly over long distances below the natural canopy where the physical environment is highly cluttered consisting of obstacles of varying shape, size and texture. While navigating within such environments animals need to perceive and disambiguate environmental features that might obstruct their flight. The most elemental aspect of aerial navigation through such environments is gap identification and passability evaluation. We used bumblebees to seek insights into the mechanisms used for gap identification when confronted with an obstacle in their flight path and behavioral compensations employed to assess gap properties. Initially, bumblebee foragers were trained to fly though an unobstructed flight tunnel that led to a foraging chamber. After the bees were familiar with this situation, we placed a wall containing a gap that unexpectedly obstructed the flight path on a return trip to the hive. The flight trajectories of the bees as they approached the obstacle wall and traversed the gap were analyzed in order to evaluate their behavior as a function of the distance between the gap and a background wall that was placed behind the gap. Bumblebees initially decelerate when confronted with an unexpected obstacle. Deceleration was first noticed when the obstacle subtended around 35° on the retina but also depended on the properties of the gap. Subsequently the bees gradually traded off their longitudinal velocity to lateral velocity and approached the gap increasing lateral displacements and lateral velocity. Bumblebees shaped their flight trajectory depending on the salience of the gap, in our case, indicated by the optic flow contrast between the region within the gap and on the obstacle, which increases with decreasing distance between the gap and the background wall. As the optic flow contrast decreased the bees spent increasing time moving laterally across the obstacles. During these repeated lateral maneuvers the bees are likely assessing gap geometry and passability.
Neolithic and Medieval virus genomes reveal complex evolution of Hepatitis B
Authors: Krause-Kyora Ben , Susat Julian , Key Felix M. , Kühnert Denise , Bosse Esther , Immel Alexander , Rinne Christoph , Kornell Sabin-Christin , Yepes Diego , Franzenburg Sören , Heyne Henrike O. , Meier Thomas , Lösch Sandra , Meller Harald , Friederich Susanne , Nicklisch Nicole , Alt Kurt Werner , Schreiber Stefan , Tholey Andreas , Herbig Alexander , Nebel Almut , Krause Johannes
Published: May 2018

The hepatitis B virus (HBV) is one of the most widespread human pathogens known today, yet its origin and evolutionary history are still unclear and controversial. Here, we report the analysis of three ancient HBV genomes recovered from human skeletons found at three different archaeological sites in Germany. We reconstructed two Neolithic and one medieval HBV genomes byde novoassembly from shotgun DNA sequencing data. Additionally, we observed HBV-specific peptides using paleo-proteomics. Our results show that HBV circulates in the European population for at least 7000 years. The Neolithic HBV genomes show a high genomic similarity to each other. In a phylogenetic network, they do not group with any human-associated HBV genome and are most closely related to those infecting African non-human primates. These ancient virus forms appear to represent distinct lineages that have no close relatives today and went possibly extinct. Our results reveal the great potential of ancient DNA from human skeletons in order to study the long-time evolution of blood borne viruses.
A Cell Penetrating Peptide from SOCS-1 Prevents Ocular Damage in Experimental Autoimmune Uveitis
Authors: Ahmed Chulbul M. , Massengill Michael T. , Ildefonso Cristhian J. , Johnson Howard M. , Lewin Alfred S.
Published: May 2018

We describe an immunosuppressive peptide corresponding to the kinase inhibitory region (KIR) of the intracellular checkpoint protein suppressor of cytokine signaling 1 (SOCS-1) that binds to the phospho-tyrosine containing regions of the tyrosine kinases JAK2 and TYK2 and the adaptor protein MAL, and thereby inhibits signaling downstream from these signaling mediators. The peptide, SOCS1-KIR, is thus capable of downregulating overactive JAK/STAT or NF-kB signaling in somatic cells, including those in many compartments of the eye. Attachment of poly-arginine to this peptide (R9-SOCS1-KIR) allows it to penetrate the plasma membrane in aqueous media. R9-SOCS1-KIR was tested in ARPE-19 cells and was found to attenuate mediators of inflammation by blocking the inflammatory effects of IFNγ, TNFα, or IL-17A. R9-SOCS1-KIR also protected against TNFα or IL-17A mediated damage to the barrier properties of ARPE-19 cells, as evidenced by immunostaining with the tight junction protein, zona occludin 1 (ZO-1), and measurement of transepithelial electrical resistance (TEER). Experimental autoimmune uveitis (EAU) was generated in B10.RIII mice using a peptide of interphotoreceptor retinal binding protein (IRBP161-180) as immunogen. Topical administration of R9-SOCS1-KIR protected ocular structure and function as seen by fundoscopy, optical coherence tomography (OCT), and electroretinography (ERG). The ability R9-SOCS1-KIR to suppress ocular inflammation and preserve barrier properties of retinal pigment epithelium makes it a potential candidate for aqueous treatment of autoimmune uveitis.

Highlights

peptide corresponding to the kinase inhibitory region of SOCS-1 linked to poly-arginine (R9-SOCS1-KIR) and its inactive control peptide were chemically synthesized.

R9-SOCS1-KIR attenuated pro-inflammatory effects of IFNγ, TNFα, and IL-17 in ARPE-19 cells, thus showing a simultaneous inhibition Th1 and Th17 cell functions.

Damage to barrier properties of ARPE-19 cells caused by TNFα or IL-17 was prevented in the presence of R9-SOCS1-KIR.

Topical administration of R9-SOCS1-KIR prevented ocular damage in a mouse model of experimental autoimmune uveitis.
Massive single-cell RNA-seq analysis and imputation via deep learning
Authors: Deng Yue , Bao Feng , Dai Qionghai , Wu Lani F. , Altschuler Steven J.
Published: May 2018

Recent advances in large-scale single cell RNA-seq enable fine-grained characterization of phenotypically distinct cellular states within heterogeneous tissues. We present scScope, a scalable deep-learning based approach that can accurately and rapidly identify cell-type composition from millions of noisy single-cell gene-expression profiles.
Improved localizers and anatomical images to enable phosphorus magnetic resonance spectroscopy of liver metastasis at 7T
Authors: Rivera Debra , Kalleveen Irene , Arteaga de Castro Catalina , van Laarhoven Hanneke , Klomp Dennis , van der Kemp Wybe , Stoker Jaap , Nederveen Aart
Published: May 2018

Phosphorus spectroscopy (31P) at 7T (300 MHz) enables clinically-relevant spatial resolutions and time scales with high potential for monitoring response to cancer treatment. However, at 7T collecting a radiological-grade anatomical image of the liver—which is required for performing localized 31P spectroscopy—presents a challenge. Unlike lower field-strength scanners, there is no body coil in the bore of the 7T and despite inadequate penetration depth (<10 cm), surface coils are the current state-of-the-art for acquiring anatomical (1H) images. Therefore, thus far, high field 31P spectroscopy has been limited to diffuse liver disease. However, the use of antennas enable improved penetration depths at 300 MHz, and when combined with parallel transmit, can enable body imaging at 7T. We have developed a protocol for imaging liver metastases of patients using parallel transmit and 31P spectroscopy at 7T. We used a custom-made liver coil consisting of eight 30-cm dipole antennas tuned to the proton (300 MHz) frequency, and two partially overlapping 20-cm-diameter loops tuned for 31P (120 MHz). The field of view afforded by the two antennas underneath the 31P loops is not sufficient to image the complete boundaries of the liver for chemical shift imaging (CSI) planning and region-of-interest-based B0 shimming. The liver and full axial slice of the abdomen was imaged with eight transmit/receive antennas using parallel transmit B1-shimming to overcome image voids. Through the use of antennas we overcome the challenges for multi-parametric body imaging, and can begin to explore the possibility of monitoring the response of patients with liver metastasis to cancer treatments.

ABBREVIATIONS

(PDE)

Phosphodiester

(GPE)

Glycerophosphoethanolamine

(GPC)

Glycerophosphocholine

(PME)

Phosphomonoesther

(PC)

Phosphocholine

(PE)

Phosphoethanalomine

(PI)

Inorganic Phosphate

(PCR)

Phosphocreatine

(PTC)

Phophotidylcholine

(CSI)

Chemical Shift Imaging

(GE)

Gradient Echo

(L)

Left

(R)

Right

(H)

Head

(F)

Foot

(A)

Anterior

(P)

Posterior

(TR)

Repetition Time

(TE)

Echo Time
Inward tubulation of the plasma membrane expedites membrane exchange and receptor presentation
Authors: Yao Long-fang , Zhou Li , Zhang Ruilin , Cai Liang
Published: May 2018

The plasma membrane is a crucial barrier between the cell and its external environment, and it also enables efficient passage of materials and information. Membrane vesicle trafficking allows precise delivery of materials but is rather inefficient. The mechanism for efficient membrane exchange remains elusive. Here we describe inward tubulation of the plasma membrane (PM tubes) that extends deep into the cytoplasm. These widespread PM tubes elongate along microtubules and are stabilized by actin filaments and cholesterol. PM tubes are preferred sites for connection between the endoplasmic reticulum and the plasma membrane. PM tubes facilitate receptor presentation at the surface of cells, possibly also shortening the distance for transported cargo to reach the external environment.

In Brief

A new type of tubular membrane structures was discovered in cells, revealing a shortcut that cells employ to expedite material exchange with their external environment.

Highlights

Inward tubulation of the plasma membrane (PM tubes), transiently interacts with the Golgi apparatus

Microtubule side-binding proteins pull PM tubes, while actin filaments and cholesterol stabilize PM tubes

PM tubes are preferred sites where ER-PM contacts form in response to increased cytoplasmic calcium concentration

PM tubes are preferred sites for the surface presentation of GLUT1 upon glucose deprivation
Detecting differential transcription factor activity from ATAC-seq data
Authors: Tripodi Ignacio J. , Allen Mary A. , Dowell Robin D.
Published: May 2018

Transcription factors are managers of the cellular factory, and key components to many diseases. Many non-coding single nucleotide polymorphisms affect transcription factors, either by directly altering the protein or its functional activity at individual binding sites. Here we first briefly summarize high throughput approaches to studying transcription factor activity. We then demonstrate, using published chromatin accessibility data (specifically ATAC-seq), that the genome wide profile of TF recognition motifs relative to regions of open chromatin can determine the key transcription factor altered by a perturbation. Our method of determining which TF are altered by a perturbation is simple, quick to implement and can be used when biological samples are limited. In the future, we envision this method could be applied to determining which TFs show altered activity in response to a wide variety of drugs and diseases.
MEF2C is a new regulator of the human articular chondrocyte phenotype
Authors: Lazzarano S. , Murphy C.L.
Published: May 2018

MEF2C plays a role in diverse tissues, most notably heart, brain, eyes and developing bones. Here we report for the first time that MEF2C is present and active in the permanent articular cartilage in humans which lines and protects our joints throughout life. We show that MEF2C directly targets cartilage master regulator gene SOX9, and SOX9, in turn, regulates MEF2C in a novel positive feedback loop maintaining high expression levels of both transcription factors, and consequently stabilising the articular chondrocyte phenotype and helping prevent hypertrophy and subsequent calcification and vascularisation. We propose that MEF2C and SOX9 may show similar cooperative activity in other tissues, and across a range of adult murine tissues we found co-expression of both transcription factors in cartilage, trachea, brain, eyes and heart. Strikingly, all of these tissues are prone to calcification and further study of MEF2C/SOX9 cooperativity in these organs will be revealing.
Observed Antibody Space: a resource for data mining next generation sequencing of antibody repertoires
Authors: Kovaltsuk Aleksandr , Leem Jinwoo , Kelm Sebastian , Snowden James , Deane Charlotte M. , Krawczyk Konrad
Published: May 2018

Antibodies are immune system proteins that recognize noxious molecules for elimination. Their sequence diversity and binding versatility have made antibodies the primary class of biopharmaceuticals. Recently it has become possible to query their immense natural diversity using next-generation sequencing of immunoglobulin gene repertoires (Ig-seq). However, Ig-seq outputs are currently fragmented across repositories and tend to be presented as raw nucleotide reads, which means nontrivial effort is required to reuse the data for analysis. To address this issue, we have collected Ig-seq outputs from 53 studies, covering more than half a billion antibody sequences across diverse immune states, organisms and individuals. We have sorted, cleaned, annotated, translated and numbered these sequences and make the data available via our Observed Antibody Space (OAS) resource at antibodymap.org. The data within OAS will be regularly updated with newly released Ig-seq datasets. We believe OAS will facilitate data mining of immune repertoires for improved understanding of the immune system and development of better biotherapeutics.
High-resolution analysis of the peptidoglycan composition inStreptomyces coelicolor
Authors: van der Aart Lizah T. , Spijksma Gerwin K. , Harms Amy , Vollmer Waldemar , Hankemeier Thomas , van Wezel Gilles P.
Published: May 2018

The bacterial cell wall maintains cell shape and protects against bursting by the turgor. A major constituent of the cell wall is peptidoglycan (PG), which is continuously modified to allow cell growth and differentiation through the concerted activity of biosynthetic and hydrolytic enzymes. Streptomycetes are Gram-positive bacteria with a complex multicellular life style alternating between mycelial growth and the formation of reproductive spores. This involves cell-wall remodeling at apical sites of the hyphae during cell elongation and autolytic degradation of the vegetative mycelium during the onset of development and antibiotic production. Here, we show that there are distinct differences in the cross-linking and maturation of the PG between exponentially growing vegetative hyphae and the aerial hyphae that undergo sporulation. LC-MS/MS analysis identified over 80 different muropeptides, revealing that major PG hydrolysis takes place over the course of mycelial growth. Half of the dimers lack one of the disaccharide units in transition-phase cells, most likely due to autolytic activity. De-acetylation of MurNAc to MurN was particularly pronounced in spores, suggesting that MurN plays a role in spore development. Taken together, our work highlights dynamic and growth phase-dependent construction and remodeling of PG inStreptomyces.

IMPORTANCE

Streptomycetes are bacteria with a complex lifestyle, which are model organisms for bacterial multicellularity. From a single spore a large multigenomic, multicellular mycelium is formed, which differentiates to form spores. Programmed cell death is an important event during the onset of morphological differentiation. In this work we provide new insights into the changes in the peptidoglycan architecture over time, highlighting changes over the course of development and between growing mycelia and spores. This revealed dynamic changes in the peptidoglycan when the mycelia age, showing extensive PG hydrolysis and in particular an increase in the proportion of 3-3-cross-links. Additionally, we identified a muropeptide that is highly abundant specifically in spores, which may relate to dormancy and germination.
Comparative metagenomics of coalbed methane microbial communities reveals biogenic methane potential in the Appalachian Basin
Authors: Ross Daniel E. , Lipus Daniel , Gregory Kelvin B. , Gulliver Djuna
Published: May 2018

Natural gas is a major source of global energy, and a large fraction is generated in subsurface coalbed deposits. Microbial communities within coalbed deposits impact methane production, and as a result contribute to global carbon cycling. The process of biogenic coal-to-methane conversion is not well understood. Here we demonstrate the first read- and assembly-based metagenome profiling of coal-associated formation waters, resulting in the recovery of over 40 metagenome-assembled genomes (MAGs) from eight individual coalbed methane wells in the Appalachian Basin. The majority of samples contained hydrogenotrophic methanogens, which were present in higher relative abundances than was previously reported for other coalbed basins. The abundance of Archaea and salinity were positively correlated, suggesting that salinity may be a controlling factor for biogenic coalbed methane. Low-abundance coalbed microbial populations were functionally diverse, while the most dominant organisms exhibit a high degree of genomic and functional similarities. Basin-specific pan-metagenome clustering suggests lower abundant and diverse bacterial communities are shaped by local basin parameters. Our analyses show Appalachian Basin coalbed microbial communities encode for the potential to convert coal into methane, which may be used as an indicator of potential biogenic methane production for future well performance and increased well longevity.
Price and perceived product quality: a comparison of denim jeans in three price categories
Authors: Ghaani Farashahi Behnoosh , Easter Elizabeth , Annett-Hitchcock Kate
Published: May 2018

Purpose

The purpose of this paper is to compare a set of product specifications to evaluate appearance and performance characteristics of denim jeans at three price categories, and identify any relationships between price and product quality.

Design/methodology/approach

This research is as a quasi-experimental laboratory study. The product specifications of jeans are identified. Next, the appearance and performance characteristics of jeans are examined initially and after one and five repeated laundering cycles. The data are analyzed within and between each price category to identify any possible relationship between price and product quality.

Findings

The price category of jeans does not necessarily reflect different dimensions of product quality. Although higher priced jeans had superior product specifications and visual appearance, they did not show superior performance with respect to all elements of fit, durability, and color performance when these three factors were measured through laboratory testing.

Research limitations/implications

The limitations of this study from a research perspective include a small sample size, gender-focused sample selection. and the focus on only three retail categories. These limitations impact the generalizability of the results but could serve as a basis for similar studies. The evaluated product quality attributes were limited to intrinsic/measurable characteristics. Future studies should consider the extrinsic attributes of quality, especially as they are related to consumer’s purchasing decision.

Practical implications

Retailers in moderate and budget price categories can benefit from educating consumers about the quality attributes of jeans that would ultimately influence their post-purchase experience and are not necessarily related to the product’s price category. Educators can use this information to assist in teaching students about the multiple dimensions of materials and assembly choices, and how this will impact their final products as they are learning the apparel product development process.

Originality/value

The focus of this study on the quantification of intrinsic product attributes is unique and provides measurable data for product evaluation by consumer researchers and industry. The results of this research identify the strengths and weaknesses in the appearance and performance characteristics of jeans in different price categories, and how those may affect consumers’ purchase intention.
Taking the technical microbiome into the next decade
Authors: De Vrieze Jo , Boon Nico , Verstraete Willy
Published: May 2018

The ‘microbiome’ has become a buzzword. Multiple new technologies allow to gather information about microbial communities as they evolve under stable and variable environmental conditions. The challenge of the next decade will be to develop strategies to compose and manage microbiomes. Here, key aspects are considered that will be of crucial importance for future microbial technological developments. First, the need to deal not only with genotypes but also particularly with phenotypes is addressed. Microbial technologies are often highly dependent on specific core organisms to obtain the desired process outcome. Hence, it is essential to combine omics data with phenotypic information to invoke and control specific phenotypes in the microbiome. Second, the development and application of synthetic microbiomes is evaluated. The central importance of the core species is a no‐brainer, but the implementation of proper satellite species is an important route to explore. Overall, for the next decade, microbiome research should no longer almost exclusively focus on its capacity to degrade and dissipate but rather on its remarkable capability to capture disordered components and upgrade them into high‐value microbial products. These products can become valuable commodities in the cyclic economy, as reflected in the case of ‘reversed sanitation’, which is introduced here.