bluuebunny/crossref_metadata_2025 huggingface dataset:
Imaging Features and Complications of Female Urethral Diverticula
Authors: Louden P. Connor , Ornan Afshan , Culp Stephen , Krishnaraj Arun
Published: November 2018

A female urethral diverticulum is a focal outpouching of the urethra into the urethrovaginal potential space.1 The reported incidence of urethral diverticula in women is approximately 1% to 6%, with the diagnosis typically occurring between the third and sixth decades of life.2 In symptomatic women, the classic clinical triad of dysuria, dyspareunia, and postvoid dribbling is present (the “three Ds”).1 However, women with urethral diverticula are more commonly asymptomatic or present with an array of nonspecific genitourinary symptoms such as urinary frequency and urgency, chronic or recurrent urinary tract infections, hematuria, and stress or urge incontinence. More atypical presentations include urinary retention, urethral pain, purulent urethral discharge, pelvic or suprapubic pain, or a tender mass.1
,
3 Because of the varied clinical presentation, a urethral diverticulum should be considered in all women with unexplained lower genitourinary tract symptoms.3 Other differential diagnoses for women presenting with unexplained lower genitourinary symptoms include interstitial cystitis, urethral syndrome (ie, urinary urgency and frequency with negative urine cultures); Skene's gland abscess; Gartner duct cyst; ectopic ureterocele; periurethral fibrosis; urethrocele; endometrioma; urethral or vaginal neoplasm; and collagen bulking agents used for the treatment of stress urinary incontinence.1
,
3 The correct diagnosis of a urethral diverticulum is critical, as potential complicating features include recurrent infection, calculus formation, and intradiverticular malignancy.2 Moreover, late diagnosis of urethral diverticulum is associated with high risk of postoperative complications, high recurrence rate after surgery, and, if malignancy is present, early metastases.1
Tenascin C, Fibronectin, and Tumor-Stroma Ratio in Pancreatic Ductal Adenocarcinoma
Authors: Leppänen Joni , Lindholm Ville , Isohookana Joel , Haapasaari Kirsi-Maria , Karihtala Peeter , Lehenkari Petri P. , Saarnio Juha , Kauppila Joonas H. , Karttunen Tuomo J. , Helminen Olli , Huhta Heikki
Published: November 2018

Objectives

Pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant stroma with increased expression of tenascin C and fibronectin. Their role and tumor-stroma ratio in PDAC are not well known. The aim of this study was to evaluate tenascin C and fibronectin expression and tumor-stroma ratio and their prognostic relevance in PDAC.

Methods

Ninety-five resected PDACs were immunohistochemically stained for tenascin C and fibronectin, and the expression was separately assessed in tumor bulk and front. Tumor-stroma ratio was determined with sections stained with hematoxylin-eosin.

Results

Tenascin C and fibronectin were abundantly expressed in the stroma of PDAC, but absent in adjacent normal pancreatic tissue. Fibronectin expression of the bulk was associated with high T class (P = 0.045). In the main analysis, tenascin C and fibronectin expression and tumor-stroma ratio were not associated with patient survival. In a subgroup analysis of early-stage PDAC (T1–T2 tumors), high tenascin C expression in the tumor bulk was associated with poor prognosis (hazard ratio, 8.23; 95% confidence interval, 2.71–24.96).

Conclusions

Tenascin C and fibronectin are abundantly expressed in PDAC, but they seem to have no major association with patient survival. However, in early-stage PDAC, tenascin C expression of the tumor bulk may have prognostic impact. Tumor-stroma ratio has no prognostic value in PDAC.
Proinsulin Expressing Neuroendocrine Tumors of the Pancreas
Authors: Celli Romulo , Tang Laura H. , Cai Guoping , Freedman-Weiss Mollie , Colunga Monica , Salem Ronald R. , Majumdar Sachin , Jain Dhanpat
Published: November 2018

Objectives

Rare cases of pancreatic neuroendocrine tumors (PNETs) that produce only proinsulin (PI) and manifest with hypoglycemia have been reported. Proinsulin expression in PNET has not been systematically studied, and the clinicopathologic features of such tumors remain unknown.

Methods

We studied expression of PI by immunohistochemistry (IHC) in 136 PNETs from 2 high-volume surgical oncology centers and assessed all available clinicopathologic data.

Results

Thirty-six (26%) of PNETs were positive for PI by IHC, most (89%) of which coexpressed insulin IHC. Nine PI-positive tumors represented functional insulinomas. Patients with PI IHC–positive tumors demonstrated significantly lower mean preoperative serum glucose compared with PI-negative PNET patients, even when insulinomas were excluded. No differences in survival between PI IHC–positive and PI IHC–negative tumors were observed. We identified 2 PI-positive PNETs from hypoglycemic patients, which were not insulinomas or other functional variants and in which serum PI was never tested. These may have been undetected proinsulinomas.

Conclusions

Proinsulin-expressing PNETs (functional or non) are not uncommon. Patients who present with hypoglycemia and normal insulin levels should be screened for proinsulinoma. Proinsulin IHC could also be used to screen for proinsulinoma. To further elucidate the clinical significance of PI expressing PNETs, prospective studies are required.
Endoscopic Resection of Duodenal Carcinoid Tumors
Authors: Mahmud Nadim , Tomizawa Yutaka , Stashek Kristen , Katona Bryson W. , Ginsberg Gregory G. , Metz David C.
Published: November 2018

Objectives

Endoscopic resection is preferred for duodenal carcinoids less than 20 mm; however, the efficacy of simple polypectomy has not been compared with advanced endoscopic resection techniques.

Methods

We performed a retrospective review of 33 patients who underwent endoscopic duodenal carcinoid resection (10 simple, 23 endoscopic mucosal resection) at the Hospital of the University of Pennsylvania between January 1, 2006, and June 15, 2017. The primary outcomes were resection margin positivity and local tumor recurrence.

Results

There were no significant differences in demographics or tumor functionality. Lesions managed with simple polypectomy had smaller median gross specimen size (6.0 mm vs 8.0 mm, P = 0.043). There was no significant difference in pathology resection margins between simple polypectomy and endoscopic mucosal resection (86% vs 68% positive, P = 0.64). Local recurrence on surveillance endoscopy was also similar (14.3% vs 17.7%, respectively; P = 1.000), with median time to recurrence 2.3 months (interquartile range, 1.2–5.4 months). The median follow-up time in patients without local recurrence was 21.4 months (interquartile range, 7.1–39.6 months).

Conclusions

Simple polypectomy may be adequate treatment of small duodenal carcinoids, although further studies are needed for validation and to define the upper limits of tumor size that can be managed with this technique.
Magnetic Resonance Imaging as a Valid Noninvasive Tool for the Assessment of Pancreatic Fibrosis
Authors: Bieliuniene Edita , Frøkjær Jens Brøndum , Pockevicius Alius , Kemesiene Jurate , Lukosevicius Saulius , Basevicius Algidas , Barauskas Giedrius , Dambrauskas Zilvinas , Gulbinas Antanas
Published: November 2018

Objectives

The aim of this study was to evaluate the utility of magnetic resonance imaging (MRI) for the noninvasive assessment of pancreatic fibrosis (PF).

Methods

Fifty-two patients who underwent surgical resection of the pancreas, histological examination of resection margins, preoperative abdominal MRI, and fecal elastase-1 test were enrolled in the study. Pancreatic tissue was identified on the MRI T1-, T2-, and diffusion-weighted imaging sequences. Apparent diffusion coefficient (ADC) was measured at the expected resection margin of the pancreas.

Results

There was a significant negative correlation between the ADC mean and histologically determined PF (r = −0.752, P = 0.001). For equal to or greater than 25% of PF, the ADC cutoff value was 1.331 or less, with a sensitivity of 77% and specificity of 88%. The unenhanced T1-weighted signal intensity ratio (T1SI) cutoff value was 172.1 or less. For equal to or greater than 50% of PF, the ADC cutoff value was 1.316 or less with a sensitivity of 85% and specificity of 88%. The highest sensitivity was obtained by combining ADC and T1SI values.

Conclusions

Combining both the ADC and T1SI measurement allows the detection of early PF with good sensitivity and specificity. Magnetic resonance imaging has the advantage of being noninvasive and widely used in the clinical setting, thus making our results easily transferable to routine clinical practice.
Herbarium specimens reveal substantial and unexpected variation in phenological sensitivity across the eastern United States
Authors: Park Daniel S. , Breckheimer Ian , Williams Alex C. , Law Edith , Ellison Aaron M. , Davis Charles C.
Published: November 2018

Phenology is a key biological trait that can determine an organism's survival and provides one of the clearest indicators of the effects of recent climatic change. Long time-series observations of plant phenology collected at continental scales could clarify latitudinal and regional patterns of plant responses and illuminate drivers of that variation, but few such datasets exist. Here, we use the web toolCrowdCurioto crowdsource phenological data from over 7000 herbarium specimens representing 30 diverse flowering plant species distributed across the eastern United States. Our results, spanning 120 years and generated from over 2000 crowdsourcers, illustrate numerous aspects of continental-scale plant reproductive phenology. First, they support prior studies that found plant reproductive phenology significantly advances in response to warming, especially for early-flowering species. Second, they reveal that fruiting in populations from warmer, lower latitudes is significantly more phenologically sensitive to temperature than that for populations from colder, higher-latitude regions. Last, we found that variation in phenological sensitivities to climate within species between regions was of similar magnitude to variation between species. Overall, our results suggest that phenological responses to anthropogenic climate change will be heterogeneous within communities and across regions, with large amounts of regional variability driven by local adaptation, phenotypic plasticity and differences in species assemblages. As millions of imaged herbarium specimens become available online, they will play an increasingly critical role in revealing large-scale patterns within assemblages and across continents that ultimately can improve forecasts of the impacts of climatic change on the structure and function of ecosystems.

This article is part of the theme issue ‘Biological collections for understanding biodiversity in the Anthropocene’.
A novel proof of concept for capturing the diversity of endophytic fungi preserved in herbarium specimens
Authors: Daru Barnabas H. , Bowman Elizabeth A. , Pfister Donald H. , Arnold A. Elizabeth
Published: November 2018

Herbarium specimens represent important records of morphological and genetic diversity of plants that inform questions relevant to global change, including species distributions, phenology and functional traits. It is increasingly appreciated that plant microbiomes can influence these aspects of plant biology, but little is known regarding the historic distribution of microbes associated with plants collected in the pre-molecular age. If microbiomes can be observed reliably in herbarium specimens, researchers will gain a new lens with which to examine microbial ecology, evolution, species interactions. Here, we describe a method for accessing historical plant microbiomes from preserved herbarium specimens, providing a proof of concept using two plant taxa from the imperiled boreal biome (Andromeda polifoliaandLedum palustresubsp. groenlandicum,Ericaceae). We focus on fungal endophytes, which occur within symptomless plant tissues such as leaves. Through a three-part approach (i.e. culturing, cloning and next-generation amplicon sequencing via the Illumina MiSeq platform, with extensive controls), we examined endophyte communities in dried, pressed leaves that had been processed as regular herbarium specimens and stored at room temperature in a herbarium for four years.We retrieved only one endophyte in culture, but cloning and especially the MiSeq analysis revealed a rich community of foliar endophytes. The phylogenetic distribution and diversity of endophyte assemblages, especially among the Ascomycota, resemble endophyte communities from fresh plants collected in the boreal biome. We could distinguish communities of endophytes in each plant species and differentiate likely endophytes from fungi that could be surface contaminants. Taxa found by cloning were observed in the larger MiSeq dataset, but species richness was greater when subsets of the same tissues were evaluated with the MiSeq approach. Our findings provide a proof of concept for capturing endophyte DNA from herbarium specimens, supporting the importance of herbarium records as roadmaps for understanding the dynamics of plant-associated microbial biodiversity in the Anthropocene.

This article is part of the theme issue ‘Biological collections for understanding biodiversity in the Anthropocene’.
Specimen-based analysis of morphology and the environment in ecologically dominant grasses: the power of the herbarium
Authors: McAllister Christine A. , McKain Michael R. , Li Mao , Bookout Bess , Kellogg Elizabeth A.
Published: November 2018

Herbaria contain a cumulative sample of the world's flora, assembled by thousands of people over centuries. To capitalize on this resource, we conducted a specimen-based analysis of a major clade in the grass tribe Andropogoneae, including the dominant species of the world's grasslands in the genera
Andropogon
,
Schizachyrium
,
Hyparrhenia
and several others. We imaged 186 of the 250 named species of the clade, georeferenced the specimens and extracted climatic variables for each. Using semi- and fully automated image analysis techniques, we extracted spikelet morphological characters and correlated these with environmental variables. We generated chloroplast genome sequences to correct for phylogenetic covariance and here present a new phylogeny for 81 of the species. We confirm and extend earlier studies to show that
Andropogon
and
Schizachyrium
are not monophyletic. In addition, we find all morphological and ecological characters are homoplasious but variable among clades. For example, sessile spikelet length is positively correlated with awn length when all accessions are considered, but when separated by clade, the relationship is positive for three sub-clades and negative for three others. Climate variables showed no correlation with morphological variation in the spikelet pair; only very weak effects of temperature and precipitation were detected on macrohair density.

This article is part of the theme issue ‘Biological collections for understanding biodiversity in the Anthropocene'.
Programmed His bundle pacing - a novel maneuver for the diagnosis of His bundle capture
Authors: Jastrzębski Marek , Moskal Paweł , Bednarek Agnieszka , Kiełbasa Grzegorz , Vijayaraman Pugazhendhi , Czarnecka Danuta
Published: November 2018

Background

During permanent non-selective (ns) His bundle (HB) pacing, it is crucial to confirm HB capture / exclude that only right ventricle (RV)-myocardial septal pacing is present. Because the effective refractory period (ERP) of the working myocardium is different than the ERP of the HB, we hypothesized that it should be possible to differentiate ns-HB capture from RV-myocardial capture using programmed extra-stimulus technique.

Methods

In consecutive patients during HB pacemaker implantation, programmed HB pacing was delivered from the screwed-in HB pacing lead. Premature beats were introduced at 10 ms steps during intrinsic rhythm and also after a drive train of 600 ms. The longest coupling interval that resulted in an abrupt change of QRS morphology was considered equal to ERP of HB or RV-myocardium.

Results

Programmed HB pacing was performed from 50 different sites in 32 patients. In 34/36 cases of ns-HB pacing, the RV-myocardial ERP was shorter than HB ERP (271.8±38 ms vs 353.0±30 ms, p < 0.0001). Programmed HB pacing using a drive train resulted in a typical abrupt change of paced QRS morphology: from ns-HB to RV-myocardial QRS (34/36 cases) or to selective HB QRS (2/36 cases). Programmed HB pacing delivered during supraventricular rhythm resulted in obtaining selective HB QRS in 20/34 and RV-myocardial QRS in 14/34 of the ns-HB cases. In RV-myocardial only pacing cases (“false ns-HB pacing”, n=14), such responses were not observed – the QRS morphology remained stable. Therefore, the PHB pacing correctly diagnosed all ns-HB cases and all RV-myocardial pacing cases.

Conclusions

A novel maneuver for the diagnosis of HB capture, based on the differences in ERP between HB and myocardium was formulated, assessed and found as diagnostically valuable. This method is unique in enabling to visualize selective HB QRS in patients with otherwise obligatory ns-HB pacing (RV-myocardial capture threshold < HB capture threshold).

What this study adds

Programmed His bundle pacing – a novel and straightforward method for unquestionable diagnosis of His bundle capture during non-selective pacing was developed and assessed.

A method for visualization of selective HB capture QRS in patients with obligatory non-selective pacing (myocardial capture threshold < His bundle capture threshold) was discovered and physiology behind it explained.
Prediction-error signals to violated expectations about person identity and head orientation are doubly-dissociated across the dorsal and ventral visual streams
Authors: Robinson Jonathan E. , Woods Will , Leung Sumie , Kaufman Jordy , Breakspear Michael , Young Andrew W. , Johnston Patrick J.
Published: November 2018

Predictive coding theories of perception suggest the importance of constantly updated internal models of the world in predicting future sensory inputs. One implication of such models is that cortical regions whose function is to resolve particular stimulus attributes should also signal prediction violations with respect to those same stimulus attributes. Previously, through carefully designed experiments, we have demonstrated early-mid latency EEG/MEG prediction-error signals in the dorsal visual stream to violated expectations about stimulus orientation/trajectory, with localisations consistent with cortical areas processing motion and orientation. Here we extend those methods to simultaneously investigate the predictive processes in both dorsal and ventral visual streams. In this MEG study we employed a contextual trajectory paradigm that builds expectations using a series of image presentations. We created expectations about both face orientation and identity, either of which can subsequently be violated. Crucially this paradigm allows us to parametrically test double dissociations between these different types of violations. The study identified double dissociations across the type of violation in the dorsal and ventral visual streams, such that the right fusiform gyrus showed greater evidence of prediction-error signals to Identity violations than to Orientation violations, whereas the left angular gyrus and postcentral gyrus showed the opposite pattern of results. Our results suggest comparable processes for error checking and context updating in high-level expectations instantiated across both perceptual streams. Perceptual prediction-error signalling is initiated in regions associated with the processing of different stimulus properties.

Significance Statement

Visual processing occurs along ‘what’ and ‘where’ information streams that run, respectively along the ventral and dorsal surface of the posterior brain. Predictive coding models of perception imply prediction-error detection processes that are instantiated at the level where particular stimulus attributes are parsed. This implies that, for instance, when considering face stimuli, signals arising through violated expectations about the person identity of the stimulus should localise to the ventral stream, whereas signals arising through violated expectations about head orientation should localise to the dorsal stream. We test this in a magnetoencephalography source localisation study. The analysis confirmed that prediction-error signals to identity versus head-orientation occur with similar latency, but activate doubly-dissociated brain regions along ventral and dorsal processing streams.
Cryo-EM structure of adenovirus type 3 fibre with desmoglein 2 shows a novel mode of receptor engagement
Authors: Vassal-Stermann Emilie , Effantin Gregory , Zubieta Chloe , Burmeister Wim , Iseni Frédéric , Wang Hongjie , Lieber André , Schoehn Guy , Fender Pascal
Published: November 2018

Attachment of adenovirus (HAd) to host cell is a critical step of infection. This work reports the cryo-electron microscopy (cryo-EM) structure of a non-symmetrical complex smaller than 100kDa formed by the trimeric human adenovirus of type 3 fibre knob (HAd3K) and human desmoglein 2 (DSG2). The structure reveals a unique stoichiometry, shedding light to new adenovirus infection strategies and providing new insights for adenoviral vector development.
On-scalp MEG system utilizing an actively shielded array of optically-pumped magnetometers
Authors: Iivanainen Joonas , Zetter Rasmus , Grön Mikael , Hakkarainen Karoliina , Parkkonen Lauri
Published: November 2018

The spatial resolution of magnetoencephalography (MEG) can be increased from that of conventional SQUID-based systems by employing on-scalp sensor arrays of e.g. optically-pumped magnetometers (OPMs). However, OPMs reach sufficient sensitivity for neuromagnetic measurements only when operated in a very low absolute magnetic field of few nanoteslas or less, usually not reached in a typical magnetically shielded room constructed for SQUID-based MEG. Moreover, field drifts affect the calibration of OPMs. Static and dynamic control of the ambient field is thus necessary for good-quality neuromagnetic measurements with OPMs. Here, we describe an on-scalp MEG system that utilizes OPMs and external compensation coils that provide static and dynamic shielding against ambient fields.

In a conventional two-layer magnetically shielded room, our coil system reduced the maximum remanent DC-field component within an 8-channel OPM array from 70 to less than 1 nT, enabling the sensors to operate in the sensitive spin exchange relaxation-free regime. When compensating field drifts below 4 Hz, a low-frequency shielding factor of 22 dB was achieved, which reduced the peak-to-peak drift from 1.3 to 0.4 nT and thereby the standard deviation of the sensor calibration from 1.6% to 0.4%. Without band-limiting the field that is compensated, a low-frequency shielding factor of 43 dB was achieved.

We validated the system by measuring brain responses to electric stimulation of the median nerve. With dynamic shielding and digital interference suppression methods, single-trial somatosensory evoked responses could be detected. Our results advance the deployment of OPM-based on-scalp MEG in lighter magnetic shields.
The microbiota influences theDrosophila melanogasterlife history strategy
Authors: Walters Amber W. , Matthews Melinda K. , Hughes Rachel , Malcolm Jaanna , Rudman Seth , Newell Peter D. , Douglas Angela E. , Schmidt Paul S. , Chaston John M.
Published: November 2018

Organismal life history traits are ideally adapted to local environments when an organism has a fitness advantage in one location relative to conspecifics from other geographies. Local adaptation has been best studied across, for example, latitudinal gradients, where organisms may tradeoff between investment in traits that maximize one, but not both, fitness components of somatic maintenance or reproductive output in the context of finite environmental resources. Latitudinal gradients in life history strategies are traditionally attributed to environmentally mediated selection on an animal’s genotype, without any consideration of the possible impact of associated microorganisms (‘microbiota’) on life history traits. Here we show that inDrosophila melanogaster, a key organism for studying local adaptation and life history strategies, associated microorganisms can drive life history variation. First, we reveal that an isogenic fly line reared with different bacteria vary the investment in early reproduction versus somatic maintenance, with little resultant variation in lifetime fitness. Next, we show that in wildDrosophilathe abundance of these same bacteria was correlated with the latitude and life history strategy of the flies, and bacterial abundance was driven at least in part by host genetic selection. Finally, by eliminating or manipulating the microbiota of fly lines collected across a latitudinal gradient, we reveal that host genotype contributes to latitude-specific life history traits independent of the microbiota; but that the microbiota can override these host genetic adaptations. Taken together, these findings establish the microbiota as an essential consideration in local adaptation and life history evolution.

Significance statement

Explanations of local adaptation have historically focused on how animal genotypes respond to environmental selection. Although the impact of variation in host life histories on the composition of the microbiota has been investigated for many associations, the scale and pattern of microbial effects on host life history strategy are largely unknown. Here we demonstrate in the fruit flyDrosophila melanogasterthat microbiota effects on host life history strategy in the laboratory are matched by patterns of microbiota composition in wild host populations. In particular, microbiota composition varies with latitude and the effects of the microbiota on life history traits are greater than host genetic adaptations. Together, these findings demonstrate that the microbiota plays an important role in local adaptation.
SKN-1/Nrf2 regulation of neuromuscular function in response to oxidative stress requires EGL-15/FGF Receptor and DAF-2/insulin Receptor signaling inCaenorhabditis elegans
Authors: Kim Sungjin , Sieburth Derek
Published: November 2018

The transcription factor Nrf2 plays a critical role in the organism wide-regulation of the antioxidant stress response. The Nrf2 homolog SKN-1 functions in the intestine cell non-autonomously to negatively regulate neuromuscular (NMJ) function inCaenorhabditis elegans. To identify additional molecules that mediate SKN-1 signaling to the NMJ, we performed a candidate screen for suppressors of aldicarb-resistance caused by acute treatment with the SKN-1 activator, arsenite. We identified two receptor tyrosine kinases, EGL-15 (fibroblast growth factor receptor, FGFR) and DAF-2 (insulin-like peptide receptor, IR) that are required for NMJ regulation in response to stress. Through double mutant analysis, we found that EGL-15 functions downstream of SKN-1 and SPHK-1 (sphingosine kinase), and that the EGL-15 ligand EGL-17 FGF and canonical EGL-15 effectors are required for oxidative stress-mediated regulation of NMJ function. DAF-2 also functions downstream of SKN-1, independently of DAF-16/FOXO, to regulate NMJ function. Through tissue-specific rescue experiments, we found that FGFR signaling functions primarily in the hypodermis, whereas IR signaling is required in multiple tissues. Our results support the idea that the regulation of NMJ function by SKN-1 occurs via a complex organism-wide signaling network involving RTK signaling in multiple tissues.
Predictive learning as a network mechanism for extracting low-dimensional latent space representations
Authors: Recanatesi Stefano , Farrell Matthew , Lajoie Guillaume , Deneve Sophie , Rigotti Mattia , Shea-Brown Eric
Published: November 2018

Artificial neural networks have recently achieved many successes in solving sequential processing and planning tasks. Their success is often ascribed to the emergence of the task’s low-dimensional latent structure in the network activity – i.e., in the learned neural representations. Here, we investigate the hypothesis that a means for generating representations with easily accessed low-dimensional latent structure, possibly reflecting an underlying semantic organization, is through learning to predict observations about the world. Specifically, we ask whether and when network mechanisms for sensory prediction coincide with those for extracting the underlying latent variables. Using a recurrent neural network model trained to predict a sequence of observations we show that network dynamics exhibit low-dimensional but nonlinearly transformed representations of sensory inputs that map the latent structure of the sensory environment. We quantify these results using nonlinear measures of intrinsic dimensionality and linear decodability of latent variables, and provide mathematical arguments for why such useful predictive representations emerge. We focus throughout on how our results can aid the analysis and interpretation of experimental data.
Border-ownership-dependent tilt aftereffect for shape defined by binocular disparity and motion parallax
Authors: Rideaux Reuben , Harrison William J
Published: November 2018

Discerning objects from their surrounds (i.e., figure-ground segmentation) in a way that guides adaptive behaviours is a fundamental task of the brain. Neurophysiological work has revealed a class of cells in the macaque visual cortex that may be ideally suited to support this neural computation: border-ownership cells (Zhou, Friedman, & von der Heydt, 2000). These orientation-tuned cells appear to respond conditionally to the borders of objects. A behavioural correlate supporting the existence of these cells in humans was demonstrated using two-dimensional luminance defined objects (von der Heydt, Macuda, & Qiu, 2005). However, objects in our natural visual environments are often signalled by complex cues, such as motion and depth order. Thus, for border-ownership systems to effectively support figure-ground segmentation and object depth ordering, they must have access to information from multiple depth cues with strict depth order selectivity. Here we measure in humans (of both sexes) border-ownership-dependent tilt aftereffects after adapting to figures defined by either motion parallax or binocular disparity. We find that both depth cues produce a tilt aftereffect that is selective for figure-ground depth order. Further, we find the effects of adaptation are transferable between cues, suggesting that these systems may combine depth cues to reduce uncertainty (Bülthoff & Mallot, 1988). These results suggest that border-ownership mechanisms have strict depth order selectivity and access to multiple depth cues that are jointly encoded, providing compelling psychophysical support for their role in figure-ground segmentation in natural visual environments.

SIGNIFICANCE STATEMENT

Segmenting a visual object from its surrounds is a critical function that may be supported by “border-ownership” neural systems that conditionally respond to object borders. Psychophysical work indicates these systems are sensitive to objects defined by luminance contrast. To effectively support figure-ground segmentation, however, neural systems supporting border-ownership must have access to information from multiple depth cues and depth order selectivity. We measured border-ownership-dependent tilt aftereffects to figures defined by either motion parallax or binocular disparity and found aftereffects for both depth cues. These effects were transferable between cues, but selective for figure-ground depth order. Our results suggest that the neural systems supporting figure-ground segmentation have strict depth order selectivity and access to multiple depth cues that are jointly encoded.
Endoparasites and vector-borne pathogens in dogs from Greek islands: pathogen distribution and zoonotic implications
Authors: Diakou Anastasia , Di Cesare Angela , Morelli Simone , Colombo Mariasole , Halos Lenaig , Simonato Giulia , Tamvakis Androniki , Beugnet Frederic , Paoletti Barbara , Traversa Donato
Published: November 2018

The present study investigated the presence of endo- and ecto-parasites, and vector-borne pathogens, in dogs from four islands of Greece. A total of 200 owned and sheltered dogs were examined with different microscopic, serological and molecular methods.

Of the examined dogs, 130 (65%) were positive for one or more parasites and/or vector-borne pathogens. The most common zoonotic intestinal helminths recorded were Ancylostomatidae (12.5%) andToxocara canis(3.5%). Ninety-three dogs (46.5%) seroreacted toRickettsia conorii. Twenty-two (11%) of them were also PCR positive and 7 (3.5%) showed corpuscoles suggestive ofRickettsiaspp. on the blood smears. Nineteen dogs (9.5%) were seropositive forEhrlichia canis, three of them being also PCR positive. Dogs positive forAnaplasma phagocytophilum-Anaplasma platys(1%),Dirofilaria immitis(0.5%) andBabesia canis(0.5%) were also found. Fleas and ticks were recorded in 53 (26.5%) and 50 (25%) dogs and all specimens were identified asCtenocephalides felis felisandRhipicephalus sanguineus sensu latu. Binary multiple univariate Generalized Linear Models were used to investigate factors and clinical signs related to the recorded positivity, while the association of specific signs with the pathogens was evaluated using tests of independence. Knowledge of occurrence and impact of zoonotic parasites and vector-borne pathogens in dog populations is crucial to prevent the infection in animals and people, and to control the risk of spreading of these pathogens in endemic and non-endemic areas.

Author summary

Both owned and sheltered dogs can harbor a variety of intestinal and extra-intestinal endoparasites, as well as vector-borne pathogens and ectoparasites, of zoonotic concern. Dog shelters and stray dogs are present in several touristic areas of Greece, including Sporades and Cyclades islands, where tourists often bring their pets with them, likely travelling from non-endemic to endemic areas. The present study has been carried out with the aim to evaluate the occurrence of the aforementioned pathogens. Data obtained showed that they are present in canine populations of Greece, with possibilities of infection for travelling dogs, which can also contribute to the spreading of zoonotic vector-borne diseases, introducing new pathogens in previously non-endemic areas. For these reasons, a constant monitoring of the epidemiological situation, improving control measures and correct diagnostic approaches are of primary importance for the prevention of canine and human infections, decreasing the spreading of potentially deadly pathogens.
Dispersal predicts hybrid zone widths across animal diversity: Implications for species borders under incomplete reproductive isolation
Authors: McEntee Jay P. , Burleigh J. Gordon , Singhal Sonal
Published: November 2018

Hybrid zones occur as range boundaries for many animal taxa. One model for how hybrid zones form and are stabilized is the tension zone model. This model predicts that hybrid zones widths are determined by a a balance between random dispersal into hybrid zones and selection against hybrids, and it does not formally account for local ecological gradients. Given the model’s simplicity, it provides a useful starting point for examining variation in hybrid zone widths across animals. Here we examine whether random dispersal and a proxy for selection against hybrids (mtDNA distance) can explain variation in hybrid zone widths across 135 hybridizing taxon pairs. We show that dispersal explains >30% of hybrid zone width variation across animal diversity and that mtDNA distance explains little variation. Clade-specific analyses revealed idiosyncratic patterns. Dispersal and mtDNA distance predict hybrid zone widths especially well in reptiles, while hybrid zone width scaled positively with mtDNA distance in birds, opposite predictions. Lastly, the data suggest that lower bounds on hybrid zone widths may be set by dispersal and the extent of molecular divergence, suggesting that hybrid zones are unlikely to form in restricted geographic spaces in highly dispersive and/or recently diverged taxa. Overall, our analyses reinforce the fundamental importance of dispersal in hybrid zone formation, and more generally in the ecology of range boundaries.
Olfactory and neuromodulatory signals reverse visual object avoidance to approach in Drosophila
Authors: Cheng Karen Y. , Frye Mark A.
Published: November 2018

Innate behavioral reactions to sensory stimuli may be subject to modulation by contextual conditions including signals from other modalities. Whereas sensory processing by individual modalities has been well-studied, the cell circuit mechanisms by which signals from different sensory systems are integrated to control behavior remains poorly understood. Here, we provide a new behavioral model to study the mechanisms of multisensory integration. This behavior, which we termed odor-induced visual valence reversal, occurs when the innate avoidance response to a small moving object by flying Drosophila melanogaster is reversed by the presence of an appetitive odor. Instead of steering away from the small object representing an approaching threat, flies begin to steer towards the object in the presence of odor. Odor-induced visual valence reversal occurs rapidly without associative learning and occurs for attractive odors including apple cider vinegar and ethanol, but not for innately aversive benzaldehyde. Optogenetic activation of octopaminergic neurons robustly induces visual valence reversal in the absence of odor, as does optogenetic activation of directional columnar motion detecting neurons that express octopamine receptors. Optogenetic activation of octopamine neurons drives calcium responses in the motion detectors. Taken together, our results implicate a multisensory processing cascade in which appetitive odor activates octopaminergic neuromodulation of visual pathways, which leads to increased visual saliency and the switch from avoidance to approach toward a small visual object.
Pioneer and nonpioneer factor cooperation drives lineage specific chromatin opening
Authors: Mayran Alexandre , Sochodolsky Kevin , Khetchoumian Konstantin , Harris Juliette , Gauthier Yves , Bemmo Amandine , Balsalobre Aurelio , Drouin Jacques
Published: November 2018

Pioneer transcription factors are coined as having the unique property of “opening closed chromatin sites” for implementation of cell fates. We previously showed that the pioneer Pax7 specifies melanotrope cells through deployment of an enhancer repertoire: this allows binding of Tpit, a nonpioneer factor that determines the related lineages of melanotropes and corticotropes. Here, we investigated the relation between these two factors in the pioneer mechanism. Cell-specific gene expression and chromatin landscapes were defined by scRNAseq and chromatin accessibility profiling. We found that in vivo deployment of the melanotrope enhancer repertoire and chromatin opening requires bothPax7andTpit. In cells, binding of heterochromatin targets by Pax7 is independent of Tpit but Pax7-dependent chromatin opening requires Tpit. The present work shows that pioneer core properties are limited to the ability to recognize heterochromatin targets and facilitate nonpioneer binding. Chromatin opening per se may be provided through cooperation with nonpioneer factors.
Exposure to a Healthy Gut Microbiome Protects Against Reproductive and Metabolic Dysregulation in a PCOS Mouse Model
Authors: Torres Pedro J. , Ho Bryan S. , Arroyo Pablo , Sau Lillian , Chen Annie , Kelley Scott T. , Thackray Varykina G.
Published: November 2018

Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting approximately 10% of reproductive-aged women worldwide. Diagnosis requires two of the following: hyperandrogenism, oligo/anovulation and polycystic ovaries. In addition to reproductive dysfunction, many women with PCOS display metabolic abnormalities associated with hyperandrogenism. Recent studies have reported that the gut microbiome is altered in women with PCOS and rodent models of the disorder. However, it is unknown whether the gut microbiome plays a causal role in the development and pathology of PCOS. Given its potential role, we hypothesized that exposure to a healthy gut microbiome would protect against development of PCOS. A co-housing study was performed using a letrozole-induced PCOS mouse model that recapitulates many reproductive and metabolic characteristics of PCOS. Since mice are coprophagic, co-housing results in repeated, non-invasive inoculation of gut microbes in co-housed mice via the fecal-oral route. In contrast to letrozole-treated mice housed together, letrozole-treated mice co-housed with placebo mice showed significant improvement in both reproductive and metabolic PCOS phenotypes. Using 16S rRNA gene sequencing, we observed that the gut microbial composition of letrozole-treated mice co-housed with placebo mice differed from letrozole mice housed together. In addition, our analyses identified several bacterial taxa includingCoprobacillus, DoreaandAdlercreutziaassociated with the improved PCOS phenotype in letrozole-treated mice co-housed with placebo mice. These results indicate that disruption of the gut microbiome may play a causal role in PCOS and that manipulation of the gut microbiome may be a potential treatment option for PCOS.

Significance

PCOS is a common cause of female infertility and ~80% of women with PCOS have metabolic dysregulation that predisposes them to type 2 diabetes and cardiovascular disease. Since treatment options for the metabolic symptoms of PCOS are limited, there is a need to develop novel therapeutic options. The gut microbiome has emerged as an important player in human health and has been shown to play a causal role in obesity. In this study, we found that exposure to a healthy gut microbiome through co-housing protected against the development of reproductive and metabolic dysregulation in a PCOS mouse model. These results suggest that manipulation of the gut microbiome may be a potential treatment option for women with PCOS.
Nanobodies reveal an extra-synaptic population of SNAP-25 and Syntaxin 1A in hippocampal neurons
Authors: Maidorn Manuel , Olichon Aurélien , Rizzoli Silvio O. , Opazo Felipe
Published: November 2018

Synaptic vesicle fusion (exocytosis) is a precisely regulated process that entails the formation of SNARE complexes between the vesicle protein synaptobrevin 2 (VAMP2) and the plasma membrane proteins Syntaxin 1 and SNAP-25. The sub-cellular localization of the latter two molecules remains unclear, although they have been the subject of many recent investigations. To address this, we generated two novel camelid single domain antibodies (nanobodies) specifically binding to SNAP-25 and Syntaxin 1A. These probes penetrated more easily into samples and detected their targets more efficiently than conventional antibodies in crowded regions. When investigated by super-resolution imaging, the nanobodies revealed substantial extra-synaptic populations for both SNAP-25 and Syntaxin 1A, which were poorly detected by antibodies. Moreover, extra-synaptic Syntaxin 1A molecules were recruited to synapses during stimulation, suggesting that these are physiologically-active molecules. We conclude that nanobodies are able to reveal qualitatively and quantitatively different organization patterns, when compared to conventional antibodies.
MosaicPlanner: Hardware Agnostic Array Tomography Acquisition Software
Authors: Serafin R. , Gliko O. , Smith S. J , Collman F.
Published: November 2018

Array tomography (AT) is a technique for acquiring high resolution highly multiplexed imagery from series of ultra-thin sections arranged as an array on a rigid substrate. Specialized microscope control has been required to utilize AT as an imaging technique, which is often time consuming, and yields small volume data sets. Here we present MosaicPlanner, an open source software platform for light level AT, that streamlines the acquisition process and utilizes the general microscope control API provided by Micro-Manager, allowing AT data to be acquired on a wide variety of microscope hardware. This report provides a description of the MosaicPlanner software design, and platform improvements that were implemented to increase the acquisition speed of high volume, multiplexed AT datasets.
Disorganization of the histone core promotes organization of heterochromatin into phase-separated droplets
Authors: Sanulli S. , Trnka MJ. , Dharmarajan V. , Tibble RW. , Pascal BD. , Burlingame A. , Griffin PR. , Gross JD. , Narlikar GJ.
Published: November 2018

The heterochromatin protein HP1 is proposed to enable chromatin compaction via liquid droplet formation. Yet, a connection between phase separation and chromatin compaction has not been experimentally demonstrated. More fundamentally, how HP1 action at the level of a single nucleosome drives chromatin compaction remains poorly understood. Here we directly demonstrate that the S.pombeHP1 protein, Swi6, compacts arrays of multiple nucleosomes into phase-separated droplets. Using hydrogen-deuterium exchange, NMR, and mass-spectrometry, we further find that Swi6 substantially increases the accessibility and dynamics of buried histone residues within a mononucleosome. Restraining these dynamics via site-specific disulfide bonds impairs the compaction of nucleosome arrays into phase-separated droplets. Our results indicate that chromatin compaction and phase separation can be highly coupled processes. Further, we find that such coupling is promoted by a counter-intuitive function of Swi6, namely disorganization of the octamer core. Phase separation is canonically mediated by weak and dynamic multivalent interactions. We propose that dynamic exposure of buried histone residues increases opportunities for multivalent interactions between nucleosomes, thereby coupling chromatin compaction to phase separation. We anticipate that this new model for chromatin organization may more generally explain the formation of highly compacted chromatin assemblies beyond heterochromatin.