bluuebunny/crossref_metadata_2025_split huggingface dataset:
A neuroendocrine feedback loop inC. elegansmales integrates food detection and biological sex to modulate chemoreceptor expression and behavioral flexibility
Authors: Wexler Leigh R. , Miller Renee M. , Portman Douglas S. 
Published: September 2019

SUMMARYDynamic integration of internal and external cues is essential for flexible, adaptive animal behavior. InC. elegans, biological sex and feeding state regulate expression of the food-associated chemoreceptorodr-10, contributing to plasticity in food detection and the decision between feeding and exploration. In adult hermaphrodites,odr-10expression is high; in well-fed adult males,odr-10expression is low, promoting exploratory mate-searching behavior. Food-deprivation transiently activates maleodr-10expression, heightening food sensitivity and reducing food-leaving. Here, we identify a neuroendocrine feedback loop that sex-specifically regulatesodr-10in response to food deprivation. In well-fed males, insulin-like (IIS) and TGFβ signaling repressodr-10expression. Upon food deprivation,odr-10is directly activated by DAF-16/FoxO, the canonicalC. elegansIIS effector. The TGFβ ligand DAF-7 acts upstream of IIS, and, likely because of its sexually dimorphic expression in the nervous system, links feeding toodr-10only in males. Surprisingly, these responses to food deprivation are not triggered by internal metabolic cues, but rather by the loss of sensory signals from food. In the presence of inedible food, males become metabolically starved but express levels ofodr-10anddaf-7comparable to those of well-fed males. Further, exposing food-deprived males to inedible food is sufficient to restore lowodr-10expression. Food signals are detected by a small number of sensory neurons whose activity non-autonomously regulatesdaf-7expression, IIS, andodr-10. Thus, adultC. elegansmales employ a neuroendocrine feedback loop that integrates food detection and genetic sex to dynamically modulate chemoreceptor expression and sensory behavior.
The versican-hyaluronan complex provides an essential extracellular matrix niche for Flk1+ hematoendothelial progenitors
Authors: Nandadasa Sumeda , O’Donnell Anna , Murao Ayako , Yamaguchi Yu , Midura Ronald J. , Olson Lorin , Apte Suneel S. 
Published: September 2019

AbstractLittle is known about extracellular matrix (ECM) contributions to formation of the earliest cell lineages in the embryo. Here, we show that the proteoglycan versican and glycosaminoglycan hyaluronan are associated with emerging Flk1+hematoendothelial progenitors at gastrulation. The mouse versican mutantVcanhdflacks yolk sac vasculature, with attenuated yolk sac hematopoiesis. CRISPR/Cas9-mediatedVcaninactivation in mouse embryonic stem cells reduced vascular endothelial and hematopoietic differentiation in embryoid bodies, which generated fewer blood colonies, and had an impaired angiogenic response to VEGF165. HA was severely depleted inVcanhdfembryos, with corresponding increase in the HA-depolymerase TMEM2. Conversely, HA-deficient mouse embryos also had vasculogenic suppression but with increased versican proteolysis. VEGF165and Indian hedgehog, crucial vasculogenic factors, utilized the versican-HA matrix, specifically versican chondroitin sulfate chains, for binding. Versican-HA ECM is an obligate requirement for vasculogenesis and primitive hematopoiesis, acts as an vasculogenic factor-enriching microniche for Flk1+progenitors from their origin at gastrulation.
Interspecies transcriptome analyses identify genes that control the development and evolution of limb skeletal proportion
Authors: Saxena Aditya , Sharma Virag , Neufeld Stanley J. , Tran Mai P. , Gutierrez Haydee L. , Erberich Joel M. , Birmingham Amanda , Cobb John , Hiller Michael , Cooper Kimberly L. 
Published: September 2019

AbstractDespite the great diversity of vertebrate limb proportion and our deep understanding of the genetic mechanisms that drive skeletal elongation, little is known about how individual bones reach different lengths in any species. Here, we directly compare the transcriptomes of homologous growth cartilages of the mouse (Mus musculus) and bipedal jerboa (Jaculus jaculus), which has extremely long metatarsals of the feet and ‘mouse-like’ arms. When we intersected gene expression differences in metatarsals of the two species with expression differences in forearms, we found that about 10% of all orthologous genes are associated with disproportionate elongation of jerboa feet. Among these,Shox2, has gained expression in jerboa metatarsals where it is not expressed in other vertebrates that have been assessed. This transcription factor is necessary for proximal limb elongation, and we show that it is sufficient to increase mouse distal limb length. Unexpectedly, we also found evidence that jerboa foot elongation occurs in part by releasing latent growth potential that is repressed in mouse feet. In jerboa metatarsals, we observed higher expression ofCrabp1, an antagonist of growth inhibitory retinoic acid, lower expression ofGdf10, an inhibitory TGFβ ligand, and lower expression ofMab21L2, a BMP signaling inhibitor that we show is sufficient to reduce limb bone elongation. By intersecting our data with prior expression analyses in other systems, we identify mechanisms that may both establish limb proportion during development and diversify proportion during evolution. The genes we identified here therefore provide a framework to understand the modular genetic control of skeletal growth and the remarkable malleability of vertebrate limb proportion.
The Role of Hvem and its Interaction with Btla and Cd160 in b-Cell Lymphoma Progression
Authors: de Juan Carla Yago-Diez 
Published: September 2019

SUMMARYDespite the fact that the cell surface receptor HVEM (TNFRSF14) appears to be implicated in the development and progression of B-cell lymphomas, its specific role in these tumours is still unclear. On the one hand, HVEM over-expression is related to worse prognosis in some types of B-cell lymphoma and other solid tumours. On the other hand, most mutations of HVEM in B-cell lymphomas are thought to promote tumour growth through the loss of function. Here, we used a CRISPR-Cas9 system to study the effect of HVEM loss on gene expression in a murine model of A20 B-cell lymphoma (belonging to the diffuse large B-cell lymphoma group). We show that loss of HVEM does not affect the doubling rate of A20 tumour cells in culture, but leads to a decrease in BTLA expression. HVEM-deficient A20 cells do not present a different pattern of metastatic dissemination to lymphoid organs compared with unmodified A20 cells. However, we observed a significant expansion of endogenous B-cells as a result of A20 tumour implantation in the thymus. Although we found no differences in the dissemination or progression of HVEM-deficient A20 cells, our results reveal that loss of HVEM alters the leukocyte recruitment capacity of A20 cells in hepatic tumour nodules at the intermediate stage of tumour development, which may be of relevance as a mechanism of immune evasion.
A semi-automated technique for adenoma quantification in the ApcMin mouse using FeatureCounter
Authors: Shepherd Amy L. , Smith A. Alexander T. , Wakelin Kirsty A. , Kuhn Sabine , Yang Jianping , Eccles David A. , Ronchese Franca 
Published: September 2019

ABSTRACTColorectal cancer is a major contributor to death and disease worldwide. The ApcMin mouse is a widely used model of intestinal neoplasia, as it carries a mutation also found in human colorectal cancers. However, the method most commonly used to quantify tumour burden in these mice is manual adenoma counting, which is time consuming and poorly suited to standardization across different laboratories. We describe a method to produce suitable photographs of the small intestine, process them with an ImageJ macro, FeatureCounter, which automatically locates image features potentially corresponding to adenomas, and a machine learning pipeline to identify and quantify them. Compared to a manual method, the specificity (or True Negative Rate, TNR) and sensitivity (or True Positive Rate, TPR) of this method in detecting adenomas are similarly high at about 80% and 87%, respectively. Importantly, total adenoma area measures derived from the automatically-called tumours were just as capable of distinguishing high-burden from low-burden mice as those established manually. Overall, our strategy is quicker, helps control experimenter bias and yields a greater wealth of information about each tumour, thus providing a convenient route to getting consistent and reliable results from a study.
Musical prediction error responses similarly reduced by predictive uncertainty in musicians and non-musicians
Authors: Quiroga-Martinez D.R. , Hansen N.C. , Højlund A. , Pearce M. , Brattico E. , Vuust P. 
Published: September 2019

AbstractAuditory prediction error responses elicited by surprising sounds can be reliably recorded with musical stimuli that are more complex and realistic than those typically employed in EEG or MEG oddball paradigms. However, these responses are reduced as the predictive uncertainty of the stimuli increases. In this study, we investigate whether this effect is modulated by musical expertise. Magnetic mismatch negativity (MMNm) responses were recorded from 26 musicians and 24 non-musicians while they listened to low-and high-uncertainty melodic sequences in a musical multi-feature paradigm that included pitch, slide, intensity, and timbre deviants. When compared to non-musicians, musically trained participants had significantly larger pitch and slide MMNm responses. However, both groups showed comparable reductions of pitch and slide MMNm amplitudes in the high-uncertainty condition compared to the low-uncertainty condition. In a separate, behavioral deviance detection experiment, musicians were more accurate and confident about their responses than non-musicians, but deviance detection in both groups was similarly affected by the uncertainty of the melodies. In both experiments, the interaction between uncertainty and expertise was not significant, suggesting that the effect is comparable in both groups. Consequently, our results replicate the modulatory effect of predictive uncertainty on prediction error; show that it is present across different types of listeners; and suggest that expertise-related and stimulus-driven modulations of predictive precision are dissociable and independent.
Decoding Odor Mixtures in the Dog Brain: An Awake fMRI Study
Authors: Prichard Ashley , Chhibber Raveena , King Jon , Athanassiades Kate , Spivak Mark , Berns Gregory S. 
Published: September 2019

AbstractIn working and practical contexts, dogs rely upon their ability to discriminate a target odor from distracting odors and other sensory stimuli. Few studies have examined odor discrimination using non-behavioral methods or have approached odor discrimination from the dog’s perspective. Using awake fMRI in 18 dogs, we examined the neural mechanisms underlying odor discrimination between two odors and a mixture of the odors. Neural activation was measured during the presentation of a target odor (A) associated with a food reward, a distractor odor (B) associated with nothing, and a mixture of the two odors (A+B). Changes in neural activation during the presentations of the odor stimuli in individual dogs were measured over time within three regions known to be involved with odor processing: the caudate nucleus, the amygdala, and the olfactory bulbs. Average activation within the amygdala showed that dogs maximally differentiated between odor stimuli based on the stimulus-reward associations by the first run, while activation to the mixture (A+B) was most similar to the no-reward (B) stimulus. To identify the neural representation of odor mixtures in the dog brain, we used a random forest classifier to compare multilabel (elemental) vs. multiclass (configural) models. The multiclass model performed much better than the multilabel (weighted-F1 0.44 vs. 0.14), suggesting the odor mixture was processed configurally. Analysis of the subset of high-performing dogs based on their brain classification metrics revealed a network of olfactory information-carrying brain regions that included the amygdala, piriform cortex, and posterior cingulate. These results add further evidence for the configural processing of odor mixtures in dogs and suggest a novel way to identify high-performers based on brain classification metrics.
Early neuronal processes interact with glia to establish a scaffold for orderly innervation of the cochlea
Authors: Druckenbrod N. R. , Hale E. B. , Olukoya O. O. , Shatzer W. E. , Goodrich L.V. 
Published: September 2019

SummaryAlthough the basic principles of axon guidance are well established, it remains unclear how axons navigate with high fidelity through the complex cellular terrains that are encounteredin vivo. To learn more about the cellular strategies underlying axon guidancein vivo, we analyzed the developing cochlea, where spiral ganglion neurons extend processes through a heterogeneous cellular environment to form tonotopically ordered connections with hair cells. Here, we show that the earliest processes are closely associated with a population of glia that grow ahead of them. By analyzing single cell morphology and imaging the real time behavior of neuronal processes and glia in embryonic cochleae, we show that spiral ganglion neurons employ different mechanisms depending on their position in the ganglion. Additionally, the pattern of outgrowth varied locally, with evidence for both glia-guided growth and fasciculation along a neuronal scaffold. These findings suggest a tiered mechanism for reliable axon guidance.
Stronger between-clan than within-clan contests and their ecological correlates in a non-territorial, fission-fusion species, the Asian elephant
Authors: Gautam Hansraj , Vidya T.N.C. 
Published: September 2019

AbstractSocioecological theory attributes variation in social organization of female-bonded species to differences in within- and between-group competition, shaped by food distribution. Strong between-group contests are expected over large, monopolisable resources, and are not generally expected in species that feed on low quality resources distributed across large, undefended home ranges. Within groups, frequent contests are expected over discrete feeding sites but not over low-quality, dispersed resources.We report on the first tests of socioecological theory, largely unexplored in non-primate species, in female Asian elephants. Asian elephants show graminivory, overlapping home ranges, and high fission-fusion dynamics, traits that are thought to be associated with infrequent contests.We studied agonistic interactions within and between female elephant clans with respect to food distribution, food abundance, and competitor density effects of group size and clan density, in a grassland habitat around the Kabini backwaters, southern India.We found that the Kabini grassland had three times the grass biomass as adjacent forests, and between-clan encounters were considerably higher than that known from a neighbouring forest. Individual-level agonism was also more frequent between clans than within clans. Thus, the food-rich habitat patch probably enabled strong between-clan contest competition under graminivory. Moreover, the rate of between-clan encounters increased when more clans were present, and the duration of encounters was positively related to grass biomass at the contested sites. Despite fission-fusion dynamics, within-clan agonism was also somewhat frequent, but not influenced by food distribution, in contradiction to classic socioecological predictions, possibly because of intensified competition due to high density. Interestingly, within-clan agonism increased with female group size until intermediate group sizes, suggesting that the tension between within-group and between-group competition might govern group size, since larger groups are advantageous in this strong between-clan contest regime.Our findings refine the current understanding of female elephant socioecology. Despite predominant graminivory and fission-fusion dynamics, within-group agonism can be frequent, especially when large groups face ecological constraints at high density. Further, frequent between-group contests may arise despite graminivory and non-territoriality when food becomes patchy and density is high. These changes may be effected by anthropogenic alteration of habitats.
Time-Resolved Correspondences Between Deep Neural Network Layers and EEG Measurements in Object Processing
Authors: Kong Nathan C. L. , Kaneshiro Blair , Yamins Daniel L. K. , Norcia Anthony M. 
Published: September 2019

AbstractThe ventral visual stream is known to be organized hierarchically, where early visual areas processing simplistic features feed into higher visual areas processing more complex features. Hierarchical convolutional neural networks (CNNs) were largely inspired by this type of brain organization and have been successfully used to model neural responses in different areas of the visual system. In this work, we aim to understand how an instance of these models corresponds to temporal dynamics of human object processing. Using representational similarity analysis (RSA) and various similarity metrics, we compare the model representations with two electroencephalography (EEG) data sets containing responses to a shared set of 72 images. We find that there is a hierarchical relationship between the depth of a layer and the time at which peak correlation with the brain response occurs for certain similarity metrics in both data sets. However, when comparing across layers in the neural network, the correlation onset time did not appear in a strictly hierarchical fashion. We present two additional methods that improve upon the achieved correlations by optimally weighting features from the CNN and show that depending on the similarity metric, deeper layers of the CNN provide a better correspondence than shallow layers to later time points in the EEG responses. However, we do not find that shallow layers provide better correspondences than those of deeper layers to early time points, an observation that violates the hierarchy and is in agreement with the finding from the onset-time analysis. This work makes a first comparison of various response features—including multiple similarity metrics and data sets—with respect to a neural network.
Simultaneously vocalizing Asian barbets adopt different frequencies without coordinating temporal rhythms
Authors: Krishnan Anand 
Published: September 2019

AbstractSound stream segregation is an important challenge faced by simultaneously vocalizing animals. Chorusing birds, for instance, coordinate vocal timing to minimize overlap. Alternatively, other birds may use frequency differences to segregate sound streams, and vocalizing at different frequencies may enable them to remain distinct from each other. Here, I show that conspecific Asian barbets vocalize at distinctly different peak frequencies from each other. Additionally, they also differ in repetition rate, as measured by the inter-phrase interval. However, conspecific individuals across species do not temporally coordinate with each other during vocal interactions, maintaining independent and highly stereotyped individual rhythms together with different peak frequencies. Frequency differences between individuals may facilitate sound stream segregation when calls overlap in time. I propose that frequency differences between conspecifics may be widespread among birds possessing stereotyped, repetitive calls such as those found in barbets. This may enable segregation of competing sound streams both during cooperative duets and competitive singing during territorial interactions.
The combination of endobronchial elastography and sonographic findings during endobronchial ultrasound‐guided transbronchial needle aspiration for predicting nodal metastasis
Authors: Fujiwara Taiki , Nakajima Takahiro , Inage Terunaga , Sata Yuki , Sakairi Yuichi , Tamura Hajime , Wada Hironobu , Suzuki Hidemi , Chiyo Masako , Yoshino Ichiro 
Published: September 2019

AbstractBackgroundDuring endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA), the sonographic findings of B‐mode imaging, as well as endobronchial elastography, can be obtained noninvasively and used for the prediction of nodal metastasis.MethodsPatients with lung cancer or suspected lung cancer who underwent EBUS‐TBNA were recorded prospectively and reviewed retrospectively. Both the B‐mode sonographic and elastographic findings were independently evaluated for each lymph node. The sonographic features were classified according to previously published criteria. If oval shape, indistinct margins, homogenous echogenicity, and the absence of coagulation necrosis sign were all observed by B‐mode imaging, then the lymph node was judged to be benign by sonographic imaging. In addition, if the stiffer area comprised more than 31% of the entire lymph node area, then the lymph node was judged to be malignant by elastography. We compared the results of these imaging‐based predictions with the pathological diagnoses.ResultsThe prevalence of nodal metastasis was 78/228 (34.2%). B‐mode sonography predicted 95.8% of benign lymph nodes, and elastography predicted 72.1% of malignant lymph nodes. By combining the two modalities, 59 of 71 (83.1%) lymph nodes judged as malignant by both analyses were pathologically proven to be malignant, and 101 of 105 (96.2%) lymph nodes judged as benign by both analyses were pathologically proven to be benign.ConclusionThe combination of elastography and sonographic findings showed good sensitivity and a high negative predictive value, which may facilitate selecting the most suspicious lymph nodes for biopsy.Key points

Significant findings of the study.
The combination of endobronchial elastography and sonography resulted in a higher diagnostic yield than either modality alone for predicting benign and malignant lymph nodes in patients with lung cancer.

What this study adds.
The combination of endobronchial elastography and sonography will help clinicians identify the most suspicious lymph nodes for puncturing during EBUS‐TBNA, which may improve the efficiency of EBUS‐TBNA.
Post‐normal conservation science fills the space between research, policy, and implementation
Authors: Buschke Falko T. , Botts Emily A. , Sinclair Samuel P. 
Published: September 2019

AbstractThe view that conservation is a linear exchange of knowledge between scientists and practitioners has led to the conceptualization of a “research‐implementation gap”. However, conservation is not only about translating science into action but also includes the interplay of values, cultural norms, social interactions, and political consequences. In response, an alternative conceptualization is one where research and implementation exist in a “space”, where conservation partners interact. Here, we argue that post‐normal science (PNS) can fill this space. PNS is used when information is incomplete, values are pluralistic, stakes are high, and decisions are urgent. It relies on an extended community of practice that aims to produce knowledge fit for end‐users, without the constraints of settled scientific paradigms. We advocate for the wider use of PNS in conservation by showing how aspects of PNS have been useful in mainstreaming conservation planning in South Africa. By following an approach typical of PNS, South Africa has made considerable progress in creating an implementation space for conserving biodiversity despite its limited resources, cultural heterogeneity, and controversial history. We outline the interventions used in South Africa to facilitate PNS and, based on this, propose an operating model that can be applied elsewhere.