bluuebunny/crossref_metadata_2025_split huggingface dataset:
The lateral hypothalamus and orexinergic transmission in the paraventricular thalamus promote the attribution of incentive salience to reward-associated cues
Authors: Haight Joshua L , Campus Paolo , Maria-Rios Cristina E , Johnson Allison M , Klumpner Marin S , Kuhn Brittany N , Covelo Ignacio R , Morrow Jonathan D , Flagel Shelly B 
Published: March 2020

AbstractRationalePrior research suggests that inputs from the lateral hypothalamic area (LHA) to the paraventricular nucleus of the thalamus (PVT) contribute to the attribution of incentive salience to Pavlovian-conditioned reward cues. However, a causal role for the LHA in this phenomenon has not been demonstrated. In addition, it is unknown which hypothalamic neurotransmitter or peptide system(s) are involved in mediating incentive salience attribution.ObjectivesTo examine: 1) the role of the LHA in the propensity to attribute incentive salience to reward cues, and 2) the role of orexinergic signaling in the PVT on the expression of Pavlovian conditioned approach (PavCA) behavior, a reflection of incentive salience attribution.MethodsMale Sprague-Dawley rats received bilateral excitotoxic lesions of the LHA prior to the acquisition of Pavlovian conditioned approach (PavCA) behavior. A separate cohort of male rats acquired PavCA behavior and were characterized as sign-trackers (STs) or goal-trackers (GTs) based on their conditioned response. The orexin 1 receptor (OX1r) antagonist SB-334867, or the orexin 2 receptor (OX2r) antagonist TCS-OX2-29, were then administered directly into the PVT to assess the effects of these pharmacological agents on the expression of PavCA behavior and on the conditioned reinforcing properties of the Pavlovian reward cue.ResultsLesions of the LHA before training attenuated the development of lever-directed (sign-tracking) behaviors in the PavCA paradigm, without affecting magazine-directed (goal-tracking) behaviors. In STs, administration of the OX1r antagonist into the PVT reduced lever-directed behaviors and increased magazine-directed behaviors; while administration of the OX2r antagonist only reduced lever-directed behaviors. Further, OX2r, but not OX1r, antagonism was able to reduce the incentive motivational value of the conditioned stimulus on a conditioned reinforcement test in STs. The behavior of GTs was unaffected by orexinergic antagonism in the PVT.ConclusionsThe LHA is necessary for the attribution of incentive salience to reward cues and, thereby, the development of a sign-tracking conditioned response. Furthermore, blockade of orexin signaling in the PVT attenuates the incentive value of a Pavlovian reward cue. These data suggest that hypothalamic orexin inputs to the PVT are a key component of the circuitry that encodes the incentive motivational value of reward cues and promotes maladaptive cue-driven behaviors.
Visualizing synaptic plasticity in vivo by large-scale imaging of endogenous AMPA receptors
Authors: Graves Austin R. , Roth Richard H. , Tan Han L. , Zhu Qianwen , Bygrave Alexei M. , Lopez-Ortega Elena , Hong Ingie , Spiegel Alina C. , Johnson Richard C. , Vogelstein Joshua T. , Tward Daniel J. , Miller Michael I. , Huganir Richard L. 
Published: March 2020

AbstractElucidating how synaptic molecules such as AMPA receptors mediate neuronal communication and tracking their dynamic expression during behavior is crucial to understand cognition and disease, but current technological barriers preclude large-scale exploration of molecular dynamics in vivo. We have developed a suite of innovative methodologies that break through these barriers: a new knockin mouse line with fluorescently tagged endogenous AMPA receptors, two-photon imaging of hundreds of thousands of labeled synapses in behaving mice, and computer-vision-based automatic synapse detection. Using these tools, we can longitudinally track how the strength of synapses changes during behavior. We used this approach to generate an unprecedentedly detailed spatiotemporal map of synaptic plasticity underlying sensory experience. More generally, these tools can be used as an optical probe capable of measuring functional synapse strength across entire brain areas during any behavioral paradigm, describing complex system-wide changes with molecular precision.
Identification and genomic analysis of pedigrees with exceptional longevity identifies candidate rare variants
Authors: Miller Justin B. , Ward Elizabeth , Staley Lyndsay A. , Stevens Jeffrey , Teerlink Craig C , Tavana Justina P. , Cloward Matthew , Page Madeline , Dayton Louisa ,   Alzheimer’s Disease Genetics Consortium, Cannon-Albright Lisa A. , Kauwe John S.K. 
Published: March 2020

AbstractBackgroundLongevity as a phenotype entails living longer than average and typically includes living without chronic age-related diseases. Recently, several common genetic components to longevity have been identified. This study aims to identify additional rare genetic variants associated with longevity using unique and powerful pedigree-based analyses of pedigrees with a statistical excess of healthy elderly individuals identified in the Utah Population Database (UPDB).MethodsFrom an existing biorepository of Utah pedigrees, four pedigrees were identified which exhibited an excess of healthy elderly individuals; whole exome sequencing (WES) was performed on one set of elderly first- or second-cousins from each pedigree. Rare (<0.01 population frequency) variants shared by at least one elderly cousin pair in a region likely to be identical by descent were identified as candidates. Ingenuity Variant Analysis was used to prioritize putative causal variants based on quality control, frequency, and gain or loss of function. The variant frequency was compared in healthy cohorts and in an Alzheimer’s disease cohort. Remaining variants were filtered based on their presence in genes reported to have an effect on the aging process, aging of cells, or the longevity process. Validation of these candidate variants included tests of segregation to other elderly relatives.ResultsFifteen rare candidate genetic variants spanning 17 genes shared within cousins were identified as having passed prioritization criteria. Of those variants, six were present in genes that are known or predicted to affect the aging process: rs78408340 (PAM), rs112892337 (ZFAT), rs61737629 (ESPL1), rs141903485 (CEBPE), rs144369314 (UTP4), and rs61753103 (NUP88 and RABEP1). ESPL1 rs61737629 and CEBPE rs141903485 show additional evidence of segregation with longevity in expanded pedigree analyses (p-values=0.001 and 0.0001, respectively).DiscussionThis unique pedigree analysis efficiently identified several novel rare candidate variants that may affect the aging process and added support to seven genes that likely contribute to longevity. Further analyses showed evidence for segregation for two rare variants, ESPL1 rs61737629 and CEBPE rs141903485, in the original longevity pedigrees in which they were originally observed. These candidate genes and variants warrant further investigation.
Switching secretory pathway direction for organelle acquisition in plants
Authors: Kanazawa Takehiko , Morinaka Hatsune , Ebine Kazuo , Shimada Takashi L. , Ishida Sakiko , Minamino Naoki , Yamaguchi Katsushi , Shigenobu Shuji , Kohchi Takayuki , Nakano Akihiko , Ueda Takashi 
Published: March 2020

AbstractEukaryotic cells acquired novel organelles during evolution through mechanisms that remain largely obscure. The existence of the unique oil body compartment is a synapomorphy of liverworts that represents lineage-specific acquisition of this organelle during evolution, although its origin, biogenesis, and physiological function are yet unknown. We found that two Syntaxin 1 paralogs in the liverwort,Marchantia polymorpha, are distinctly targeted to forming cell plates and the oil body, suggesting these structures share some developmental similarity. Oil body formation is under the regulation of an ERF/AP2-type transcription factor and loss of the oil body increasedM. polymorphaherbivory. These findings highlight a common strategy for the acquisition of organelles with distinct functions in plants, via periodical switching in secretion direction depending on cellular phase transition.
The Madingley General Ecosystem Model predicts bushmeat yields, species extinction rates and ecosystem-level impacts of bushmeat harvesting
Authors: Barychka Tatsiana , Mace Georgina M. , Purves Drew W. 
Published: March 2020

AbstractTraditional approaches to guiding decisions about harvesting bushmeat often employ single-species population dynamic models, which require species- and location-specific data, are missing ecological processes such as multi-trophic interactions, cannot represent multi-species harvesting, and cannot predict the broader ecosystem impacts of harvesting. In order to explore an alternative approach to devising sustainable harvesting strategies, we employ the Madingley General Ecosystem Model, which can simulate ecosystem dynamics in response to multi-species harvesting given nothing other than location-specific climate data. We used the model to examine yield, extinctions, and broader ecosystem impacts, for a range of harvesting intensities of duiker-sized ectothermic herbivores. Duiker antelope (such asCephalophus callipygusandCephalophus dorsalis) are the most heavily hunted species in sub-Saharan Africa, contributing 34%-95% of all bushmeat in the Congo Basin. Across a range of harvesting rates, the Madingley model gave estimates for optimal harvesting rate, and extinction rate, that were qualitatively and quantitatively similar to the estimates from single-species Beverton-Holt model. Predicted yields were somewhat greater (around 5 times, on average) for the Madingley model, which would be expected given that the Madingley simulates multi-species harvesting from an initially pristine ecosystem. This match increased the degree of confidence with which we could examine other predictions from the ecosystem model, as follows. At medium and high levels of harvesting of duiker-sized herbivores, there were statistically significant, but moderate, reductions in the densities of the targeted functional group; increases in small-bodied herbivores; decreases in large-bodied carnivores; and minimal ecosystem-level impacts overall. The results suggest that general ecosystem models such as the Madingley model could be used more widely to help estimate sustainable harvesting rates, bushmeat yields and broader ecosystem impacts across different locations and target species.
Amorphous nickel titanium alloy film: a new choice for cryo electron microscopy sample preparation
Authors: Huang Xiaojun , Zhang Lei , Wen Zuoling , Chen Hui , Li Shuoguo , Ji Gang , Yin Chang-cheng , Sun Fei 
Published: March 2020

ABSTRACTCryo-electron microscopy (cryoEM) has become one of the most important approach for structural biology. However, barriers are still there for an increase successful rate, a better resolution and improved efficiency from sample preparation, data collection to image processing. CryoEM sample preparation is one of the bottlenecks with many efforts made recently, including the optimization of supporting substrate (e.g. ultra-thin carbon, graphene, pure gold, 2d crystal of streptavidin, and affinity modification), which was aimed to solve air-water interface problem, or reduce beam induced motion (BIM), or change particle distribution in the grid hole. Here, we report another effort of developing a new supporting substrate, the amorphous nickel-titanium alloy (ANTA) film, for cryoEM sample preparation. Our investigations showed advantages of ANTA film in comparison with conventional carbon film, including superior electron conductivity and trace non-specific interaction with protein. These advantages yield less BIM and significantly improved particle distribution during cryoEM experiment of human apo-ferritn, thus resulting an improved reconstruction resolution from a reduced number of micrographs and particles. Unlike the pure gold film, the usage of the ANTA film is just same with the carbon film, compatible to conventional automatic cryoEM data collection procedure.
Honey bees solve a multi-comparison ranking task by probability matching
Authors: MaBouDi HaDi , Marshall James A.R. , Barron Andrew B. 
Published: March 2020

AbstractHoney bees forage on a range of flowers, all of which can vary unpredictably in the amount and type of rewards they offer. In this environment bees are challenged with maximising the resources they gather for their colony. That bees are effective foragers is clear, but how bees solve this type of complex multi-choice task is unknown. Here we challenged bees with a five-comparison choice task in which five colours differed in their probability of offering reward and punishment. The colours were ranked such that high ranked colours were more likely to offer reward, and the ranking was unambiguous. Bees choices in unrewarded tests matched their individual experiences of reward and punishment of each colour, indicating bees solved this test not by comparing or ranking colours but by matching their preferences to their history of reinforcement for each colour. We used a computational model to explore the feasibility of this probability matching strategy for the honey bee brain. The model suggested a structure like the honey bee mushroom body with reinforcement-related plasticity at both input and output was sufficient for this cognitive strategy. We discuss how probability matching enables effective choices to be made without a need to compare any stimuli directly, and the utility and limitations of this simple cognitive strategy for foraging animals.
A DOT1B/Ribonuclease H2 protein complex is involved in R-loop processing, genomic integrity and antigenic variation inTrypanosoma brucei
Authors: Eisenhuth Nicole , Vellmer Tim , Butter Falk , Janzen Christian J. 
Published: March 2020

ABSTRACTThe parasiteTrypanosoma bruceiperiodically changes the expression of protective variant surface glycoproteins (VSGs) to evade its host’s immune system in a process known as antigenic variation. One route to change VSG expression is the transcriptional activation of a previously silent VSG expression site (ES), a subtelomeric region containing theVSGgenes. Homologous recombination of a differentVSGfrom a large reservoir into the active ES represents another route. The conserved histone methyltransferase DOT1B is involved in transcriptional silencing of inactive ES and influences ES switching kinetics. The molecular machinery that enables DOT1B to execute these regulatory functions remains elusive, however. To better understand DOT1B-mediated regulatory processes, we purified DOT1B-associated proteins using complementary biochemical approaches. We identified several novel DOT1B-interactors. One of these was the Ribonuclease H2 complex, previously shown to resolve RNA-DNA hybrids, maintain genome integrity, and play a role in antigenic variation. Our study revealed that DOT1B depletion results in an increase in RNA-DNA hybrids, accumulation of DNA damage and recombination-based ES switching events. Surprisingly, a similar pattern of VSG deregulation was observed in Ribonuclease H2 mutants. We propose that both proteins act together in resolving R-loops to ensure genome integrity and contribute to the tightly-regulated process of antigenic variation.
Early-life social experience shapes social avoidance reactions in larval zebrafish
Authors: Groneberg Antonia H. , Marques João C. , Martins A. Lucas , de Polavieja Gonzalo G. , Orger Michael B. 
Published: March 2020

SummarySocial experiences greatly define successive social behavior. Lack of such experiences, especially during critical phases of development, can severely impede the ability to behave adequately in social contexts. To date it is not well characterized how early-life social isolation leads to social deficits and impacts development. In many model species, it is challenging to fully control social experiences, because they depend on parental care. Moreover, complex social behaviors involve multiple sensory modalities, contexts, and actions. Hence, when studying social isolation effects, it is particularly important to parse apart social deficits from general developmental effects, such as abnormal motor learning. Here, we characterized how social experiences during early development of zebrafish larvae modulate their social behavior, at one week of age, when social avoidance reactions can be measured as discrete swim events. We show that raising larvae in social isolation leads to enhanced social avoidance, in terms of reaction distance and reaction strength. Specifically, larvae raised in isolation use a high-acceleration escape swim bout, the short latency C-start, more frequently during social interactions. These behavioral differences are absent in non-social contexts. By ablating the lateral line and presenting the fish with local water vibrations, we show that lateral line inputs are both necessary and sufficient to drive enhanced social avoidance reactions. Taken together, our results show that social experience during development is a critical factor in shaping mechanosensory avoidance reactions in larval zebrafish.HighlightsLarval zebrafish raised in isolation show enhanced social avoidance reactionsEnhanced avoidance is composed of increased avoidance distances and usage of high acceleration escape swimsThe lateral line sensory organ is necessary and sufficient for the increased usage of high acceleration escape swims
Unraveling reproducible dynamic states of individual brain functional parcellation
Authors: Boukhdhir Amal , Zhang Yu , Mignotte Max , Bellec Pierre 
Published: March 2020

AbstractData-driven parcellations are widely used for exploring the functional organization of the brain, and also for reducing the high dimensionality of fMRI data. Despite the flurry of methods proposed in the literature, functional brain parcellations are not highly reproducible at the level of individual subjects, even with very long acquisitions. Some brain areas are also more difficult to parcellate than others, with association heteromodal cortices being the most challenging. An important limitation of classical parcellations is that they are static, i.e. they neglect dynamic reconfigurations of brain networks. In this paper, we proposed a new method to identify dynamic states of parcellations, which we hypothesized would improve reproducibility over static parcellation approaches. For a series of seed voxels in the brain, we applied a cluster analysis to regroup short (3 minutes) time windows into “states” with highly similar seed parcels. We splitted individual time series of the Midnight scan club sample into two independent sets of 2.5 hours (test and retest). We found that average within-state parcellations, called stability maps, were highly reproducible (over .9 test-retest spatial correlation in many instances) and subject specific (fingerprinting accuracy over 70% on average) between test and retest. Consistent with our hypothesis, seeds in heteromodal cortices (posterior and anterior cingulate) showed a richer repertoire of states than unimodal (visual) cortex. Taken together, our results indicate that static functional parcellations are incorrectly averaging well-defined and distinct dynamic states of brain parcellations. This work calls to revisit previous methods based on static parcellations, which includes the majority of published network analyses of fMRI data. Our method may, thus, impact how researchers model the rich interactions between brain networks in health and disease.
Shape-to-graph Mapping Method for Efficient Characterization and Classification of Complex Geometries in Biological Images
Authors: Pilcher William , Yang Xingyu , Zhurikhina Anastasia , Chernaya Olga , Xu Yinghan , Qiu Peng , Tsygankov Denis 
Published: March 2020

AbstractWith the ever-increasing quality and quantity of imaging data in biomedical research comes the demand for computational methodologies that enable efficient and reliable automated extraction of the quantitative information contained within these images. One of the challenges in providing such methodology is the need for tailoring algorithms to the specifics of the data, limiting their areas of application. Here we present a broadly applicable approach to quantification and classification of complex shapes and patterns in biological or other multi-component formations. This approach integrates the mapping of all shape boundaries within an image onto a global information-rich graph and machine learning on the multidimensional measures of the graph. We demonstrated the power of this method by (1) extracting subtle structural differences from visually indistinguishable images in our phenotype rescue experiments using the endothelial tube formations assay, (2) training the algorithm to identify biophysical parameters underlying the formation of different multicellular networks in our simulation model of collective cell behavior, and (3) analyzing the response of U2OS cell cultures to a broad array of small molecule perturbations.Author SummaryIn this paper, we present a methodology that is based on mapping an arbitrary set of outlines onto a complete, strictly defined structure, in which every point representing the shape becomes a terminal point of a global graph. Because this mapping preserves the whole complexity of the shape, it allows for extracting the full scope of geometric features of any scale. Importantly, an extensive set of graph-based metrics in each image makes integration with machine learning routines highly efficient even for a small data sets and provide an opportunity to backtrack the subtle morphological features responsible for the automated distinction into image classes. The resulting tool provides efficient, versatile, and robust quantification of complex shapes and patterns in experimental images.
Alleviating chronic ER stress by p38-Ire1-Xbp1 pathway and insulin-associated autophagy inC. elegansneurons
Authors: Guan Liying , Zhan Zhigao , Yang Yongzhi , Miao Yue , Huang Xun , Ding Mei 
Published: March 2020

AbstractER stress occurs in many physiological and pathological conditions. However, how chronic ER stress is alleviated in specific cells in an intact organism is an outstanding question. Here, overexpressing the gap junction protein UNC-9 (Uncoordinated) inC. elegansneurons triggers the Ire1-Xbp1-mediated stress response in an age-dependent and cell-autonomous manner. The p38 MAPK PMK-3 acts upon the phosphorylation of IRE-1 to regulate chronic stress. Overexpressing gap junction protein also activates autophagy and the insulin pathway functions through autophagy, but not the transcription of genes encoding ER chaperones, to counteract the p38-Ire1-Xbp1-mediated stress response. Together, these results reveal an intricate cellular regulatory network in response to chronic stress in a subset of cells in multicellular organism.Author SummaryThe accumulation of unfolded proteins triggers the ER stress response (UPR), which allows cells to fight against fluctuations in protein expression under both physiological and pathological conditions. Severe acute ER stress responses can be induced by drug treatment. However, such intense ER stress rarely occurs ubiquitously in every cell typein vivo. Here, we designed a genetic system in the nematodeC. elegans, which allows us to induce ER stress in specific cells, without drug treatment or any other external stimuli, and then to monitor the stress response. Using this system, genetic screens identified that the p38 MAPK directly acts through the IRE-1-XBP-1 branch of the UPR to promote the stress response. Meanwhile, the insulin receptor functions through autophagy activation to counteract the p38-IRE-1-XBP-1 pathway. Together, these results reveal an intricate cellular regulatory network in response to chronic stress in multicellular organism.