bluuebunny/crossref_metadata_2025_split huggingface dataset:
The what and where of synchronous sound perception
Authors: Van Bentum Guus C. , Van Opstal A. John , Van Wanrooij Marc M. 
Published: December 2021

AbstractSound localization and identification are challenging in acoustically rich environments. The relation between these two processes is still poorly understood. As natural sound-sources rarely occur exactly simultaneously, we wondered whether the auditory system could identify (“what”) and localize (“where”) two spatially separated sounds with synchronous onsets. While listeners typically report hearing a single source at an average location, one study found that both sounds may be accurately localized if listeners are explicitly being told two sources exist. We here tested whether simultaneous source identification (one vs. two) and localization is possible, by letting listeners choose to make either one or two head-orienting saccades to the perceived location(s). Results show that listeners could identify two sounds only when presented on different sides of the head, and that identification accuracy increased with their spatial separation. Notably, listeners were unable to accurately localize either sound, irrespective of whether one or two sounds were identified. Instead, the first (or only) response always landed near the average location, while second responses were unrelated to the targets. We conclude that localization of synchronous sounds in the absence of prior information is impossible. We discuss that the putative cortical ‘what’ pathway may not transmit relevant information to the ‘where’ pathway. We examine how a broadband interaural correlation cue could help to correctly identify the presence of two sounds without being able to localize them. We propose that the persistent averaging behavior reveals that the ‘where’ system intrinsically assumes that synchronous sounds originate from a single source.Significance StatementIt is poorly understood whether identification (‘what’) of sounds and their localization (‘where’) are inter-related, or independent neural processes. We measured sound-localization responses towards synchronous sounds to examine potential coupling of these processes. We varied the spatial configurations of two sounds and found that although identification improved considerably with larger spatial separation, their localization was unaffected: responses were always directed towards the average location. This shows absence of mutual coupling of information between the ‘what’ and ‘where’ streams in the auditory system. We also show how broadband interaural correlation could explain the improved identification results, without affecting localization performance, and explain how the persistent spatial averaging could be understood from strong internal priors regarding sound synchronicity.
Impact of carbon monoxide on early cardiac development in an avian model
Authors: Matias Filipa Rombo , Groves Ian , Herigstad Mari 
Published: December 2021

ABSTRACTCarbon monoxide (CO) is a toxic gas that can be lethal in large doses and may also cause physiological damage in lower doses. Epidemiological studies suggest that CO in lower doses over time may impact on embryo development, in particular cardiac development, however other studies have not observed this association. Here, we exposed chick embryosin ovoto CO at three different concentrations (1ppm, 8ppm, 25ppm) plus air control (4 protocols in total) for the first nine days of development, at which point we assessed egg and embryo weight, ankle length, developmental stage, heart weight and ventricular wall thickness. We found that heart weight was reduced for the low and moderate exposures compared to air, and that ventricular wall thickness was increased for the moderate and high exposures compared to air. Ventricular wall thickness was also significantly positively correlated with absolute CO exposures across all protocols. This intervention study thus suggests that CO even at very low levels may have a significant impact on cardiac development.
PeracetylN-cyclobutanoyl-D-mannosamine enhances expression of sialyl-Lewis X (sLeX / CD15s) and adhesion of leukocytes
Authors: Tasneem Anam , Parashar Shubham , Aittan Simran , Jain Tanya , Chauhan Charu , Rautela Jyoti , Bhat Zahoor Ahmad , Raza Kaisar , Madhumalar Arumugam , Sampathkumar Srinivasa-Gopalan 
Published: December 2021

AbstractSialyl-Lewis-X (sLeX/CD15s) epitopes regulate cell adhesionviainteractions with selectins. High levels of sLeX are associated with chronic inflammation. Intense efforts have been devoted for the development of sLeX mimetics for the prevention of atherosclerosis. By contrast, low levels of sLeX are associated with leukocyte adhesion deficiency (LAD) disorders. In this context, we employed metabolic glycan engineering to alter the fine structures of sialoglycans. Treatment of HL-60 (human acute myeloid leukemia) cells with peracetylN-cyclobutanoyl-D-mannosamine (Ac4ManNCb) resulted in a four-fold increase in both sLeX levels and adhesion to E-selectin-Fc chimera. Enhanced sLeX levels on CD162/PSGL-1, CD43, and CD44 were observed through immunoprecipitation. Molecular dynamics (MD) simulations on interactions with E-selectin revealed dramatic differentials in the conformational dynamics of sLeX-Cb compared to sLeX, highlighting the significance of remoteN-acyl side chains of sialic acids in facilitating bio-active conformations. These results provide opportunities for pharmacological interventions in both LAD and chronic inflammation.Table of ContentsRemote substituents on the tetrasaccharide sialyl-Lewis X (sLeX / CD15s) influence ensembles of bio-active conformations and alter biological outcomes. Treatment with peracetylN-cyclobutanoyl-D-mannosamine (Ac4ManNCb) results in four-fold enhancement in the expression of sialyl-Lewis-X (sLeX / CD15s) and adhesion to E-selectin (CD62E). Molecular dynamics simulations show that the sLeX-Cb prefers a flatter bio-active conformation (gray) compared to wild-type sLeX (cyan).Institute and/or researcher Twitter usernames: @NImmunology @Gops_GlycoIndia
Cannabinoid during adolescence phenocopies reelin haploinsufficiency in prefrontal cortex synapses
Authors: Thenzing Juda Silva-Hurtado T.J. , Giua Gabriele , Lassalle Olivier , Murphy Michelle N. , Wager-Miller Jim , Mackie Ken , Manzoni Olivier J. , Pascale Chavis P. 
Published: December 2021

ABSTRACTIn humans and rodents, the protracted development of the prefrontal cortex (PFC) throughout adolescence represents a time for marked vulnerability towards environmental adversities, such as stress or drug exposure. We previously showed that the extracellular matrix protein reelin is an instrumental synaptic modulator that shapes medial PFC’s (mPFC) circuitry during maturation and is a critical mediator of the vulnerability to environmental stress. Emerging evidence highlight the role of the endocannabinoid system in the postnatal maturation of the PFC and reelin deficiency influences behavioral abnormalities caused by heavy consumption of THC during adolescence. Could the reelin-dependent maturation of prefrontal networks may be vulnerable to cannabinoid exposure during adolescence? To explore this hypothesis, we studied the effects of a single in-vivo exposure to a synthetic cannabinoid on reelin expression and mPFC functions in adolescent male mice. The results show that a single cannabinoid exposure mimics reelin haploinsufficiency by decreasing prefrontal reelin expression in a layer-specific pattern without changing its transcriptional levels. Furthermore, this treatment impeded synaptic plasticity: adolescent cannabinoid lowered long-term potentiation to the magnitude observed in age-matched reelin haploinsufficient males. Quantitative PCR analysis showed that changes in the mRNA levels of NMDARs does not account for the reduction of TBS-LTP. Together, the data show that exposure to cannabinoid during adolescence phenocopies reelin haploinsufficiency and further identifies reelin as a key component of the vulnerability of PFC to environmental insults.
Natural variation in the control of flowering and shoot architecture in diploid Fragaria species
Authors: Fan Guangxun , Andrés Javier , Olbricht Klaus , Koskela Elli , Hytönen Timo 
Published: December 2021

AbstractIn perennial fruit and berry crops of the Rosaceae family, flower initiation occurs in late summer or autumn after downregulation of a strong repressor TERMINAL FLOWER1 (TFL1) and flowering and fruiting takes place the following growing season. Rosaceous fruit trees typically form two types of axillary shoots, short flower-bearing shoots called spurs and long shoots that are respectively analogous to branch crowns and stolons in strawberry. However, regulation of flowering and shoot architecture differs between species and environmental and endogenous controlling mechanisms have just started to emerge. In woodland strawberry (Fragaria vesca L.), long days maintain vegetative meristems and promote stolon formation by activating TFL1 and GIBBERELLIN 20-OXIDASE4 (GA20ox4), respectively, while silencing of these factors by short days and cool temperatures induces flowering and branch crown formation. We characterized flowering responses of 14 accessions of seven diploid Fragaria species native to diverse habitats in the northern hemisphere, and selected two species with contrasting environmental responses, F. bucharica Losinsk. and F. nilgerrensis Schlecht. ex J. Gay for detailed studies together with F. vesca. Similar to F. vesca, F. bucharica was induced to flower in short days at 18°C and regardless of photoperiod at 11°C after silencing of TFL1. F. nilgerrensis maintained higher TFL1 expression level and likely required cooler temperatures or longer exposure to inductive treatments to flower. We also found that high expression of GA20ox4 was associated with stolon formation in all three species, and its downregulation by short days and cool temperature caused branch crown formation in F. vesca and F. nilgerrensis, although the latter did not flower. F. bucharica, in contrast, rarely formed branch crowns, regardless of flowering or GA20ox4 expression level. Our findings highlighted diploid Fragaria species as a rich source of genetic variation controlling flowering and plant architecture, with potential applications in breeding of Rosaceous crops.
Positive supercoiling buildup is a trigger of E. coli’s short-term response to cold shock
Authors: Dash Suchintak , Palma Cristina S.D. , Baptista Ines S.C. , Bahrudeen Mohamed N.M. , Almeida Bilena L.B. , Chauhan Vatsala , Jagadeesan Rahul , Ribeiro Andre S. 
Published: December 2021

AbstractAdaptation to cold shock (CS) is a key survival skill of gut bacteria of warm-blooded animals. In E. coli, this skill emerges from a complex transcriptional program of multiple, timely-ordered shifts in gene expression. We identified short-term, cold shock repressed (CSR) genes by RNA-seq and provide evidence that their variability in evolutionary fitness is low and that their responsiveness to cold emanates from intrinsic features. Given that their single-cell variability in protein numbers increases after CS, we hypothesized that the responsiveness of a large portion of CSR genes is triggered by the high propensity for transcription locking due to positive supercoiling buildup (PSB). We then proposed a model of this phenomenon and, in support, show that nearly half of CSR genes are highly responsive to Gyrase inhibition. Also, their response strengths to CS and Gyrase inhibition correlate and most CSR genes increase their single-cell variability in protein numbers. Further, during CS, the cells’ nucleoid density increases (in agreement with increased numbers of positive supercoils), their energy levels become depleted (while the resolving of positive supercoils is ATP dependent), and the colocalization of Gyrases and the nucleoid increases (in agreement with increased time length for resolving supercoils). We conclude that high sensitivity to PSB is at the core of the short-term, cold shock responsive transcriptional program of E. coli and propose that this gene feature may be useful for providing temperature sensitivity to chromosome-integrated synthetic circuits.
Cultural diffusion dynamics depend on behavioural production rules
Authors: Chimento Michael , Barrett Brendan J. , Kandler Anne , Aplin Lucy M. 
Published: December 2021

AbstractCulture is an outcome of both the acquisition of knowledge about behaviour through social transmission, and its subsequent production by individuals. Acquisition and production are often discussed interchangeably or modeled separately, yet to date, no study has accounted for both processes and explored their interaction. We present a generative model that integrates the two to explore how variation in production rules might shape cultural diffusion dynamics. Agents make behavioural choices that change as they learn from their productions. Their repertoires also change over time, and the social transmission of behaviours depends on their frequency. We diffuse a novel behaviour through social networks across a large parameter space to demonstrate how individual-level behavioural production rules influence population-level diffusion dynamics. We then investigate how linking transmission and production might affect the performance of two commonly used inferential models for social learning; Network-based Diffusion Analysis, and Experienced Weighted Attraction models. Clarifying the distinction between acquisition and production yields predictions for how production influences diffusion that are generalisable across species, and has consequences for how inferential methods are applied to empirical data. Our model illuminates the differences between social learning and social influence, demonstrates the overlooked role of reinforcement learning in cultural diffusions, and allows for clearer discussions about social learning strategies.
Life-stage and sex influencePhilornisectoparasitism in a Neotropical woodpecker (Melanerpes striatus) with essential male parental care
Authors: Lapergola Joshua B. 
Published: December 2021

AbstractThe nestlings of many Neotropical bird species suffer fromPhilornis(Diptera: Muscidae) ectoparasitism. While nestlings are typically considered the intended targets, recent work indicates thatPhilornisinfest adult birds more frequently than previously appreciated, yet few studies have concurrently surveyed nestlings and adults forPhilornisin the same population. Over six field seasons (2012–2017), I documented the presence of current or recent subcutaneousPhilornisinfestations on adult and nestling Hispaniolan WoodpeckersMelanerpes striatusfrom the same population in the central Dominican Republic. I tested the following three non-mutually exclusive hypotheses regarding occurrence ofPhilornison adult birds: (1) nestlings are more vulnerable toPhilornisparasitism than adults, (2) nesting is associated withPhilornisparasitism in adults, and (3)Philornisparasitism is associated with incubation and brooding investment. While nestling and adult woodpeckers exhibited similar prevalence of parasitism, parasitized nestlings hosted on average 3.5 times morePhilorniswounds (larvae plus empty wounds) than parasitized adults. Nestingper sewas not significantly associated with parasitism among adults, as breeding and non-breeding adults showed similar prevalence and intensity. However, nests withPhilornis-infested young were significantly more likely to have one or both parents also be infested in contrast to nests with infestation-free young. Furthermore, adult males, which perform overnight incubation and brooding, were significantly more likely to be parasitized than adult females. This last result supports the hypothesis that incubation and brooding investment increase the risk ofPhilornisparasitism for adults, but this conclusion is complicated by the lack of an association between parasitism and nesting status. Together, these results raise questions about the degree of host life-stage specialization and whether adult parasitism is incidental or part of an alternative parasitic strategy forPhilornis.
The Biomechanics of the Locust Ovipositor Valves: a Unique Digging Apparatus
Authors: Das Rakesh , Gershon Shmuel , Bar-On Benny , Tadayon Maryam , Ayali Amir , Pinchasik Bat-El 
Published: December 2021

AbstractThe female locust has a unique mechanism for digging in order to deposit its eggs deep in the ground. It utilizes two pairs of sclerotized valves to displace the granular matter, while extending its abdomen as it propagates underground. This ensures optimal conditions for the eggs to incubate, and provides them with protection from predators. Here, two major axes of operation of the digging valves are identified, one in parallel to the propagation direction of the ovipositor, and one perpendicular to it. The direction-dependent biomechanics of the locust major, dorsal digging valves are quantified and analyzed, under forces in the physiological range and beyond, considering hydration level, as well as the females’ age, or sexual maturation state. Our findings reveal that the responses of the valves to compression forces in the specific directions change upon sexual maturation to follow their function, and depend on environmental conditions. Namely, in the physiological force range, the valves are resistant to mechanical failure. In addition, mature females, which lay eggs, have stiffer valves, up to roughly nineteen times the stiffness of the pre-mature locusts. The valves are stiffer in the major working direction, corresponding to soil shuffling and compression, compared to the direction of propagation. Hydration of the valves reduces their stiffness but increases their resilience against failure. These findings provide mechanical and materials guidelines for the design of novel non-drilling excavating tools, including 3D-printed anisotropic materials based on composites.Statement of significanceThe female locust lay its eggs underground in order to protect them from predators and to provide them with optimal conditions for hatching. In order to dig into the ground, it uses two pairs of valves: The ventral pair is plugged as a wedge, while the dorsal pair performs the digging of the oviposition tunnel. We study the mechanical response of the digging valves, depending on age, hydration level and direction of operation. Our findings show that during the course of roughly two weeks in the life of the adult female, the digging valves become up to nineteen-fold stiffer against failure, in order to fulfill their function as diggers. While hydration reduces the stiffness, it also increases the resilience against failure and renders the valves unbreakable within the estimated physiological force range and beyond. The digging valves are consistently stiffer in the digging direction than in the perpendicular direction, implying on their form-follows-function design.Graphical Abstract
Molecular liver fingerprint reflects the seasonal physiology of the grey mouse lemur (Microcebus murinus) during winter
Authors: Chazarin Blandine , Benhaim-Delarbre Margaux , Brun Charlotte , Anzeraey Aude , Bertile Fabrice , Terrien Jérémy 
Published: December 2021

AbstractGrey mouse lemurs (Microcebus murinus) are a primate species exhibiting strong physiological seasonality in response to environmental energetic constraint. They notably store large amounts of lipids during early winter (EW), which are thereafter mobilized during late winter (LW), when food availability is low. In addition, they develop glucose intolerance in LW only. To decipher how the hepatic mechanisms may support such metabolic flexibility, we analyzed the liver proteome of adult captive male mouse lemurs, which seasonal regulations of metabolism and reproduction are comparable to their wild counterparts, during the phases of either constitution or use of fat reserves. We highlight profound changes that reflect fat accretion in EW at the whole-body level, however, without triggering an ectopic storage of fat in the liver. Moreover, molecular regulations would be in line with the lowering of liver glucose utilization in LW, and thus with reduced tolerance to glucose. However, no major regulation was seen in insulin signaling/resistance pathways, which suggests that glucose intolerance does not reach a pathological stage. Finally, fat mobilization in LW appeared possibly linked to reactivation of the reproductive system and enhanced liver detoxification may reflect an anticipation to return to summer levels of food intake. Altogether, these results show that the physiology of mouse lemurs during winter relies on solid molecular foundations in liver processes to adapt fuel partitioning while avoiding reaching a pathological state despite large lipid fluxes. This work emphasizes how the mouse lemur is of primary interest for identifying molecular mechanisms relevant to biomedical field.
A rhythmically pulsing leaf-spring nanoengine that drives a passive follower
Authors: Centola Mathias , Poppleton Erik , Centola Martin , Valero Julián , Šulc Petr , Famulok Michael 
Published: December 2021

AbstractMolecular engineering seeks to create functional entities for the modular use in the bottom-up design of nanoassemblies that can perform complex tasks. Such systems require fuel-consuming nanomotors that can actively drive downstream passive followers. Most molecular motors are driven by Brownian motion, but the generated forces are scattered and insufficient for efficient transfer to passive second-tier components, which is why nanoscale driver-follower systems have not been realized. Here, we describe bottom-up construction of a DNA-nanomachine that engages in an active, autonomous and rhythmical pulsing motion of two rigid DNA-origami arms, driven by chemical energy. We show the straightforward coupling of the active nanomachine to a passive follower unit, to which it then transmits its own motion, thus constituting a genuine driver-follower pair. Our work introduces a versatile fuel-consuming nanomachine that can be coupled with passive modules in nanoassemblies, the function of which depends on downstream sequences of motion.
Comparative oncology reveals DNMT3B as a molecular vulnerability in soft-tissue sarcoma
Authors: Fuller Ashley M. , DeVine Ann , Murazzi Ileana , Mason Nicola J. , Weber Kristy , Eisinger-Mathason T. S. Karin 
Published: December 2021

ABSTRACTUndifferentiated pleomorphic sarcoma (UPS), an aggressive subtype of soft-tissue sarcoma (STS), is exceedingly rare in humans and lacks effective, well-tolerated therapies. In contrast, STS are relatively common in canine companion animals; thus, incorporation of veterinary patients into studies of UPS offers an exciting opportunity to develop novel therapeutic strategies for this rare human disease. Genome-wide studies have demonstrated that UPS is characterized by aberrant patterns of DNA methylation. However, the mechanisms and impact of this epigenetic modification on UPS biology and clinical behavior are poorly understood. Leveraging cell lines and tissue specimens derived from human and canine patients, we discovered that the DNA methyltransferase DNMT3B is overexpressed in UPS relative to normal mesenchymal tissues and associated with a poor prognosis. Consistent with these findings, genetic DNMT3B depletion strongly inhibited UPS cell proliferation and tumor progression. However, existing hypomethylating agents, including the clinically approved drug 5-aza-2’-deoxycytidine and the DNMT3B-inhibiting tool compound nanaomycin A, were ineffective in UPS due to cellular uptake and toxicity issues. Thus, further development of DNMT3B-targeting strategies for these patients is critical.