bluuebunny/crossref_metadata_2025 huggingface dataset:
Pair housing does not alter incubation of craving, extinction, and reinstatement after heroin self-administration in female and male rats
Authors: Nett Kelle E. , LaLumiere Ryan T.
Published: August 2022

Rationale

Evidence suggests that single housing in rats acts as a chronic stressor, raising the possibilities that it contributes to measures of heroin craving and that pair housing ameliorates such measures.

Objectives

This study aimed to determine whether pair housing after heroin self-administration reduces the incubation of craving, extinction, and reinstatement of heroin seeking.

Methods

Single-housed female and male Sprague-Dawley rats underwent daily 6-h heroin self-administration, wherein active lever presses produced a heroin infusion paired with light/tone cues. One d after self-administration, rats underwent a baseline cued-seeking test wherein active lever presses only produced light/tone cues. Immediately following this cued-seeking test, rats were either pair-housed with a weight- and sex-matched naïve rat or remained single-housed for the rest of the study. For 14 d, rats remained in their homecages, after which they underwent a cued-seeking test to assess the incubation of craving compared to their baseline test. Rats then underwent extinction sessions followed by cue-induced and heroin-primed reinstatements.

Results

The findings reveal that pair-housed rats did not differ from single-housed rats in terms of the incubation of craving, extinction, or reinstatement of heroin seeking. Additionally, the results did not reveal any evidence of sex-based differences in the study.

Conclusions

The present work indicates that pair housing during the forced abstinence period does not alter measures of heroin craving/seeking. These findings suggest that the chronic stress of single housing specifically during forced abstinence does not contribute to the degree of such measures.
Electrophysiological signature of the interplay between habits and inhibition in response to smoking-related cues in individuals with a smoking habit: an ERP study
Authors: Dampuré Julien , Agudelo-Orjuela Paola , Van Der Meij Maartje , Belin David , Barber Horacio A.
Published: August 2022

The rigid, stimulus-bound nature of drug seeking that characterizes Substance-use disorder (SUD) has been related to a dysregulation of motivational and early attentional reflexive and inhibitory reflective systems. However, the mechanisms by which these systems are engaged by drug-paired conditioned stimuli CSs) when they promote the enactment of seeking habits in individuals with a SUD have not been elucidated. The present study aimed behaviorally and electrophysiologically to characterize the nature of the interaction between the reflexive and reflective systems recruited by CSs in individuals with a smoking habit. For this, we measured the behavioral performance and associated ERPs of 20 individuals with a smoking habit and 20 controls, who never smoked regularly, in a modified Go/NoGo task during which smoking-related CSs, appetitive, and neutral pictures, presented either in first-person or as a third-person visual perspective were displayed 250 ms before the Go/NoGo cue. We show that smoking-related cues selectively influence early incentive motivation-related attentional bias (N2 after picture onset), motor readiness and behavioral inhibition (Go-P3, NoGo-P3 and Pc) of individuals with a smoking habit only when presented from a first-person perspective. These data together identify the neural signature of the aberrant engagement of the reflexive and reflective systems during the recruitment of an incentive habit by CSs presented as if they had been response-produced, i.e., as conditioned reinforcers.
A Tale of Two Trees: Modeling Apical and Basal Tree Contribution to L2/3 V1 Pyramidal Cell Orientation Selectivity
Authors: Petousakis Konstantinos-Evangelos , Park Jiyoung , Papoutsi Athanasia , Smirnakis Stelios , Poirazi Panayiota
Published: August 2022

Pyramidal neurons, a mainstay of cortical regions, receive a plethora of inputs from various areas onto their morphologically distinct apical and basal trees. Both trees differentially contribute to the somatic response, defining distinct anatomical and possibly functional sub-units. To elucidate the contribution of each tree to the encoding of visual stimuli at the somatic level, we modeled the response pattern of a L2/3 V1 pyramidal neuron to orientation tuned synaptic input. Towards this goal, we used a morphologically detailed computational model of a single cell that replicates electrophysiological and two-photon imaging data. Our simulations predict a synergistic effect of apical and basal trees on somatic action potential generation: basal tree activity, in the form of either depolarization or dendritic spiking, is necessary for producing somatic activity, despite the fact that most somatic spikes are heavily driven by apical dendritic spikes. This model provides evidence for synergistic computations taking place in the basal and apical trees of the L2/3 V1 neuron along with mechanistic explanations for tree-specific contributions and emphasizes the potential role of predictive and attentional feedback input in these cells.

Abstract Figure

Abstract Figure

Graphical Representation of AP Generation in a L2/3 V1 Pyramidal Neuron Model

Action potential generation requires the spatiotemporal coincidence of apical sodium spikes with either basal sodium spikes or significant basal depolarizations, allowing the neuron to respond to salient stimuli that may or may not be affected by attentional and/or predictive signals from higher-order areas.
Gender imbalances in citation rates are mediated by field specific author gender distributions
Authors: Riemann Steffen , Roheger Mandy , Kohlschmidt Jan , Kirschke Jennifer , Lillo Margherita , Flöel Agnes , Meinzer Marcus
Published: August 2022

Gender biases are well documented in science and typically favor male scientists. In this context, a particularly pervasive gender bias is undercitation of publications authored by women, resulting in profound negative effects on academic visibility and career advancement. This bias has been well documented in fields where author gender distributions are strongly skewed towards men (e.g., astronomy, physics, neuroscience). By investigating citation practices in a field that has traditionally been more accessible to female scientists (Speech and Language Pathology, SLP), we demonstrate that gendered citation practices are mediated by author gender distribution, rather than being a universal pattern. Specifically, our results revealed a citation pattern in SLP that (a) overall tends to favor female authors, (b) persists after controlling for potential confounding factors and, (c) is particularly strong when female authors are citing publications involving female first and senior author teams. This research also implies that the implementation of effective measures to increase the number and influence of underrepresented individuals in specific fields of science may be suitable to mitigate downstream disadvantages for career advancement of either sex.
Temporal Mapper: transition networks in simulated and real neural dynamics
Authors: Zhang Mengsen , Chowdhury Samir , Saggar Manish
Published: August 2022

Characterizing large-scale dynamic organization of the brain relies on both data-driven and mechanistic modeling, which demands a low vs. high level of prior knowledge and assumptions about how constituents of the brain interact. However, the conceptual translation between the two is not straightforward. The present work aims to provide a bridge between data-driven and mechanistic modeling. We conceptualize brain dynamics as a complex landscape that is continuously modulated by internal and external changes. The modulation can induce transitions between one stable brain state (attractor) to another. Here, we provide a novel method – Temporal Mapper – built upon established tools from the field of Topological Data Analysis to retrieve the network of attractor transitions from time-series data alone. For theoretical validation, we use a biophysical network model to induce transitions in a controlled manner, which provides simulated time series equipped with a ground-truth attractor transition network. Our approach reconstructs the ground-truth transition network from simulated time-series data better than existing time-varying approaches. For empirical relevance, we apply our approach to fMRI data gathered during a continuous multitask experiment. We found that occupancy of the high-degree nodes and cycles of the transition network was significantly associated with subjects’ behavioral performance. Taken together, we provide an important first step towards integrating data-driven and mechanistic modeling of brain dynamics.
Exact polynomial-time isomorphism testing in directed graphs through comparison of vertex signatures in Krylov subspaces
Authors: O’Shea Robert John
Published: August 2022

Motivation

The complexity of the isomorphism problem in directed graphs has remained unsolved to date. This study examines the properties of Krylov matrices, demonstrating that they may be used to generate vertex “signatures” to allow exact analogy testing in directed graphs.

Results

A “vertex signature” is defined by initialising a Krylov matrix with a binary vector indicating the vertex position. This study demonstrates that signatures of analogous vertices are related by a linear-ordering transformation. It is demonstrated that equality of ordered vertex signatures is necessary and sufficient to demonstrate analogy. Thus, analogous vertices may be identified by checking each of the n candidates sequentially. This result is extended to analogous vertex sets. Thus, the isomorphic mapping may be constructed iteratively ℴ(n5) time by building a set of vertex analogies sequentially. The algorithm is applied to a dataset of enzyme structures, with comparison to a common heuristic algorithm.

Availability and Implementation

Source code is provided at github.com/robertoshea/graph_isomorphism_directed.

Contact

robert.1.oshea@kcl.ac.uk

Supplementary Data

Supplementary results are attached.
Basolateral amygdala and orbitofrontal cortex, but not dorsal hippocampus, are necessary for the control of reward-seeking by occasion setters
Authors: Fraser Kurt M. , Janak Patricia H.
Published: August 2022

Reward-seeking in the world is driven by cues that can have ambiguous predictive and motivational value. To produce adaptive, flexible reward-seeking it is necessary to exploit occasion setters, other distinct features in the environment, to resolve the ambiguity of Pavlovian reward-paired cues. Despite this, very little research has investigated the neurobiological underpinnings of occasion setting and as a result little is known about which brain regions are critical for occasion setting. To address this, we exploited a recently developed task that was amenable to neurobiological inquiry where a conditioned stimulus is only predictive of reward delivery if preceded in time by the non-overlapping presentation of a separate cue - an occasion setter. This task required male rats to maintain and link cue-triggered expectations across time to produce adaptive reward-seeking. We interrogated the contributions of the basolateral amygdala and orbitofrontal cortex to occasion setting as these regions are thought to be critical for the computation and exploitation of state value, respectively. Reversible inactivation of either structure prior to the occasion-setting task resulted in a profound inability of rats to use the occasion setter to guide reward seeking. In contrast, inactivation of the dorsal hippocampus, a region fundamental for context-specific responding was without effect nor did inactivation of the basolateral amygdala or orbitofrontal cortex in a standard Pavlovian conditioning preparation affect conditioned responding. We conclude that neural activity within the orbitofrontal cortex and basolateral amygdala circuit is necessary to update and resolve ambiguity in the environment to promote cue-driven reward-seeking.
Using agent-based models to predict pollen deposition in a dioecious crop
Authors: Broussard Melissa A. , Jochym Mateusz , Tomer Nathan , Jesson Linley , Shaw Allison K. , Crowder David W. , Bosque-Pérez Nilsa A. , Li Jing , Peace Angela , Fonseka Dilini , Howlett Brad , Pattemore David
Published: August 2022

Pollination involves complex interactions between plants and pollinators, and variation in plant or pollinator biology can lead to variability in pollination services that are difficult to predict. Models that effectively predict pollination services could enhance the ability to conserve plant-pollinator mutualisms in natural systems and increase crop yields in managed systems. However, while most pollination models have focused either on effects of plant or pollination biology, few models have integrated plant-pollinator interactions. Moreover, crop management causes variation in plant-pollinator interactions and pollination services, but management is rarely considered in pollination models. Here we used extensive datasets for kiwifruit (Actinidia chinensis var. deliciosa) to develop an agent-based model to track insect-provided pollination services with variation in crop cultivars, pollinator traits, and orchard layouts. This allowed us to predict pollination outcomes in a dioecious crop under a range of management scenarios. Our sensitivity analysis indicated that flower density and the proportion of female flowers are the most important factors in successful pollination, both of which growers control via cultivar selection and cultural management practices. Our analysis also indicated that economically viable pollination services and crop yields are attained with ∼60% female flowers and a peak foraging activity of 6 to 8 bees per 1,000 open flowers with diminishing returns for additional pollinators. The quality of pollination service varied across simulated orchard layouts, highlighting the potential use of this model as a framework to screen novel orchard configurations. More broadly, linking complex plant and pollinator interactions in pollination models can help identify factors that may improve crop yields and provide a framework for identifying factors important to pollination in natural ecosystems.

HIGHLIGHTS

- We develop a model using extensive empirical datasets to predict pollen deposition based on the interactions between flowers and pollinators in a dioecious crop system

- We conducted a thorough sensitivity analysis, and analysis of the effect of stochastic variance between model runs, which can be used to inform future design of stochastic agent-based models

- Our model effectively predicted the outcomes of varying management regimes of orchard layouts and pollinator introductions on pollination in a dioecious crop

- Our model can be extended for other functionally dioecious crops or plant communities where managers want to understand how their decisions impact pollination
Acrylamide Induces Protein Aggregation in CNS through Suppression of FoxO1-mediated Autophagy
Authors: He Xi-Biao , Huang Haozhi , Wu Yi , Guo Fang
Published: August 2022

Proteotoxic stress is a major stimulus and risk factor for the neuropathogenesis in central nervous system (CNS), which is tightly associated with neurodegenerative diseases. Here, we identify acrylamide (ACR), a type-2 alkene that is commonly detected in deep-fried starch food and used in water industry and biomedical laboratories, as a potent and universal inducer of proteotoxic stress in mouse brain, as well as in cultured mouse neural stem cells, neurons and astrocytes, three major cell types in CNS. Aggregations of ubiquitin-labeled misfolded proteins and neurodegeneration-related proteins including amyloid precursor protein and presenilin 1 were drastically induced by ACR, leading to cell-defensive aggresome formation that was able to temporarily counteract with ACR toxicity. However, a defected clearance of aggresomes eventually led to apoptotic cell death, which was largely attributed to the breakdown of cytoskeleton and impairment of macroautophagy/autophagy, as evidenced by an aggregation of filament actin and an almost complete loss of LC3-positive autophagosomes. A series of core autophagy-related genes responsible for autophagosome formation were down-regulated, indicating an ACR-induced transcriptional suppression of autophagy. In addition, FoxO1, the master transactivator of these genes, were both transcriptionally repressed and nuclear excluded by ACR. Overexpression of FoxO1 rescued ACR-induced autophagy defects and attenuated the proteotoxicity. In summary, we spotlight proteotoxic stress as a novel feature of ACR neurotoxicity in CNS, and implicate FoxO1 as a critical therapeutic target.
Emergence of CC17 vancomycin variable Enterococcus faecium in India
Authors: Sugumar Madhan , Peela Sreeram Chandra Murthy , Viswanath Lakshmi Shree , Walia Kamini , Sistla Sujatha
Published: August 2022

Vancomycin variable enterococci (VVE) are those isolates that are susceptible to glycopeptide like vancomycin but harbour the resistance determinants like vanA gene. Globally the emergence of such strains was reported, and from India our centre was the first to report them. The present study focussed on analysing genome content of these strains from India to assess their genetic diversity. While the five isolates belonged to three sequence types, all the isolates were of clonal complex CC17. This supports that VVE from India are genetically closely related and are emerging from a single clone.
The molecular foundation of proprioceptor muscle-type identity
Authors: Dietrich Stephan , Company Carlos , Song Kun , Lowenstein Elijah David , Riedel Levin , Birchmeier Carmen , Gargiulo Gaetano , Zampieri Niccolò
Published: August 2022

The precise execution of coordinated movements depends on proprioception, the sense of body position in space. However, the molecular underpinnings of proprioceptive neuron subtype identities are not clear yet. In this study, we searched for molecular correlates of proprioceptor subtypes defined according to the identity of the muscle they innervate. We identified and validated signatures for subtypes monitoring the activity of back, abdominal, and hindlimb muscles. We found that proprioceptor muscle identity is acquired early in development and comprise programs controlling wiring specificity. Altogether this work paves the way for defining the mechanisms underlying the development of proprioceptor subtypes to the single muscle level and dissect their contributions to motor control.
Age-related differences in ocular features of a naturalistic free-ranging population of rhesus macaques
Authors: Fernandes Arthur G , Alexopoulos Palaiologos , Burgos-Rodriguez Armando , Martinez Melween I ,   Cayo Biobank Research Unit, Ghassibi Mark , Leskov Ilya , Brent Lauren J N , Snyder-Mackler Noah , Danias John , Wollstein Gadi , Higham James P , Melin Amanda D
Published: August 2022

Purpose

Rhesus macaques (Macaca mulatta) are the premier nonhuman primate model for studying human health and disease. We aimed to investigate if age was associated with ocular features of clinical relevance in a large cohort of free-ranging rhesus macaques from Cayo Santiago, Puerto Rico.

Methods

We evaluated 120 rhesus macaques (73 males, 47 females) aged from 0 to 29 years old (mean±SD: 12.6±6.4) from September to December, 2021. The ophthalmic evaluation included IOP assessment, corneal pachymetry, anterior segment biomicroscopy, A-Scan biometry, automated refraction, and fundus photography after pupil dilation. The effects of age on the outcome variables were investigated through multilevel mixed-effects models adjusted for sex and weight.

Results

On average, IOP, pachymetry, axial length, and automated refraction spherical equivalent were 15.47±2.47 mmHg, 474.43±32.21 μm, 19.49±1.24 mm, and 0.30±1.70 D, respectively. Age was significantly associated with pachymetry (Coef.= -1.20; 95%CI: -2.27 to -0.14; p=0.026), axial length (Coef.= 0.03; 95%CI: 0.01 to 0.05; p=0.002), and spherical equivalent (Coef.= -0.12; 95%CI: -0.22 to -0.02; p=0.015). No association was detected between age and IOP. The prevalence of cataracts in either eye was 10.83% (95% CI: 6.34 – 17.89%) and was significantly associated with age (OR= 1.20; 95%CI: 1.06 – 1.36; p=0.004). Retinal drusen in either eye was observed in 15.00% (95% CI: 9.60 – 22.68%) of the animals, which was also significantly associated with age (OR=1.14; 95%CI: 1.02 – 1.27; p=0.020).

Conclusions

Rhesus macaques exhibit age-related ocular associations similar to those observed in human aging, including decreased corneal thickness, increased axial length, myopic shift, and higher occurrence of cataract and retinal drusen.
Boolean dynamic modeling of TNFR1 signaling predicts a nested feedback loop regulating the apoptotic response at single-cell level
Authors: Sherekar Shubhank , Viswanathan Ganesh
Published: August 2022

Cell-to-cell variability during Tumor Necrosis Factor Receptor 1 (TNFR1) signaling triggered by the pleiotropic cytokine TNFα can lead to pro-survival and apoptotic phenotypic responses at single-cell level. Harnessing the ability to modulate the signal flow responsible for the balance between these two phenotypes and make cells favour apoptosis have been considered in cancer therapies. We show that a 6-node nested feedback loop facilitates the crucial crosstalk regulation modulating the signal flow between these two responses. We identify this by systematically analysing the partial state transition graph (pSTG) underlying a Boolean dynamic model of the TNFR1 signaling network that accounts for signal flow path variability. We demonstrate a novel approach “Boolean Modeling based Prediction of Steady-state probability of Phenotype Reachability (BM-ProSPR)” that enables constructing a reliable pSTG in a computationally efficient manner and predicting accurately the network’s ability to settle into different phenotypes. We deduce that knocking-off Comp1 – IKK* complex tweaks the signal flow paths leading to a 62% increase in the steady state probability of TNFR1 signaling culminating in apoptosis and thereby favours phenotype switching from pro-survival to apoptosis. Priming cancerous cells with inhibitors targeting the interaction involving Comp1 and IKK* prior to TNFα exposure could be a potential therapeutic strategy.
Complement-dependent loss of inhibitory synapses on pyramidal neurons followingToxoplasma gondiiinfection
Authors: Carrillo Gabriela L. , Su Jianmin , Cawley Mikel L. , Wei Derek , Gill Simran K. , Blader Ira J. , Fox Michael A.
Published: August 2022

The apicomplexan parasiteToxoplasma gondiihas developed mechanisms to establish a central nervous system infection in virtually all warm-blooded animals. AcuteT. gondiiinfection can cause neuroinflammation, encephalitis, and seizures. Meanwhile, studies in humans, non-human primates, and rodents have linked chronicT. gondiiinfection with altered behavior and increased risk for neuropsychiatric disorders, including schizophrenia. We previously demonstrated thatT. gondiiinfection triggers the loss of perisomatic inhibitory synapses, an important source of inhibition on excitatory pyramidal cells, and a type of synapse that is disrupted in neurological and neuropsychiatric disorders. Similar to other instances of inflammation and neurodegeneration, we showed that phagocytic cells (including microglia and infiltrating monocytes) contribute to the loss of these inhibitory synapses. However, in the case ofT. gondii-induced synapse loss, phagocytic cells target and ensheath the cell bodies of telencephalic neurons. Here, we show that these phagocytic cells specifically ensheath excitatory pyramidal neurons, leading to the preferential loss of perisomatic synapses on these neurons. In contrast, inhibitory cortical interneuron subtypes are not extensively ensheathed by phagocytic cells following infection. Moreover, we show that infection induces expression of complement C3 protein by these excitatory neurons and that C3 is required for the loss of perisomatic inhibitory synapses, albeit not through activation of the classical complement pathway. Together, these findings provide evidence thatT. gondiiinfection induces changes in excitatory pyramidal neurons that trigger selective removal of inhibitory perisomatic synapses in the infected neocortex and provide a novel role for complement in remodeling of inhibitory circuits in the infected brain.
Imaging the columnar functional organization of human area MT+ to axis-of-motion stimuli using VASO at 7 Tesla
Authors: Pizzuti Alessandra , Huber Laurentius (Renzo) , Gulban Omer Faruk , Benitez-Andonegui Amaia , Peters Judith , Goebel Rainer
Published: August 2022

Cortical columns of direction-selective neurons in the motion sensitive area (MT) have been successfully established as a microscopic feature of the neocortex in animals. The same property has been investigated at mesoscale (<1 mm) in the homologous brain area (hMT+, V5) in living humans by using ultra-high field functional magnetic resonance imaging (fMRI). Despite the reproducibility of the selective response to axis-of-motion stimuli, clear quantitative evidence for the columnar organization of hMT+ is still lacking. Using cerebral blood volume (CBV)-sensitive fMRI at 7 Tesla with submillimeter resolution and high spatial specificity to microvasculature, we investigate the columnar functional organization of hMT+ in 5 participants perceiving axis-of-motion stimuli for both blood oxygenation level dependent (BOLD) and vascular space occupancy (VASO) contrast mechanisms provided by the used Slab-Selective Slice Inversion (SS-SI)-VASO sequence. With the development of a new searchlight algorithm for column detection, we provide the first quantitative columnarity map that characterizes the entire 3D hMT+ volume. Using voxel-wise measures of sensitivity and specificity, we demonstrate the advantage of using CBV-sensitive fMRI to detect mesoscopic cortical features by revealing higher specificity of axis-of-motion cortical columns for VASO as compared to BOLD contrast. These voxel-wise metrics also provide further insights on how to mitigate the highly debated draining veins effect. We conclude that using CBV-VASO fMRI together with voxel-wise measurements of sensitivity, specificity and columnarity offers a promising avenue to quantify the mesoscopic organization of hMT+ with respect to axis-of-motion stimuli. Furthermore, our approach and methodological developments are generalizable and applicable to other human brain areas where similar mesoscopic research questions are addressed.
Insecticides, more than herbicides, land use, and climate, are associated with declines in butterfly species richness and abundance in the American Midwest
Authors: Deynze Braeden Van , Swinton Scott M. , Hennessy David A. , Haddad Nick M. , Ries Leslie
Published: August 2022

Mounting evidence shows overall insect abundances are in decline globally. Habitat loss, climate change, and pesticides have all been implicated, but their relative effects have never been evaluated in a comprehensive large-scale study. We harmonized 17 years of land use, climate, multiple classes of pesticides, and butterfly survey data across 81 counties in five states in the US Midwest. We find community-wide declines in total butterfly abundance and species richness to be most strongly associated with pesticides in general, and for butterflies species richness the use of neonicotinoid-treated seeds in particular. This included the abundance of the migratory monarch (Danaus plexippus), whose decline is the focus of intensive debate and public concern. Insect declines cannot be understood without comprehensive data on all putative drivers, and the 2015 cessation of neonicotinoid data releases in the US will impede future research.

One Sentence Summary

Shifts in insecticide use towards neonicotinoid-treated seeds are associated with an 8 percent decline in butterfly species diversity across the American Corn Belt.
Lectocyte secrete novel leukolectinsin ovofor first-line innate immunity defence
Authors: Miftari Mirushe H. , Walther Bernt T.
Published: August 2022

Atlantic salmon hatching fluid (HF) contains numerous polypeptides. A component unidentified by proteomics, was cloned from tryptic peptides and characterized as lectin-like (LL-) proteins in the tectonin-family. Purified salmon LL-proteins elicited high-titre, LL-specific polyclonal antibodies. This study aims to delineate the cellular and genetic basis of fish embryonic LL-expression. LL-proteins were detected in salmon, cod, rainbow trout and zebrafish HFs. LL-immunoreactive cells were numerous in salmon and rainbow trout embryos, but fewer in zebrafish, cod and halibut. Peridermal salmon LL-positive cells (lectocytes) corresponded to non-eosinophilic cells stained by PAS-reagent. Northern blots revealed two transcripts in salmon and zebrafish embryos, and LL-transcripts were detected specifically in lectocytes. Dualin situhybridization distinguished lectocytes from hatching glands. BAC-library screening yielded salmon Leukolectin’s gene-structure with 4 introns, 5 exons, TATA-box, multiple upstream putative transcription-factor binding-sites, and polyadenylation site. Sequence-analysis indicated zebrafish LL’s conserved nt-sequences and gene-structure, which exhibited mature and truncated LL-transcripts. Zebrafish LL-expression was detected at 6 hpf (yolk syncytium) and 19 hpf (lectocytes and PVF). In dermal mucus, Leukolectins with TECPR-domains may function as pathogen-recognition receptors in first-line innate immunity defence.

SUMMARY STATEMENT:

At hatching, embryos lose maternal chorions, their first-line innate immuno-protection. Novel leukolectin-genes specifically expressed in non-eosinophilic peridermal cells (lectocytes) help explain how embryos develop innate immuno-competency to survive as larvae.
HiFi chromosome-scale diploid assemblies of the grape rootstocks 110R, Kober 5BB, and 101-14 Mgt
Authors: Minio Andrea , Cochetel Noé , Massonnet Mélanie , Figueroa-Balderas Rosa , Cantu Dario
Published: August 2022

Cultivated grapevines are commonly grafted on closely related species to cope with specific biotic and abiotic stress conditions. The three North American Vitis species V. riparia, V. rupestris, and V. berlandieri, are the main species used for breeding grape rootstocks. Here, we report the diploid chromosome-scale assembly of three widely used rootstocks derived from these species: Richter 110 (110R), Kober 5BB, and 101-14 Millardet et de Grasset (Mgt). Draft genomes of the three hybrids were assembled using PacBio HiFi sequences at an average coverage of 53.1 X-fold. Using the tool suite HaploSync, we reconstructed the two sets of nineteen chromosome-scale pseudomolecules for each genome with an average haploid genome size of 494.5 Mbp. Residual haplotype switches were resolved using shared-haplotype information. These three reference genomes represent a valuable resource for studying the genetic basis of grape adaption to biotic and abiotic stresses, and designing trait-associated markers for rootstock breeding programs.
Deducing genotypes for loci of interest from SNP array data via haplotype sharing, demonstrated for apple and cherry
Authors: Schaller Alexander , Vanderzande Stijn , Peace Cameron
Published: August 2022

Breeders, collection curators, and other germplasm users require genetic information, both genome-wide and locus-specific, to effectively manage their genetically diverse plant material. SNP arrays have become the preferred platform to provide genome-wide genetic profiles for elite germplasm and could also provide locus-specific genotypic information. However, genotypic information for loci of interest such as those within PCR-based DNA fingerprinting panels and trait-predictive DNA tests is not readily extracted from SNP array data, thus creating a disconnect between historic and new data sets. This study aimed to establish a method for deducing genotypes at loci of interest from their associated SNP haplotypes, demonstrated for two fruit crops and three locus types: quantitative trait loci Ma and Ma3 for acidity in apple, apple fingerprinting microsatellite marker GD12, and Mendelian trait locus Rf for sweet cherry fruit color. Using phased data from an apple 8K SNP array and sweet cherry 6K SNP array, unique haplotypes spanning each target locus were associated with alleles of important breeding parents. These haplotypes were compared via identity-by-descent (IBD) or identity-by-state (IBS) to haplotypes present in germplasm important to U.S. apple and cherry breeding programs to deduce target locus alleles in this germplasm. While IBD segments were confidently tracked through pedigrees, confidence in allele identity among IBS segments used a shared length threshold. At least one allele per locus was deduced for 64–93% of the 181 individuals. Successful validation compared deduced Rf and GD12 genotypes with reported and newly obtained genotypes. Our approach can efficiently merge and expand genotypic data sets, deducing missing data and identifying errors, and is appropriate for any crop with SNP array data and historic genotypic data sets, especially where linkage disequilibrium is high. Locus-specific genotypic information extracted from genome-wide SNP data is expected to enhance confidence in management of genetic resources.
Sensitivity analysis of genome-scale metabolic flux prediction
Authors: Niu Puhua , Soto Maria J. , Huang Shuai , Yoon Byung-Jun , Dougherty Edward R. , Alexander Francis J. , Blaby Ian , Qian Xiaoning
Published: August 2022

TRIMER, Transcription Regulation Integrated with MEtabolic Regulation, is a genome-scale modeling pipeline targeting at metabolic engineering applications. Using TRIMER, regulated metabolic reactions can be effectively predicted by integrative modeling of metabolic reactions with Transcription Factor (TF)-gene regulatory network (TRN), where the TRN is modeled via Bayesian network (BN). In this paper, we focus on sensitivity analysis of metabolic flux prediction considering potential model uncertainty in TRIMER. We propose a computational strategy to construct the uncertainty class of TRN models based on the inferred regulatory order uncertainty when learning from given transcriptomic expression data and analyze the prediction sensitivity of the TRIMER pipeline for the metabolite yield of interest. The obtained sensitivity analyses can provide a useful guidance for Optimal Experimental Design (OED) to help acquire new data that can enhance TRN modeling and effectively achieve specific metabolic engineering objectives, including metabolite yield alterations. We have performed simulation experiments to demonstrate the effectiveness of our developed sensitivity analysis strategy and its potential to effectively guide OED.

ACM Reference Format

Puhua Niu, Maria J. Soto, Shuai Huang, Byung-Jun Yoon, Edward R. Dougherty,, Francis J. Alexander, Ian Blaby, Xiaoning Qian. 2018. Sensitivity analysis of genome-scale metabolic flux prediction. InProceedings of Make sure to enter the correct conference title from your rights confirmation email (CNB-MAC 2022). ACM, New York, NY, USA, 9 pages.https://doi.org/XXXXXXX.XXXXXXX
Standing balance in aging is robust against head rotation during visual tracking
Authors: Georgiadis Petros , Chatzinikolaou Konstantinos , Voudouris Dimitrios , Van Dieen Jaap , Hatzitaki Vassilia
Published: August 2022

Standing balance is relatively more unstable when visually pursuing a moving target than when fixating a stationary one. These effects are common across age groups if the head is restrained during visual task performance. The present study focused on the role of the head motion on standing balance during the pursuit of a moving target as a function of age. Three predictions were tested: a) standing balance is compromised to a greater extent in older than young adults by gaze target pursuit compared to fixation, b) older adults pursue a moving target with greater and more variable head rotation than young adults, and c) greater and more variable head rotation during the gaze pursuit task is associated with greater postural sway. Twenty-two (22) older (age: 71.7±8.1, 12 M / 10 F) and twenty-three (23) young adults (age: 23.6±2.5, 12 M / 11 F) stood on a force plate in front of a 60-inch monitor while performing two visual tasks: fixation at a stationary target and gaze pursuit of a horizontally moving target. Centre of pressure (CoP) and head kinematics were synchronously recorded with the Vicon motion analysis system, while head-unconstrained gaze was captured by the Pupil Labs Invisible mobile tracking system. Postural sway, reflected in the interquartile CoP range and the root mean square (RMS) of CoP velocity increased during the gaze pursuit compared to the fixation task (p<.05), and this effect was more pronounced in older than young participants (p<.05). Older adults pursued the moving target employing more variable (p=.022) head yaw rotation than young participants although the amplitude of head rotation was not systematically different between groups (p=. 077). The amplitude and variance of head yaw rotation did not correlate with postural sway measures. Results suggest that older adults may engage more variable head rotation when tracking a moving target to compensate for age-related deficits in eye smooth pursuit movement. However, this strategy does not seem to compromise standing balance.
A Graph Coarsening Algorithm for Compressing Representations of Single-Cell Data with Clinical or Experimental Attributes
Authors: Chen Chi-Jane , Crawford Emma , Stanley Natalie
Published: August 2022

Graph-based algorithms have become essential in the analysis of single-cell data for numerous tasks, such as automated cell-phenotyping and identifying cellular correlates of experimental perturbations or disease states. In large multi-patient, multi-sample single-cell datasets, the analysis of cell-cell similarity graphs representations of these data becomes computationally prohibitive. Here, we introduce cytocoarsening, a novel graph-coarsening algorithm that significantly reduces the size of single-cell graph representations, which can then used as input to downstream bioinformatics algorithms for improved computational efficiency. Uniquely, cytocoarsening considers both phenotypical similarity of cells and similarity of cells’ associated clinical or experimental attributes in order to more readily identify condition-specific cell populations. The resulting coarse graph representations were evaluated based on both their structural correctness and the capacity of downstream algorithms to uncover the same biological conclusions as if the full graph had been used. Cytocoarsening is provided as open source code at https://github.com/ChenCookie/cytocoarsening.
High-precision neural stimulation by a highly efficient candle soot fiber optoacoustic emitter
Authors: Chen Guo , Shi Linli , Lan Lu , Wang Runyu , Li Yueming , Du Zhiyi , Hyman Mackenzie , Cheng Ji-Xin , Yang Chen
Published: August 2022

Highly precise neuromodulation with a high efficacy poses great importance in neuroscience. Here, we developed a candle soot fiber optoacoustic emitter (CSFOE), capable of generating a high pressure of over 10 MPa, enabling highly efficient neuromodulation in vitro. The design of the fiber optoacoustic emitter, including the choice of the material and the thickness of the layered structure, was optimized in both simulations and experiments. The optoacoustic conversion efficiency of the optimized CSFOE was found to be ten times higher than the other carbon-based fiber optoacoustic emitters. Driven by a single laser, the CSFOE can perform dual-site optoacoustic activation of neurons, confirmed by calcium (Ca) imaging. Our work opens potential avenues for more complex and programmed control in neural circuits using a simple design for multisite neuromodulation in vivo.
The ENCODE Imputation Challenge: A critical assessment of methods for cross-cell type imputation of epigenomic profiles
Authors: Schreiber Jacob , Boix Carles , Lee Jin wook , Li Hongyang , Guan Yuanfang , Chang Chun-Chieh , Chang Jen-Chien , Hawkins-Hooker Alex , Schölkopf Bernhard , Schweikert Gabriele , Carulla Mateo Rojas , Canakoglu Arif , Guzzo Francesco , Nanni Luca , Masseroli Marco , Carman Mark James , Pinoli Pietro , Hong Chenyang , Yip Kevin Y. , Spence Jeffrey P. , Batra Sanjit Singh , Song Yun S. , Mahony Shaun , Zhang Zheng , Tan Wuwei , Shen Yang , Sun Yuanfei , Shi Minyi , Adrian Jessika , Sandstrom Richard , Farrell Nina , Halow Jessica , Lee Kristen , Jiang Lixia , Yang Xinqiong , Epstein Charles , Strattan J. Seth , Snyder Michael , Kellis Manolis , Noble William Stafford , Kundaje Anshul ,   ENCODE Imputation Challenge Participants
Published: August 2022

Functional genomics experiments are invaluable for understanding mechanisms of gene regulation. However, comprehensively performing all such experiments, even across a fixed set of sample and assay types, is often infeasible in practice. A promising alternative to performing experiments exhaustively is to, instead, perform a core set of experiments and subsequently use machine learning methods to impute the remaining experiments. However, questions remain as to the quality of the imputations, the best approaches for performing imputations, and even what performance measures meaningfully evaluate performance of such models. In this work, we address these questions by comprehensively analyzing imputations from 23 imputation models submitted to the ENCODE Imputation Challenge. We find that measuring the quality of imputations is significantly more challenging than reported in the literature, and is confounded by three factors: major distributional shifts that arise because of differences in data collection and processing over time, the amount of available data per cell type, and redundancy among performance measures. Our systematic analyses suggest several steps that are necessary, but also simple, for fairly evaluating the performance of such models, as well as promising directions for more robust research in this area.
An economic and robust TMT labeling approach for high throughput proteomic and metaproteomic analysis
Authors: Creskey Marybeth , Li Leyuan , Ning Zhibin , Brown Emily EF , Mayne Janice , Walker Krystal , Ampaw Anna , Ben Robert , Zhang Xu , Figeys Daniel
Published: August 2022

Multiplexed quantitative proteomics using tandem mass tag (TMT) is increasingly used in –omic study of complex samples. While TMT-based proteomics has the advantages of the higher quantitative accuracy, fewer missing values, and reduced instrument analysis time, it is limited by the increased cost due to the use of labeling reagents. In addition, current TMT labeling workflows involve repeated small volume pipetting of reagents in volatile organic solvents, which may increase the sample-to-sample variations and is not readily suitable for high throughput applications. In this study, we demonstrated that the TMT labeling procedures could be streamlined by using pre-aliquoted dry TMT reagents in a 96 well plate or 12-tube strip. As little as 50 μg dry TMT per channel effectively labels 6-12 μg peptides, yielding efficient TMT labeling efficiency (∼99%) in both microbiome and mammalian cell line samples. This streamlined workflow decreases reagent loss and reduces inter-sample variations. We applied this workflow to analyze 97 samples in a study to evaluate whether ice recrystallization inhibitors improve the cultivability and activity of frozen microbiota. The results demonstrated tight sample clustering corresponding to groups and consistent microbiome responses to prebiotic treatments. This study supports the use of TMT reagents that are pre-aliquoted, dried, and stored for streamlined and robust quantitative proteomics and metaproteomics in high throughput applications.
The microRNA processing subunit DGCR8 is required for a T cell-dependent germinal center response
Authors: Daum Patrick , Meinzinger Julia , Schulz Sebastian R. , Côrte-Real Joana , Hauke Manuela , Roth Edith , Schuh Wolfgang , Mielenz Dirk , Wittmann Jürgen , Jäck Hans-Martin , Pracht Katharina
Published: August 2022

We have previously shown that the microRNA (miRNA) processor complex consisting of the RNAse Drosha and the DiGeorge Critical Region (DGCR) 8 protein is essential for central B cell maturation. To determine whether miRNA processing is required to initiate T cell-mediated antibody responses, we deleted DGCR8 in maturing B-2 cells by crossing a mouse with loxP-flanked DGCR8 alleles with a CD23-Cre mouse. As expected, non-immunized mice showed reduced numbers of mature B-2 cells and IgG-secreting cells and diminished serum IgG titers. In accordance, germinal centers and antigen-specific IgG-secreting cells were absent in mice immunized with T cell-dependent antigens. Therefore, DGCR8 is required to mount an efficient T cell-dependent antibody response. However, DGCR8 deletion in B-1 cells was incomplete, which explains relatively unaffected B-1 cell numbers and adequate IgM and IgA titers in DGCR8-knock out mice and suggests that this mouse model could be used to analyze B-1 responses in the absence of functional B-2 cells.
Necrosis reduction efficacy of subdermal biomaterial mediated oxygen delivery in ischemic skin flaps
Authors: Rastinfard Arghavan , Dalisson Benjamin , Gilardino Mirko , Watters Kevin , Job Dario , Merle Geraldine , Lasagabaster Arturo Vela , Ouhaddi Yassine , Barralet Jake
Published: August 2022

Inadequate tissue blood supply (e.g., in a wound or a poorly vascularised graft) can result in tissue ischemia and necrosis. As revascularization is a slow process relative to the proliferation of bacteria and the onset and spread of tissue necrosis, extensive tissue damage and loss can occur. Necrosis can spread rapidly, and treatment options are limited such that loss of tissue in ischemic tissue following necrosis onset is considered unavoidable and irreversible.

Oxygen delivery from biomaterials exploiting aqueous decomposition of peroxy-compounds has shown some potential in overcoming the supply limitations caused by quite short oxygen diffusion distances in tissues by creating higher concentration gradients than can be attained by air saturated solutions or by distributing oxygen supply throughout a scaffold or construct by using particulate formulations. These have found application in tissue preservation, bioinks, creation of 3D tissue analogues etc. In preclinical models among the more exciting reports was a single study demonstrating reduction of ischemic skin necrosis albeit only short term using short term sub dermal delivery of oxygen below ischemic skin flaps. To explore this effect further, we developed an implantable solid peroxide-biomaterial based system with reduced hydrogen peroxide release by virtue of incorporation of minerals to catalytically decompose it in a much longer flap than examined previously. Blood flow in this flap reduced from essentially normal to essentially zero, along its 9cm length. Without treatment ∼50% of the total flap was necrotic in 2-4 days. In both groups, complete necrosis in the distal third of the flap with no observable flood flow was observed. But in the middle low blood flow region of the flap, treatment did prevent necrosis. This study indicated that subdermal oxygen delivery alone cannot completely mitigate dermal necrosis if no blood flow is present, but it could improve the survival of partially tissue at least in the short term which could find application to augment conventional treatments or to gain time until surgical intervention.