bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of IgG isotype on the induction of antibody-dependent cellular phagocytosis of HIV by human milk leukocytes
Authors: Fox Alisa , Liu Xiaomei , Zolla-Pazner Susan , Powell Rebecca L.
Published: October 2021

Approximately 100,000 mother-to-child transmission (MTCT) events of HIV via human milk feeding occur each year (1). However, only about 15% of infants milk-fed by untreated HIV+ mothers become infected, suggesting a protective effect of the milk itself (1, 2). Infants ingest 105-108 maternal leukocytes daily via milk, which remain functional beyond ingestion (3–9). Such function may be elicited by maternal milk antibody (Ab). Though IgA is dominant in milk, most HIV-specific milk Abs are of the IgG subclass, highlighting the importance of investigating the function of each IgG isotype in the milk context (10–16). Though Ab effector function mediated by the constant (Fc) domain via interaction with Fc Receptors (FcRs), such as Ab-dependent cellular phagocytosis (ADCP), are critical in protecting against HIV infection, ADCP is largely unexplored as it relates to mitigation of MTCT (17–21). Presently we report the ADCP activity of milk leukocytes against HIV particles and immune complexes (ICs), using 57 unique samples from 34 women, elicited by IgG1/2/3/4 of monoclonal (m)Ab 246-D. Granulocyte ADCP of HIV was most potent compared to other phagocytes when elicited by IgG1/3/4. IgG1/3 activated granulocytes similarly, exhibiting 1.6x-4.4x greater activity compared to IgG2/4, and a preference for virus compared to ICs. Notably, CD16-monocyte ADCP of a given target were unaffected by isotype, and CD16+ monocytes were poorly stimulated by IgG1. IgG2/4 elicited potent IC ADCP, and in terms of total leukocyte IC ADCP, IgG4 and IgG3 exhibited similar function, with IgG4 eliciting 1.6x-2.1x greater activity compared to IgG1/IgG2, and CD16+ monocytes most stimulated by IgG2. These data contribute to a more comprehensive understanding of Fc-mediated functionality of milk leukocytes, which is critical in order to develop therapeutic approaches to eliminating this route of MTCT, including mucosal administration of mAbs and/or a maternal vaccination aimed to elicit a potent milk Ab response.
Using a Homeogram to Detect Sleep in Free-living Animals
Authors: Gaidica Matt , Studd Emily , Wishart Andrea E , Gonzalez William , Lane Jeffrey E , McAdam Andrew G , Boutin Stan , Dantzer Ben
Published: October 2021

Sleep is appreciated as a behavior critical to homeostasis, performance, and fitness. Yet, most of what we know about sleep comes from humans or controlled laboratory experiments. Assessing sleep in wild animals is challenging, as it is often hidden from view, and electrophysiological recordings that define sleep states are difficult to obtain. Accelerometers have offered great insight regarding gross movement, although ambiguous quiescent states like sleep have been largely ignored, limiting our understanding of this ubiquitous behavior.

We developed a broadly applicable sleep detection method called a homeogram that can be applied to accelerometer data collected from wild animals. We applied our methodology to detect sleep in free-ranging North American red squirrels (Tamiasciurus hudsonicus) in a region that experiences drastic seasonal shifts in light, temperature, and behavioral demands.

Our method characterized sleep in a manner consistent with limited existing studies and expanded those observations to provide evidence that red squirrels apply unique sleep strategies to cope with changing environments.

Applying our analytical strategy to accelerometer data from other species may open new possibilities to investigate sleep patterns for researchers studying wild animals.
Stimulus-dependent orientation strategies in monarch butterflies
Authors: Franzke Myriam , Kraus Christian , Gayler Maria , Dreyer David , Pfeiffer Keram , Jundi Basil el
Published: October 2021

Insects are well-known for their ability to keep track of their heading direction based on a combination of skylight cues and visual landmarks. This allows them to navigate back to their nest, disperse throughout unfamiliar environments, as well as migrate over large distances between their breeding and non-breeding habitats. The monarch butterfly (Danaus plexippus) for instance is known for its annual southward migration from North America to certain trees in Central Mexico. To maintain a constant flight route, these butterflies use a time-compensated sun compass for orientation which is processed in a region in the brain, termed the central complex. However, to successfully complete their journey, the butterflies’ brain must generate a multitude of orientation strategies, allowing them to dynamically switch from sun-compass orientation to a tactic behavior toward a certain target. To study if monarch butterflies exhibit different orientation modes and if they can switch between them, we observed the orientation behavior of tethered flying butterflies in a flight simulator while presenting different visual cues to them. We found that the butterflies’ behavior depended on the presented visual stimulus. Thus, while a dark stripe was used for flight stabilization, a bright stripe was fixated by the butterflies in their frontal visual field. If we replaced a bright stripe by a simulated sun stimulus, the butterflies switched their orientation behavior and exhibited compass orientation. Taken together, our data show that monarch butterflies rely on and switch between different orientation modes, allowing them to adjust orientation to the actual behavioral demands of the animal.
Intrinsic maturation of sleep output neurons regulates sleep ontogeny in Drosophila
Authors: Gong Naihua N. , Dang An H. , Mainwaring Benjamin , Shields Emily , Schmeckpeper Karl , Bonasio Roberto , Kayser Matthew S.
Published: October 2021

The maturation of sleep behavior across a lifespan (sleep ontogeny) is an evolutionarily conserved phenomenon. Mammalian studies have shown that in addition to increased sleep duration, early life sleep exhibits stark differences compared to mature sleep with regard to the amount of time spent in certain sleep states. How intrinsic maturation of sleep output circuits contributes to sleep ontogeny is poorly understood. The fruit fly Drosophila melanogaster exhibits multifaceted changes to sleep from juvenile to mature adulthood. Here, we use a non-invasive probabilistic approach to investigate changes in sleep architecture in juvenile and mature flies. Increased sleep in juvenile flies is driven primarily by a decreased probability of transitioning to wake, and characterized by more time in deeper sleep states. Functional manipulations of sleep-promoting neurons in the dFB suggest these neurons differentially regulate sleep in juvenile and mature flies. Transcriptomic analysis of dFB neurons at different ages and a subsequent RNAi screen implicate genes involved in distinct molecular processes in sleep control of juvenile and mature flies. These results reveal that dynamic transcriptional states of sleep output neurons contribute to changes in sleep across the lifespan.
A Genomic Perspective on the Evolutionary Diversification of Turtles
Authors: Gable Simone M. , Byars Michael I. , Literman Robert , Tollis Marc
Published: October 2021

To examine phylogenetic heterogeneity in turtle evolution, we collected thousands of high-confidence single-copy orthologs from 19 genome assemblies representative of extant turtle diversity and estimated a phylogeny with multispecies coalescent and concatenated partitioned methods. We also collected next-generation sequences from 26 turtle species and assembled millions of biallelic markers to reconstruct phylogenies based on annotated regions from the western painted turtle (Chrysemys picta bellii) genome (coding regions, introns, untranslated regions, intergenic, and others). We then measured gene tree-species tree discordance, as well as gene and site heterogeneity at each node in the inferred trees, and tested for temporal patterns in phylogenomic conflict across turtle evolution. We found strong and consistent support for all bifurcations in the inferred turtle species phylogenies. However, a number of genes, sites, and genomic features supported alternate relationships between turtle taxa. Our results suggest that gene tree-species tree discordance in these datasets is likely driven by population-level processes such as incomplete lineage sorting. We found very little effect of substitutional saturation on species tree topologies, and no clear phylogenetic patterns in codon usage bias and compositional heterogeneity. There was no correlation between gene and site concordance, node age, and DNA substitution rate across most annotated genomic regions. Our study demonstrates that heterogeneity is to be expected even in well resolved clades such as turtles, and that future phylogenomic studies should aim to sample as much of the genome as possible in order to obtain accurate phylogenies for assessing conservation priorities in turtles.
A Hydrogel Microneedle-assisted Assay Integrating Aptamer Probes and Fluorescence Detection for Reagentless Biomarker Quantification
Authors: Zheng Hanjia , GhavamiNejad Amin , GhavamiNejad Peyman , Samarikhalaj Melisa , Giacca Adria , Poudineh Mahla
Published: October 2021

Analyzing interstitial fluid (ISF) via microneedle (MN) devices enables patient health monitoring in a minimally invasive manner and at point-of-care settings. However, most MN-based diagnostic approaches require complicated fabrication processes or post-processing of the extracted ISF. Here we show in-situ and on-needle measurement of target analytes by integrating hydrogel microneedles (HMN) with aptamer probes as the target recognition elements. Fluorescently tagged aptamer probes are chemically attached to the hydrogel matrix while a crosslinked patch is formed. We use the assay for specific and sensitive quantification of glucose concentrations in an animal model of diabetes to track hypoglycemia, euglycemia, and hyperglycemia conditions. The assay can track the rising and falling concentrations of glucose and the extracted measurements closely match those from the gold standard techniques. The assay enables rapid and reagentless target detection and can be readily modified to measure other target analytes in vivo. Our system has the potential to improve the quality of life of patients who are in need of close monitoring of biomarkers of health and disease.
Interferon-Gamma Signaling Promotes Melanoma Progression and Metastasis
Authors: Zhou Bo , Basu Jayati , Kazmi Hasan R. , Mo Xuan , Preston-Alp Sarah , Cai Kathy Q. , Kappes Dietmar , Zaidi M. Raza
Published: October 2021

Interferon-gamma (IFNG) has long been regarded as the flag-bearer for the anti-cancer immunosurveillance mechanisms. However, relatively recent studies have suggested a dual role of IFNG, albeit there is no direct experimental evidence for its potential pro-tumor functions. Here we providein vivoevidence that treatment of mouse melanoma cell lines with physiological levels of Ifng enhances their tumorigenicity and metastasis in lung colonization allograft assays performed in immunocompetent syngeneic host mice, but not in immunocompromised host mice. We also show that this enhancement is dependent on downstream signaling via Stat1 but not Stat3, providing evidence of an oncogenic function of Stat1 in melanoma. The experimental results suggest that melanoma cell-specific Ifng signaling modulates the tumor microenvironment and its pro-tumorigenic effects are dependent on the γδ T cells, as Ifng-enhanced tumorigenesis was inhibited in the TCR-δ knockout mice. Overall, these results show that Ifng signaling may have tumor-promoting effects in melanoma by modulating the immune cell composition of the tumor microenvironment.
Polypolish: short-read polishing of long-read bacterial genome assemblies
Authors: Wick Ryan R. , Holt Kathryn E.
Published: October 2021

Long-read-only bacterial genome assemblies usually contain residual errors, most commonly homopolymer-length errors. Short-read polishing tools can use short reads to fix these errors, but most rely on short-read alignment which is unreliable in repeat regions. Errors in such regions are therefore challenging to fix and often remain after short-read polishing. Here we introduce Polypolish, a new short-read polisher which uses all-per-read alignments to repair errors in repeat sequences that other polishers cannot. Polypolish performed well in benchmarking tests using both simulated and real reads, and it almost never introduced errors during polishing. The best results were achieved by using Polypolish in combination with other short-read polishers.

Author summary

Recent improvements in Oxford Nanopore Technologies sequencing platforms and assembly algorithms have made it easier than ever to generate complete bacterial genome sequences. However, Oxford Nanopore genome sequences suffer from errors that limit their utility in downstream analyses. To fix these errors, one can ‘polish’ the genome with Illumina sequencing, exploiting the fact that Oxford Nanopore and Illumina sequencing have different error profiles. There are several polishing tools which can fix most errors in an Oxford Nanopore genome, but they struggle with errors in repetitive regions of the genome. With this in mind, we have developed a polisher, Polypolish, which uses a novel approach that allows it to fix more errors in genomic repeats. Our results show that Polypolish is both effective at repairing sequence errors and very unlikely to introduce new errors. Polypolish can often fix errors that other polishers cannot and vice versa, so the best results come from using a combination of tools. Polypolish therefore has an important role in bacterial genome assembly methods that aim for the highest possible sequence accuracy.
Single-cell Networks Reorganise to Facilitate Whole-brain Supercritical Dynamics During Epileptic Seizures
Authors: Burrows DRW , Diana G , Pimpel B , Moeller F , Richardson MP , Bassett DS , Meyer MP , Rosch RE
Published: October 2021

Excitation-inhibition (EI) balance may be required for the organisation of brain dynamics to a phase transition, criticality, which confers computational benefits. Brain pathology associated with EI imbalance may therefore occur due to a deviation from criticality. However, evidence linking critical dynamics with EI imbalance-induced pathology is lacking. Here, we studied the effect of EI imbalance-induced epileptic seizures on brain dynamics, usingin vivowhole-brain 2-photon imaging of GCaMP6s larval zebrafish at single-neuron resolution. We demonstrate the importance of EI balance for criticality, with EI imbalance causing a loss of whole-brain critical statistics. Using network models we show that a reorganisation of network topology drives this loss of criticality. Seizure dynamics match theoretical predictions for networks driven away from a phase transition into disorder, with the emergence of chaos and a loss of network-mediated separation, dynamic range and metastability. These results demonstrate that EI imbalance drives a pathological deviation from criticality.
Into the range: a latitudinal gradient or a center-margins differentiation of ecological strategies in Arabidopsis thaliana?
Authors: Estarague Aurélien , Vasseur François , Sartori Kevin , Bastias Cristina , Cornet Denis , Rouan Lauriane , Beurier Gregory , Exposito-Alonso Moises , Herbette Stéphane , Bresson Justine , Vile Denis , Violle Cyrille
Published: October 2021

Background and Aims

Determining within-species large-scale variation in phenotypic traits is central to elucidate the drivers of species’ ranges. Intraspecific comparisons offer the opportunity to understand how trade-offs and biogeographical history constrain adaptation to contrasted environmental conditions. Here we test whether functional traits, ecological strategies and phenotypic plasticity in response to abiotic stress vary along a latitudinal or a center-margins gradient within the native range of Arabidopsis thaliana.

Methods

The phenotypic outcomes of plant adaptation at the center and margins of its geographic range were experimentally examined in 30 accessions from southern, central and northern Europe. The variation of traits related to stress tolerance, resource use, colonization ability as well as survival and fecundity was determined in response to high temperature (34°C) or frost (- 6°C), in combination with response to water deficit.

Key Results

Both evidence for a latitudinal and a center-margins differentiation was found. Traits related to the acquisitive/conservative strategy trade-off varied along a latitudinal gradient. Northern accessions presented a greater survival to stress than central and southern accessions. Traits related to a colonization-competition trade-off followed a center-margin differentiation. Central accessions presented a higher phenotypic plasticity and trait values associated with a higher colonization ability than northern and southern accessions which instead had a higher competition ability.

Conclusions

Intraspecific phenotypic variation helps us understand how the distribution range has evolved in Arabidopsis thaliana, which is shaped both by climate and the population migratory history. We advocate to consider intraspecific trait variation in species range studies instead of species means only as classically done in macroecology.
Chemophoresis Engine: Universal Principle of ATPase-driven Cargo Transport
Authors: Sugawara Takeshi , Kaneko Kunihiko
Published: October 2021

Cell polarity regulates the orientation of the cytoskeleton members that directs intracellular transport for cargo-like organelles, using chemical gradients sustained by ATP or GTP hydrolysis. However, how cargo transports are directly mediated by chemical gradients remains unknown. We previously proposed a physical mechanism that enables directed movement of cargos, referred to as chemophoresis. According to the mechanism, a cargo with reaction sites is subjected to a chemophoresis force in the direction of the increased concentration. Based on this, we introduce an extended model, the chemophoresis engine, as a general mechanism of cargo motion, which transforms chemical free energy into directed motion through the catalytic ATP hydrolysis. We applied the engine to plasmid motion in a parABS system to demonstrate the the self-organization system for directed plasmid movement and pattern dynamics of ParA-ATP concentration, thereby explaining plasmid equi-positioning and pole-to-pole oscillation observed in bacterial cells and in vitro experiments. We mathematically show the existence and stability of the plasmid-surfing pattern, which allows the cargo-directed motion through the symmetry-breaking transition of the ParA-ATP spatiotemporal pattern. Finally, based on its generality, we discuss the chemophoresis engine as a universal principle of hydrolysis-driven intracellular transport.

SIGNIFICANCE

The formation of organelle/macromolecule patterns depending on chemical concentration under non-equilibrium conditions, first observed during macroscopic morphogenesis (1), has recently been observed at the intracellular level as well, and its relevance as intracellular morphogen has been demonstrated in the case of bacterial cell division. These studies have discussed how cargos maintain positional information provided by chemical concentration gradients/localization. However, how cargo transports are directly mediated by chemical gradients remains unknown. Based on the previously proposed mechanism of chemotaxis-like behavior of cargos (referred to as chemophoresis, (2, 3)), we introduce a chemophoresis engine as a physicochemical mechanism of cargo motion, which transforms chemical free energy to directed motion. The engine is based on the chemophoresis force to make cargoes move in the direction of the increasing ATPase(-ATP) concentration and an enhanced catalytic ATPase hydrolysis at the positions of the cargoes. Applying the engine to ATPase-driven movement of plasmid-DNAs in bacterial cells, we constructed a mathematical model to demonstrate the self-organization for directed plasmid motion and pattern dynamics of ATPase concentration, as is consistent with in vitro and in vivo experiments. We propose that this chemophoresis engine works as a universal principle of hydrolysis-driven intracellular transport.
Extremely reduced supergroup F Wolbachia: transition to obligate insect symbionts
Authors: Mahmood Sazzad , Nováková Eva , Martinů Jana , Sychra Oldřich , Hypša Václav
Published: October 2021

Wolbachia are widely distributed symbionts among invertebrates that manifest by a broad spectrum of lifestyles from parasitism to mutualism. Wolbachia Supergroup F is considered a particularly interesting group which gave rise to symbionts of both arthropods and nematodes, and some of its members are obligate mutualists. Further investigations on evolutionary transitions in symbiosis have been hampered by a lack of genomic data for Supergroup F members. In this study, we present genomic data for five new supergroup F Wolbachia strains associated with four chewing lice species. These new strains in different evolutionary stages show genomic characteristics well-illustrating the evolutionary trajectory which symbiotic bacteria experience during their transition to mutualism. Three of the strains have not yet progressed with the transition, the other two show typical signs of ongoing gene deactivation and removal (genome size, coding density, low number of pseudogenes). Particularly, wMeur1, a symbiont fixed in all Menacanthus eurysternus populations across four continents, possesses a highly reduced genome of 733,850 bp with a horizontally acquired capacity for pantothenate synthesis. Comparing with other strains showed wMeur1 genome as the smallest currently known among all Wolbachia and the first example of Wolbachia which has completed genomic streamlining known from the gammaproteobacterial obligate symbionts.
The biological sink of atmospheric H2 is more sensitive to spatial variation of microbial diversity than N2O and CO2 emissions in an agroecosystem
Authors: Baril Xavier , Durand Audrey-Anne , Srei Narin , Lamothe Steve , Provost Caroline , Martineau Christine , Guertin Claude , Dunfield Kari , Constant Philippe
Published: October 2021

The relationship between soil microbial diversity and agroecosystem functioning is controversial due to the elevated diversity level and the functional redundancy of microorganisms. A field trial was established to test the hypothesis that enhanced crop diversity with the integration of winter cover crops (WCC) in a conventional maize-soy rotation promotes microbial diversity and the biological sink of H2 in soil, while reducing N2O emissions to the atmosphere. Vicia villosa (hairy vetch), Avena sativa (oat), and Raphanus sativus (Daikon radish) were cultivated alone or in combinations and flux measurements were performed throughout two subsequent growing seasons. Soil acted as a net sink for H2 and as a net source for CO2 and N2O. CO2 flux was the most sensitive to WCC whereas a significant spatial variation was observed for H2 flux with soil uptake rates observed in the most productive area two-fold greater than the baseline level. Sequencing and quantification of taxonomic and functional genes were integrated to explain variation in trace gas fluxes with compositional changes in soil microbial communities. Fungal communities were the most sensitive to WCC, but neither community abundance nor beta diversity were found to be indicative of fluxes. The alpha diversity of taxonomic and functional genes, expressed as the number of effective species, was integrated into composite variables extracted from multivariate analyses. Only the composite variable computed with the inverse Simpson’s concentration index displayed a reproducible pattern throughout both growing seasons, with functional genes and bacterial 16S rRNA gene defining the two most contrasting gradients. The composite variable was decoupled from WCC treatment and explained 19-20% spatial variation of H2 fluxes. Sensitivity of the trace gas exchange process to soil properties at the local scale was inconsistent among H2, N2O and CO2, with the former being the most related to microbial diversity distribution pattern.
Endogenous recruitment of frontal-sensory circuits during visual discrimination
Authors: Broom Eluned , Imbriotis Vivian , Sengpiel Frank , Connelly William M. , Ranson Adam
Published: October 2021

A long-range circuit linking anterior cingulate cortex (ACC) to primary visual cortex (V1) has been previously proposed to mediate visual selective attention in mice during visually guided behaviour. Here we used in vivo two-photon functional imaging to measure endogenous activity of ACC neurons projecting to layer 1 of V1 (ACC-V1axons) in mice either passively viewing stimuli or performing a go/no-go visually guided task. We observed that while ACC-V1axons were recruited under these conditions, this was not linked to enhancement of neural or behavioural measures of sensory coding. Instead, ACC-V1axon activity was observed to be associated with licking behaviour, modulated by reward, and biased towards task relevant sensory cortex.
Comparative reconstruction of the predatory feeding structures of the polyphenic nematode Pristionchus pacificus
Authors: Harry Clayton J. , Messar Sonia M. , Ragsdale Erik J.
Published: October 2021

Pristionchus pacificus is a nematode model for the developmental genetics of morphological polyphenism, especially at the level of individual cells. Morphological polyphenism in this species includes an evolutionary novelty, moveable teeth, which have enabled predatory feeding in this species and others in its family (Diplogastridae). From transmission electron micrographs of serial thin sections through an adult hermaphrodite of P. pacificus, we three-dimensionally reconstructed all epithelial and myoepithelial cells and syncytia, corresponding to 74 nuclei, of its face, mouth, and pharynx. We found that the epithelia that produce the predatory morphology of P. pacificus are identical to Caenorhabditis elegans in the number of cell classes and nuclei. However, differences in cell form, spatial relationships, and nucleus position correlate with gross morphological differences from C. elegans and outgroups. Moreover, we identified fine-structural features, especially in the anteriormost pharyngeal muscles, that underlie the conspicuous, left-right asymmetry that characterizes the P. pacificus feeding apparatus. Our reconstruction provides an anatomical map for studying the genetics of polyphenism, feeding behavior, and the development of novel form in a satellite model to C. elegans.
Single-Shot Optical Projection tomography for high-speed volumetric imaging
Authors: Darling Connor , Davis Samuel P.X. , Kumar Sunil , French Paul M.W. , McGinty James
Published: October 2021

We present a single-shot adaptation of Optical Projection Tomography (OPT) for high-speed volumetric snapshot imaging of dynamic mesoscopic samples. Conventional OPT has been applied to in vivo imaging of animal models such as D. rerio but the sequential acquisition of projection images required for volumetric reconstruction typically requires samples to be immobilised during the acquisition of an OPT data set. We present a proof-of-principle system capable of single-shot imaging of a 1 mm diameter volume, demonstrating camera-limited rates of up to 62.5 volumes/second, which we have applied to 3D imaging of a freely-swimming zebrafish embryo. This is achieved by recording 8 projection views simultaneously on 4 low-cost CMOS cameras. With no stage required to rotate the sample, this single-shot OPT system can be implemented with a component cost of under £5,000. The system design can be adapted to different sized fields of view and may be applied to a broad range of dynamic samples, including fluid dynamics.
A network information theoretic framework to characterise muscle synergies in space and time
Authors: Reilly David Ó’ , Delis Ioannis
Published: October 2021

Objective

Current approaches to muscle synergy extraction rely on linear dimensionality reduction algorithms that make specific assumptions on the underlying signals. However, to capture nonlinear time varying, large-scale but also muscle-specific interactions, a more generalised approach is required.

Approach

Here we developed a novel framework for muscle synergy extraction that relaxes model assumptions by using a combination of information- and network theory and dimensionality reduction. We first quantify informational dynamics between muscles, time-samples or muscle-time pairings using a novel mutual information formulation. We then model these pairwise interactions as multiplex networks and identify modules representing the network architecture. We employ this modularity criterion as the input parameter for dimensionality reduction, which verifiably extracts the identified modules, and also to characterise salient structures within each module.

Main results

This novel framework captures spatial, temporal and spatiotemporal interactions across two benchmark datasets of reaching movements, producing distinct spatial groupings and both tonic and phasic temporal patterns. Readily interpretable muscle synergies spanning multiple spatial and temporal scales were identified, demonstrating significant task dependence, ability to capture trial-to-trial fluctuations and concordance across participants. Furthermore, our framework identifies submodular structures that represent the distributed networks of co-occurring signal interactions across scales.

Significance

The capabilities of this framework are illustrated through the concomitant continuity with previous research and novelty of the insights gained. Several previous limitations are circumvented including the extraction of functionally meaningful and multiplexed pairwise muscle couplings under relaxed model assumptions. The extracted synergies provide a holistic view of the movement while important details of task performance are readily interpretable. The identified muscle groupings transcend biomechanical constraints and the temporal patterns reveal characteristics of fundamental motor control mechanisms. We conclude that this framework opens new opportunities for muscle synergy research and can constitute a bridge between existing models and recent network-theoretic endeavours.
Bilaterally Reduced Rolandic Beta Band Activity in Minor Stroke Patients
Authors: Kulasingham Joshua P. , Brodbeck Christian , Khan Sheena , Marsh Elisabeth B. , Simon Jonathan Z.
Published: October 2021

Stroke patients with hemiparesis display decreased beta band (13-25 Hz) rolandic activity, correlating to impaired motor function. However, patients without significant weakness, with small lesions far from sensorimotor cortex, nevertheless exhibit bilateral decreased motor dexterity and slowed reaction times. We investigate whether these minor stroke patients also display abnormal beta band activity.

Magnetoencephalographic (MEG) data were collected from nine minor stroke patients (NIHSS < 4) without significant hemiparesis, at ~1 and ~6 months postinfarct, and eight age-similar controls. Rolandic relative beta power during matching tasks and resting state, and Beta Event Related (De)Synchronization (ERD/ERS) during button press responses were analyzed.

Regardless of lesion location, patients had significantly reduced relative beta power and ERS compared to controls. Abnormalities persisted over visits, and were present in both ipsi- and contra-lesional hemispheres, consistent with bilateral impairments in motor dexterity and speed.

Minor stroke patients without severe weakness display reduced rolandic beta band activity in both hemispheres, which may be linked to bilaterally impaired dexterity and processing speed, implicating global connectivity dysfunction affecting sensorimotor cortex. Rolandic beta band activity may be a potential biomarker and treatment target, even for minor stroke patients with small lesions far from sensorimotor areas.
Separating neural oscillations from aperiodic 1/f activity: challenges and recommendations
Authors: Gerster Moritz , Waterstraat Gunnar , Litvak Vladimir , Lehnertz Klaus , Schnitzler Alfons , Florin Esther , Curio Gabriel , Nikulin Vadim
Published: October 2021

Electrophysiological power spectra typically consist of two components: An aperiodic part usually following an 1/f power law P∝1/fβand periodic components appearing as spectral peaks. While the investigation of the periodic parts, commonly referred to as neural oscillations, has received considerable attention, the study of the aperiodic part has only recently gained more interest. The periodic part is usually quantified by center frequencies, powers, and bandwidths, while the aperiodic part is parameterized by the y-intercept and the 1/f exponent β. For investigation of either part, however, it is essential to separate the two components.

In this article, we scrutinize two frequently used methods, FOOOF (Fitting Oscillations & One-Over-F) and IRASA (Irregular Resampling Auto-Spectral Analysis), that are commonly used to separate the periodic from the aperiodic component. We evaluate these methods using diverse spectra obtained with electroencephalography (EEG), magnetoencephalography (MEG), and local field potential (LFP) recordings relating to three independent research datasets. Each method and each dataset poses distinct challenges for the extraction of both spectral parts. The specific spectral features hindering the periodic and aperiodic separation are highlighted by simulations of power spectra emphasizing these features. Through comparison with the simulation parameters defined a priori, the parameterization error of each method is quantified. Based on the real and simulated power spectra, we evaluate the advantages of both methods, discuss common challenges, note which spectral features impede the separation, assess the computational costs, and propose recommendations on how to use them.
Thermal boldness: Volunteer exploration of extreme temperatures in Drosophila melanogaster
Authors: Navas Carlos A. , Agudelo-Cantero Gustavo A. , Loeschcke Volker
Published: October 2021

A dominant perception is that small and motile ectothermic animals must use behavior to avoid exposure to critical or sub-critical temperatures impairing physiological performance. Concomitantly, volunteer exploration of extreme environments by some individuals may promote physiological adjustments and enhance ecological opportunity. Here we introduce to the literature a Thermal Decision System (TDS) which is fully modular, thermally stable, versatile, and adaptable to study navigation through thermal landscapes in insects and other small motile animals. We used a specific setting of the TDS to investigate volunteer navigation through critical cold and hot temperatures in Drosophila melanogaster. We demonstrate that a thermally bold behavior (volunteer crossings through a Critical Temperature Zone, CTZ) characterized a fraction of flies in a sample, and that such a fraction was higher in an outbred population relative to isofemale lines. As set, the TDS generated a thermal gradient within the cold and hot CTZs, and the exploration of this gradient by flies did not relate simply with a tendency to be thermally bold. Mild fasting affected thermal exploration and boldness in complex manners, but thermal boldness was evident in both fasted and fed flies. Also, thermal boldness was not associated with individual critical temperatures. Finally, some flies showed consistent thermal boldness, as flies that performed an extreme thermal cross were more likely to perform a second cross compared with untested flies. We hypothesize that a simple “avoidance principle” is not the only behavioral drive for D. melanogaster facing extreme temperatures over space, and that this pattern may characterize other small motile ectothermic animals with analogous natural history. The physiological correlates, genetic architecture, and interspecific variation of thermal boldness deserve further consideration.
Effects of early and late life environments on ageing
Authors: Sanghvi Krish , Iglesias-Carrasco Maider , Zajitschek Felix , Kruuk Loeske E.B. , Head Megan L.
Published: October 2021

Early and late life environments can interact in complex ways to influence the fitness of individuals. Most studies investigating effects of the environment on fitness focus on environments experienced and traits expressed at a single point in an organism’s life. However, environments vary with time, thus the environments organisms experience at different ages may interact to affect how traits change throughout life. Here, we test whether thermal stress experienced during development leads individuals to cope better with thermal stress as adults. We manipulated temperature during both development and adulthood and measured a range of life-history traits, including senescence, in male and female seed beetles,Callosobruchus maculatus. We found that favourable developmental conditions increased reproductive performance of females (i.e. silver-spoon effects). In contrast, non-reproductive traits such as lifespan and survival senescence were only affected by adult environments- high adult temperatures decreased longevity and survival. Additionally, developmental and adult environments interacted to affect age-dependent changes in male weight. Overall, our results show that effects of early and late environments can be both sex- and trait- specific, and that a full understanding of how environments interact to affect fitness and ageing requires the integrated study of conditions experienced during different stages of ontogeny.
Cyperus rotundus root extract inhibits progress of lymphedema in mouse tail model
Authors: Pandey Nikhil , Mishra Priyanka , Tripathi Yamini.B.
Published: October 2021

Lymphedema is clinically manifested as swelling due to abnormal accumulation of interstitial fluid attributed to inefficient fluid uptake and reduced lymphatic flow. Here we have evaluated the effect of Cyperus rotundus root (CRR) ethanolic extract in a mouse tail model of lymphedema and hypothesized that Cyperus rotundus plant known for its anti-inflammatory effect through inhibition of TNF alpha will be effective in managing this condition. The skin was removed after leaving 1cm of distance from the base of the trunk. Cut was introduced in sterile condition. The animals were divided into Experimental control(EC) and Cyperus rotundus (CRR) treated groups. A change in tail volume around the wound was monitored upto the 20 days. Kinetics of the swelling was calculated for statistical significance. Further TS of upper part of the wound was stained with H&E stain and documented for histological changes

RESULTS

In EC group, gradual rise in swelling was recorded, which peaked on 10th day and continued up to 15th day, followed by gradual decrease. In CR extract treated group, the swelling was significantly low and peak was obtained on 8th day, while in EC group the swelling was significantly higher and peak was obtained 11th day. The histological section show, fibrous band intersection the lobules of adipocyte and lymphatic vascular channel and muscles in the sub epithelium region in the EC group, which was very less in CRR group.

CONCLUSIONS

Polar fraction of CRR significantly prevents the progress of lymphedema and which lays an important role of this plant as for the drug development in future.
Simulation atomic force microscopy to predict correlated conformational dynamics in proteins from topographic imaging
Authors: Flechsig Holger
Published: October 2021

Atomic force microscopy (AFM) of proteins can detect only changes within the scanned molecular surface, missing all motions in other regions and thus information about functionally relevant conformational couplings. We show that simulation AFM can overcome this drawback by reconstruction of 3D molecular structures from topographic AFM images. A proof of principle demonstration is provided for an in-silico AFM experiment visualizing the conformational dynamics of a membrane transporter. The application shows that the alternating access mechanism underlying its operation can be retrieved from only AFM imaging of one membrane side. Simulation AFM is implemented in the freely available BioAFMviewer software platform, providing the convenient applicability to better understand experimental AFM observations.
Effect of different ambient temperatures on reproductive outcome and wellbeing of lactating females in two mouse strains
Authors: Kolbe Thomas , Lassnig Caroline , Poelzl Andrea , Palme Rupert , Auer Kerstin E. , Rülicke Thomas
Published: October 2021

Ambient temperature is an important non-biotic environmental factor influencing immunological and oncological parameters in laboratory mice. It is under discussion which temperature is more appropriate and whether the commonly used room temperature in rodent facilities of about 21°C represents a chronic cold stress or the 30°C of the thermoneutral zone constitutes heat stress for the animals. In this study we selected the physiological challenging period of lactation to investigate the influence of a cage temperature of 20°C, 25°C, and 30°C, respectively, on reproductive performance and stress hormone levels in two frequently used mouse strains. We found that more pups were weaned from B6D2F1 hybrids compared to C57BL/6N mothers and that the number of weaned pups was strongly reduced if mothers of both strains were kept at 30°C. Furthermore, at 30°C mothers and pups showed reduced body weight at weaning and offspring had longer tails. Despite pronounced temperature effects on reproductive parameters, we did not find any impact on adrenocortical activity in breeding and control mice. Independent of the ambient temperature however, we found that females raising pups showed elevated levels of fecal corticosterone metabolites (FCMs) compared to controls. Increased levels of stress hormone metabolites were measured specially around birth and during the third week of lactation. Our results provide no evidence for reduced or improved wellbeing of lactating mice at different ambient temperatures, but we found that a 30°C cage temperature impairs reproductive performance.
Fetal programming by sodium saccharin and damage on male offspring reproductive
Authors: Godoi Alana Rezende , Fioravante Vanessa Caroline , Santos Beatriz Melo , Martinez Francisco Eduardo , Felipe Pinheiro Patricia Fernanda
Published: October 2021

Male infertility is responsible for 20-70% of infertility in couples. We investigated the effects of fetal programming with sodium saccharin consumption in testis structure and function and in male offspring fertility. Feed intake and efficiency, organ and fat weight, quantification and expression of AR and PCNA proteins, sperm count and hormonal dosages were performed. Changes in consumption were found in the final weeks of the experiment. Decreases in the expression and quantification of AR and PCNA, tubular diameter and luminal volume, and increase in epithelial and interstitial relative volumes were observed. Lower sperm count and transit and lower estradiol concentration were also found. The consumption of sodium saccharin by the dams programmed the male offspring affecting the HPG axis with alterations in Sertoli cell proliferation, AR expression and quantification, and sperm count. We hypothesize that these changes may be due to the reduction of estradiol that caused the loosening of the tight junctions of the blood-testis-barrier (BTB), causing cell losses during spermatogenesis, also reflecting, under the decrease in tubular diameter with an increase in epithelial volume and consequent decrease in luminal volume. Sodium saccharin programming directly affected the reproductive parameters of male offspring and adult fertility.
SURFMAP: a software for mapping in two dimensions protein surface features
Authors: Schweke Hugo , Mucchielli Marie-Hélène , Chevrollier Nicolas , Gosset Simon , Lopes Anne
Published: October 2021

Molecular cartography using two-dimensional (2D) representation of protein surfaces has been shown to be very promising for protein surface analysis. Here, we present SURFMAP, a free standalone and easy-to-use software that enables the fast and automated 2D projection of either predefined features of protein surface (i.e., electrostatic potential, Kyte-Doolittle hydrophobicity, stickiness, and surface relief) or any descriptor encoded in the temperature factor column of a PDB file. SURFMAP uses a pseudo-cylindrical sinusoidal “equal-area” projection that has the advantage of preserving the area measures. It provides the user with (i) 2D maps that enable the easy and visual analysis of protein surface features of interest and (ii) maps in a text file format allowing the fast and straightforward quantitative comparison of 2D maps of homologous proteins.
KRAS is vulnerable to reversible switch-II pocket engagement in cells
Authors: Vasta James D. , Peacock D. Matthew , Zheng Qinheng , Walker Joel A. , Zhang Ziyang , Zimprich Chad A. , Thomas Morgan R. , Beck Michael T. , Binkowski Brock F. , Corona Cesear R. , Robers Matthew B. , Shokat Kevan M.
Published: October 2021

Current small molecule inhibitors of KRAS(G12C) bind irreversibly in the switch-II pocket, exploiting the strong nucleophilicity of the acquired cysteine as well as the preponderance of the GDP-bound form of this mutant. Nevertheless, many oncogenic KRAS mutants lack these two features, and it remains unknown whether targeting the switch-II pocket is a practical therapeutic approach for KRAS mutants beyond G12C. Here we use NMR spectroscopy and a novel cellular KRAS engagement assay to address this question by examining a collection of SII-P ligands from the literature and from our own laboratory. We show that the switch-II pockets of many GTP hydrolysis-deficient KRAS hotspot (G12, G13, Q61) mutants are accessible using non-covalent ligands, and that this accessibility is not necessarily coupled to the GDP state of KRAS. The results we describe here emphasize the switch-II pocket as a privileged drug binding site on KRAS and unveil new therapeutic opportunities in RAS-driven cancer.
Connexin Hemichannels with Prostaglandin Release in Anabolic Function of Bone to Mechanical Loading
Authors: Zhao Dezhi , Riquelme Manuel A. , Guda Teja , Tu Chao , Xu Huiyun , Gu Sumin , Jiang Jean X.
Published: October 2021

Mechanical stimulation, such as physical exercise, is essential for bone formation and health. Here, we demonstrate the critical role of osteocytic Cx43 hemichannels in anabolic function of bone in response to mechanical loading. Two transgenic mouse models, R76W and Δ130-136, expressing dominant-negative Cx43 mutants in osteocytes were adopted. Mechanical loading of tibial bone increased cortical bone mass and mechanical properties in wild-type and gap junction-impaired R76W mice through increased PGE2, endosteal osteoblast activity, and decreased sclerostin. These anabolic responses were impeded in gap junction/hemichannel-impaired Δ130-136 mice and accompanied by increased endosteal osteoclast activity. Specific inhibition of Cx43 hemichannels by Cx43(M1) antibody suppressed PGE2secretion and impeded loading-induced endosteal osteoblast activity, bone formation and anabolic gene expression. PGE2administration rescued the osteogenic response to mechanical loading impeded by impaired hemichannels. Together, osteocytic Cx43 hemichannels could be a potential new therapeutic target for treating bone loss and osteoporosis.