bluuebunny/crossref_metadata_2025_split huggingface dataset:
A promoter-proximal silencer modifies the activity of a shared enhancer to mediate divergent expression of nub and pdm2 paralogs in wing development
Authors: Loker Ryan , Mann Richard S. 
Published: March 2022

AbstractDuplication of genes and their associated cis-regulatory elements, or enhancers, is a key contributor to genome evolution and biological complexity. Moreover, many paralogs, particularly tandem duplicates, are fixed for long periods of time under the control of shared enhancers. However, in most cases the mechanism by which gene expression and function diverge following duplication is not known. Here we dissect the regulation and function of the paralogous nubbin/pdm2 genes during wing development in Drosophila melanogaster. We show that these paralogs play a redundant role in the wing and that their expression relies on a single shared wing enhancer. However, the two genes differ in their ability to respond to this enhancer, with nub responding in all wing progenitor cells and pdm2 only in a small subset. This divergence is a result of a pdm2-specific silencer element at the pdm2 promoter that receives repressive input from the transcription factor Rotund. Repression through this silencer also depends on nub, allowing pdm2 to fully respond to the wing enhancer when nub expression is perturbed and functional compensation to occur. Thus, expression divergence downstream of a shared enhancer arises as a consequence of silencing the promoter of one paralog.
Motion of the Cochlear Reticular Lamina Varies Radially Across Outer-Hair-Cell Rows
Authors: Cho Nam Hyun , Puria Sunil 
Published: March 2022

AbstractThe basilar membrane (BM) is connected to the reticular lamina (RL) through three rows of Y-shaped structures consisting of an outer hair cell (OHC) and a Deiters’ cell (DC) with a phalangeal process (PhP) that forms part of the RL mosaic surface. Morphological differences in the anatomy of the Y-shaped structures across the three OHC rows suggest differences in motion across the rows. Here we report OoC transverse motions measured across several radial locations for the gerbil basal region corresponding to ~45 kHz. Cross-sectional imaging and vibrometry measurements were made using a high-resolution (2.23 um axially in water) spectral-domain optical-coherence-tomography (SD-OCT) system. The stimuli were pure tones (2–63 kHz) at ear-canal sound pressure levels (SPLs) of 30–95 dB SPL in anesthetized gerbils (N=9) with healthy cochleae. We report displacements at the RL regions of OHC rows 1–3 (RL1–3), at the OHC-DC junctions of OHC rows 1–3 (OHC-DC-junction1–3), and at the arcuate zone, arcuate-pectinate junction, and pectinate zone of the BM (BMAZ, BMAPJ, and BMPZ, respectively). The in vivo BM displacements showed classic compressive nonlinearity and traveling-wave delays. The RL gain was similar to the BM gain at low frequencies (<20 kHz), but increased with frequency. Near the best frequency (BF), the RL gain was greater than the high-level BM gain by 40 ±5 dB (mean±std), and had greater compressive nonlinearity. RL motion varied radially, and the RL3gain was significantly greater than that of RL1by 10 ±1 dB (p<0.001). In contrast, the OHC-DC-junction gain varied little radially across OHCs. At low frequencies the OHC-DC-junction gain was constant across SPLs, and 14 ± 3 dB greater than the BM gain. As the frequency increased, the OHC-DC-junction gain decreased to a level similar to the BM gain at BF. The RL2, 3phase was advanced by 0.25–0.375 cycles relative to the BM phase at low frequencies, but the RL2, 3phase lead decreased as the frequency increased, became similar to the BM phase at BF, and lagged behind the BM phase by 0.25–0.5 cycles above BF. The OHC-DC-junction phases were mostly similar to the BM phase at low frequencies, but became delayed relative to the BM as the frequency increased, typically by 0.25–0.5 cycles near BF and by up to 1 cycle above BF. Our results show the most detailed picture of motion around the three OHC rows yet published, indicating that RL motion varied radially. Surprisingly, there was little motion difference across the three OHC rows in the OHC-DC-junction region, indicating that the tops of the DCs move in unison. Our data show a rich array of OoC amplitude and phase variations that are not explained by current theories.
VALIDATION OF AN INSTRUMENTED MOUTHGUARD
Authors: Jones Christopher M. , Brown M Rowan. 
Published: March 2022

ABSTRACTThe purpose of this study was to determine the validity of an raw and filtered acceleration time-series data from an instrumented mouthguard system against an anthropometric testing device. Testing was conducted in a laboratory using a standard impact protocol utilising the head-form of reference system and the mouthguard system. Testing occurred at 5 impact locations: facemask, front, oblique, side and back, and at four velocities (3.6, 5.5, 7.4, and 9.3 m/s) to attain a total of 55 impacts. A 160 Hz Low-pass 4th order Butterworth filter was applied to the time-series data, and was reported as raw and filtered. Peak linear acceleration, peak rotational velocity and peak rotational acceleration was statistically compared to the reference measurement system. Total concordance correlation coefficient was 90.7% and 96.9%, for raw and filtered data set. Raw and filtered had intraclass correlation coefficients of 0.85 and 0.95 for peak linear acceleration, 0.99 and 0.99 for peak rotational velocity and 0.94 and 0.95 peak rotational acceleration respectively. The instrumented mouthguard displayed high accuracy when measuring head impact kinematics in a laboratory setting. The results presented in this study provide the basis on which the instrumented mouthguard can be further developed for deployment and application within sport quantify head impact collision dynamics in order to optimise performance and brain health.
Low Haemoglobin Levels are Associated with Reduced Psychomotor and Language Abilities in Young Ugandan Children
Authors: Nampijja Margaret , Mutua Agnes M , Elliott Alison M , Muriuki John Muthii , Abubakar Amina , Webb Emily L , Atkinson Sarah H 
Published: March 2022

AbstractChildren living in Sub-Saharan Africa are vulnerable to developmental delay, particularly in the critical first five years due to various adverse exposures including disease and nutritional deficiencies. Anaemia and iron deficiency (ID) are highly prevalent in pregnant mothers and young children and are implicated in abnormal brain development. However, available evidence on the association between anaemia, ID and neurodevelopment in Sub-Saharan Africa is limited. Using data from the Entebbe Mother and Baby Study prospective birth cohort, we examined the effect of maternal and child haemoglobin (Hb) levels and child iron status on developmental scores in 933 and 530 pre-school Ugandan children respectively. Associations between Hb levels, iron status and developmental scores were assessed using regression analyses adjusting for potential confounders. Lower maternal and child Hb levels were associated with reduced psychomotor scores at 15 months, while only lower Hb levels in infancy were associated with reduced language scores. We found no evidence that anaemia or ID was associated with cognitive or motor scores at five years. This study emphasizes the importance of managing anaemia in pregnancy and infancy and highlights the need for further studies on the effects of anaemia and ID in children living in Sub-Saharan Africa.
Profiling the plasmid conjugation potential of urinary E. coli
Authors: Hernandez Cesar Montelongo , Putonti Catherine , Wolfe Alan J. 
Published: March 2022

AbstractEscherichia coli is often associated with urinary tract infection (UTI). Antibiotic resistance in E. coli is an ongoing challenge in managing UTI. Extrachromosomal elements – plasmids – are vectors for clinically relevant traits, such as antibiotic resistance, with conjugation being one of the main methods for horizontal propagation of plasmids in bacterial populations. Targeting of conjugation components has been proposed as a strategy to curb spread of plasmid-borne antibiotic resistance. Understanding the types of conjugative systems present in urinary E. coli isolates is fundamental to assessing the viability of these strategies. In this study, we profile the two well studied conjugation systems (F-type and P-type) in the draft genomes of 65 urinary isolates of E. coli obtained from bladder urine of adult women with and without UTI-like symptoms. Most of these isolates contained plasmids and we found that conjugation genes are abundant/ubiquitous, diverse, and often associated with IncF plasmids. To validate conjugation of these urinary plasmids, we conjugated the plasmids from two urinary isolates, UMB1223 (predicted to have F-type genes) and UMB1284 (predicted to have P-type genes), into the K-12 E. coli strain MG1655. Overall, the findings of this study support the notion that care should be taken in targeting any individual component of a urinary E. coli isolate’s conjugation system, given the inherent mechanistic redundancy, gene diversity, and different types of conjugation systems in this population.
Gene Expression and Tracer-Based Metabolic Flux Analysis Reveals Tissue-Specific Metabolic Scaling in vitro, ex vivo, and in vivo
Authors: Akingbesote Ngozi D. , Leitner Brooks P. , Jovin Daniel G. , Desrouleaux Reina , Zhu Wanling , Li Zongyu , Pollak Michael N. , Perry Rachel J. 
Published: March 2022

AbstractMetabolic scaling, the inverse correlation of metabolic rates to body mass, has been appreciated for more than 80 years. Studies of metabolic scaling have almost exclusively been restricted to mathematical modeling of oxygen consumption. The possibility that other metabolic processes scale with body size has not been studied. To address this gap in knowledge, we employed a systems approach spanning from transcriptomics to in vitro and in vivo tracer-based flux. Gene expression in livers of five species spanning a 30,000-fold range in mass revealed differential expression of genes related to cytosolic and mitochondrial metabolic processes, in addition to detoxication of oxidative damage. This suggests that transcriptional scaling of damage control mechanisms accommodates increased oxidative metabolism in smaller species. To determine whether flux through key implicated metabolic pathways scaled, we applied stable isotope tracer methodology to study multiple cellular compartments, tissues, and species. Comparing mice and rats, we demonstrate that while scaling of metabolic fluxes is not observed in the cell-autonomous setting, it is present in liver slices and in vivo. Together, these data reveal that metabolic scaling extends beyond oxygen consumption to numerous other metabolic pathways, and is likely regulated at the level of gene expression and substrate supply.
Focal adhesion-based cell migration is differentially regulated in vivo versus in vitro by Paxillin phosphorylation
Authors: Xue Qian , Varady Sophia R. S. , Alaka’i Waddell Trinity Q , Carrington James , Roh-Johnson Minna 
Published: March 2022

SummaryFocal adhesions are important subcellular structures that physically link the cell to the extracellular matrix (ECM), thus facilitating efficient cell migration. Although in vitro cell culture studies have provided a wealth of information regarding focal adhesion biology, it is critical to understand how focal adhesions are dynamically regulated in their native environment. We developed a zebrafish transplantation system in which we could efficiently visualize focal adhesion structures during single cell migration in vivo with high-resolution live cell imaging. By comparing focal adhesions between this in vivo system and the traditional in vitro cell culture model, we show differential regulation of a core focal adhesion protein, Paxillin. We find that a key site of phosphoregulation on Paxillin, tyrosine 118 (Y118), exhibits reduced phosphorylation in migrating cells in vivo in both zebrafish and mouse melanoma models, contrary to the pivotal role for this phosphorylation event in cell culture studies. Furthermore, direct modulation of this residue by site directed mutagenesis leads to opposite cell migration phenotypes in vivo versus in vitro in both migrating cancer cells and macrophages. Unexpectedly, expression of a non-phosphorylatable version of Y118-Paxillin promotes cell migration in vivo, despite inhibiting cell migration in the in vitro cell culture conditions. To further understand the mechanism of this regulation, we find that the upstream kinase, focal adhesion kinase (FAK), is downregulated in cells in vivo, and that cells expressing non-phosphorylatable Y118-Paxillin exhibit increased interactions between Paxillin and CRKII, an adaptor protein known to promote cell migration signaling. Collectively, our findings provide significant new insight into how focal adhesions are regulated in cells migrating in their native environment.
Regulation associated modules reflect 3D genome modularity associated with chromatin activity
Authors: Zheng Lina , Wang Wei 
Published: March 2022

ABSTRACTThe 3D genome has been shown to be organized into modules including topologically associating domains (TADs) and compartments that are primarily defined by spatial contacts from Hi-C or other experiments. There exists a gap to investigate whether and how the spatial modularity of the chromatin is related to the functional modularity resulting from the chromatin activity. Increasing evidence shows a tight interplay between histone modifications and 3D chromatin organization. As the histone modifications reflect the chromatin activity, it is tempting to infer the spatial modularity of the genome directly from the histone modification patterns, which would establish the connection between the spatial and functional modularity of the genome. However, uncovering the 3D genomic modules using histone modifications has not been well explored. Here, we report that the histone modifications show a modular pattern (referred to as regulation associated modules, RAMs) that reflects the spatial modularity of the chromatin structure. We found that enhancer-promoter interactions and extrachromosomal DNAs (ecDNAs) occur more often within the same RAMs than within the same TADs, indicating stronger insulation of the RAM boundaries and a modularization of the 3D genome at a scale better aligned with the chromatin activity. Consistently, compared to the TAD boundaries, in silico predictions showed that deletions of RAM boundaries perturb the chromatin structure more severely and somatic variants in the cancer samples are more enriched in the RAM boundaries. These observations suggest that RAMs reflect a modular organization of the 3D genome at a scale better aligned with chromatin activity, providing a bridge connecting the structural and functional modularity of the genome.
Inhibition is a prevalent mode of activity in the neocortex around awake hippocampal ripples
Authors: Abadchi Javad Karimi , Rezaei Zahra , Knöpfel Thomas , McNaughton Bruce L. , Mohajerani Majid H. 
Published: March 2022

AbstractCoordinated peri-ripple activity in the hippocampal-neocortical network is essential for mnemonic information processing in the brain. Hippocampal ripples likely serve different functions in sleep and awake states. Thus, the corresponding neocortical activity patterns may differ in important ways. We addressed this possibility by conducting voltage and glutamate wide-field imaging of the neocortex with concurrent hippocampal electrophysiology in awake mice. Contrary to our previously published sleep results, deactivation and activation were dominant in post-ripple neocortical voltage and glutamate activity, respectively, especially in the agranular retrosplenial cortex (aRSC). Additionally, the spiking activity of aRSC neurons, estimated by two-photon calcium imaging, revealed the existence of two subpopulations of excitatory neurons with opposite peri-ripple modulation patterns: one increases and the other decreases firing rate. These differences in peri-ripple spatiotemporal patterns of neocortical activity in sleep versus awake states might underlie the reported differences in the function of sleep versus awake ripples.
Morpho-functional analysis of the head glands in three Auchenorrhyncha species and their possible biological significance
Authors: Sevarika Milos , Di Giulio Andrea , Rondoni Gabriele , Conti Eric , Romani Roberto 
Published: March 2022

AbstractThe CicadomorphaPhilaenus spumarius, Neophilaenus campestrisandCicadella viridisare known transmitters of the bacteriumXylella fastidiosa. Here, we studied the ultrastructural organization of their cephalic glands. Our investigations with scanning, transmission, FIB-SEM electron microscope and light microscope revealed for the first time in Auchenorrhyncha the presence of two types of cephalic glands. Both belonged to the class III epidermal glands, according to Noirot and Quennedey classification. Type I glands were the most common, being mainly located around antennae, lorum and gena. Moreover, these glands were observed also on the abdomen and thorax, always in association with sensilla trichoidea. The second type of glands were located exclusively at the apical part of the postclypeus inP. spumariusandN. campestris.The ultrastructural organization was similar in both types, being composed of a secretory cell and a conducting canal. Differences were observed in the width of the cuticular opening, being smaller in the type II glands. In addition, we have recorded the presence of a maxillary sensory pit in all species and described sensilla trichoidea ultrastructural organization. Finally, we discussed the ultrastructural organization of the glands and their potential biological role.
EEG Responses to Auditory Figure-Ground Perception
Authors: Guo Xiaoxuan , Dheerendra Pradeep , Benzaquén Ester , Sedley William , Griffiths Timothy D 
Published: March 2022

AbstractSpeech-in-noise difficulty is commonly reported among hearing-impaired individuals. Recent work has established generic behavioural measures of sound segregation and grouping that are related to speech-in-noise processing but do not require language. In this study, we assessed potential clinical electroencephalographic (EEG) measures of central auditory grouping (stochastic figure-ground test) and speech-in-noise perception (speech-in-babble test) with and without relevant tasks. Auditory targets were presented within background noise (16 talker-babble or randomly generated pure-tones) in 50% of the trials and composed either a figure (pure-tone frequency chords repeating over time) or speech (English names). EEG was recorded while participants were presented with the target stimuli (figure or speech) under different attentional states (relevant task or visual-distractor task). EEG time-domain analysis demonstrated enhanced negative responses during detection of both types of auditory targets within the time window 650-850 ms but only figure detection produced significantly enhanced responses under the distracted condition. Further single-channel analysis showed that simple vertex-to-mastoid acquisition defines a very similar response to more complex arrays based on multiple channels. Evoked-potentials to the generic figure-ground task therefore represent a potential clinical measure of grouping relevant to real-world listening that can be assessed irrespective of language knowledge and expertise even without a relevant task.
Aeration Strategy at Birth Does Not Impact Carotid Haemodynamics in Preterm Lambs
Authors: Dahm Sophia I , Kenna Kelly R , Stewart David , Pereira-Fantini Prudence M , McCall Karen E , Perkins Liz , Sourial Magdy , Tingay David G 
Published: March 2022

ABSTRACTBackgroundThe impact of different respiratory strategies at birth on the preterm lung is well understood, however, concerns have been raised that lung recruitment may impede cerebral haemodynamics. This study aims to examine the effect of three different ventilation strategies on cerebral haemodynamics and oxygenation.Methods124-127 day gestation apnoeic intubated preterm lambs (n=68) being studied as part of a larger program primarily assessing lung injury were randomised to positive pressure ventilation with positive end-expiratory pressure (PEEP) 8 cmH2O (No-RM; n=12), sustained inflation (SI; n=15) or dynamic PEEP strategy (DynPEEP; maximum PEEP 14 or 20 cmH2O, n=41) at birth, followed by 90 minutes of standardised ventilation. Haemodynamic data was continuously recorded, with intermittent arterial blood gas analysis. Main outcome measures for this study included carotid blood flow, carotid artery oxygen content and carotid oxygen delivery.ResultsOverall carotid blood flow measures were comparable between strategies, with the exception of mean carotid blood flow which was significantly lower for the SI group compared to the No-RM and DynPEEP groups respectively over the first 3 minutes (p<0.0001, mixed-effects model). Carotid oxygen content and oxygen delivery were similar between strategies. Maximum PEEP did not alter cerebral haemodynamic measures.ConclusionAlthough there were some short-term variations in cerebral haemodynamics between different PEEP strategies and SI, these were not sustained.ImpactDifferent pressure strategies to facilitate lung aeration at birth in preterm infants have been proposed. There is minimal information on the effect of lung recruitment on cerebral haemodynamics.This is the first study that compares the effect of sustained lung inflation, and dynamic and static positive end-expiratory pressure on cerebral haemodynamics.We found that the different ventilation strategies did not alter carotid blood flow, carotid oxygen content or carotid oxygen delivery.This preclinical study provides some reassurance that respiratory strategies designed to focus on lung aeration at birth may not impact cerebral haemodynamics in preterm neonates.
Effect of larval diet on adult immune function is contingent upon selection history and host sex inDrosophila melanogaster
Authors: Singh Aparajita , Basu Aabeer Kumar , Bansal Nitin , Shit Biswajit , Hegde Tejashwini , Prasad Nagaraj Guru 
Published: March 2022

ABSTRACTMounting an immune response requires a considerable energy investment by the host. This makes expression of immune phenotypes susceptible to changes in availability of resources. There is ample evidence in scientific literature to suggest that hosts become more vulnerable to infection by pathogens and parasites when access to nutrition is limited. Using populations ofDrosophila melanogasterexperimentally evolved to better survive bacterial infections, we explore if host selection history influences host response to resource deprivation in terms of immune function. We find that when reared on a suboptimal diet (both in larval and adult stages), adult flies from evolved populations are still more immune to infections compared to flies from control populations. Furthermore, we observe a sex-dependent effect of interaction between selection history and diet on immune function. We thus conclude that immune function of hosts adapted to pathogen challenge is less affected by resource limitation compared to non-adapted hosts.