bluuebunny/crossref_metadata_2025_split huggingface dataset:
Volutrauma Increases Exhaled Pentanal in Rats: A Potential Breath Biomarker for Ventilator-Induced Lung Injury
Authors: Müller-Wirtz Lukas Martin , Kiefer Daniel , Maurer Felix , Floss Maximilian Alexander , Doneit Jonas , Hüppe Tobias , Shopova Theodora , Wolf Beate , Sessler Daniel I. , Volk Thomas , Kreuer Sascha , Fink Tobias 
Published: April 2021

BACKGROUND:
Mechanical ventilation injures lungs, but there are currently no reliable methods for detecting early injury. We therefore evaluated whether exhaled pentanal, a lipid peroxidation product, might be a useful breath biomarker for stretch-induced lung injury in rats.

METHODS:
A total of 150 male Sprague-Dawley rats were investigated in 2 substudies. The first randomly assigned 75 rats to 7 hours of mechanical ventilation at tidal volumes of 6, 8, 12, 16, and 20 mL·kg−1. The second included 75 rats. A reference group was ventilated at a tidal volume of 6 mL·kg−1 for 10 hours 4 interventional groups were ventilated at a tidal volume of 6 mL·kg−1 for 1 hour, and then for 0.5, 1, 2, or 3 hours at a tidal volume of 16 mL.kg−1 before returning to a tidal volume of 6 mL·kg−1 for additional 6 hours. Exhaled pentanal was monitored by multicapillary column–ion mobility spectrometry. The first substudy included cytokine and leukocyte measurements in blood and bronchoalveolar fluid, histological assessment of the proportion of alveolar space, and measurements of myeloperoxidase activity in lung tissue. The second substudy included measurements of pentanal in arterial blood plasma, cytokine and leukocyte concentrations in bronchoalveolar fluid, and cleaved caspase 3 in lung tissue.

RESULTS:
Exhaled pentanal concentrations increased by only 0.5 ppb·h−1 (95% confidence interval [CI], 0.3–0.6) when rats were ventilated at 6 mL·kg−1. In contrast, exhaled pentanal concentrations increased substantially and roughly linearly at higher tidal volumes, up to 3.1 ppb·h−1 (95% CI, 2.3–3.8) at tidal volumes of 20 mL·kg−1. Exhaled pentanal increased at average rates between 1.0 ppb·h−1 (95% CI, 0.3–1.7) and 2.5 ppb·h−1 (95% CI, 1.4–3.6) after the onset of 16 mL·kg−1 tidal volumes and decreased rapidly by a median of 2 ppb (interquartile range [IQR], 0.9–3.2), corresponding to a 38% (IQR, 31–43) reduction when tidal volume returned to 6 mL·kg−1. Tidal volume, inspiratory pressure, and mechanical power were positively associated with pentanal exhalation. Exhaled and plasma pentanal were uncorrelated. Alveolar space decreased and inflammatory markers in bronchoalveolar lavage fluid increased in animals ventilated at high tidal volumes. Short, intermittent ventilation at high tidal volumes for up to 3 hours increased neither inflammatory markers in bronchoalveolar fluid nor the proportion of cleaved caspase 3 in lung tissue.

CONCLUSIONS:
Exhaled pentanal is a potential biomarker for early detection of ventilator-induced lung injury in rats.
Mouse models for dominant dystrophic epidermolysis bullosa carrying common human point mutations recapitulate the human disease
Authors: Smith Blake R. C. , Nyström Alexander , Nowell Cameron J. , Hausser Ingrid , Gretzmeier Christine , Robertson Susan J. , Varigos George A. , Has Cristina , Kern Johannes S. , Pang Ken C. 
Published: April 2021

ABSTRACT
Heterozygous missense mutations in the human COL7A1 gene – coding for collagen VII – lead to the rare, dominantly inherited skin disorder dominant dystrophic epidermolysis bullosa (DDEB), which is characterised by skin fragility, blistering, scarring and nail dystrophy. To better understand the pathophysiology of DDEB and develop more effective treatments, suitable mouse models for DDEB are required but to date none have existed. We identified the two most common COL7A1 mutations in DDEB patients (p.G2034R and p.G2043R) and used CRISPR-Cas9 to introduce the corresponding mutations into mouse Col7a1 (p.G2028R and p.G2037R). Dominant inheritance of either of these two alleles results in a phenotype that closely resembles that seen in DDEB patients. Specifically, mice carrying these alleles show recurrent blistering that is first observed transiently around the mouth and paws in the early neonatal period and then again around the digits from 5-10 weeks of age. Histologically, the mice show micro-blistering and reduced collagen VII immunostaining. Biochemically, collagen VII from these mice displays reduced thermal stability, which we also observed to be the case for DDEB patients carrying the analogous mutations. Unlike previous rodent models of epidermolysis bullosa, which frequently show early lethality and severe disease, these mouse models, which to our knowledge are the first for DDEB, show no reduction in growth and survival, and – together with a relatively mild phenotype – represent a practically and ethically tractable tool for better understanding and treating epidermolysis bullosa.
This article has an associated First Person interview with the first author of the paper.
Ccdc103 promotes myeloid cell proliferation and migration independent of motile cilia
Authors: Falkenberg Lauren G. , Beckman Sarah A. , Ravisankar Padmapriyadarshini , Dohn Tracy E. , Waxman Joshua S. 
Published: April 2021

ABSTRACT
The pathology of primary ciliary dyskinesia (PCD) is predominantly attributed to impairment of motile cilia. However, PCD patients also have perplexing functional defects in myeloid cells, which lack motile cilia. Here, we show that coiled-coil domain-containing protein 103 (CCDC103), one of the genes that, when mutated, is known to cause PCD, is required for the proliferation and directed migration of myeloid cells. CCDC103 is expressed in human myeloid cells, where it colocalizes with cytoplasmic microtubules. Zebrafish ccdc103/schmalhans (smh) mutants have macrophages and neutrophils with reduced proliferation, abnormally rounded cell morphology and an inability to migrate efficiently to the site of sterile wounds, all of which are consistent with a loss of cytoplasmic microtubule stability. Furthermore, we demonstrate that direct interactions between CCDC103 and sperm associated antigen 6 (SPAG6), which also promotes microtubule stability, are abrogated by CCDC103 mutations from PCD patients, and that spag6 zebrafish mutants recapitulate the myeloid defects observed in smh mutants. In summary, we have illuminated a mechanism, independent of motile cilia, to explain functional defects in myeloid cells from PCD patients.
This article has an associated First Person interview with the first author of the paper.
Interferon regulatory factor 7 impairs cellular metabolism in aging adipose-derived stromal cells
Authors: Nodari Alice , Scambi Ilaria , Peroni Daniele , Calabria Elisa , Benati Donatella , Mannucci Silvia , Manfredi Marcello , Frontini Andrea , Visonà Silvia , Bozzato Andrea , Sbarbati Andrea , Schena Federico , Marengo Emilio , Krampera Mauro , Galiè Mirco 
Published: April 2021

ABSTRACT
Dysregulated immunity and widespread metabolic dysfunctions are the most relevant hallmarks of the passing of time over the course of adult life, and their combination at midlife is strongly related to increased vulnerability to diseases; however, the causal connection between them remains largely unclear. By combining multi-omics and functional analyses of adipose-derived stromal cells established from young (1 month) and midlife (12 months) mice, we show that an increase in expression of interferon regulatory factor 7 (IRF7) during adult life drives major metabolic changes, which include impaired mitochondrial function, altered amino acid biogenesis and reduced expression of genes involved in branched-chain amino acid (BCAA) degradation. Our results draw a new paradigm of aging as the ‘sterile’ activation of a cell-autonomous pathway of self-defense and identify a crucial mediator of this pathway, IRF7, as driver of metabolic dysfunction with age.
Acoustically eavesdropping bat predators take longer to capture katydid prey signalling in aggregation
Authors: Prakash Harish , Greif Stefan , Yovel Yossi , Balakrishnan Rohini 
Published: April 2021

ABSTRACTPrey that are signalling in aggregation become more conspicuous with increasing numbers and tend to attract more predators. Such grouping may, however, benefit prey by lowering the risk of being captured because of the predator's difficulty in targeting individuals. Previous studies have investigated anti-predatory benefits of prey aggregation using visual predators, but it is unclear whether such benefits are gained in an auditory context. We investigated whether katydids of the genus Mecopoda gain protection from their acoustically eavesdropping bat predator Megaderma spasma when calling in aggregation. In a choice experiment, bats approached calls of prey aggregations more often than those of prey calling alone, indicating that prey calling in aggregation are at higher risk. In prey capture tasks, however, the average time taken and the number of flight passes made by bats before capturing a katydid were significantly higher for prey calling in aggregation than when calling alone, indicating that prey face lower predation risk when calling in aggregation. Another common anti-predatory strategy, calling from within vegetation, increased the time taken by bats to capture katydids calling alone but did not increase the time taken to capture prey calling from aggregations. The increased time taken to capture prey calling in aggregation compared with solitary calling prey offers an escape opportunity, thus providing prey that signal acoustically in aggregations with anti-predatory benefits. For bats, greater detectability of calling prey aggregations is offset by lower foraging efficiency, and this trade-off may shape predator foraging strategies in natural environments.
Scavenging of reactive oxygen species mimics the anoxic response in goldfish pyramidal neurons
Authors: Pillai Varshinie , Buck Leslie , Lari Ebrahim 
Published: April 2021

ABSTRACT
Goldfish are one of a few species able to avoid cellular damage during month-long periods in severely hypoxic environments. By suppressing action potentials in excitatory glutamatergic neurons, the goldfish brain decreases its overall energy expenditure. Coincident with reductions in O2 availability is a natural decrease in cellular reactive oxygen species (ROS) generation, which has been proposed to function as part of a low-oxygen signal transduction pathway. Using live-tissue fluorescence microscopy, we found that ROS production decreased by 10% with the onset of anoxia in goldfish telencephalic brain slices. Employing whole-cell patch-clamp recording, we found that, similar to severe hypoxia, the ROS scavengers N-acetyl cysteine (NAC) and MitoTEMPO, added during normoxic periods, depolarized membrane potential (severe hypoxia −73.6 to −61.4 mV, NAC −76.6 to −66.2 mV and MitoTEMPO −71.5 mV to −62.5 mV) and increased whole-cell conductance (severe hypoxia 5.7 nS to 8.0 nS, NAC 6.0 nS to 7.5 nS and MitoTEMPO 6.0 nS to 7.6 nS). Also, in a subset of active pyramidal neurons, these treatments reduced action potential firing frequency (severe hypoxia 0.18 Hz to 0.03 Hz, NAC 0.27 Hz to 0.06 Hz and MitoTEMPO 0.35 Hz to 0.08 Hz). Neither severe hypoxia nor ROS scavenging impacted action potential threshold. The addition of exogenous hydrogen peroxide could reverse the effects of the antioxidants. Taken together, this supports a role for a reduction in [ROS] as a low-oxygen signal in goldfish brain.
Mouse vocal emission and acoustic complexity do not scale linearly with the size of a social group
Authors: Warren Megan R. , Spurrier Morgan S. , Sangiamo Daniel T. , Clein Rachel S. , Neunuebel Joshua P. 
Published: April 2021

ABSTRACT
Adult mice emit ultrasonic vocalizations (USVs), sounds above the range of human hearing, during social encounters. While mice alter their vocal emissions between isolated and social contexts, technological impediments have hampered our ability to assess how individual mice vocalize in group social settings. We overcame this challenge by implementing an 8-channel microphone array system, allowing us to determine which mouse emitted individual vocalizations across multiple social contexts. This technology, in conjunction with a new approach for extracting and categorizing a complex, full repertoire of vocalizations, facilitated our ability to directly compare how mice modulate their vocal emissions between isolated, dyadic and group social environments. When comparing vocal emission during isolated and social settings, we found that socializing male mice increase the proportion of vocalizations with turning points in frequency modulation and instantaneous jumps in frequency. Moreover, males change the types of vocalizations emitted between social and isolated contexts. In contrast, there was no difference in male vocal emission between dyadic and group social contexts. Female vocal emission, while predominantly absent in isolation, was also similar during dyadic and group interactions. In particular, there were no differences in the proportion of vocalizations with frequency jumps or turning points. Taken together, the findings lay the groundwork necessary for elucidating the stimuli underlying specific features of vocal emission in mice.
11-Deoxycortisol is a stress responsive and gluconeogenic hormone in a jawless vertebrate, the sea lamprey (Petromyzon marinus)
Authors: Shaughnessy Ciaran A. , McCormick Stephen D. 
Published: April 2021

ABSTRACTAlthough corticosteroid-mediated hepatic gluconeogenic activity in response to stress has been extensively studied in fishes and other vertebrates, there is little information on the stress response in basal vertebrates. In sea lamprey (Petromyzon marinus), a representative member of the most basal extant vertebrate group Agnatha, 11-deoxycortisol and deoxycorticosterone are the major circulating corticosteroids. The present study examined changes in circulating glucose and 11-deoxycortisol concentrations in response to a physical stressor. Furthermore, the gluconeogenic actions of 11-deoxycortisol and deoxycorticosterone were examined. Within 6 h of exposure of larval and juvenile sea lamprey to an acute handling stress, plasma 11-deoxycortisol levels increased 15- and 6-fold, respectively, and plasma glucose increased 3- and 4-fold, respectively. Radiometric receptor binding studies revealed that a corticosteroid receptor (CR) is present in the liver at lower abundance than in other tissues (gill and anterior intestine) and that the binding affinity of the liver CR was similar for 11-deoxycortisol and deoxycorticosterone. Transcriptional tissue profiles indicate a wide distribution of cr transcription, kidney-specific transcription of steroidogenic acute regulatory protein (star) and liver-specific transcription of phosphoenolpyruvate carboxykinase (pepck). Ex vivo incubation of liver tissue with 11-deoxycortisol resulted in dose-dependent increases in pepck mRNA levels. Finally, intraperitoneal administration of 11-deoxycortisol and deoxycorticosterone demonstrated that only 11-deoxycortisol resulted in an increase in plasma glucose. Together, these results provide the first direct evidence for the gluconeogenic activity of 11-deoxycortisol in an agnathan, indicating that corticosteroid regulation of plasma glucose is a basal trait among vertebrates.
Hard limits to cognitive flexibility: ants can learn to ignore but not avoid pheromone trails
Authors: Wenig Katharina , Bach Richard , Czaczkes Tomer J. 
Published: April 2021

ABSTRACTLearning allows animals to respond to changes in their environment within their lifespan. However, many responses to the environment are innate, and need not be learned. Depending on the level of cognitive flexibility an animal shows, such responses can either be modified by learning or not. Many ants deposit pheromone trails to resources, and innately follow such trails. Here, we investigated cognitive flexibility in the ant Lasius niger by asking whether ants can overcome their innate tendency and learn to avoid conspecific pheromone trails when these predict a negative stimulus. Ants were allowed to repeatedly visit a Y-maze, one arm of which was marked with a strong but realistic pheromone trail and led to a punishment (electric shock and/or quinine solution), and the other arm of which was unmarked and led to a 1 mol l−1 sucrose reward. After ca. 10 trials, ants stopped relying on the pheromone trail, but even after 25 exposures they failed to improve beyond chance levels. However, the ants did not choose randomly: rather, most ants began to favour just one side of the Y-maze, a strategy which resulted in more efficient food retrieval over time, when compared with the first visits. Even when trained in a go/no-go paradigm which precludes side bias development, ants failed to learn to avoid a pheromone trail. These results show rapid learning flexibility towards an innate social signal, but also demonstrate a rarely seen hard limit to this flexibility.
The existence and characteristics of rats and shrews in endemic leptospirosis areas and types of ectoparasites: a case study of West Jakarta, Indonesia
Authors: Susanna Dewi , Nova Rusyda Ihwani Tantia , Rozek Laura 
Published: April 2021

Background: This study aimed to determine the presence and species of the rats and shrews that can potentially cause leptospirosis in West Jakarta, Indonesia, and the species of ectoparasites found in them. Methods: The research was a descriptive study employing a cross-sectional approach. The study population was all species of rats and shrews in the region and the sample collection technique used was purposive sampling. The traps were installed in the homes of respondents who had suffered from leptospirosis and their closest neighbors, with a total of 521 traps. Leptospirosis data based on secondary data was obtained from West Jakarta Health Office (2016-August 2019). The technique for catching rats involved using humane live traps, while the identification of the rats and ectoparasites was done in the laboratory. Results: It was found that more rats were caught in Cengkareng Timur sub-district, Cengkareng District, with a percentage of 14.8%, while the least in Duri Kepa, Kapuk, Kedaung Kali Angke and Kedoya Utara with a percentage of 3.7%. The rats were mostly found in East Cengkareng Sub-District, with the most common type being Rattus rattus (74.1 %) and the least Suncus murinus (11.1%); more male rats were caught (66.7%) than female (33.3%). The type of ectoparasite found in the rats was fleas. Xenopsylla cheopis was the most common type, at 83.3% and more fleas were male, at 66.7%. The most common rat species was Rattus rattus. The ectoparasite most commonly found in them was the female flea Xenopsylla cheopis. Conclusions: Rattus rattus and Xenopsylla cheopis were found in an East Cengkareng sub-district. Surveys, monitoring, and control of rats and ectoparasites are essential for the preparedness and development of an early warning system of possible diseases that they can cause.
Risk factors for major external structural birth defects among children in Kiambu County, Kenya: a case-control study
Authors: Agot George N. , Mweu Marshal M. , Wang'ombe Joseph K. 
Published: April 2021

Background:Although major external structural birth defects continue to occur globally, the greatest burden is shouldered by resource-constrained countries with no surveillance systems. To our knowledge, many studies have been published on risk factors for major external structural birth defects, however, limited studies have been published in developing countries. The objective of this study was to identify risk factors for major external structural birth defects among children in Kiambu County, Kenya.Methods:A hospital-based case-control study was used to identify the risk factors for major external structural birth defects. A structured questionnaire was used to gather information retrospectively on maternal exposure to environmental teratogens, multifactorial inheritance, and sociodemographic-environmental factors during the study participants' last pregnancies. Descriptive analyses (means, standard deviations, medians, and ranges) were used to summarize continuous variables, whereas categorical variables were summarized as proportions and percentages in frequency tables. Afterward, logistic regression analyses were conducted to estimate the effects of the predictors on the odds of major external structural birth defects in the country.Results:Women who conceived when residing in Ruiru sub-county (adjusted odds ratio [aOR]: 5.28; 95% CI; 1.68-16.58; P<0.01), and Kiambu sub-county (aOR: 0.27; 95% CI; 0.076-0.95; P=0.04), and preceding siblings with history of birth defects (aOR: 7.65; 95% CI; 1.46-40.01; P=0.02) were identified as the significant predictors of major external structural birth defects in the county.Conclusions:These findings pointed to MESBDs of genetic, multifactorial inheritance, and sociodemographic-environmental etiology. Thus, we recommend regional defect-specific surveillance programs, public health preventive measures, and treatment strategies to understand the epidemiology and economic burden of these defects in Kenya. We specifically recommend the integration of clinical genetic services with routine reproductive health services because of potential maternal genetic predisposition in the region.
ImageM: a user-friendly interface for the processing of multi-dimensional images with Matlab
Authors: Legland David , Devaux Marie-Françoise 
Published: April 2021

Modern imaging devices provide a wealth of data often organized as images with many dimensions, such as 2D/3D, time and channel. Matlab is an efficient software solution for image processing, but it lacks many features facilitating the interactive interpretation of image data, such as a user-friendly image visualization, or the management of image meta-data (e.g. spatial calibration), thus limiting its application to bio-image analysis. The ImageM application proposes an integrated user interface that facilitates the processing and the analysis of multi-dimensional images within the Matlab environment. It provides a user-friendly visualization of multi-dimensional images, a collection of image processing algorithms and methods for analysis of images, the management of spatial calibration, and facilities for the analysis of multi-variate images. ImageM can also be run on the open source alternative software to Matlab, Octave. ImageM is freely distributed on GitHub: https://github.com/mattools/ImageM.
Uncertainty and the Shadow Banking Crisis: Estimates from a Dynamic Model
Authors: Tian Xu 
Published: April 2021

Shadow banks play an important role in the modern financial system and are arguably the source of key vulnerabilities that led to the 2007–2009 financial crisis. I develop a quantitative framework with uncertainty fluctuations and endogenous bank default to study the dynamics of shadow banking. I argue that the increase in asset return uncertainty during the crisis results in a spread spike, making it more costly for shadow banks to roll over their debt in the short-term debt market. As a result, these financial institutions are forced to deleverage, leading to a decrease in credit intermediation. The model is estimated using a bank-level data set of shadow banks in the United States. The parameter estimates imply that uncertainty shocks can explain 72% of asset contraction and 70% of deleveraging in the shadow banking sector. Maturity mismatch and asset fire-sales amplify the impact of the uncertainty shocks. First-moment shocks to bank asset return, financial shocks, or fire-sale cost shocks alone cannot reproduce the large interbank spread spike, dramatic deleveraging, or contraction in the U.S. shadow banking sector during the crisis. The model also allows for policy experiments. I analyze how unconventional monetary policies can help to counter the rise in the interbank spread, thus stabilizing the credit supply. Taking bank moral hazard into consideration, I find that government bailout might be counterproductive as it might result in more aggressive risk-taking among shadow banks, especially when bailout decisions are based on bank characteristics. This paper was accepted by Gustavo Manso, finance.