bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a non-invasive method for testicular toxicity evaluation using a novel compact magnetic resonance imaging system
Authors: Yokota Satoshi , Miyaso Hidenobu , Hirai Toshinori , Suga Kousuke , Wakayama Tomohiko , Taquahashi Yuhji , Kitajima Satoshi 
Published: August 2022

AbstractIn non-clinical animal studies for drug discovery, histopathological evaluation is the most powerful tool to assess testicular toxicity. However, histological analysis is extremely invasive; many experimental animals are needed to evaluate changes in the pathology and anatomy of the testes over time. As an alternative, small animal magnetic resonance imaging (MRI) offers a non-invasive methodology to examine testicular toxicity without radiation. The present study demonstrated the suitability of a new, ready-to-use compact MRI platform using a high-field permanent magnet to assist with the evaluation of testicular toxicity. To validate the utility of the MRI platform, male mice were treated with busulfan (40 mg/kg, intraperitoneal injection). Tenty-eight days after treatment, both testes in busulfan-treated and control mice (n = 3/group) were non-invasively scanned in situ by MRI at 1 tesla. On a T1-weighted, 3D gradient-echo MRI sequences (voxel size: 0.23 × 0.23 × 0.50 mm), the total testicular volume in busulfan-treated mice was significantly smaller than in controls. On T1-weighted images, the signal intensity of the testes was significantly higher in busulfan-treated mice than in controls. The mice were sacrificed, and the testes were isolated for histopathological analysis. The weight of the testes in busulfan-treated mice significantly decreased, similar to the results of the non-invasive analysis. Additionally, periodic acid-Schiff stain–positive effusions were observed in the interstitium of the busulfan-treated mouse testes, potentially explaining T1 shortening due to a high concentration of glycoproteinaceous content. The present data demonstrated a rapid evaluation of testicular toxicity in vivo by compact MRI.
Growth of Mesenchymal Stem Cells at the Surface of Silicone, Mineral and Plant-Based Oils
Authors: Peng Lihui , Gautrot Julien E. 
Published: August 2022

AbstractBioemulsions are attractive platforms for the expansion of adherent cells in bioreactors. Their design relies on the self-assembly of protein nanosheets at liquid-liquid interfaces, displaying strong interfacial mechanical properties and promoting integrin-mediated cell adhesion. However, most systems developed to date have focused on fluorinated oils, which are unlikely to be accepted for direct implantation of resulting cell products for regenerative medicine, and protein nanosheets self-assembly at other interfaces has not been investigated. In this report, the composition of aliphatic pro-surfactants palmitoyl chloride and sebacoyl chloride, on the assembly kinetics of poly(L-lysine) at silicone oil interfaces and characterisation of ultimate interfacial shear mechanics and viscoelasticity is presented. The impact of the resulting nanosheets on the adhesion of mesenchymal stem cells (MSCs) is investigated via immunostaining and fluorescence microscopy, demonstrating the engagement of the classic focal adhesion-actin cytoskeleton machinery. The ability of MSCs to proliferate at the corresponding interfaces is quantified. In addition, expansion of MSCs at other non-fluorinated oil interfaces, based on mineral and plant-based oils is investigated. Finally, the proof-of-concept of such non-fluorinated oil systems for the formulation of bioemulsions supporting stem cell adhesion and expansion is demonstrated.
Differential global distribution of marine picocyanobacteria gene clusters reveals distinct niche-related adaptive strategies
Authors: Doré Hugo , Guyet Ulysse , Leconte Jade , Farrant Gregory K. , Alric Benjamin , Ratin Morgane , Ostrowski Martin , Ferrieux Mathilde , Brillet-Guéguen Loraine , Hoebeke Mark , Siltanen Jukka , Corguillé Gildas Le , Corre Erwan , Wincker Patrick , Scanlan David J. , Eveillard Damien , Partensky Frédéric , Garczarek Laurence 
Published: August 2022

AbstractThe ever-increasing number of available microbial genomes and metagenomes provide new opportunities to investigate the links between niche partitioning and genome evolution in the ocean, notably for the abundant and ubiquitous marine picocyanobacteria Prochlorococcus and Synechococcus. Here, by combining metagenome analyses of the Tara Oceans dataset with comparative genomics, including phyletic patterns and genomic context of individual genes from 256 reference genomes, we first showed that picocyanobacterial communities thriving in different niches possess distinct gene repertoires. We then managed to identify clusters of adjacent genes that display specific distribution patterns in the field (CAGs) and are thus potentially involved in the adaptation to particular environmental niches. Several CAGs are likely involved in the uptake or incorporation of complex organic forms of nutrients, such as guanidine, cyanate, cyanide, pyrimidine or phosphonates, which might be either directly used by cells, for e.g. the biosynthesis of proteins or DNA, or degraded into inorganic nitrogen and/or phosphorus forms. We also highlight the frequent presence of CAGs involved in polysaccharide capsule biosynthesis in Synechococcus populations thriving in both nitrogen- and phosphorus-depleted areas, which are absent in low-iron regions, suggesting that the complexes they encode may be too energy-consuming for picocyanobacteria thriving in these areas. In contrast, Prochlorococcus populations thriving in iron-depleted areas specifically possess an alternative respiratory terminal oxidase, potentially involved in the reduction of Fe(III) into Fe(II). Together, this study provides insights into how these key members of the phytoplankton community might behave in response to ongoing global change.Significance StatementPicocyanobacteria face various environmental conditions in the ocean and numerous studies have shown that genetically distinct ecotypes colonize different niches. Yet the functional basis of their adaptation remains poorly known, essentially due to the large number of genes of yet unknown function, many of which have little or no beneficial effect on fitness. Here, by combining comparative genomics and metagenomics approaches, we have identified not only single genes but also entire gene clusters, potentially involved in niche adaptation. Although being sometimes present in only one or a few sequenced strains, they occur in a large part of the population in specific ecological niches and thus constitute precious targets for elucidating the biochemical function of yet unknown niche-related genes.
Strong effects of parasite genotype on drug susceptibility in the Indian subcontinent
Authors: Grace Cooper Alastair , Reis-Cunha João Luís , Jeffares Daniel C. 
Published: August 2022

AbstractIntracellular parasites of the Leishmania donovani species complex cause visceral leishmaniasis (VL). For parasitic diseases, VL has a mortality rate second only to malaria, and is associated with poverty-stricken areas of the world: primarily Brazil, East Africa and the Indian subcontinent (ISC). Miltefosine (MIL) and the antimonal sodium stibogluconate (SSG) are drugs used in the treatment of leishmaniasis. However, treatment efficacy is variable, and the numbers of reports of parasite resistance to both drugs have risen since their introductions, particularly in the ISC. To assess the level of parasite genotype contribution to drug resistance, we utilised the sequencing and associated drug susceptibility data from Imamura et al. (2016) to estimate heritability and GWAS using LDAK. We obtained strong heritability results, with mainly SNP/indel variations associated with SSG and copy number variants associated with MIL resistance, respectively. However, GWAS results were inconclusive, suggesting that, although the parasite genotype directly influences drug resistance, the effect might be multifactorial.
Automated assembly of high-density carbon fiber electrode arrays for single unit electrophysiological recordings
Authors: Dong Tianshu , Chen Lei , Patel Paras R , Richie Julianna M , Chestek Cynthia A , Shih Albert J 
Published: August 2022

AbstractObjectiveCarbon fiber (CF) is good for chronic neural recording due to the small diameter (7 µm), high Young’s modulus, and low electrical resistance, but most high-density carbon fiber (HDCF) arrays are manually assembled with labor-intensive procedures and limited by the accuracy and repeatability of the operator handling. A machine to automate the assembly is desired.ApproachThe HDCF array assembly machine contains: 1) a roller-based CF extruder, 2) a motion system with three linear and one rotary stages, 3) an imaging system with two digital microscope cameras, and 4) a laser cutter. The roller-based extruder automatically feeds single CF as raw material. The motion system aligns the CF with the array backend then places it. The imaging system observes the relative position between the CF and the backend. The laser cutter cuts off the CF. Two image processing algorithms are implemented to align the CF with the support shanks and circuit connection pads.Main resultsThe machine was capable of precisely handling 6.8 μm carbon fiber electrodes. Each electrode was placed into a 12 μm wide trenches in a silicon support shank. Two HDCF arrays with 16 CF electrodes populated on 3 mm shanks (with 80 μm pitch) were fully assembled. Impedance measurements were found to be in good agreement with manual assembled arrays. One HDCF array was implanted in the motor cortex in an anesthetized rat and was able to detect single unit activity.SignificanceThis machine can eliminate the manual labor-intensive handling, alignment and placement of single carbon fiber during assembly, providing a proof-of-concepts towards fully automated HDCF array assembly and batch production.
E. faecalisacquires resistance to antimicrobials and insect immunity via common mechanisms
Authors: Wadhawan Ashima , Simoes da Silva Carolina J. , Nunes Catarina D. , Edwards Andrew M. , Dionne Marc S. 
Published: August 2022

SummaryEnterococcus faecalisis a normal member of the gut microbiota and an opportunistic pathogen of many animals, including mammals, birds, and insects. It is a common cause of nosocomial infections, and is particularly troublesome due to extensive intrinsic and acquired antimicrobial resistance. Using experimental evolution, we generatedDrosophila-adaptedE. faecalisstrains, which exhibited immune resistance, resulting in increasedin vivogrowth and virulence. Resistance was characterised by mutations in bacterial pathways responsive to cell envelope stress.Drosophila-adapted strains exhibited changes in sensitivity to relevant antimicrobials, including daptomycin and vancomycin. Evolved daptomycin-resistant strains harboured mutations in the same signalling systems, with some strains showing increased virulence similar toDrosophila-adapted strains. Our results show that common mechanisms provide a route to resistance to both antimicrobials and host immunity inE. faecalisand demonstrate that the selection and emergence of antibiotic resistancein vivodoes not require antibiotic exposure.One sentence summaryHost interaction can promote antimicrobial resistance and antimicrobial treatment can promote virulence inE. faecalis.
The olfactory bulb carries out concentration invariance calculations by itself and does it very quickly
Authors: Choi Yunsook , Cohen Lawrence B. 
Published: August 2022

ABSTRACTThe olfactory bulb is known to carry out computations for the olfactory perception of concentration invariance of odor recognition, a perception that is essential for life as we know it. However it is not known whether these computations require the extensive feedback to the bulb from the many brain regions which send this feedback. We have measured the concentration dependence of the mitral cell output of the bulb before and after blocking this feedback by lidocaine infusion into the medial olfactory peduncle. Surprisingly we found that the concentration dependence of the mitral cell output was unaffected by the lidocaine block of feedback. Furthermore the computation is rapid; it is complete within a single 250 msec inhalation. The computations for concentration invariance are most likely carried out within the olfactory bulb itself and they are carried out quickly.
Soil depth governs microbial community assembly and enzymatic activity in extreme environments
Authors: Jing Xin , Classen Aimée T. , Li Daijiang , Lin Litao , Lu Mingzhen , Sanders Nathan J. , Wang Yugang , Feng Wenting 
Published: August 2022

AbstractAimA fundamental challenge in soil macroecology is to understand how microbial community structure shapes ecosystem functions along environmental gradients of land surface (i.e., horizontal dimension). However, little is known of microbial community structure-function relationships along environmental gradients of soil depth (i.e., vertical dimension) in extreme environments. A full understanding of the consequences of environmental change for microbial communities structure and subsequent changes in microbial functions could enable more accurate predictions of extreme environmental change effects. Here, we leveraged a 200-km desert soil salinity gradient that is created by a 12-year saline-water irrigation to evaluate how soil microbial community structure-function relationships change with soil salinity in the horizontal and vertical dimensions.LocationThe Tarim basin of Taklamakan desert.TaxaSoil bacteria and fungi.MethodsWe assessed the prime ecological processes controlling the assembly of microbial communities and the activity of enzymes relevant to carbon, nitrogen, and phosphorus cycling along soil salinity gradients across study sites (horizontal dimension) and soil depths (vertical dimension) by using the general linear model, hierarchical variance partitioning, and path model.ResultsDifferences in soil depth (on the scale of meters) was as important as geographic distance (on the scale of kilometers) in shaping the structure of bacterial and fungal communities, while both the vertical and horizontal variability in enzymatic activity were largely attributed to the increase in the heterogeneity of soil properties, such as soil texture, water content, and pH.Main conclusionsOur results suggest that dispersal limitation and environmental heterogeneity, not soil salinization, along soil depth governs microbial community assembly and enzymatic activity, respectively. This work highlights that conservation efforts of soil macroecology should consider soil depth as a key attribute in the face of ongoing salinization in arid ecosystems.
Structure-activity relationship of 2,4-D correlates auxin activity with the induction of somatic embryogenesis in Arabidopsis thaliana
Authors: Karami Omid , de Jong Hanna , Somovilla Victor J. , Acosta Beatriz Villanueva , Sugiarta Aldo Bryan , Wennekes Tom , Offringa Remko 
Published: August 2022

Abstract2,4-dichlorophenoxyacetic acid (2,4-D) is a synthetic analogue of the plant hormone auxin that is commonly used in many in vitro plant regeneration systems, such as somatic embryogenesis (SE). Its effectiveness in inducing SE, compared to the natural auxin indole-3-acetic acid (IAA), has been attributed to the stress triggered by this compound rather than its auxin activity. However, this hypothesis has never been thoroughly tested. Here we used a library of 40 2,4-D analogues to test the structure-activity relationship with respect to the capacity to induce SE and auxin activity in Arabidopsis thaliana. Four analogues induced SE as effectively as 2,4-D and 13 analogues induced SE but were less effective. Based on root growth inhibition and auxin response reporter expression, the 2,4-D analogues were classified into different groups, ranging from very active auxins to not active. A halogen at the 4-position of the aromatic ring was important for auxin activity, whereas a halogen at the 3-position resulted in reduced activity. Moreover, a small substitution at the carboxylate chain was tolerated, as was extending the carboxylate chain with two but not with one carbon. In the process, we also identified two 2,4-D analogues as efficient inducers of adventitious root formation and several possible anti-auxins. The auxin activity of the 2,4-D analogues was consistent with their simulated TIR1-Aux/IAA coreceptor binding characteristics. A strong correlation was observed between SE induction efficiency and auxin activity, indicating that the stress-related effects triggered by 2,4-D that are considered important for SE induction are down-stream of auxin signaling.
Cellular Harmonics for the Morphology-invariant Analysis of Molecular Organization at the Cell Surface
Authors: Mazloom-Farsibaf Hanieh , Zou Qiongjing , Hsieh Rebecca , Danuser Gaudenz , Driscoll Meghan 
Published: August 2022

AbstractThe spatiotemporal organization of membrane-associated molecules is central to the regulation of the vast signaling network that control cellular functions. Powerful new microscopy techniques enable the 3D visualization of the localization and activation of these molecules. However, quantitatively interpreting and comparing the spatial organization of molecules on the 3D cell surface remains challenging because cells themselves vary greatly in their morphology. Here, we introduce u-signal3D, a framework to assess the spatial scales of molecular organization at the cell surface in a cell-morphology invariant manner. We validated our framework by analyzing both synthetic polka dot patterns painted onto observed cell morphologies, as well as measured distributions of cytoskeletal and signaling molecules. To demonstrate the framework’s versatility, we further compared the spatial organization of cell surface signaling both within and between cell populations and powered an upstream machine-learning based analysis of signaling motifs. U-signal3D is open source and is available at https://github.com/DanuserLab/u-signal3D.
The centromere/kinetochore is assembled through CENP-C oligomerization
Authors: Hara Masatoshi , Ariyoshi Mariko , Sano Tomoki , Nozawa Ryu-suke , Shinkai Soya , Onami Shuichi , Jansen Isabelle , Hirota Toru , Fukagawa Tatsuo 
Published: August 2022

SummaryThe kinetochore is an essential protein complex for accurate chromosome segregation. The constitutive centromere-associated network (CCAN), a subcomplex of the kinetochore, associates with centromeric chromatin providing a platform for the kinetochore assembly. A CCAN protein, CENP-C, is thought to be a central hub for the centromere/kinetochore organization. However, the crucial role of CENP-C in centromeres remains to be elucidated. Here, we demonstrated that both the CCAN-binding domain and C-terminal Cupin domain of CENP-C are necessary and sufficient for chicken CENP-C function. Our structural and biochemical analyses revealed that the Cupin domain of chicken and human CENP-C is self-oligomerization domain, which is crucial for centromeric chromatin organization. CENP-C mutants lacking the oligomerization interface cause mislocalization of CCAN and cell death. Based on these results, we conclude that the CENP-C oligomerization plays a crucial role in centromere function via providing the robust centromeric chromatin in vertebrate cells.
Supraorbital whiskers act as wind-antennae in rat anemotaxis
Authors: Mugnaini Matias , Mehrotra Dhruv , Davoine Federico , Sharma Varun , Mendes Ana Rita , Gerhardt Ben , Concha-Miranda Miguel , Brecht Michael , Clemens Ann M. 
Published: August 2022

AbstractWe know little about mammalian anemotaxis, wind-sensing. Recently, however, Hartmann and colleagues showed whisker-based anemotaxis in rats. To investigate how whiskers sense airflow, we tracked whisker tips in anesthetized or cadaver rats under no airflow, low airflow and high (fan-blowing) airflow. Whisker tips showed little movement under no airflow conditions and all whisker tips moved during high airflow. Low airflow conditions – most similar to naturally occurring wind stimuli – engaged whisker tips differentially. Most whiskers moved little, the long supraorbital whisker showed maximal displacement and α, A1, β, and γ whiskers also showed movements. The long supraorbital whisker differs from other whiskers in its exposed dorsal position, upward bending, length and thin diameter.Ex vivoextracted long supraorbital whiskers also showed exceptional airflow displacement, suggesting whisker-intrinsic biomechanics mediate the unique airflow-sensitivity. Micro computed tomography revealed that the ring-wulst – the follicle structure receiving the most sensitive afferents – was more complete/ closed in supraorbital and other wind-sensitive whiskers than in non-wind-sensitive whiskers, suggesting specialization of the supraorbital for omni-directional sensing. We localized and targeted the cortical supraorbital whisker representation in simultaneous Neuropixels recordings with D/E-row whisker barrels. Responses to wind-stimuli were stronger in the supraorbital whisker representation than in D/E-row barrel cortex. We assessed the behavioral significance of whiskers in an airflow-sensing paradigm. We observed that rats spontaneously turn towards airflow stimuli in complete darkness. Selective trimming of wind-responsive whiskers diminished airflow turning responses more than trimming of non-wind-responsive whiskers. Lidocaine injections targeted to supraorbital whisker follicles also diminished airflow turning responses compared to control injections. We conclude that supraorbital whiskers act as wind antennae.New and NoteworthyAnimals rely on sensory processing of airflow (anemotaxis) to guide navigation and survival. We examined mechanisms of rat anemotaxis by combining whisker tracking, biomechanical analysis, micro computed tomography of follicle structure, Neuropixels recordings in the barrel field, behavior of airflow turning and whisker interference by trimming and lidocaine injections. This diversity of methods led to a coherent pattern of results. Whiskers greatly differ in their airflow sensitivity and strongly wind-responsive whiskers – in particular long supraorbital whiskers – determine behavioral responses to airflow stimuli in rats.
Sex inclusion in transcriptome studies of daily rhythms
Authors: Obodo Dora , Outland Elliot H. , Hughey Jacob J. 
Published: August 2022

AbstractBiomedical research on mammals has traditionally neglected females, raising the concern that some scientific findings may generalize poorly to half the population. Although this lack of sex inclusion has been broadly documented, its extent within circadian genomics remains undescribed. To address this gap, we examined sex inclusion practices in a comprehensive collection of publicly available transcriptome studies on daily rhythms. Among 148 studies having samples from mammals in vivo, we found strong underrepresentation of females across organisms and tissues. Overall, only 23 of 123 studies in mice, 0 of 10 studies in rats, and 9 of 15 studies in humans included samples from females. In addition, studies having samples from both sexes tended to have more samples from males than from females. These trends appear to have changed little over time, including since 2016, when the US NIH began requiring investigators to consider sex as a biological variable. Our findings highlight an opportunity to dramatically improve representation of females in circadian research and to explore sex differences in daily rhythms at the genome level.