bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic force measurements on swimming
Chlamydomonas
cells using micropipette force sensors
Authors: Böddeker Thomas J. , Karpitschka Stefan , Kreis Christian T. , Magdelaine Quentin , Bäumchen Oliver
Published: January 2020

Flagella and cilia are cellular appendages that inherit essential functions of microbial life including sensing and navigating the environment. In order to propel a swimming microorganism they displace the surrounding fluid by means of periodic motions, while precisely timed modulations of their beating patterns enable the cell to steer towards or away from specific locations. Characterizing the dynamic forces, however, is challenging and typically relies on indirect experimental approaches. Here, we present direct
in vivo
measurements of the dynamic forces of motile
Chlamydomonas reinhardtii
cells in controlled environments. The experiments are based on partially aspirating a living microorganism at the tip of a micropipette force sensor and optically recording the micropipette’s position fluctuations with high temporal and sub-pixel spatial resolution. Spectral signal analysis allows for isolating the cell-generated dynamic forces caused by the periodic motion of the flagella from background noise. We provide an analytic, elasto-hydrodynamic model for the micropipette force sensor and describe how to obtain the micropipette’s full frequency response function from a dynamic force calibration. Using this approach, we measure the amplitude of the oscillatory forces during the swimming activity of individual
Chlamydomonas reinhardtii
cells of 26 ± 5 pN, resulting from the coordinated flagellar beating with a frequency of 49 ± 5 Hz. This dynamic micropipette force sensor technique generalizes the applicability of micropipettes as force sensors from static to dynamic force measurements, yielding a force sensitivity in the piconewton range. In addition to measurements in bulk liquid environment, we study the dynamic forces of the biflagellated microswimmer in the vicinity of a solid/liquid interface. As we gradually decrease the distance of the swimming microbe to the interface, we measure a significantly enhanced force transduction at distances larger than the maximum extent of the beating flagella, highlighting the importance of hydrodynamic interactions for scenarios in which flagellated microorganisms encounter surfaces.
‘As to the plan of this work … we think Dr. Baillie has done wrong’: changing the study of disease through epistemic genre in Georgian Britain
Authors: Bellis Richard T.
Published: January 2020

In the eighteenth century, the writing of case histories, incorporating findings at post-mortem, was central to how the study of disease was practised. The use of this epistemic genre reflected the work of medical practitioners with their patients. By contrast, Matthew Baillie's
Morbid Anatomy
(1793) was a work of anatomy on the subject of disease that promoted an anatomical approach to the study of disease and stemmed from his own, different practice, which was anatomical. This was criticized by contemporaries who were sceptical that such an approach would prove useful to the physician's practice. Baillie's work took on the features of anatomy books, and omitted many of the features central to the writing of case histories, such as patient narratives. Instead he focused on describing, in generalized terms, the changes in structure caused by disease. These descriptions were valued by contemporaries, who incorporated his descriptions into their own works, changing the way that cases included anatomical findings. At the same time, Baillie's later editions contained more features of cases, such as descriptions of symptoms. Thus, individual books worked to integrate epistemic genres, and change practice in the study of disease.
Intermediacy of publications
Authors: Šubelj Lovro , Waltman Ludo , Traag Vincent , van Eck Nees Jan
Published: January 2020

Citation networks of scientific publications offer fundamental insights into the structure and development of scientific knowledge. We propose a new measure, called intermediacy, for tracing the historical development of scientific knowledge. Given two publications, an older and a more recent one, intermediacy identifies publications that seem to play a major role in the historical development from the older to the more recent publication. The identified publications are important in connecting the older and the more recent publication in the citation network. After providing a formal definition of intermediacy, we study its mathematical properties. We then present two empirical case studies, one tracing historical developments at the interface between the community detection literature and the scientometric literature and one examining the development of the literature on peer review. We show both conceptually and empirically how intermediacy differs from main path analysis, which is the most popular approach for tracing historical developments in citation networks. Main path analysis tends to favour longer paths over shorter ones, whereas intermediacy has the opposite tendency. Compared to the main path analysis, we conclude that intermediacy offers a more principled approach for tracing the historical development of scientific knowledge.
Communicating the effectiveness and ineffectiveness of government policies and their impact on public support: a systematic review with meta-analysis
Authors: Reynolds J. P. , Stautz K. , Pilling M. , van der Linden S. , Marteau T. M.
Published: January 2020

Low public support for government interventions in health, environment and other policy domains can be a barrier to implementation. Communicating evidence of policy effectiveness has been used to influence attitudes towards policies, with mixed results. This review provides the first systematic synthesis of such studies. Eligible studies were randomized controlled experiments that included an intervention group that provided evidence of a policy's effectiveness or ineffectiveness at achieving a salient outcome, and measured policy support. From 6498 abstracts examined, there were 45 effect sizes from 36 eligible studies. In total, 35 (N= 30 858) communicated evidence of effectiveness, and 10 (N= 5078) communicated evidence of ineffectiveness. Random effects meta-analysis revealed that communicating evidence of a policy's effectiveness increased support for the policy (SMD = 0.11, 95% CI [0.07, 0.15],p< 0.0001), equivalent to support increasing from 50% to 54% (95% CI [53%, 56%]). Communicating evidence of ineffectiveness decreased policy support (SMD = −0.14, 95% CI [−0.22, −0.06],p< 0.001), equivalent to support decreasing from 50% to 44% (95% CI [41%, 47%]). These findings suggest that public support for policies in a range of domains is sensitive to evidence of their effectiveness, as well as their ineffectiveness.
ALOX5,LPA,MMP9andTPOgene polymorphisms increase atherothrombosis susceptibility in middle-aged Mexicans
Authors: Camacho-Mejorado Rafael , Gómez Rocío , Torres-Sánchez Luisa E. , Alhelí Hernández-Tobías Esther , Noris Gino , Santana Carla , Magaña Jonathan J. , Orozco Lorena , de la Peña-Díaz Aurora , de la Luz Arenas-Sordo María , Meraz-Ríos Marco Antonio , Majluf-Cruz Abraham
Published: January 2020

Atherothrombosis is the cornerstone of cardiovascular diseases and the primary cause of death worldwide. Genetic contribution to disturbances in lipid metabolism, coagulation, inflammation and oxidative stress increase the susceptibility to its development and progression. Given its multifactorial nature, the multiloci studies have been proposed as potential predictors of susceptibility. A cross-sectional study was conducted to explore the contribution of nine genes involved in oxidative stress, inflammatory and thrombotic processes in 204 subjects with atherothrombosis matched by age and gender with a healthy group (n= 204). To evaluate the possibility of spurious associations owing to the Mexican population genetic heterogeneity as well as its ancestral origins, 300 unrelated mestizo individuals and 329 Native Americans were also included.ALOX5,LPA,MMP9andTPOgene polymorphisms, as well as their multiallelic combinations, were twice to four times more frequent in those individuals with clinical manifestations of atherothrombosis than in the healthy group. Once adjusting for population stratification was done, these differences remained. Our results add further evidence on the contribution ofALOX5,LPA,MMP9andTPOpolymorphisms to atherothrombosis development in the middle-aged group, emphasizing the multiethnic studies in search of gene risk polymorphisms.
The cell uptake properties and hyperthermia performance of Zn
0.5
Fe
2.5
O
4
/SiO
2
nanoparticles as magnetic hyperthermia agents
Authors: Wang Runsheng , Liu Jianheng , Liu Yihao , Zhong Rui , Yu Xiang , Liu Qingzu , Zhang Li , Lv Chenhui , Mao Keya , Tang Peifu
Published: January 2020

Zn
0.5
Fe
2.5
O
4
nanoparticles (NPs) of 22 nm are synthesized by a one-pot approach and coated with silica for magnetic hyperthermia agents. The NPs exhibit superparamagnetic characteristics, high-specific absorption rate (SAR) (1083 wg
−1
,
f
= 430 kHz,
H
= 27 kAm
−1
), large saturation magnetization (
M
s
= 85 emu g
−1
), excellent colloidal stability and low cytotoxicity. The cell uptake properties have been investigated by Prussian blue staining, transmission electron microscopy and the inductively coupled plasma-mass spectrometer, which resulted in time-dependent and concentration-dependent internalization. The internalization appeared between 0.5 and 2 h, the NPs were mainly located in the lysosomes and kept in good dispersion after incubation with human osteosarcoma MG-63 cells. Then, the relationship between cell uptake and magnetic hyperthermia performance was studied. Our results show that the hyperthermia efficiency was related to the amount of internalized NPs in the tumour cells, which was dependent on the concentration and incubation time. Interestingly, the NPs could still induce tumour cells to apoptosis/necrosis when extracellular NPs were rinsed, but the cell kill efficiency was lower than that of any rinse group, which indicated that local temperature rise was the main factor that induced tumour cells to death. Our findings suggest that this high SAR and biocompatible silica-coated Zn
0.5
Fe
2.
O
4
NPs could serve as new agents for magnetic hyperthermia.
How the thermal environment shapes the structure of termite mounds
Authors: Fagundes Tadeu Mendonca , Ordonez Juan Carlos , Yaghoobian Neda
Published: January 2020

A computational model has been developed to predict the role of environment in the forms and functions of termite mounds. The proposed model considers the most relevant forces involved in the heat transfer process of termite mounds, while also reflecting their gas-exchange function. The method adopts a system configuration procedure to determine thermally optimized mound structures. The model successfully predicts the main architectural characteristics of typicalMacrotermes michaelsenimounds for the environmental conditions they live in. The results indicate that the mound superstructure and internal condition strongly depend on the combined effect of environmental forces. It is noted that mounds being exposed to higher solar irradiances develop intricate lateral channels, inside, and taller and more pronounced spire tilt towards the Sun, outside. It is also found that the mounds' spire tilt angle depends on the geographical location, following the local average solar zenith angle for strong irradiances. Although wind does not influence the overall over-ground mound shape, it significantly affects the mound internal condition. The results of this study resonate with what is seen in nature. The proposed approach provides a broader view of the factors that are effective in the form and function of a naturally made structure.
The role of symmetry in the post-buckling behaviour of structures
Authors: Zucco G. , Weaver P. M.
Published: January 2020

Symmetry plays an integral role in the post-buckling analysis of elastic structures. We show that the post-buckling response of engineering systems with given symmetry properties can be described using a preselected set of buckling modes. Therefore, the main original contribution of this paper is to prove the existence of these influential buckling modes and reveal some insights about them. From an engineering point of view, this study leads to the possibility of reducing computational effort in the analysis of large-scale systems. Firstly, symmetry groups for nonlinear elastic structural problems are discussed. Then, we invoke Curie’s principle and describe the relationship between these groups and related pre-buckling and linear buckling deformation patterns. Then, for structural systems belonging to a given symmetry group, we re-invoke Curie’s principle for describing the relationship between linear buckling modes and post-buckled deformation of the structure. Subsequently, we furnish a simplified asymptotic description which is obtained by projecting the equilibrium equations onto the subset of the most representative modes. As examples, classic bifurcation problems including isotropic and composite laminate panels under compression loading are investigated. Finally, the accuracy and computational advantages given by this new approach are discussed.
My niche: individual spatial niche specialization affects within- and between-species interactions
Authors: Schirmer Annika , Hoffmann Julia , Eccard Jana A. , Dammhahn Melanie
Published: January 2020

Intraspecific trait variation is an important determinant of fundamental ecological interactions. Many of these interactions are mediated by behaviour. Therefore, interindividual differences in behaviour should contribute to individual niche specialization. Comparable with variation in morphological traits, behavioural differentiation between individuals should limit similarity among competitors and thus act as a mechanism maintaining within-species variation in ecological niches and facilitating species coexistence. Here, we aimed to test whether interindividual differences in boldness covary with spatial interactions within and between two ecologically similar, co-occurring rodent species (Myodes glareolus,Apodemus agrarius). In five subpopulations in northeast Germany, we quantified individual differences in boldness via repeated standardized tests and spatial interaction patterns via capture–mark–recapture (n= 126) and automated VHF telemetry (n= 36). We found that boldness varied with space use in both species. Individuals of the same population occupied different spatial niches, which resulted in non-random patterns of within- and between-species spatial interactions. Behavioural types mainly differed in the relative importance of intra- versus interspecific competition. Within-species variation along this competition gradient could contribute to maintaining individual niche specialization. Moreover, behavioural differentiation between individuals limits similarity among competitors, which might facilitate the coexistence of functionally equivalent species and, thus, affect community dynamics and local biodiversity.
Selection for increased male size predicts variation in sexual size dimorphism among fish species
Authors: Horne Curtis R. , Hirst Andrew G. , Atkinson David
Published: January 2020

Variation in the degree of sexual size dimorphism (SSD) among taxa is generally considered to arise from differences in the relative intensity of male–male competition and fecundity selection. One might predict, therefore, that SSD will vary systematically with (1) the intensity of sexual selection for increased male size, and (2) the intensity of fecundity selection for increased female size. To test these two fundamental hypotheses, we conducted a phylogenetic comparative analysis of SSD in fish. Specifically, using records of body length at first sexual maturity from FishBase, we quantified variation in the magnitude and direction of SSD in more than 600 diverse freshwater and marine fish species, from sticklebacks to sharks. Although female-biased SSD was common, and thought to be driven primarily by fecundity selection, variation in SSD was not dependent on either the allometric scaling of reproductive energy output or fecundity in female fish. Instead, systematic patterns based on habitat and life-history characteristics associated with varying degrees of male–male competition and paternal care strongly suggest that adaptive variation in SSD is driven by the intensity of sexual selection for increased male size.
Identification of miRNAs and their corresponding mRNA targets from chickpea nodules and functional characterization of candidate miRNAs by overexpression in chickpea roots
Authors: Tiwari Manish , Singh Baljinder , Yadav Manisha , Pandey Vimal , Bhatia Sabhyata
Published: January 2020

Legumes developed symbiotic associations with rhizobia to meet its nitrogen requirement. The nitrogen fixation takes place in root nodules which involves bacterial colonization, organogenesis and nitrogen fixation.

One microRNA and four parallel analysis of RNA ends (PARE) libraries were sequenced to unravel the miRNA mediated regulation of symbiosis in chickpea.

Sequencing of microRNA library identified a set of 91 miRNAs comprising of 84 conserved and 7 novel miRNAs. Additionally, PARE library analysis revealed 564 genes being targeted by 85 miRNAs.

Phylogenetic analysis of the precursor sequences of the 91 miRNAs clearly indicated a clustering of two distinct miRNAs in the same clade representing a close ancestral precursor.

Further, biogenesis of miRNAs was predicted using the miRNAs identified from different legume genomes.

The miRNA reads from the nodule library were also mapped onto bacterial genomes from which bacterial small RNA were predicted.

The antagonistic expression of some of the miRNA-target pairs was investigated and the negative co-related expression profiling proved the validity of the libraries and the miRNA-target pairs. Four miRNAs were selected based on the antagonistic expression profiling and were ectopically expressed in chickpea roots by hairy root transformation.

The overexpression lines showed significant change in nodule numbers. The target of miR171f (NRK), miR394 (HP) and miR1509 (AK) are novel ones being reported for the first time. This analysis opens a wide arena for investigation of the novel miRNAs and target pairs, polycistronic miRNAs and the bacterial derived smRNAs predicted in this study.
Increased fronto-temporal connectivity by modified melody in real music
Authors: Kim Chan Hee , Seol Jaeho , Jin Seung-Hyun , Kim June Sic , Kim Youn , Yi Suk Won , Chung Chun Kee
Published: January 2020

In real music, the original melody may appear intact, with little elaboration only, or significantly modified. Since a melody is most easily perceived in music, hearing significantly modified melody may change a brain connectivity. Mozart KV 265 is comprised of a theme with an original melody of “Twinkle Twinkle Little Star” and its significant variations. We studied whether effective connectivity changes with significantly modified melody, between bilateral inferior frontal gyri (IFGs) and Heschl’s gyri (HGs) using magnetoencephalography (MEG). Among the 12 connectivities, the connectivity from the left IFG to the right HG was consistently increased with significantly modified melody compared to the original melody in 2 separate sets of the same rhythmic pattern with different melody (p= 0.005 and 0.034, Bonferroni corrected). Our findings show that the modification of an original melody in a real music changes the brain connectivity.
Canopy parkour: movement ecology of post-hatch dispersal in a gliding nymphal stick insect (Extatosoma tiaratum)
Authors: Zeng Yu , Chang Sofia W. , Williams Janelle Y. , Nguyen Lynn Y-Nhi , Tang Jia , Naing Grisanu , Dudley Robert
Published: January 2020

For flightless arboreal arthropods, moving from the understory into tree canopies is cognitively and energetically challenging because vegetational structures present complex three-dimensional landscapes with substantial gaps. Predation risk and wind-induced perturbations in the canopy may further impede the movement process. In the Australian stick insectExtatosoma tiaratum, first-instar nymphs hatch on the forest floor and disperse toward tree canopies in the daytime. Here, we address such vertical movements and associated sensory cues inE. tiaratumnymphs. Newly hatched nymphs ascend with high endurance, travelling >100 m within 60 minutes. Navigation toward open canopies is underpinned by negative gravitaxis, positive phototaxis, and visual responses to vertically oriented contrast patterns. NymphalE. tiaratumalso use directed jumping to cross air gaps, and respond to tactile stimulation and potential threat with a self-dropping reflex, resulting aerial descent. Post-hatch dispersal inE. tiaratumthus consists of visually mediated displacement both on vegetational structures and in the air; within the latter context, gliding is then an effective mechanism enabling recovery after predator- and perturbation-induced descent. These results further support the importance of a diurnal niche, in addition to the arboreal spatial niche, in the evolution of gliding in wingless arboreal invertebrates.

Summary statement

To effectively disperse into canopies, ground-hatched stick insects use gravity and visual cues to navigate during midday, jump to cross air gaps and respond to threat or perturbation with self-dropping.
A behavioral polymorphism caused by a single gene inside a supergene
Authors: Merritt Jennifer R. , Grogan Kathleen E. , Zinzow-Kramer Wendy M. , Sun Dan , Ortlund Eric A. , Yi Soojin V. , Maney Donna L.
Published: January 2020

Behavioral evolution relies on genetic changes, yet few social behaviors can be traced to specific genetic sequences in vertebrates. Here, we show experimental evidence that differentiation of a single gene has contributed to divergent behavioral phenotypes in the white-throated sparrow, a common North American songbird. In this species, one of two alleles ofESR1, encoding estrogen receptor α (ERα), has been captured inside a differentiating supergene that segregates with an aggressive phenotype, such thatESR1expression predicts aggression. Here, we show that the aggressive phenotype associated with the supergene is prevented byESR1knockdown in a single brain region. Next, we show that in a free-living population, aggression is predicted by allelic imbalance favoring the supergene allele.Cis-regulatory variation between the two alleles affects transcription factor binding sites, DNA methylation, and rates of transcription. This work provides a rare illustration of how genotypic divergence has led to behavioral phenotypic divergence in a vertebrate.
Diagnostic Cerebrospinal Fluid Biomarker Discovery and Validation in Patients with Central Nervous System Infections
Authors: Thanh Tran Tan , Casals-Pascual Climent , Ny Nguyen Thi Han , Ngoc Nghiem My , Geskus Ronald , Nhu Le Nguyen Truc , Hong Nguyen Thi Thu , Duc Du Trong , Thu Do Dang Anh , Uyen Phan Nha , Ngoc Vuong Bao , Chau Le Thi My , Quynh Van Xuan , Hanh Nguyen Ho Hong , Thuong Nguyen Thuy Thuong , Diem Le Thi , Hanh Bui Thi Bich , Hang Vu Thi Ty , Oanh Pham Kieu Nguyet , Fischer Roman , Phu Nguyen Hoan , Nghia Ho Dang Trung , Chau Nguyen Van Vinh , Hoa Ngo Thi , Kessler Benedikt M. , Thwaites Guy , Tan Le Van
Published: January 2020

Background

Central nervous system (CNS) infections are common causes of morbidity and mortality worldwide. Rapid, accurate identification of the likely cause is essential for clinical management and the early initiation of antimicrobial therapy, which potentially improves clinical outcome.

Methods

We applied liquid chromatography tandem mass-spectrometry on 45 cerebrospinal fluid (CSF) samples from a cohort of adults with/without CNS infections to discover potential diagnostic protein biomarkers. We then validated the diagnostic performance of a selected biomarker candidate in an independent cohort of 364 consecutively treated adults with CNS infections admitted to a referral hospital in southern Vietnam.

Results

In the discovery cohort, we identified lipocalin 2 (LCN2) as a potential biomarker of bacterial meningitis. The analysis of the validation cohort showed that LCN2 could discriminate bacterial meningitis from other CNS infections, including tuberculous meningitis, cryptococcal meningitis and viral/antibody-mediated encephalitis (sensitivity: 0.88 (95% confident interval (CI): 0.77–0.94), specificity: 0.91 (95%CI: 0.88–0.94) and diagnostic odd ratio: 73.8 (95%CI: 31.8–171.4)). LCN2 outperformed other CSF markers (leukocytes, glucose, protein and lactate) commonly used in routine care worldwide. The combination of LCN2 and these four routine CSF markers resulted in the highest diagnostic performance for bacterial meningitis (area under receiver-operating-characteristic-curve 0.96; 95%CI: 0.93–0.99).

Conclusions

Our results suggest that LCN2 is a sensitive and specific biomarker for discriminating bacterial meningitis from a broad spectrum of CNS infections. A prospective study is needed to further assess the diagnostic utility of LCN2 in the diagnosis and management of CNS infections.
Topographic organization of the human subcortex unveiled with functional connectivity gradients
Authors: Tian Ye , Margulies Daniel S. , Breakspear Michael , Zalesky Andrew
Published: January 2020

Understanding the topographic organization of the human brain remains a major goal in neuroscience. Brain atlases are fundamental to this goal, yet many contemporary human atlases cover only the cerebral cortex, leaving the subcortex aterra incognita. We revealed the complex topographic organization of the human subcortex by disambiguating smooth connectivity gradients from discrete areal boundaries in resting-state fMRI data acquired from more than 1000 healthy adults. This unveiled four scales of subcortical organization, recapitulating well-known anatomical nuclei at the coarsest scale and delineating 27 new bilateral regions at the finest. Ultra-high field strength fMRI corroborated and extended this organizational structure, enabling delineation of finer subdivisions of hippocampus and amygdala, while task-evoked fMRI revealed a subtle reorganization of subcortical topography in response to changing cognitive demands. A new subcortical atlas was delineated, personalized to account for individual connectivity differences and utilized to uncover reproducible relationships between subcortical connectivity and individual variation in human behaviors. Linking cortical networks to subcortical regions recapitulated a task-positive to task-negative organizational axis. The new atlas enables holistic connectome mapping and characterization of cortico-subcortical connectivity.
Collective decision making by rational agents with differing preferences
Authors: Mann Richard P.
Published: January 2020

Collective decisions can emerge from individual-level interactions between members of a group. These interactions are often seen as social feedback rules, whereby individuals copy the decisions they observe others making, creating a coherent group decision. The benefit of these behavioural rules to the individual agent can be understood as a transfer of information, whereby a focal individual learns about the world by gaining access to the information possessed by others. Previous studies have analysed this exchange of information by assuming that all agents share common goals. While differences in information and differences in preferences have often been conflated, little is known about how differences between agents’ underlying preferences affects the use and efficacy of social information. In this paper I develop a model of social information use by rational agents with differing preferences, and demonstrate that the resulting collective behaviour is strongly dependent on the structure of preference sharing within the group, as well as the quality of information in the environment. In particular, I show that strong social responses are expected by individuals that are habituated to noisy, uncertain environments where private information about the world is relatively weak. Furthermore, by investigating heterogeneous group structures I demonstrate a potential influence of cryptic minority subgroups that may illuminate the empirical link between personality and leadership.
Tidal volume and respiration phase modulate cortico-muscular communication
Authors: Kluger Daniel S. , Gross Joachim
Published: January 2020

Recent studies in animals have convincingly demonstrated that respiration cyclically modulates oscillatory neural activity across diverse brain areas. To what extent this generalises to humans in a way that is relevant for behaviour is yet unclear. We used magnetoencephalography (MEG) to assess the potential influence of tidal volume and respiration phase on the human motor system. We obtained simultaneous recordings of brain activity, muscle activity, and respiration while participants performed an isometric contraction task. We used corticomuscular coherence as a measure of efficient long-range cortico-peripheral communication.

We found coherence within the beta range over sensorimotor cortex to be reduced during voluntary deep compared to involuntary normal breathing. Moreover, beta coherence was found to be cyclically modulated by respiration phase in both conditions. Overall, these results demonstrate how respiratory rhythms actively influence brain oscillations in an effort to synchronise neural activity for the sake of computational efficiency. Intriguing questions remain with regard to the shape of these modulatory processes and how they influence perception, cognition, and behaviour.
Green tea infusion aggravates nutritional status of the juvenile untreated STZ-induced type 1 diabetic rat
Authors: Ladeira Luiz Carlos Maia , dos Santos Eliziária Cardoso , Mendes Bruno Ferreira , Gutierrez Eliana Alviarez , Santos Cynthia Fernandes Ferreira , de Souza Fernanda Batista , Machado-Neves Mariana , Maldonado Izabel Regina dos Santos Costa
Published: January 2020

We have described for the first time the potential harmful effects of green tea on the metabolism and body composition of untreated juvenile experimental type 1 diabetic rats. The treatment containing 19.38% of epigallocatechin-3-gallate, its main catechin, increased blood glucose and water intake. It also increased oxygen consumption, enhanced energy expenditure and led to a lipid oxidation tendency in diabetic animals, which worsened the development of body fat in a way significantly more aggravated than diabetes alone. Taken together, our findings indicate that green tea treatment, when provided to juvenile diabetics, increases glycaemia, changes the body composition by reducing fat content and increases oxygen consumption, besides affecting energy expenditure. Therefore, the nutritional status of the juvenile type 1 diabetic rat is aggravated.
Molecular Choreography of Acute Exercise
Authors: Contrepois Kévin , Wu Si , Moneghetti Kegan J , Hornburg Daniel , Ahadi Sara , Tsai Ming-Shian , Metwally Ahmed A , Wei Eric , Lee-McMullen Brittany , Quijada Jeniffer V , Chen Songjie , Christle Jeffrey W , Ellenberger Mathew , Balliu Brunilda , Taylor Shalina , Durrant Matthew , Knowles David A , Choudhry Hany , Ashland Melanie , Bahmani Amir , Enslen Brooke , Amsallem Myriam , Kobayashi Yukari , Avina Monika , Perelman Dalia , Rose Sophia Miryam Schüssler-Fiorenza , Zhou Wenyu , Ashley Euan A , Montgomery Stephen B , Chaib Hassan , Haddad Francois , Snyder Michael P.
Published: January 2020

Exercise testing is routinely used in clinical practice to assess fitness - a strong predictor of survival - as well as causes of exercise limitations. While these studies often focus on cardiopulmonary response and selected molecular pathways, the dynamic system-wide molecular response to exercise has not been fully characterized. We performed a longitudinal multi-omic profiling of plasma and peripheral blood mononuclear cells including transcriptome, immunome, proteome, metabolome and lipidome in 36 well-characterized volunteers before and after a controlled bout of acute exercise (2, 15, 30 min and 1 hour in recovery). Integrative analysis revealed an orchestrated choreography of biological processes across key tissues. Most of these processes were dampened in insulin resistant participants. Finally, we discovered biological pathways involved in exercise capacity and developed prediction models revealing potential resting blood-based biomarkers of fitness.
A multi-phase flux balance model reveals flexibility of guard cell central carbon metabolism
Authors: Tan Joshua XL , Cheung C. Y. Maurice
Published: January 2020

Experimental research in guard cell metabolism has revealed the roles of the accumulation of various metabolites in guard cell function, but a comprehensive understanding of their metabolism over the diel cycle is still incomplete, given the limitations of current experimental methods. In this study, we constructed a four-phase flux balance model of guard cell metabolism to investigate the changes in guard cell metabolism over the diel cycle, including the day and night and stomata opening and closing. Our model demonstrated the metabolic flexibility in guard cells, showing that multiple metabolic processes can contribute to the synthesis and metabolism of malate and sucrose as osmolytes during stomatal opening and closing. We showed that guard cells can adapt to varying light availability and sucrose uptake from the apoplast during the day by operating in a mixotrophic mode with a switch between sucrose synthesis via the Calvin-Benson cycle and sucrose degradation via the oxidative pentose phosphate pathway. During stomatal opening, our model predicted an alternative flux mode of the Calvin-Benson cycle with all dephosphorylating steps diverted to diphosphate—fructose-6-phosphate 1-phosphotransferase to produce PPi, which is used to pump protons across the tonoplast for the accumulation of osmolytes. An analysis of the energetics of the use of different osmolytes in guard cells showed that malate and Cl-are similarly efficient as the counterion of K+during stomatal opening.

Significance statement

This work presents the first four-phase metabolic model for predicting guard cell metabolism over the diel cycle, which predicted an alternative flux model of the Calvin-Benson cycle that maximises the production of PPiduring stomatal opening. While multiple metabolic processes were shown be important in synthesising and metabolising osmolytes in guard cells of different experimental systems, our model demonstrated that these processes can operate simultaneously and at different rates depending on conditions.
Taking extreme measures: A quantitative study of multiple stress interactions at the limits of life
Authors: Cane Rosie , Cockell Charles
Published: January 2020

Environments exposed to simultaneously occurring extremes are prevalent in the natural world, yet analysis of such settings tends to focus on the effect of single environmental stresses. In this study, quantitative multiplicative and minimising models previously used to study nutrient limitation were applied to the growth of the hydrothermal vent-dwelling organismHalomonas hydrothermaliswhen subjected to combined nutrient limitation and NaCl-salt stress. Results showed an interactive effect from both salt and nutrient stresses under optimal conditions. However, the fit became more non-interactive as salinity is increased; at which point NaCl-salt had a more dominating effect on growth than inorganic phosphate (Pi). We discuss biochemical hypotheses to explain these data. This work shows that models developed to understand nutrient limitation can be used to quantify and separate the contributions of stresses under other physical and chemical extremes, such as extreme salinity, and facilitate the development of biochemical hypotheses of how extremes may be influencing cell physiology.

Importance

Very few environments in the natural world are exposed to just one extreme or stress at a time. To understand life’s ability to survive in multiple-extreme environments, we must be able to quantify how different extremes interact. Using methods developed for the study of multiple nutrient limitation, this study uses kinetic growth models to investigate at the effect of extreme environments on bacterial growth. Results show that closer to the extremes of life, individual stresses dominate growth; whereas under optimal conditions there is a multiplicative effect from both salt and nutrient stresses. This approach offers a new way to quantify and potentially understand and develop hypotheses for how life operates under multiple extremes.
Adaptive repulsion of long-term memory representations is triggered by event similarity
Authors: Chanales Avi J. H. , Tremblay-McGaw Alexandra G. , Kuhl Brice A.
Published: January 2020

We tested whether similarity between events triggers an adaptive repulsion of long-term memories. Subjects completed an associative learning task in which objects were paired with faces. Critically, the objects consisted of pairs that were identical except for their color values, which were parametrically varied in order to manipulate interference. Performance on associative memory tests confirmed that color similarity robustly influenced interference. Separate tests of color memory showed that high similarity triggered a repulsion of long-term memories, wherein remembered colors were biased away from colors of competing objects. This repulsion effect was replicated across three experiments. In a fourth experiment, the repulsion effect was fully eliminated when task demands promoted integration, instead of discrimination, of similar memories. Finally, we show that repulsion of color memory was highly adaptive: greater repulsion was associated with less memory interference. These findings reveal that similarity between events triggers adaptive distortions in how events are remembered.

SUPPLEMENTARY INFORMATION

Three supplementary figures are included.
Myofiber stretch induces tensile and shear deformation of muscle stem cells in their native niche
Authors: Haroon Mohammad , Klein-Nulend Jenneke , Bakker Astrid D. , Jin Jianfeng , Offringa Carla , Grand Fabien Le , Giordani Lorenzo , Liu Karen J. , Knight Robert D. , Jaspers Richard T.
Published: January 2020

Background

Muscle stem cells (MuSCs) are requisite for skeletal muscle regeneration and homeostasis. Proper functioning of MuSCs, including activation, proliferation, and fate decision, is determined by an orchestrated series of events and communication between MuSCs and their niche consisting of the host myofiber and neighbouring cells. A multitude of biochemical stimuli are known to regulate fate and function of MuSCs. However, in addition to biochemical factors, it is conceivable that MuSCs residing between basal lamina and sarcolemma of myofibers are subjected to mechanical forces during muscle stretch-shortening cycles due to myofascial connections between MuSCs and myofibers. MuSCs have been shown to respond to mechanical forcesin vitrobut it remains to be proven whether physical forces are also exerted on MuSCs in their native niche and whether they contribute to the functioning and fate of MuSCs.

Methods

MuSCs deformation in their native niche resulting from mechanical loading ofex vivomyofiber bundles were visualized utilizingmT/mGdouble-fluorescent Cre-reporter mouse and multiphoton microscopy. MuSCs were subjected to 1 hour pulsating fluid shear stress with a peak shear stress rate of 8.8 Pa/s. After treatment, nitric oxide and mRNA expression levels of genes involved in regulation of MuSC proliferation and differentiation were determined.

Results

Ex vivostretching of extensor digitorum longus and soleus myofiber bundles caused compression as well as tensile and shear deformation of MuSCs in their niche. MuSCs responded to pulsating fluid shear stressin vitrowith increased nitric oxide production and an upward trend iniNOSmRNA levels, whilenNOSexpression was unaltered. Pulsating fluid shear stress enhanced gene expression ofc-Fos, Cdk4, andIL-6, while expression ofWnt1, MyoD, Myog, Wnt5a, COX2, Rspo1, Vangl2, Wnt10b, andMGFremained unchanged.

Conclusions

We conclude that MuSCs in their native niche are subjected to force-induced deformations due to myofiber stretch-shortening. Moreover, MuSCs are mechanoresponsive as evident by pulsating fluid shear stress-mediated expression of factors by MuSCs known to promote proliferation.
Condensin I subunit Cap-G is essential for proper gene expression during the maturation of post-mitotic neurons
Authors: Hassan Amira , Rodriguez Pablo Araguas , Heidmann Stefan K. , Walmsley Emma L. , Aughey Gabriel N. , Southall Tony D.
Published: January 2020

The condensin complex is essential for mitotic chromosome assembly and segregation during cell divisions, however, little is known about its function in post-mitotic, differentiated cells. Here we report a novel role for the condensin I subunit Cap-G inDrosophilaneurons. We show that, despite not requiring condensin for mitotic chromosome compaction, post-mitotic neurons express Cap-G and that knockdown of Cap-G specifically in neurons (from their birth onwards) results in developmental arrest, behavioural defects, and dramatic gene expression changes. These include reduced expression of a subset of neuronal genes and aberrant expression of genes that are not normally expressed in the developing brain. Knockdown of Cap-G in more mature neurons also results in similar phenotypes but to a lesser degree. Furthermore, we see dynamic binding of Cap-G to chromatin at distinct loci in neural stem cells and differentiated neurons. Therefore, Cap-G is essential for proper gene expression in neurons and plays an important role during the early stages of neuronal development.
NLRP3 inflammasome priming and activation are regulated by a novel phosphatidylinositol-dependent mechanism
Authors: Hamilton Claire , Olona Antoni , Leishman Stuart , MacDonald-Ramsahai Kelly , Cockcroft Shamshad , Larrouy-Maumus Gerald , Anand Paras K.
Published: January 2020

Imbalance in lipid homeostasis is associated with discrepancies in immune signalling and is tightly linked to metabolic disorders. The diverse ways in which lipids impact immune signalling, however, remain ambiguous. The phospholipid phosphatidylinositol (PI), which is implicated in numerous immune disorders, is chiefly defined by its phosphorylation status. By contrast, the significance of the two fatty acid chains attached to the PI remains unknown. Here, by employing a mass-spectrometry-based assay, we demonstrate a role for PI acyl group chains in regulating both the priming and activation steps of the NLRP3 inflammasome in mouse macrophages. In response to NLRP3 stimuli, cells deficient in ABC transporter ABCB1, which effluxes lipid derivatives, revealed defective inflammasome activation. Mechanistically,Abcb1-deficiency shifted the total PI configuration exhibiting a reduced ratio of short-chain to long-chain PI-acyl lipids. Consequently,Abcb1-deficiency resulted in rapid degradation of TIRAP, the TLR adaptor protein which binds PI(4,5)-phosphate. Moreover, this accompanied increased NLRP3 phosphorylation at the Ser293 position and blunted inflammasome activation. Exogenously supplementing WT cells with linoleic acid, but not arachidonic acid, reconfigured PI acyl chains. Accordingly, linoleic acid supplementation increased TIRAP degradation, elevated NLRP3 phosphorylation, and abrogated inflammasome activation. Altogether, our study reveals a novel metabolic-inflammatory circuit which contributes to calibrating immune responses.
Predicting transcription factor binding in single cells through deep learning
Authors: Fu Laiyi , Zhang Lihua , Dollinger Emmanuel , Peng Qinke , Nie Qing , Xie Xiaohui
Published: January 2020

Characterizing genome-wide binding profiles of transcription factor (TF) is essential for understanding many biological processes. Although techniques have been developed to assess binding profiles within a population of cells, determining binding profiles at a single cell level remains elusive. Here we report scFAN (Single Cell Factor Analysis Network), a deep learning model that predicts genome-wide TF binding profiles in individual cells. scFAN is pre-trained on genome-wide bulk ATAC-seq, DNA sequence and ChIP-seq data, and utilizes single-cell ATAC-seq to predict TF binding in individual cells. We demonstrate the efficacy of scFAN by studying sequence motifs enriched within predicted binding peaks and investigating the effectiveness of predicted TF peaks for discovering cell types. We develop a new metric “TF activity score” to characterize each cell, and show that the activity scores can reliably capture cell identities. The method allows us to discover and study cellular identities and heterogeneity based on chromatin accessibility profiles.
Correlative Fluorescence- and Electron Microscopy of Whole Breast Cancer Cells Reveals Different Distribution of ErbB2 Dependent on Underlying Actin
Authors: Dahmke Indra Navina , Trampert Patrick , Weinberg Florian , Mostajeran Zahra , Lautenschläger Franziska , de Jonge Niels
Published: January 2020

Epidermal growth factor receptor 2 (ErbB2) is found overexpressed in several cancers, such as gastric, and breast cancer, and is, therefore, an important therapeutic target. ErbB2 plays a central role in cancer cell invasiveness, and is associated with cytoskeletal reorganization. In order to study the spatial correlation of single ErbB2 proteins and actin filaments, we applied correlative fluorescence microscopy, and scanning transmission electron microscopy (STEM) to image specifically labeled SKBR3 breast cancer cells. The breast cancer cells were grown on microchips, transformed to express an actin-green fluorescent protein (GFP) fusion protein, and labeled with quantum dot (QD) nanoparticles attached to specific anti-ErbB2 Affibodies. Fluorescence microscopy was performed to identify cellular regions with spatially correlated actin and ErbB2 expression. For STEM of the intact plasma membrane of whole cells, the cells were fixed and covered with graphene. Spatial distribution patterns of ErbB2 in the actin rich ruffled membrane regions were examined, and compared to adjacent actin-low regions of the same cell, revealing an association of putative signaling active ErbB2 homodimers with actin-rich regions. ErbB2 homodimers were found absent from actin-low membrane regions, as well as after treatment of cells with Cytochalasin D, which breaks up larger actin filaments. In both latter data sets, a significant inter-label distance of 36 nm was identified, possibly indicating an indirect attachment to helical actin filaments via the formation of heterodimers of ErbB2 with epidermal growth factor receptor (EGFR). The possible attachment to actin filaments was further explored by identifying linear QD-chains in actin-rich regions, which also showed an inter-label distance of 36 nm.