bluuebunny/crossref_metadata_2025 huggingface dataset:
Mean-field theory for double-well systems on degree-heterogeneous networks
Authors: Kundu Prosenjit , MacLaren Neil G. , Kori Hiroshi , Masuda Naoki
Published: August 2022

Many complex dynamical systems in the real world, including ecological, climate, financial and power-grid systems, often show critical transitions, or tipping points, in which the system’s dynamics suddenly transit into a qualitatively different state. In mathematical models, tipping points happen as a control parameter gradually changes and crosses a certain threshold. Tipping elements in such systems may interact with each other as a network, and understanding the behaviour of interacting tipping elements is a challenge because of the high dimensionality originating from the network. Here, we develop a degree-based mean-field theory for a prototypical double-well system coupled on a network with the aim of understanding coupled tipping dynamics with a low-dimensional description. The method approximates both the onset of the tipping point and the position of equilibria with a reasonable accuracy. Based on the developed theory and numerical simulations, we also provide evidence for multistage tipping point transitions in networks of double-well systems.
Alarm cues and alarmed conspecifics: neural activity during social learning from different cues in Trinidadian guppies
Authors: Fan Raina , Reader Simon M. , Sakata Jon T.
Published: August 2022

Learning to respond appropriately to novel dangers is often essential to survival and success, but carries risks. Learning about novel threats from others (social learning) can reduce these risks. Many species, including the Trinidadian guppy (
Poecilia reticulata
), respond defensively to both conspecific chemical alarm cues and conspecific anti-predator behaviours, and in other fish such social information can lead to a learned aversion to novel threats. However, relatively little is known about the neural substrates underlying social learning and the degree to which different forms of learning share similar neural mechanisms. Here, we explored the neural substrates mediating social learning of novel threats from two different conspecific cues (i.e. social cue-based threat learning). We first demonstrated that guppies rapidly learn about threats paired with either alarm cues or with conspecific threat responses (demonstration). Then, focusing on acquisition rather than recall, we discovered that phospho-S6 expression, a marker of neural activity, was elevated in guppies during learning from alarm cues in the putative homologue of the mammalian lateral septum and the preoptic area. Surprisingly, these changes in neural activity were not observed in fish learning from conspecific demonstration. Together, these results implicate forebrain areas in social learning about threat but raise the possibility that circuits contribute to such learning in a stimulus-specific manner.
Within-population variability in coral heat tolerance indicates climate adaptation potential
Authors: Humanes Adriana , Lachs Liam , Beauchamp Elizabeth A. , Bythell John C. , Edwards Alasdair J. , Golbuu Yimnang , Martinez Helios M. , Palmowski Paweł , Treumann Achim , van der Steeg Eveline , van Hooidonk Ruben , Guest James R.
Published: August 2022

Coral reefs are facing unprecedented mass bleaching and mortality events due to marine heatwaves and climate change. To avoid extirpation, corals must adapt. Individual variation in heat tolerance and its heritability underpin the potential for coral adaptation. However, the magnitude of heat tolerance variability within coral populations is largely unresolved. We address this knowledge gap by exposing corals from a single reef to an experimental marine heatwave. We found that double the heat stress dosage was required to induce bleaching in the most-tolerant 10%, compared to the least-tolerant 10% of the population. By the end of the heat stress exposure, all of the least-tolerant corals were dead, whereas the most-tolerant remained alive. To contextualize the scale of this result over the coming century, we show that under an ambitious future emissions scenario, such differences in coral heat tolerance thresholds equate to up to 17 years delay until the onset of annual bleaching and mortality conditions. However, this delay is limited to only 10 years under a high emissions scenario. Our results show substantial variability in coral heat tolerance which suggests scope for natural or assisted evolution to limit the impacts of climate change in the short-term. For coral reefs to persist through the coming century, coral adaptation must keep pace with ocean warming, and ambitious emissions reductions must be realized.
A central place foraging seabird flies at right angles to the wind to jointly optimize locomotor and olfactory search efficiency
Authors: Ventura Francesco , Catry Paulo , Dias Maria P. , Breed Greg A. , Folch Arnau , Granadeiro José Pedro
Published: August 2022

To increase the probability of detecting odour plumes, and so increase prey capture success, when winds are stable central place foraging seabirds should fly crosswind to maximize the round-trip distance covered. At present, however, there is no empirical evidence of this theoretical prediction. Here, using an extensive GPS tracking dataset, we investigate, for the first time, the foraging movements of Bulwer's petrels (Bulweria bulwerii) in the persistent North Atlantic trade winds. To test the hypotheses that, in stable winds, petrels use crosswind to maximize both the distance covered and the probability of detecting olfactory cues, we combine state-space models, generalized additive models and Gaussian plume models. Bulwer's petrels had the highest degree of selectivity for crosswinds documented to date, often leading to systematic zig-zag flights. Crosswinds maximized both the distance travelled and the probability of detecting odour plumes integrated across the round-trip (rather than at any given point along the route, which would result in energetically costly return flight). This evidence suggests that petrels plan round-trip flights at departure, integrating expected costs of homeward journeys. Our findings, which are probably true for other seabirds in similar settings, further highlight the critical role of wind in seabird foraging ecology.
Multiple-batch spawning: a risk-spreading strategy disarmed by highly intensive size-selective fishing rate
Authors: Hočevar Sara , Hutchings Jeffrey A. , Kuparinen Anna
Published: August 2022

Can the advantage of risk-managing life-history strategies become a disadvantage under human-induced evolution? Organisms have adapted to the variability and uncertainty of environmental conditions with a vast diversity of life-history strategies. One such evolved strategy is multiple-batch spawning, a spawning strategy common to long-lived fishes that ‘hedge their bets' by distributing the risk to their offspring on a temporal and spatial scale. The fitness benefits of this spawning strategy increase with female body size, the very trait that size-selective fishing targets. By applying an empirically and theoretically motivated eco-evolutionary mechanistic model that was parameterized for Atlantic cod (Gadus morhua), we explored how fishing intensity may alter the life-history traits and fitness of fishes that are multiple-batch spawners. Our main findings are twofold; first, the risk-spreading strategy of multiple-batch spawning is not effective against fisheries selection, because the fisheries selection favours smaller fish with a lower risk-spreading effect; and second, the ecological recovery in population size does not secure evolutionary recovery in the population size structure. The beneficial risk-spreading mechanism of the batch spawning strategy highlights the importance of recovery in the size structure of overfished stocks, from which a full recovery in the population size can follow.
A Phase I, Prospective, Randomized, Open-labeled Study to Evaluate the Safety, Tolerability, and Immunogenicity of Booster Dose with MVC-COV1901 or MVC-COV1901(Beta) SARS-CoV-2 Vaccine in Adults
Authors: Lien Chia En , Liu Ming-Che , Wang Ning-Chi , Liu Luke Tzu-Chi , Wu Chung-Chin , Tang Wei-Hsuan , Lian Wei-Cheng , Huang Kuan-Ying A. , Chen Charles
Published: August 2022

Background

The use of variant-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine as a booster is being evaluated to overcome reduced neutralisation of variants induced by the original SARS-CoV-2 vaccine and waning protection over time.

Methods

This is a phase one, prospective, randomized, and open-labeled trial to study the safety and immunogenicity of a booster dose consisting of a subunit vaccine based on the stabilized prefusion SARS-CoV-2 spike protein, MVC-COV1901 or its Beta version, MVC-COV1901-Beta. One-hundred and seven participants aged ≥18 and <55 years, who received two or three prior doses of MVC-COV1901 vaccines, were enrolled and were to receive a booster dose of either 15 mcg of MVC-COV1901, 15 mcg or 25 mcg of MVC-COV1901-Beta in 1:1:1 ratio. The primary endpoints were the incidences of adverse events and immunogenicity of the booster dose from Visit 2 (the day of the booster) to Visit 5 (four weeks after the booster). Cellular immunity was also investigated with memory B cell (MBC) and T cell assays.

Findings

Adverse reactions after either MVC-COV1901 or MVC-COV1901-Beta booster doses after two or three doses of MVC-COV1901 were comparable and mostly mild and transient. At four weeks after the booster dose, participants with two prior doses of MVC-COV1901 exhibited numerically higher levels of neutralising antibodies against SARS-CoV-2 or Beta variant than participants with three prior doses of MVC-COV1901 regardless of the type of booster used. However, compared to 15 mcg of MVC-COV1901, 25 mcg of MVC-COV1901-Beta significantly improved neutralising antibody titre against Beta variant and BA.4/BA.5 Omicron variant pseudoviruses. The booster dose also significantly increased the proportion of spike-specific MBCs, including those of Beta and Omicron variants.

Interpretation

MVC-COV1901-Beta can be effectively used as a booster dose against SARS-CoV-2, including the circulating BA.4/BA.5 Omicron variant.

Funding

Medigen Vaccine Biologics Corporation
S1 represents multisensory contexts and somatotopic locations within and outside the bounds of the cortical homunculus
Authors: Rosenthal Isabelle A. , Bashford Luke , Kellis Spencer , Pejsa Kelsie , Lee Brian , Liu Charles , Andersen Richard A.
Published: August 2022

The responsiveness of primary somatosensory cortex (S1) to physical tactile stimuli is well documented but the extent to which it is modulated by vision is unresolved. Additionally, recent literature has suggested that tactile events are represented in S1 in a more complex, generalized manner than its long-established topographic organization. To better characterize S1 function, neural activity was recorded from a tetraplegic patient implanted with microelectrode arrays in S1 during 1s stroking touches to the forearm (evoking numb sensation) or finger (naturalistic sensation). Touch conditions included visually observed first person physical touches, physical touches without vision, and visual touches without physical contact which occurred either to a third person, an inanimate object, or the patient’s own body in virtual reality. Two major findings emerged from this dataset. The first was that vision strongly modulates S1 activity, but only if there is a physical element to the touch, suggesting that passive observation of touches is not sufficient to recruit S1 neurons. The second was that despite the location of the recording arrays in a putative arm area of S1, neural activity was able to represent both arm and finger touches in physical touch conditions. Arm touches were encoded more strongly and specifically, supporting the idea that S1 encodes tactile events primarily through its topographic organization, as well as in a more general manner encompassing larger areas of the body.
The action of antimicrobial peptide LL37 is slow but effective against non-growing Escherichia coli cells
Authors: Mohammadi Salimeh , Taheri-Araghi Sattar
Published: August 2022

Antimicrobial peptides (AMPs) are amino-acid based antibiotics that primarily attack bacteria by perturbing their membranes. It has long been suggested that AMPs are effective against non-growing cells that tolerate conventional antibiotics. Despite recent advances in quantifying the action of AMPs at the single-cell level, we still do not have a clear picture of how this action is correlated with the physiology of target cells. Here we take complementary approaches, from single-cell and population-level experiments, to investigate the efficacy of human AMP LL37 against Escherichia coli cells at different growth phases. We first analyze time-lapse, single-cell data of the action of LL37 peptides on exponentially growing cells, which reveals that they act faster on long, dividing cells than on small, newborn cells. Next, we test the consequence of this cell-age dependence on the efficacy of LL37 against non-growing E. coli cells in stationary phase. We observe a consistent trend that the action of LL37 is, on average, ≈5.0 minutes slower on non-growing cells as compared to that on exponentially growing cells. However, this difference in the rate of action is not reflected in the minimum bactericidal concentration (MBC) of LL37 peptides. Contrary to our expectation, the MBC measured for non-growing cells is smaller than that for exponentially growing cells, indicating that over a long period of time the LL37 peptides are more potent against non-growing cells.

Author summary

Antibiotic treatments can fail due to regrowth of a bacterial subpopulation that start proliferation after the treatment is over. The regrowth is often from non-growing, dormant cells that persist the action of antibiotics without being resistant. In this work, we demonstrate that human antimicrobial peptide LL37 is potent against non-growing Escherichia coli cells.
Syntaxin 3-SPI 2 dependent cross-talk facilitates the division of Salmonella containing vacuole (SCV)
Authors: Chatterjee Ritika , Mehta Nishi , Gangi Setty Subba Rao , Chakravortty Dipshikha
Published: August 2022

Intracellular membrane fusion is mediated by membrane-bridging complexes of soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). SNARE proteins are one of the key players in the vesicular transport. Several reports shed light on intracellular bacteria modulating host SNARE machinery to establish infection successfully. The critical SNAREs in macrophages responsible for phagosome maturation are Syntaxin 3 (STX3) and Syntaxin 4 (STX4). Salmonella actively modulates its vacuole membrane composition to escape lysosomal fusion. A report showed that Salmonella containing vacuole (SCV) harbors recycling endosomal SNARE Syntaxin 12 (STX12). However, the role of host SNAREs in SCV biogenesis and pathogenesis is unclear. Upon knockdown of STX3, we have observed a reduction in bacterial proliferation and is restored upon the overexpression of STX3. Post infected live-cell imaging of cells showed STX3 localises to the SCV membranes and thus might help in fusion of SCV with intracellular vesicles to acquire membrane for its division. We also found this interaction abrogated when we infected with SPI-2 encoded T3SS apparatus mutant (STM ΔssaV) but not with SPI-1 encoded T3SS (STM ΔinvC). These observations were also consistent in mice model of Salmonella infection. Together, these results shed a light on the effector molecules secreted through SPI-2 encoded by T3SS possibly involved in interaction with host SNARE STX3, which is essential to maintain the division of Salmonella in SCV and maintenance the principle single bacterium per vacuole.

Synopsis

Salmonella Typhimurium infection in murine macrophage leads to upregulation of host Syntaxin 3 both at transcript and protein levels at late stage of infection. Syntaxin 3 cross-talk with Salmonella containing vacuoles (SCVs) is essential for establishment of replicative niche in host macrophages. The cross-talk between STX3 and SCVs is Salmonella pathogenicity island 2 (SPI-2) dependent and is consistent in mice model of Salmonella Typhimurium infection.
Hormone-sleep interactions predict cerebellar connectivity and behavior in aging females
Authors: Ballard Hannah K. , Jackson T. Bryan , Hicks Tracey H. , Cox Sydney J. , Miller Abigail C. , Maldonado Ted , Bernard Jessica A.
Published: August 2022

Sex hormones fluctuate over the course of the female lifespan and are associated with brain health and cognition. Thus, hormonal changes throughout female adulthood, and with menopause in particular, may contribute to sex differences in brain function and behavior. Further, sex hormones have been correlated with sleep patterns, which also exhibit sex-specific impacts on the brain and behavior. As such, the interplay between hormones and sleep may contribute to late-life brain and behavioral outcomes in females. Here, in a sample of healthy middle-aged and older females (n = 79, ages 35-86), we evaluated the effect of hormone-sleep interactions on cognitive and motor performance as well as cerebellar-frontal network connectivity. Salivary samples were used to measure 17β-estradiol, progesterone, and testosterone levels while overnight actigraphy was used to quantify sleep patterns. Cognitive behavior was quantified using the composite average of standardized scores on memory, processing speed, and attentional tasks, and motor behavior was indexed with sequence learning, balance, and dexterity tasks. We analyzed resting-state connectivity correlations for two specific cerebellar-frontal networks: a Crus I to dorsolateral prefrontal cortex network and a Lobule V to primary motor cortex network. In sum, results indicate that sex hormones and sleep patterns interact to predict cerebellar-frontal connectivity and behavior in aging females. Together, the current findings further highlight the potential consequences of endocrine aging in females and suggest that the link between sex hormones and sleep patterns may contribute, in part, to divergent outcomes between sexes in advanced age.

Highlights

Hormone-sleep interactions influence resting-state cerebellar-frontal connectivity

Cognitive and motor behavior are impacted by hormone-sleep relationships

Sex hormones and sleep patterns may contribute to aging outcomes in females
Geometric Effects Position Renal Vesicles During Kidney Development
Authors: Mederacke Malte , Conrad Lisa , Doumpas Nikolaos , Vetter Roman , Iber Dagmar
Published: August 2022

During kidney development, reciprocal signalling between the epithelium and the mesenchyme coordinates nephrogenesis with branching morphogenesis of the collecting ducts. The mechanism that positions the renal vesicles, and thus the nephrons, relative to the branching ureteric buds has remained elusive. By combining computational modelling and experiments, we show that geometric effects concentrate the key regulator, WNT9b, at the junctions between parent and daughter branches where renal vesicles emerge, even when uniformly expressed in the ureteric epithelium. This curvature effect might be a general paradigm to create non-uniform signalling in development.
Molecular mechanism underlying desensitization of the proton-activated chloride channel PAC
Authors: Osei-Owusu James , Ruan Zheng , Matasic Daniel S. , Lü Wei , Qiu Zhaozhu
Published: August 2022

Desensitization is a common property of membrane receptors, including ion channels. The newly identified proton-activated chloride (PAC) channel plays an important role in regulating the pH and size of organelles in the endocytic pathway, and is also involved in acid-induced cell death. However, how the PAC channel desensitizes is largely unknown. Here, we show by patch-clamp electrophysiological studies that PAC undergoes pH-dependent desensitization upon prolonged acid exposure. Through structure-guided and comprehensive mutagenesis, we identified several residues critical for PAC desensitization, including histidine (H) 98, glutamic acid (E) 94, and aspartic acid (D) 91 at the extracellular extension of the transmembrane helix 1 (TM1), as well as E107, D109, and E250 at the extracellular domain (ECD)–transmembrane domain (TMD) interface. Structural analysis and molecular dynamic simulations revealed extensive interactions between residues at the TM1 extension and those at the ECD–TMD interface. These interactions likely facilitate PAC desensitization by stabilizing the desensitized conformation of TM1, which undergoes a characteristic rotational movement from the resting and activated states to the desensitized state. Our studies establish a new paradigm of channel desensitization in this ubiquitously expressed ion channel and pave the way for future investigation of its relevance in cellular physiology and disease.
Evidence for coordinated evolution at amino acid sites of SARS-CoV-2 spike
Authors: Neverov A.D. , Fedonin G.G. , Popova A.V. , Bykova D.I. , Bazykin G.A.
Published: August 2022

It is currently unclear why SARS-Cov-2 has adapted in a stepwise manner, with multiple beneficial mutations accumulating in a rapid succession at the origins of VOCs. Here, we searched for coordinated evolution of amino acid sites in the spike protein of SARS-Cov-2. We searched for concordantly evolving site pairs (CSP) for which changes at one site were rapidly followed by changes at the other site in the same lineage. We detected 46 sites which formed 45 CSP. Sites in CSP were closer to each other in the protein structure than random pairs, indicating that concordant evolution has a functional basis. Notably, site pairs carrying lineage defining mutations of the four VOCs that circulated before May 2021 are enriched in CSP, indicating that the origin of these VOCs could have been facilitated by positive epistasis. Additionally, we detected four discordantly evolving pairs of sites where mutations at one site unexpectedly rarely occurred on the background of a specific allele at another site, namely on the wild-type D at site 614 (for two pairs) or at derived Y in the site 501 (for two other pairs). Our findings hint that positive epistasis between accumulating mutations could have delayed the assembly of advantageous combinations of mutations comprising at least some of the VOCs.
Signature of random connectivity in the distribution of neuronal tuning curves
Authors: Orhan Pierre , Duszkiewicz Adrian , Peyrache Adrien
Published: August 2022

Understanding the relationship between circuit properties and the organization of neuronal population activity is a fundamental question in neuroscience. The fine tuning of neuronal activity to specific values of environmental or internal features are canonical examples of how information is encoded in the brain, possibly resulting from precisely organized inputs. Yet, in the cortex, finely tuned neurons are often recorded together with neurons whose tuning is much less specific, for example those of inhibitory neurons, and the connectivity statistics accounting for the overall distribution of tuning curves is unclear. Here, using recordings in the mouse head-direction system, we first show both in simulation and analytically that random linear combinations of ideal finely tuned inputs reproduce the distribution of fast-spiking neuron tuning curves, a class of neurons believed to operate in the linear regime. This transformation preserves, on the population level, the singular spectrum of the input tuning curves but the relative power of each singular component is independently distributed in each output cell, leading to a distribution ranging from uni-modal to symmetrically tuned cells. We then generalize the model to a non-linear transformation of the inputs, combined with background inhibition. Using recordings from input neurons in the thalamus, where tuning curves are near-ideal, the model reproduces for various levels of inhibition the entire range of observed neuronal responses in the cortex, from precisely and narrowly tuned neurons to multipeak excitatory cells, as well as symmetrical tuning curves of inhibitory neurons. We replicate these findings in a dataset of hippocampal recordings. In conclusion, the full distribution of tuning curves is a signature of input connectivity statistics, which, for fast-spiking neurons and thalamocortical circuits, is likely to be random rather than specifically organized.
Direct measurement of appressorium turgor using a molecular mechanosensor in the rice blast fungus Magnaporthe oryzae
Authors: Ryder Lauren S. , Lopez Sergio G. , Michels Lucile , Eseola Alice B. , Sprakel Joris , Ma Weibin , Talbot Nicholas J.
Published: August 2022

Many plant pathogenic fungi forcibly enter their hosts to cause disease. The rice blast fungus Magnaporthe oryzae, for example, infects plants using a specialised infection cell called an appressorium, which generates enormous turgor to drive a rigid penetration peg through the rice leaf cuticle. While these vast internal pressures are a critical weapon in fungal host penetration, they have remained very challenging to probe directly during host invasion, leaving our understanding of these extreme cellular mechanics incomplete. Here, we combine Fluorescence Lifetime Imaging (FLIM) with a membrane-targeting molecular mechanoprobe to quantify changes in membrane tension as a direct proxy for appressorial turgor in M. oryzae. We report that mature melanin-pigmented M. oryzae appressoria display a heterogeneous low fluorescence lifetime and high membrane tension, consistent with enormous turgor. These extreme pressures lead to large-scale spatial heterogeneities in membrane mechanics, much greater than observed in any other cell type previously, highlighting the extreme mechanics of turgor-driven appressorium-mediated plant infection. By contrast, appressoria of non-pathogenic melanin-deficient mutants, alb1 and buf1, or immature non-melanised appressoria, exhibit high fluorescence lifetime, consistent with low membrane tension and turgor, that remain spatially homogeneous. To evaluate the method, we investigated turgor dynamics in a range of mutants impaired in appressorium function. We show that the turgor sensor kinase mutant Δsln1, recently proposed to generate excess appressorium turgor, displayed a significantly higher membrane tension compared to an isogenic wild type M. oryzae strain. This non-invasive, live cell imaging technique allows direct quantification and visualization of the enormous turgor pressures deployed during pathogen infection.
Alveolar epithelial progenitor cells drive lung regeneration via dynamic changes in chromatin topology modulated by lineage-specific Nkx2-1 activity
Authors: Toth Andrea , Kannan Paranthaman , Snowball John , Kofron J. Matthew , Wayman Joseph A. , Bridges James P. , Miraldi Emily R. , Swarr Daniel , Zacharias William J.
Published: August 2022

Lung epithelial regeneration after acute injury requires coordination of extensive cellular and molecular processes controlling proliferation and differentiation of specialized alveolar cells to pattern the morphologically complex alveolar gas exchange surface. During regeneration, specialized Wnt-responsive alveolar epithelial progenitor (AEP) cells, a subset of alveolar type 2 (AT2) cells, proliferate and transition to alveolar type 1 (AT1) cells, though the precise molecular and epigenetic determinants of these processes remain unclear. Here, we report a refined primary murine alveolar organoid assay which recapitulates critical aspects of in vivo regeneration, providing a tractable model to dissect these regenerative processes. Clonal expansion of single AEPs generate complex alveolar organoids with extensive structural maturation and organization. These organoids contain properly patterned AT1 and AT2 cells surrounding numerous alveolar-like cavities with minimal structural contribution from mesenchymal cells, implying extensive cell autonomous regenerative function encoded in adult AEPs. Leveraging a time series of paired scRNAseq and scATACseq, we identified the AEP state at single cell resolution and described two distinct AEP to AT1 intermediate states: a widely reported Krt8+ transitional state defined by cell stress markers and a second state defined by differential activation of signaling pathways mediating AT1 cell differentiation. Transcriptional regulatory network (TRN) analysis demonstrated that these AT1 transition states were driven by distinct regulatory networks controlled in part by differential activity of Nkx2-1. Genetic ablation of Nkx2-1 in AEP-derived organoids was sufficient to cause transition to a proliferative stressed Krt8+ state characterized by disorganized, uncontrolled growth. Finally, AEP-specific deletion of Nkx2-1 in adult mice led to rapid loss of AEP state, clonal expansion, and disorganization of alveolar structure, implying a continuous requirement for Nkx2-1 in maintenance and function of adult lung progenitors. Together, these data provide new insight into cellular hierarchies in lung regeneration and implicate dynamic epigenetic maintenance via lineage transcription factors as central to control of facultative progenitor activity in AEPs.
Negative allosteric modulation of the glucagon receptor by RAMP2
Authors: Kumar Kaavya Krishna , O’Brien Evan S. , Habrian Chris H. , Latorraca Naomi R. , Wang Haoqing , Tuneew Inga , Montabana Elizabeth , Marqusee Susan , Hilger Daniel , Isacoff Ehud Y. , Mathiesen Jesper Mosolff , Kobilka Brian K.
Published: August 2022

Receptor activity-modifying proteins (RAMPs) modulate the activity of many Family B heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs). The glucagon receptor (GCGR), a Family B GPCR responsible for maintenance of proper blood sugar levels, interacts with RAMP2, though the purpose and consequence of this interaction is poorly understood. Using a series of biochemical and cell-based assays, we show that RAMP2 interacts with and broadly inhibits GCGR-induced downstream signaling. Hydrogen-deuterium exchange monitored by mass spectrometry (HDX-MS) demonstrates that RAMP2 enhances local flexibility in select locations in and near the receptor extracellular domain (ECD) as well as at a key region in the 6th transmembrane helix, while single-molecule fluorescence resonance energy transfer (smFRET) experiments show that this RAMP2-induced ECD disorder results in inhibition of active and intermediate states of the intracellular face of the receptor. Using cryo-electron microscopy (cryoEM), we determined the structure of the GCGR-Gs complex at 2.9 Å resolution in the presence of RAMP2. RAMP2 apparently does not interact with GCGR in an ordered manner, yet the ECD of GCGR is indeed largely disordered in the presence of RAMP2. This disorder is accompanied by rearrangements of several key areas of the receptor, resulting in the formation of a likely unproductive complex. Together, our studies suggest that RAMP2 acts as a negative allosteric modulator of GCGR by enhancing conformational sampling of the ECD.
Bis(nitrato-κO)(1,4,8,11-tetraazacyclotetradecane-κ4
N)zinc(II) methanol monosolvate
Authors: Ichimaru Yoshimi , Kato Koichi , Kurihara Masaaki , Jin Wanchun , Koike Tohru , Kurosaki Hiromasa
Published: August 2022

The two ZnII atoms in the crystal structure of the title complex, [Zn(NO3)2(C10H24N4)]·CH3OH, have a distorted octahedral coordination sphere, defined by 1,4,8,11-tetraazacyclotetradecane (cyclam) N atoms in the equatorial plane and nitrate O atoms in the axial sites. The conformation of the cyclam is trans-III (R, R, S, S), which is typical for metal–cyclam complexes. Nitrate anions are involved in intra- and intermolecular hydrogen bonding with the N–H groups of the ZnII–cyclam unit. Together with the methanol solvent molecule, the hydrogen-bonding network connects the ZnII–cyclam units into ribbons running parallel to the a axis.
Effects of the manager's goal orientation on frontline service employees' service–sales ambidexterity conversion
Authors: Yen HsiuJu Rebecca , Hu Paul Jen-Hwa , Liao Yi-Chun , Wu Jiun-Yu
Published: August 2022

Purpose

Ambidextrous frontline service employees (FSEs), capable of delivering quality services and carrying out sales responsibilities too, are crucial to service firms. This study seeks to extend ambidexterity research by examining how a manager's goal orientation could influence FSEs' ambidextrous conversion. The authors draw on achievement goal theory and conceptualize a link between a manager's achievement goal orientation and employees' service–sales ambidexterity (SSA). The authors then apply conservation of resources theory to complement this high-level conceptualization, hypothesize mediating roles of important resources that can facilitate employees' SSA, and the authors test them empirically.

Design/methodology/approach

This study adopts a questionnaire survey design. The empirical test relies on multilevel path analyses of dyadic data from 341 FSEs and 39 managers of a major logistics service company in Taiwan.

Findings

Managers with a prominent learning goal orientation can facilitate and foster FSEs' SSA through developmental inducements and change-related self-efficacy, two important resources for their ambidextrous conversion. Managers with a strong performance-avoid goal orientation instead might hinder employees' SSA conversion, due to a negative impact on developmental inducements. Furthermore, SSA enhances FSEs' service delivery value and sales performance.

Originality/value

By analyzing and empirically testing the influence pathways of essential resources perceived by FSEs, which channel the effects of a manager's goal orientation to employees' SSA conversion, this study offers insights about how managers can support and foster FSEs' service–sales ambidextrous conversion.
Rates and physicochemical drivers of microbial anabolic activity in deep‐sea sediments and implications for deep time
Authors: Meyer Nicolette R. , Parada Alma E. , Kapili Bennett J. , Fortney Julian L. , Dekas Anne E.
Published: August 2022

Sediment microorganisms influence global climate and redox by altering rates of organic carbon burial. However, the activity and ecology of benthic microorganisms are poorly characterized, especially in the deep sea. Here, we conducted nearly 300 stable isotope tracer experiments in sediments from the Pacific and Atlantic oceans (100–4500 m water depth) to determine the rates, spatial distribution, and physicochemical controls on microbial total anabolic activity, nitrogen fixation, and inorganic/organic carbon uptake. Using correlative and manipulative approaches, we find that total activity is limited primarily by organic carbon and/or energy. Activity correlates significantly with distance from shore, sediment depth, C:N ratios, and overlying chlorophyll concentrations and is stimulated by carbon but not nitrogen additions. Consistent with this, nitrogen fixation was undetected despite relatively low concentrations of porewater ammonium and the previous detection of nifH genes. Inorganic carbon uptake accounted for 7%–55% of carbon assimilation per sample (median 21%), suggesting chemoautotrophy is an important and unappreciated source of labile carbon in deep‐sea sediments. Community 16S rRNA was dominated by Bacteria (<2% Archaea), primarily Desulfobacterales of the Deltaproteobacteria. Leveraging our findings, we modelled global benthic microbial activity through geologic time and find the potential for significant shifts in total activity with supercontinental cycles.
Border carbon adjustments: rationale, design and impact
Authors: Keen Michael , Parry Ian , Roaf James
Published: August 2022

This paper assesses the rationale, design and impact of border carbon adjustments (BCAs). Large disparities in carbon pricing between countries raise concerns about competitiveness and emissions leakage. BCAs are potentially the most effective domestic instrument for addressing these challenges – but design details are critical. For example, limiting coverage of the BCA to energy‐intensive, trade‐exposed industries facilitates administration, and initially benchmarking BCAs on domestic emissions intensities would ease the transition for trading partners with emission‐intensive production. It is also important to consider how to apply BCAs across countries with different approaches to the mitigation of emissions, and the treatment of exports. BCAs alone do not solve the free‐rider problem in carbon pricing, but might ease it, and be a step towards an effective international carbon price floor.
Simple method for evaluating achievement degree of lung dose optimization in individual patients with locally advanced non‐small cell lung cancer treated with intensity modulated radiotherapy
Authors: Abe Takanori , Iino Misaki , Saito Satoshi , Aoshika Tomomi , Ryuno Yasuhiro , Ohta Tomohiro , Igari Mitsunobu , Hirai Ryuta , Kumazaki Yu , Miura Yu , Kaira Kyoichi , Kagamu Hiroshi , Noda Shinei , Kato Shingo
Published: August 2022

Background

In this study, we developed a simple method for evaluating achievement degree of lung dose optimization in individual patients with locally advanced non‐small cell lung cancer (NSCLC) treated with intensity modulated radiotherapy (IMRT).

Methods

Data of 28 patients with stage IIB to IIIC NSCLC were retrospectively analyzed. All patients were treated with IMRT and a simulated three‐dimensional conformal radiotherapy (3D‐CRT) plan created for them. Dose‐volume parameters of lung were analyzed for their correlation with radiation pneumonitis (RP).

Results

Over a median follow‐up of 14 months, grade 1 pneumonitis was diagnosed in 14 patients (50%), grade 2 pneumonitis in 11 (39%), and grade 3 pneumonitis in one (4%). Two patients did not develop pneumonitis. None of the patients developed grade 4 or 5 pneumonitis. Regarding dose‐volume parameter ratios between IMRT and simulated 3D‐CRT, receiver operating characteristic analysis showed that mean lung dose (MLD)IMRT/MLD3D‐CRT had the largest area under curve (0.750). Cumulative 6‐month incidences of grade 2 or greater RP were 78.4% versus 19.5% (MLDIMRT/MLD3D‐CRT, ≥1.0 or less); this difference was significant (p < 0.05).

Conclusions

We found that cutoff values for dose volume parameter ratios significantly predict grade 2 or greater RP. We believe that these parameter ratios could be useful in assisting evaluation of achievement degree of lung dose optimization in IMRT for LA‐NSCLC.
Belgium: Political Developments and Data in 2021
Authors: RIHOUX BENOÎT , VANDELEENE AUDREY , DE WINTER LIEVEN , BAUDEWYNS PIERRE , DERUETTE SERGE
Published: August 2022

The year 2021 was the first full year for the De Croo I Cabinet, which had been installed in October 2020 after difficult and lengthy negotiations. The oversized and ideologically diverse ‘Vivaldi’ coalition government struggled as it was confronted with the management of the COVID‐19 pandemic, amidst frequent tensions between the coalition partners, with the two largest Flemish parties (Flemish Interest/Vlaams Belang and New Flemish Alliance/Nieuw‐Vlaamse Alliantie) shooting from the opposition. Further, usual disagreements continued to prevail between Flemish and Francophone parties and their respective executives at the subnational level. Hence, discussions on the contours of a – still very tentative – seventh state reform did not make much progress. Wallonia, the country's southern region, was hit by catastrophic floods in July. The whole public response to these floods added up to the massive costs of handling COVID‐19, which resulted in a structurally large budget deficit.

L'année 2021 fut la première année complète pour le gouvernement De Croo I entré en fonction en octobre 2020 au terme de longues et difficiles négociations. La coalition ‘Vivaldi’, très large et idéologiquement diversifiée, rencontra bien des difficultés dans sa gestion de la pandémie COVID‐19; cette dernière suscita de fréquentes tensions entre les partenaires de la coalition alors que les deux plus grands partis flamands (le VB et la N‐VA) menaient une opposition active. Par ailleurs, les désaccords habituels se prolongèrent entre les partis flamands et francophones et leurs exécutifs respectifs à l’échelon subnational. Dans ces conditions, les discussions autour d'une septième réforme de l'Etat aux contours encore très vagues ne progressèrent guère. La Wallonie, la région du Sud du pays, fut frappée par des inondations catastrophiques en juillet. La réponse des autorités publiques à ces inondations, conjuguée aux coûts très élevés de la gestion COVID‐19, se traduisit par un déficit budgétaire structurellement élevé.
Memories, museum artefacts and excavations in resolving the history of maternal lineages in the Finnhorse
Authors: Kvist Laura , Honka Johanna , Salazar Daniela , Kirkinen Tuija , Hemmann Karin
Published: August 2022

We used historical DNA samples to examine the history of a native horse breed, the Finnhorse. Samples were collected from private collections, museums, schools and excavations, representing the times prior to, during, and after the foundation of the breed; from the end of the 19th century and throughout the 20th century. We sequenced a fragment of mitochondrial DNA from these historical samples to study the history and evolution of maternal lineages of horses back to the early days of the breed, compared the mitochondrial DNA sequence diversity of different historical periods and modern day Finnhorses, estimated the effective population sizes, and searched for both temporal and geographic population genetic structure. We observed high maternal haplotype and nucleotide diversity at the time during the foundation of the breed, and a decrease in both measures during 1931–1970. In addition, we observed losses of some haplotypes present in the early stages of the breed. There was only slight evidence of geographical or temporal population structure. This study is, to our knowledge, the first to use such temporal sampling to reveal the history of a specific animal breed.
Retroperitoneoscopic resection of a primary retroperitoneal paraganglioma occurring between the aorta and vena cava: A case report
Authors: Nishikimi Toshinori , Kashima Ayano , Yamada Hiroshi , Mizuno Hideki , Ohashi Tomoyoshi , Ishiguro Shigeki , Morikami Hiroko
Published: August 2022

A 67‐year‐old man presented with lower limb weakness, palpitations, and insomnia. His urinary total metanephrine and normetanephrine levels were high. Computed tomography showed a 48 × 34‐mm oval mass on the dorsal side of the pancreas and portal vein between the aorta and vena cava. Because of the tumor location, we performed laparoscopic surgery using a retroperitoneal approach. We described a case of a patient with primary retroperitoneal paraganglioma between the aorta and vena cava who underwent retroperitoneoscopic resection. Our case suggests that this procedure can be safely performed.
Plus de transparence, plus de confiance? Regard critique sur un principe clé de bonne gouvernance et ses attentes
Authors: Mabillard Vincent , Caron Daniel J.
Published: August 2022

Sommaire

Il est attendu du fonctionnement plus ouvert des administrations un regain de confiance citoyenne et de légitimité. Toutefois, les effets produits par la transparence alimentent de nombreux débats. D'abord, la relation entre transparence et confiance peut être multidirectionnelle. Ensuite, elle correspond à un équilibre fragile dans la mesure où un surplus de communication sur des enjeux sensibles peut réduire la confiance dans les organisations publiques. Enfin, la confiance se crée à partir de multiples facteurs, réduisant ainsi l'impact de la transparence. Ces différents enjeux sont analysés sur la base d'une revue de la littérature scientifique et médiatique et d'exemples.
The In‐Out Effect in the Perception and Production of Real Words
Authors: Engelen Jan A. A.
Published: August 2022

The in‐out effect refers to the tendency that novel words whose consonants follow an inward‐wandering pattern (e.g., P‐T‐K) are rated more positively than stimuli whose consonants follow an outward‐wandering pattern (e.g., K‐T‐P). While this effect appears to be reliable, it is not yet clear to what extent it generalizes to existing words in a language. In two large‐scale studies, we sought to extend the in‐out effect from pseudowords to real words and from perception to production. In Study 1, we investigated whether previously collected affective ratings for English and Dutch words were more positive for inward‐wandering words and more negative for outward‐wandering words. No systematic relationship between wandering direction and affective valence was found. In Study 2, we investigated whether inward‐wandering words are more likely to occur in positive online consumer restaurant reviews written in English and Dutch, compared to negative reviews, and whether this association was stronger for food ratings than for decor ratings. Again, no systematic relationship between wandering direction and review rating emerged. We suggest that the affective states triggered by different consonantal wandering directions might be used as a cue for forming judgments in the absence of other information, but that wandering direction is too low in salience to drive the shape of words in the lexicon.
Kant on the givenness of space and time
Authors: Chaplin Rosalind
Published: August 2022

Famously, Kant describes space and time as infinite “given” magnitudes. An influential interpretative tradition reads this as a claim about phenomenological presence to the mind: in claiming that space and time are given, this reading holds, Kant means to claim that we have phenomenological access to space and time in our original intuitions of them. In this paper, I argue that we should instead understand givenness as a metaphysical notion. For Kant, space and time are “given” in virtue of three related facts: (a) they are necessary grounds for the existence of all other spatial and temporal possibilities; (b) in virtue of being such grounds, they are metaphysically linked to all other represented spatiotemporal things; and (c) as representations, space and time issue from the nature of our faculty of sensibility rather than from an arbitrary act of choice. Understanding givenness in this non‐epistemological way helps us recover what is plausible in both “intellectualist” and “anti‐intellectualist” readings of the Transcendental Aesthetic. Anti‐intellectualists are correct that space and time are given in mere sensibility, but intellectualists are correct that we depend on the understanding for consciousness of space and time.
Random fatigue life prediction of automobile lower arm via modified Corten–Dolan model
Authors: Yang Xizhou , Liu Xintian , Wang Yuhan
Published: August 2022

The fatigue life for the rear suspension lower arm of the passenger car is investigated. The road load signals collected by the sextant force measuring instrument are processed. And the frequency histogram of it is plotted and its distribution characteristics are analyzed. The load signal is extrapolated to a cumulative frequency of 106using the parametric method, and the one‐dimensional load spectrum of the lower arm is compiled. Based on the nonlinear fatigue cumulative damage theory, Corten–Dolan model is modified by introducing thekth power of the stress ratio between two adjacent levels. The improved fatigue life prediction model is established and the validity of the model was determined by experimental data. And the improved Corten–Dolan and the linear cumulative damage model are used to predict the life of the lower arm under one‐dimensional load spectrum respectively.