bluuebunny/crossref_metadata_2025 huggingface dataset:
A high-accuracy and high-efficiency digital volume correlation method to characterize in-vivo optic nerve head biomechanics from optical coherence tomography
Authors: Zhong Fuqiang , Wei Junchao , Hua Yi , Wang Bo , Reynaud Juan , Fortune Brad , Sigal Ian A.
Published: August 2021

In-vivo optic nerve head (ONH) biomechanics characterization is emerging as a promising way to study eye physiology and pathology. We propose a high-accuracy and high-efficiency digital volume correlation (DVC) method for the purpose of characterizing the in-vivo ONH deformation from volumes acquired by optical coherence tomography (OCT). Using a combination of synthetic tests and analysis of OCTs from monkey ONHs subjected to acute and chronically elevated intraocular pressure, we demonstrate that our proposed methodology overcomes several challenges for conventional DVC methods. First, it accounts for large ONH rigid body motion in the OCT volumes which could otherwise lead to analysis failure; second, sub-voxel-accuracy displacement can be guaranteed despite high noise and low image contrast of some OCT volumes; third, computational efficiency is greatly improved, such that the memory consumption of our method is substantially lower than with conventional methods; fourth, we introduce a parameter measuring displacements confidence. Test of image noise effects showed that the proposed DVC method had displacement errors smaller than 0.028 voxels with speckle noise and smaller than 0.037 voxels with Gaussian noise; The absolute (relative) strain errors in the three directions were lower than 0.0018 (4%) with speckle noise and than 0.0045 (8%) with Gaussian noise. Compared with conventional DVC methods, the proposed DVC method had substantially improved overall displacement and strain errors under large body motions (lower by up to 70%), with 75% lower computation times, while saving about 30% memory. The study thus demonstrates the potential of the proposed technique to investigate ONH biomechanics.
The degree of context un/familiarity impacts the emotional feeling and preaware cardiac-brain activity: a study with emotionally salient naturalistic paradigm using DENS Dataset
Authors: Mishra Sudhakar , Tiwary U.S.
Published: August 2021

Emotion experiments with naturalistic paradigms are emerging and giving new insights into dynamic brain activity. Context familiarity is considered as an important dimensions of emotion processing by appraisal theorists. However, how the context un/familiarity of the naturalistic stimuli influences the central and autonomic activity is not probed yet [check it]. Hence, we tried to address this issue in this work by breaking it down into three questions. 1) What is the relation between context un/familiarity with the neural correlates of self-assessment affective dimensions viz. valence and arousal; 2) the influence of context un/familiarity in cardiac-brain mutual interaction during emotion processing; 3.) brain network reorganization to accommodate the degree of context familiarity. We found that the less-context familiarity is primarily attributed to negative emotion feeling mediated by lack of predictability of sensory experience. Whereas, with high-context familiarity, both positive and negative emotions are felt. For less-context familiarity, the arousal activity is negatively correlated with EEG power. In addition, the cardiac activity for both high and less context familiarity is modulated before the reported self-awareness of emotional feeling. The correlation of cortical regions with cardiac activity and connectivity patterns reveals that ECG is modulated by salient feature during pre-awareness and correlates with AIC and conceptual hub in high-familiarity. Whereas, for the low familiarity, the cardiac activity is correlated with the exteroceptive sensory regions. In addition, we found that OFC and dmPFC have high connectivity with less-context familiarity, whereas AIC has high connectivity with high-context familiarity. To the best of our knowledge, the context familiarity and its influence on cardiac and brain activity have never been reported with a naturalistic paradigm. Hence, this study significantly contributes to understanding automatic processing of emotions by analyzing the effect of context un/familiarity on affective feelings, the dynamics of cardiac-brain mutual interaction, and the brain’s effective connectivity during pre-awareness.
Gpr19 is a circadian clock-controlled orphan GPCR with a role in modulating free-running period and light resetting capacity of the circadian clock
Authors: Yamaguchi Yoshiaki , Murai Iori , Goto Kaoru , Doi Shotaro , Zhou Huihua , Setsu Genzui , Shimatani Hiroyuki , Okamura Hitoshi , Miyake Takahito , Doi Masao
Published: August 2021

Background and Purpose: Gpr19 encodes an evolutionarily conserved orphan G-protein-coupled receptor (GPCR) with no established physiological function in vivo. The purpose of this study was to determine the role of Gpr19 in the circadian clock system. Experimental Approach: We examined whether and how the master circadian clock neurons in the suprachiasmatic nucleus (SCN) express Gpr19. By analysing Gpr19-deficient (Gpr19−/−) mice, we asked whether Gpr19 has a role in modulating free-running period and light resetting capacity of the circadian clock. Key Results: Compared with the known common core clock genes, Gpr19 was identified to show several distinct yet limited features related to the circadian clock. Gpr19 mRNA was mainly expressed in the middle-to-dorsal region of the SCN. A conserved cAMP-responsive element within the Gpr19 promoter drove the circadian expression of Gpr19. Gpr19−/− mice exhibited a prolonged circadian period and a delayed initiation of daily locomotor activity in a 12-h light/12-h dark cycle. Gpr19 deficiency caused the downregulation of several genes that normally peak during the night, including Bmal1 and Gpr176. Gpr19−/− mice had a reduced capacity for phase shift to early subjective night light. The defect was only observed for phase-delay, but not phase-advance, and accompanied by reduced response of c-Fos expression in the dorsal region of the SCN, while apparently normal in the ventral part of the SCN, in Gpr19−/− mice. Conclusion and Implications: Gpr19 is an SCN-enriched orphan GPCR with a distinct role in circadian regulation and thus may be a potential target for alleviating circadian clock disorders.
The looping lullaby: closed-loop neurostimulation decreases sleepers’ sensitivity to environmental noise
Authors: Pathak Vidushi , Juan Elsa , van der Goot Reina , Talamini Lucia M.
Published: August 2021

Study Objective

Sleep is critical for physical and mental health. However, sleep disruption due to noise is a growing problem, causing long-lasting distress and fragilizing entire populations mentally and physically. Here for the first time, we tested an innovative and non-invasive potential countermeasure for sleep disruptions due to noise.

Methods

We developed a new, modeling-based, closed-loop acoustic neurostimulation procedure (CLNS) to precisely phase-lock stimuli to slow oscillations (SO). We used CLNS to align, soft sound pulses to the start of the SO positive deflection to boost SO and sleep spindles during non-rapid eye movement (NREM) sleep. Participants underwent three overnight EEG recordings. The first night served to determine each participant’s individual noise arousal threshold. The remaining two nights occurred in counterbalanced order: in the “Disturbing night”, loud, real-life noises were repeatedly presented; in the “Intervention night”, similar loud noises were played while using the CLNS to boost SO. All experimental manipulations were performed in the first three hours of sleep; participants slept undisturbed for the rest of the night.

Results

In contrast to the Disturbing night, the probability of arousals caused by noise was significantly decreased in the Intervention night. Moreover, the CLNS intervention increased NREM duration and sleep spindle power across the night.

Conclusions

These results show that our CLNS procedure can effectively protect sleep from disruptions caused by noise. Remarkably, even in the presence of loud environmental noise, CLNS’ soft and precisely timed sound pulses played a beneficial role in protecting sleep continuity. This represents the first successful attempt at using CLNS in a noisy environment.

Statement of Significance

Exposure to noise during sleep impairs sleep quality, leading to impaired biological functioning, decreased day-time performance and higher occurrence of accidents. Slow wave sleep is hallmarked by slow oscillations (SO) and sleep spindles, both of which are markers of sleep stability. In previous experiments, acoustic stimulation has shown potential in enhancing SO and sleep spindles. Whether these manipulations also work to stabilize sleep against the disrupting effects of environmental noise remains unclear. Here we use a new closed-loop approach to precisely align subtle acoustic stimuli with SO phase. We show that this method effectively stabilizes sleep in the presence of noise. Our results bear crucial relevance for improving sleep in the general public and in many high-risk professions.
The initial response of females towards congeneric males matches the propensity to hybridise in Ophthalmotilapia
Authors: Van Steenberge Maarten , Jublier Noémie , Kéver Loïc , Gresham Sophie , Derycke Sofie , Snoeks Jos , Parmentier Eric , Poncin Pascal , Verheyen Erik
Published: August 2021

Abstract

Cichlid radiations often harbour closely related species with overlapping niches and distribution ranges. Such species sometimes hybridise in nature, which raises the question how can they coexist. This also holds for the Tanganyika mouthbrooders Ophthalmotilapia ventralis and O. nasuta. Earlier studies found indications of asymmetrical hybridisation with females of O. ventralis accepting males of O. nasuta, but not the other way around. We hypothesised that this was due to differences in the capacity for species recognition. Given the higher propensity of O. ventralis females towards hybridisation, we expect a reduced ability for species recognition in O. ventralis females, compared to O. nasuta females. We staged two experiments, one focusing on 22 female O. nasuta and one on 21 female O. ventralis. These fish were placed in one half of a tank and briefly exposed to a conspecific or a heterospecific male, a conspecific female, or nothing (control). Female response was evaluated by scoring six tracking parameters and by noting the occurrence of ten discrete behaviours before and during the encounter. Females always responded to the presence of another fish by approaching it. Remarkably, for both O. nasuta and O. ventralis, we did not find a different response between encounters with conspecific males and females. However, in agreement with our hypothesis, O. nasuta females behaved differently towards conspecific or heterospecific males, whereas O. ventralis females did not. When presented with a heterospecific male, O. nasuta females performed a lower number of ‘ram’ behaviours. Additionally, they never displayed the ‘flee’ behaviour, a component of the species’ mating repertoire that was seen in all but one of the presentations with a conspecific male. Our findings show that differences in species recognition at first encounter predict to a large degree the outcome of the mating process, even in the absence of mating behaviour.
Continuous sensing of nutrients and growth factors by the mTORC1-TFEB axis
Authors: Sparta Breanne , Pargett Michael , Kosaisawe Nont , Albeck John G.
Published: August 2021

mTORC1 senses nutrient and growth factor status and phosphorylates downstream targets, including the transcription factor TFEB, to coordinate metabolic supply and demand. The molecular mechanisms of mTORC1 activation are thought to enforce a strict requirement for simultaneous amino acid and growth factor stimuli, but this model has not been evaluated with quantitative or single-cell methods. Here, we develop a series of fluorescent protein-TFEB fusions and investigate how combinations of stimuli jointly regulate signaling from mTORC1 to TFEB at the single-cell level. Live-cell imaging of individual cells revealed that mTORC1-TFEB signaling responds with graded changes to individual amino acid and growth factor inputs, rather than behaving as a logical “AND” gate. We find that mTORC1 inputs can be sequentially sensed, with responses that vary between mTORC1 substrates and are amplified by input from other kinases, including GSK3β. In physiologically relevant concentrations of amino acids, we observe fluctuations in mTORC1-TFEB signaling that indicate continuous responsiveness to nutrient availability. Our results clarify how the molecular regulation of mTORC1 enables homeostatic processes at the cellular level and provide a more precise understanding of its behavior as an integrator of multiple inputs.
Augmenting Neutralization breadth against Diverse HIV-1 by increasing the Ab-Ag interface on V2
Authors: Gao Nan , Gai Yanxin , Meng Lina , Wang Chu , Wang Wei , Li Xiaojun , Gu Tiejun , Louder Mark K. , Doria-Rose Nicole A. , Wiehe Kevin , Nazzari Alexandra F. , Olia Adam S. , Gorman Jason , Rawi Reda , Wu Wenmin , Smith Clayton , Khant Htet , de Val Natalia , Yu Bin , Luo Junhong , Niu Haitao , Tsybovsky Yaroslav , Liao Huaxin , Kepler Thomas B. , Kwong Peter D. , Mascola John R. , Qin Chuan , Zhou Tongqing , Yu Xianghui , Gao Feng
Published: August 2021

Understanding maturation pathways of broadly neutralizing antibodies (bnAbs) against HIV-1 in non-human primates can be highly informative for HIV-1 vaccine development. We now obtained a lineage of J038 from Chinese rhesus macaques after 7-years of SHIV infection. J038 has short complementary determining loops and neutralizes 54% of global circulating HIV-1 strains. Its binding induces a unique “up” conformation for one of the V2 loops in the trimeric envelope glycoprotein (Env) and is heavily dependent on glycan, which provides nearly half of the binding surface. The unmutated common ancestor of the J038 lineage antibodies binds monomeric gp120 and neutralizes the autologous virus. Continuous maturation enhances neutralization potency and breadth of J038 lineage antibodies via expanding antibody-Env contact areas surrounding the core region contacted by germline-encoded residues. Developmental details and recognition features of J038 lineage antibodies revealed here provide a new pathway for maturation elicitation of V2-targeting bnAbs.

Highlights

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Long-term infected NHPs develop antibodies neutralizing up to 54% of HIV-1 strains

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Antibody J038 binds one V2 loop on HIV-1 Env trimer in a unique “up” position

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UCA of the J038 lineage effectively neutralizes the autologous virus

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J038 lineage antibodies mature through gradually increased contact to glycans
DAAM mediates the assembly of long-lived, treadmilling stress fibers in collectively migrating epithelial cells in Drosophila
Authors: Sherrard Kristin M , Cetera Maureen , Horne-Badovinac Sally
Published: August 2021

Stress fibers (SFs) are actomyosin bundles commonly found in individually migrating cells in culture. However, whether and how cells use SFs to migrate in vivo or collectively is largely unknown. Studying the collective migration of the follicular epithelial cells in Drosophila, we found that the SFs in these cells show a novel treadmilling behavior that allows them to persist as the cells migrate over multiple cell lengths. Treadmilling SFs grow at their fronts by adding new integrin-based adhesions and actomyosin segments over time. This causes the SFs to have many internal adhesions along their lengths, instead of adhesions only at the ends. The front-forming adhesions remain stationary relative to the substrate and typically disassemble as the cell rear approaches. By contrast, a different type of adhesion forms at the SF’s terminus that slides with the cell’s trailing edge as the actomyosin ahead of it shortens. We further show that SF treadmilling depends on cell movement and identify a developmental switch in the formins that mediate SF assembly, with DAAM acting during migratory stages and Diaphanous acting during post-migratory stages. We propose that treadmilling SFs keep each cell on a linear trajectory, thereby promoting the collective motility required for epithelial migration.
Regeneration of the larval sea star nervous system by wounding induced respecification to the sox2 lineage
Authors: Zheng Minyan , Zueva Olga , Hinman Veronica F.
Published: August 2021

The ability to restore lost body parts following traumatic injury is a fascinating area of biology that challenges current understanding of the ontogeny of differentiation. The origin of new cells needed to regenerate lost tissue, and whether they are pluripotent stem cells, tissue-specific stem cells or have de- or trans- differentiated, remains one of the most important open questions in regeneration. Additionally, it is not clearly known whether developmental gene regulatory networks (GRNs) are reused to direct specification in these cells or whether regeneration specific networks are deployed. Echinoderms, including sea stars, have extensive ability for regeneration and have therefore been the subject of many thorough studies on the ultrastructural and molecular properties of cells needed for regeneration. However, the technologies for obtaining transgenic echinoderms are limited and tracking cells involved in regeneration, and thus identifying the cellular sources and potencies has proven challenging. In this study we develop new transgenic tools for cell tracking in the regenerating bipinnaria larva of the sea star Patira minaita. We show that the larval serotonergic nervous system can regenerate following decapitation. Using a BAC-transgenesis approach with photoconvertible fluorescent proteins, we show that expression of the pan ectodermal marker, sox2, is induced in previously sox2 minus cells at the wound site, even when cell division is inhibited. sox2+ cells give rise to new sox4+ neural precursors that then proceed along an embryonic neurogenesis pathway to reform the anterior nervous systems. sox2+ cells contribute to only neural and ectoderm lineages, indicating that these progenitors maintain their normal, embryonic lineage restriction. This indicates that sea star larval regeneration uses a combination of existing lineage restricted stem cells, as well as respecification of cells into neural lineages, and at least partial reuse of developmental GRNs to regenerate their nervous system.
A method for simultaneously monitoring phloem and xylem reconnections in grafted watermelon seedlings
Authors: Xu Jianuo , Wei Xiaoyang , Xiong Mu , Zhang Ting , Liu Changjin , Bie Zhilong , Huang Yuan
Published: August 2021

Grafting is an effective way to increase watermelon tolerance to biotic and abiotic stresses. However, the survival of grafted seedlings largely depends on successful graft formation. Therefore, understanding the graft formation process, particularly the vascular reconnection process is of critical importance. This study found that lignin in watermelon stem shows strong auto-fluorescence under blue-light excitation which makes blue-light excited fluorescent tracers (FTs) such as 5(6)-carboxy fluorescein diacetate (CFDA) become unsuitable for assaying vascular connectivity in watermelon. In contrast, UV-light excited esculin and red-light excited acid fuchsin were proved to be efficient FTs for monitoring the phloem and xylem connectivity, respectively, in self-grafted watermelon. Furthermore, a combined application of esculin to the scion cotyledon and acid fuchsin to the rootstock root enabled simultaneous monitoring of the phloem and xylem connectivity in individual self-grafted watermelon seedlings. In addition, this method is also applicable in investigating the phloem and xylem reconnections in self-grafted melon and cucumber, and heterograft of watermelon, melon and cucumber onto pumpkin rootstock. Based on this established method, we found that phloem and xylem reconnections are not timely separated in self-grafted watermelon. Furthermore, low temperature and removal of the rootstock cotyledons both delayed the vascular reconnection process in watermelon. In conclusion, this new method provides a convenient, accurate and rapid way to analyze the vascular connectivity not only in watermelon, but also in other cucurbit crops.
Ccr4-Not complex reduces transcription efficiency in heterochromatin
Authors: Monteagudo Pablo , Brönner Cornelia , Kohvaei Parastou , Amedi Haris , Canzar Stefan , Halic Mario
Published: August 2021

Heterochromatic silencing is thought to occur through a combination of transcriptional silencing and RNA degradation, but the relative contribution of each pathway is not known. In this study we analyzed RNA Polymerase II (RNA Pol II) occupancy and levels of nascent and steady-state RNA in different strains of fission yeast, in order to quantify the contribution of each pathway to heterochromatic silencing. We found that transcriptional silencing consists of two components, reduced RNA Pol II accessibility and, unexpectedly, reduced transcriptional efficiency. Heterochromatic loci showed lower transcriptional output compared to euchromatic loci, despite the presence of comparable amounts of RNA Pol II in both types of regions. We determined that the Ccr4-Not complex and H3K9 methylation are required for reduced transcriptional efficiency in heterochromatin and that a subset of heterochromatic RNA is degraded more rapidly than euchromatic RNA. Finally, we quantified the contribution of different chromatin modifiers, RNAi and RNA degradation to each silencing pathway. Our data show that several pathways contribute to heterochromatic silencing in a locus-specific manner and reveal transcriptional efficiency as a new mechanism of silencing.
ChemPLAN-Net: A deep learning framework to find novel inhibitor fragments for proteins
Authors: Suarez Vasquez Michael A. , Xue Mingyi , Lam Jordy H. , Goonetilleke Eshani C. , Gao Xin , Huang Xuhui
Published: August 2021

Fragment-based drug design plays an important role in the drug discovery process by reducing the complex small-molecule space into a more manageable fragment space. We leverage the power of deep learning to design ChemPLAN-Net; a model that incorporates the pairwise association of physicochemical features of both the protein drug targets and the inhibitor and learns from thousands of protein co-crystal structures in the PDB database to predict previously unseen inhibitor fragments. Our novel protocol handles the computationally challenging multi-label, multi-class problem, by defining a fragment database and using an iterative featurepair binary classification approach. By training ChemPLAN-Net on available co-crystal structures of the protease protein family, excluding HIV-1 protease as a target, we are able to outperform fragment docking and recover the target’s inhibitor fragments found in co-crystal structures or identified by in-vitro cell assays.
BioPhi: A platform for antibody design, humanization and humanness evaluation based on natural antibody repertoires and deep learning
Authors: Prihoda David , Maamary Jad , Waight Andrew , Juan Veronica , Fayadat-Dilman Laurence , Svozil Daniel , Bitton Danny A.
Published: August 2021

Despite recent advances in transgenic animal models and display technologies, humanization of mouse sequences remains the primary route for therapeutic antibody development. Traditionally, humanization is manual, laborious, and requires expert knowledge. Although automation efforts are advancing, existing methods are either demonstrated on a small scale or are entirely proprietary. To predict the immunogenicity risk, the human-likeness of sequences can be evaluated using existing humanness scores, but these lack diversity, granularity or interpretability. Meanwhile, immune repertoire sequencing has generated rich antibody libraries such as the Observed Antibody Space (OAS) that offer augmented diversity not yet exploited for antibody engineering. Here we present BioPhi, an open-source platform featuring novel methods for humanization (Sapiens) and humanness evaluation (OASis). Sapiens is a deep learning humanization method trained on the OAS database using language modeling. Based on anin silicohumanization benchmark of 177 antibodies, Sapiens produced sequences at scale while achieving results comparable to that of human experts. OASis is a granular, interpretable and diverse humanness score based on 9-mer peptide search in the OAS. OASis separated human and non-human sequences with high accuracy, and correlated with clinical immunogenicity. Together, BioPhi offers an antibody design interface with automated methods that capture the richness of natural antibody repertoires to produce therapeutics with desired properties and accelerate antibody discovery campaigns.

BioPhi is accessible athttps://biophi.dichlab.organdhttps://github.com/Merck/BioPhi.
Charting Brain Growth and Aging at High Spatial Precision
Authors: Rutherford Saige , Fraza Charlotte , Dinga Richard , Kia Seyed Mostafa , Wolfers Thomas , Zabihi Mariam , Berthet Pierre , Worker Amanda , Verdi Serena , Andrews Derek , Han Laura , Bayer Johanna , Dazzan Paola , McGuire Phillip , Mocking Roel T. , Schene Aaart , Pennix Brenda W. , Sripada Chandra , Tso Ivy F. , Duval Elizabeth R. , Chang Soo-Eun , Heitzeg Mary , Burt S. Alexandra , Hyde Luke , Amaral David , Nordahl Christine Wu , Andreasssen Ole A. , Westlye Lars T. , Zahn Roland , Ruhe Henricus G. , Beckmann Christian , Marquand Andre F.
Published: August 2021

Defining reference models for population variation, and the ability to study individual deviations is essential for understanding inter-individual variability and its relation to the onset and progression of medical conditions. In this work, we assembled a reference cohort of neuroimaging data from 82 sites (N=58,836; ages 2-100) and use normative modeling to characterize lifespan trajectories of cortical thickness and subcortical volume. Models are validated against a manually quality checked subset (N=24,354) and we provide an interface for transferring to new data sources. We showcase the clinical value by applying the models to a transdiagnostic psychiatric sample (N=1,985), showing they can be used to quantify variability underlying multiple disorders whilst also refining case-control inferences. These models will be augmented with additional samples and imaging modalities as they become available. This provides a common reference platform to bind results from different studies and ultimately paves the way for personalized clinical decision making.
Overexpression of SHORT-ROOT2 transcription factor enhanced the outgrowth of mature axillary buds in poplar trees
Authors: Yi Minglei , Yang Heyu , Yang Shaohui , Wang Jiehua
Published: August 2021

Plant branching is usually prevented by an actively proliferating apex. In poplars, one GRAS family member, SHORT-ROOT2 (PtSHR2), was preferentially expressed in axillary buds (AXBs) and was inducible during bud maturation and activation. Overexpression of PtSHR2 (PtSHR2OE) in hybrid poplar impaired the apical dominance and simultaneously promoted the outgrowth of axillary branches below the maturation point (BMP), accompanied by regulated expression of genes critical for axillary meristem initiation and bud formation.

Following a detained phenotypic characterization, we compared the IAA and trans-zeatin levels in apical shoots and AXBs of wild-type and PtSHR2OE trees, together with gene expression analyses and defoliation, decapitation, and hormone reapplication assays.

PtSHR2OE AXBs contained a significantly lower ratio of auxin to cytokinin than wild-type AXBs, particularly in those below the BMP. Decapitation induced a faster bud burst in PtSHR2OE trees than in wild-type plants, and it could be strongly inhibited by exogenously applied auxin and cytokinin biosynthesis inhibitor, but only partially inhibited by N-1-naphthylphthalamic acid (NPA).

An impaired basipetal auxin transport, rather than an insufficient auxin biosynthesis or auxin insensitivity, disturbed the local hormonal homeostasis in PtSHR2OE AXBs, which in turn enhanced the axillary bud initiation and promoted the bud release.

Highlight

Overexpression of PtSHR2 in poplar impaired the apical dominance and promoted axillary bud outgrowth below the maturation point through disturbing the basipetal auxin transport and auxin and cytokinin homeostasis.
Strong regulatory effects of vgll3 genotype on reproductive axis gene expression in immature male Atlantic salmon
Authors: Ahi Ehsan Pashay , Sinclair-Waters Marion , Moustakas-Verho Jacqueline , Jansouz Shadi , Primmer Craig R.
Published: August 2021

Age at maturity is a major contributor to the diversity of life history strategies in organisms. The process of maturation is influenced by both genetics and the environment, and includes changes in levels of sex hormones and behavior, but the specific factors leading to variation in maturation timing are not well understood. gnrh1 regulates the transcription of gonadotropin genes at the onset of puberty in many species, but this gene is lacking in certain teleost species including Atlantic salmon (Salmo salar), which raises the possibility of the involvement of other important regulatory factors during this process. Earlier research has reported a strong association of alternative alleles of the vgll3 gene with maturation timing in Atlantic salmon, suggesting it as a potential candidate regulating reproductive axis genes. Here, we investigated the expression of reproductive axis genes in immature Atlantic salmon males with different vgll3 genotypes during the spawning period. We detected strong vgll3 genotype-dependent differential expression of reproductive axis genes (such as fshb, lhb, amh and igf3) tested in the pituitary, and testis of one-year-old immature male Atlantic salmon. In addition, we observed differential expression of jun (ap1) and nr5a1b (sf1), potential upstream regulators of gonadotropins in the pituitary, as well as axin2, id3, insl3, itch, ptgs2a and ptger4b, the downstream targets of amh and igf3 in the testis. Hereby, we provide evidence of strong vgll3 genotype-dependent transcriptional regulation of reproductive axis genes prior to sexual maturation together with models for distinct actions of vgll3 genotypes on the molecular processes controlling spermatogenesis in Atlantic salmon.
A warmer growing season triggers earlier following spring phenology
Authors: Gu Hongshuang , Qiao Yuxin , Xi Zhenxiang , Rossi Sergio , Smith Nicholas G. , Liu Jianquan , Chen Lei
Published: August 2021

Under global warming, advances in spring phenology due to the rising temperature have been widely reported. However, the physiological mechanisms underlying the warming-induced earlier spring phenology remain poorly understood. Here, using multiple long-term and large-scale phenological datasets between 1951 and 2018, we show that warmer temperatures during the previous growing season between May and September led to earlier spring phenology in the Northern Hemisphere. We also found that warming-induced increases in maximum photosynthetic rate in the previous year advanced spring phenology, with an average of 2.50 days °C-1. Furthermore, we found a significant decline in the advancing effect of warming during the previous growing season on spring phenology from cold to warm periods over the past decades. Our results suggest that the observed warming-induced earlier spring phenology may be driven by increased photosynthetic carbon assimilation in the previous season, while the slowdown in the advanced spring phenology arise likely from decreased carbon assimilation when warming exceeding the optimal temperatures for photosynthesis. Our study highlights the vital role of photosynthetic carbon assimilation during growing season in spring phenology under global warming.
Distinct progressions of neuronal activity changes underlie the formation and consolidation of a gustatory associative memory
Authors: Arieli Elor , Younis Nadia , Moran Anan
Published: August 2021

Acquiring new memories is a multi-stage process. Ample of studies have convincingly demonstrated that initially acquired memories are labile, and only stabilized by later consolidation processes. These multiple phases of memory formation are known to involve modification of both cellular excitability and synaptic connectivity, which in turn change neuronal activity at both the single neuron and ensemble levels. However, the specific mapping between the known phases of memory and the observed changes in neuronal activity remains unknown. Here we address this unknown in the context of conditioned taste aversion learning by continuously tracking gustatory cortex (GC) neuronal taste responses from alert rats in the 24 hours following a taste-malaise pairing. We found that the progression of neuronal activity changes in the GC depend on the neuronal organizational level. The population response changed continuously; these changes, however, were only reflected in the population mean amplitude during the acquisition and consolidation phases, and in the known quickening of the ensemble state dynamics after the time of consolidation. Together our results demonstrate how complex dynamics in different representational level of cortical activity underlie the formation and stabilization of memory within the cortex.

Significant Statement

Memories are formed through a multi-phase process; an early initial acquired memory consolidates into a stable form over hours and days. While the underlying phase-specific molecular pathways are fairly known, the neuronal activity changes during these different phases remain elusive. Here we studied this unknown by tracking cortical neuronal activity over 24h as the taste becomes aversive following association with malaise. We found that that the progression of activity changes is organization-level dependent: The population response changed continuously; the population mean amplitude was time-locked to the acquisition and consolidation phases, and the quickening of the known ensemble state dynamics appear only after consolidation. Our results reveal the complex organizational-level neuronal interactions that underlie the progression of memory formation.
Improving the analysis of biological ensembles through extended similarity measures
Authors: Chang Liwei , Perez Alberto , Miranda-Quintana Ramón Alain
Published: August 2021

We present new algorithms to classify structural ensembles of macromolecules, based on the recently proposed extended similarity measures. Molecular Dynamics provides a wealth of structural information on systems of biologically interest. As computer power increases we capture larger ensembles and larger conformational transitions between states. Typically, structural clustering provides the statistical mechanics treatment of the system to identify relevant biological states. The key advantage of our approach is that the newly introduced extended similiarity indices reduce the computational complexity of assessing the similarity of a set of structures from O(N2) to O(N). Here we take advantage of this favorable cost to develop several highly efficient techniques, including a linear-scaling algorithm to determine the medoid of a set (which we effectively use to select the most representative structure of a cluster). Moreover, we use our extended similarity indices as a linkage criterion in a novel hierarchical agglomerative clustering algorithm. We apply these new metrics to analyze the ensembles of several systems of biological interest such as folding and binding of macromolecules (peptide,protein,DNA -protein). In particular, we design a new workflow that is capable of identifying the most important conformations contributing to the protein folding process. We show excellent performance in the resulting clusters (surpassing traditional linkage criteria), along with faster performance and an efficient cost-function to identify when to merge clusters.
Phyllotaxis Models: from the Inhibition Potential to the Real Plant
Authors: Jean-Paul Walch
Published: August 2021

Previous phyllotaxis models allowed the initiation of new primordia when a threshold of inhibition potential is reached on the meristem front: their adequacy to botanical reality is only qualitative. We formulated the hypothesis that it is not the value of the inhibition threshold that remains constant as the meristem develops, but the difference of the inhibition thresholds during the initiation of two successive primordia. We were thus able to model with accuracy the sequence of plastochron ratios observed by Williams (1975) on the leaf meristem of flax: an outstanding result. More generally, we have shown that the evolution trajectories of the phyllotaxis modes as a function of the plastochron ratios follow the minima of the potential under decreasing plastochron ratios constraint and bifurcate when the number of these minima increases, thus giving physicochemical foundations to the famous van Iterson diagram. This historical representation of rising phyllotaxis shows the trajectories, but doesn’t give the velocity of the movement: our plastochron ratio sequence adds this major dynamical information.
Metataxonomic review to elucidate the role of the microbiome in Celiac disease across the gastrointestinal tract
Authors: Arcila Juliana , Loria-Kohen Viviana , Ramírez de Molina Ana , Carrillo de Santa Pau Enrique , Marcos-Zambrano Laura Judith
Published: August 2021

Background

Dysbiosis of the microbiome has been related to the Celiac disease (CeD) progress, an autoimmune disease characterised by gluten intolerance developed in genetically susceptible individuals under certain environmental factors. The microbiome contributes to CeD pathophysiology modulating the immune response by the action of short-chain fatty acids (SCFA), affecting gut barrier integrity allowing the entrance of gluten derived proteins, and degrading immunogenic peptides of gluten through endoprolyl peptidase enzymes. We reviewed state of the art in taxonomic composition for CeD and compiled the larger dataset of 16S prokaryotic ribosomal RNA (rRNA) gene high-throughput sequencing for consensus profiling. We present for the first time an integrative analysis of metataxonomic data from CeD patients, including samples from different body sites (saliva, pharynx, duodenum, and stool). We found the presence of coordinated changes through the gastrointestinal tract characterised by an increase in Actinobacteria species in the upper tract (pharynx and duodenum), and an increase in Proteobacteria in the lower tract (duodenum and stool), as well as site- specific changes evidencing a dysbiosis in CeD patients’ microbiota. Moreover, we described the effect of adherence to a gluten-free diet (GFD) evidenced by an increase in beneficial bacteria and a decrease in some Betaproteobacteriales but not fully restoring CeD-related dysbiosis. We illustrate that the gut microbiota acts as an enhancer of immune response in CeD through the production of lipopolysaccharides and other bacterial components that activate the immune response and by decrease SCFA producers bacteria. Furthermore, microbial changes observed through the gastrointestinal tract of CeD patients may help manage the disease and follow-up GFD treatment.
How Filopodia Respond to Calcium in the Absence of a Calcium-binding Structural Protein: They Use Rapid Transit
Authors: Heckman C. A. , Ademuyiwa O. M. , Cayer M. L
Published: August 2021

During directional locomotion, cells must reorient themselves in response to attractive or repulsive cues. Filopodia are narrow actin-based protrusions whose prevalence at the leading edge of a migrating cell is related to the persistence of locomotion. Although there is a marked absence of calcium-binding components in their structure, they responded to store-operated calcium entry (SOCE). Here, we used a two-phase protocol to determine how they responded. In the first phase, extracellular calcium was removed and ER calcium lowered by blocking reuptake through the calcium pump. This was known to activate stromal interacting molecule (STIM) and cause its microtubule-mediated translocation to the cell surface. In the second phase, extracellular calcium and calcium influx into the ER were restored. ER depletion caused filopodia to increase, followed by a spontaneous decrease that was blocked by inhibiting endocytosis. The intracellular calcium concentration increased during depletion, while the size of the exchangeable compartment of vesicles, measured by fluid-phase marker uptake, shrank. When SOCE mediators and the aquaporin, AQP4, were localized, STIM and transient receptor potential canonical (TPRC) channels occupied vesicular profiles side-by-side in linear arrays. STIM1 was translocated, as expected. TRPC1 was initially in a rapidly recycling pool (RRP) where it partially colocalized with Vamp2. Calcium restoration caused TRPC1 exocytosis, while STIM1 reverted toward its original pattern associated with the ER. The exchangeable compartment was restored and this enabled filopodia extension, which was blocked by inhibitors of TRPC1/4/5 and endocytosis. That vesicle recycling was essential for extension during calcium readdition was indicated by reversal of the effect of endocytosis inhibitors in the depletion and readdition phases. The results suggest that SOCE regulates the size of the RRP in epithelial cells, and vesicle recycling is the immediate mechanism affecting filopodia extension. The conclusions are discussed in light of factors regulating protrusion formation, namely surface tension and vesicle trafficking.
Physiologically relevant miRNAs in mammalian oocytes are rare and highly abundant
Authors: Kataruka Shubhangini , Kinterova Veronika , Horvat Filip , Kanka Jiri , Svoboda Petr
Published: August 2021

miRNAs, ~22nt small RNAs associated with Argonaute (AGO) proteins, are important negative regulators of gene expression in mammalian cells. However, mammalian maternal miRNAs show negligible repressive activity and the miRNA pathway is dispensable for oocytes and maternal-to-zygotic transition. The stoichiometric hypothesis proposed that this is caused by dilution of maternal miRNAs during oocyte growth. As the dilution affects miRNAs but not mRNAs, it creates unfavorable miRNA:mRNA stoichiometry for efficient repression of cognate mRNAs. Here we report that porcine ssc-miR-205 and bovine bta-miR-10b are exceptional miRNAs, which resist the diluting effect of oocyte growth and can efficiently suppress gene expression. Additional analysis of ssc-miR-205 shows that it has higher stability, reduces expression of endogenous targets, and contributes to porcine oocyte-to-embryo transition. Consistent with the stoichiometric hypothesis, our results show that the endogenous miRNA pathway in mammalian oocytes is intact and that maternal miRNAs can efficiently suppress gene expression when a favorable miRNA:mRNA stoichiometry is established.
Study on microstructure and properties of Zn-Sn coating on sintered Nd-Fe-B magnets by grain boundary diffusion process
Authors: Hu Zhihua
Published: August 2021

Purpose

The microstructure and properties of Zn-Sn coating on sintered Nd-Fe-B magnets were investigated by the grain boundary diffusion process, to improve the corrosion resistance of magnet surface and explore the feasibility of realizing the lower-temperature grain boundary diffusion.

Design/methodology/approach

The Zn-Sn coating was deposited on sintered Nd-Fe-B magnets by magnetron sputtering, and then the Zn-Sn coated magnets were put into the vacuum tube furnace for grain boundary diffusion process. The morphology and structure of Zn-Sn coating as well as its mechanical properties and corrosion resistance were investigated.

Findings

Results showed that the particle size of vacuum diffusion-treated Zn-Sn coating increased and the particle agglomeration was weakened with increasing diffusion temperature, and the non-vacuum diffusion-treated Zn-Sn coating was oxidized to generate SnO2 and ZnO compounds. The binding force of coating first increased and then decreased with increasing diffusion temperature, and the maximum binding force was obtained at 540 °C. The binding force and corrosion resistance of non-vacuum diffusion-treated Zn-Sn coating were higher than the vacuum diffusion-treated Zn-Sn coating at the same diffusion temperature.

Originality/value

The Zn-Sn coating after diffusion treatment can provide complete protection, and the coating elements diffusion can be carried out at the same temperature as the secondary aging of sintered Nd-Fe-B magnets. Simultaneously, further diffusion process optimization needs to be completed because the diffusion depth is very low and only about 10 µm, which does not meet the requirements of traditional grain boundary diffusion method.
Entire functions of restricted hyper-order sharing a set of two small functions IM with their linear c-shift operators
Authors: Banerjee Abhijit , Roy Arpita
Published: August 2021

Purpose

The paper aims to build the relationship between an entire function of restricted hyper-order with its linear c-shift operator.

Design/methodology/approach

Standard methodology for papers in difference and shift operators and value distribution theory have been used.

Findings

The relation between an entire function of restricted hyper-order with its linear c-shift operator was found under the periphery of sharing a set of two small functions IM (ignoring multiplicities) when exponent of convergence of zeros is strictly less than its order. This research work is an improvement and extension of two previous papers.

Originality/value

This is an original research work.
Latent class analysis and individuals' preferences mapping: the new consumption orientations and perspectives for craft beer in North-West Italy
Authors: Massaglia Stefano , Merlino Valentina Maria , Blanc Simone , Bargetto Aurora , Borra Danielle
Published: August 2021

Purpose

In Italy, the craft beer (CB) market has undergone a trend of exponential growth in recent years, showing, at the same time, differences among different geographical areas. This research aimed to define the consumer preferences towards different CB attributes by involving a sample of individuals from Piedmont (from North-West Italy). Furthermore, the experimentation was designed to distinguish heterogeneous individuals' consumption profiles each characterised by different CB preferences, drinking habits and socio-demographic characteristics.

Design/methodology/approach

The exploration of individuals' preferences towards 12 CB quality attributes was made throughout a choice experiment based on the Best-Worst Scaling (BWS) methodology approach. In addition, the BWS results were employed in the latent class analysis to identify the best sample segmentation in relation to attributes preferences.

Findings

The “Brand knowledge”, “I have already tried it” were the most important attributes for CB choice. On the contrary, the “Type of packaging” and “Price” were the least important for CB choice. The “Loyal”, “Attentive to quality composition” and “Territorial brand” clusters were defined in function of CB consumers preferences and described in terms of individuals consumption habits and socio-demographic characteristics.

Originality/value

The BWS methodology allowed the definition of a preference index for each selected CB attributes. These indications could have concrete importance on production and marketing choices in an increasingly extended and globalised market, also at large-scale distribution level. Furthermore, the definition of different consumption profiles allowed to highlight the heterogeneity of consumption (preferences and habits) towards CB.