bluuebunny/crossref_metadata_2025 huggingface dataset:
Nitrate-regulated growth processes involve activation of gibberellin pathway
Authors: Camut Lucie , Gallova Barbora , Jilli Lucas , Sirlin-Josserand Mathilde , Carrera Esther , Sakvarelidze-Achard Lali , Zumsteg Julie , Heintz Dimitri , Ruffel Sandrine , Krouk Gabriel , Thomas Stephen G. , Hedden Peter , Phillips Andrew L. , Davière Jean-Michel , Achard Patrick
Published: July 2021

Nitrate, one of the main nitrogen (N) sources for crops, acts as a nutrient and key signaling molecule coordinating gene expression, metabolism and various growth processes throughout the plant life cycle. It is widely accepted that nitrate-triggered developmental programs cooperate with hormone synthesis and transport, to finely adapt plant architecture to N availability. Here, we report that nitrate, acting through its signaling pathway, promotes growth in Arabidopsis and wheat, in part by modulating the accumulation of gibberellin (GA)-regulated DELLA growth repressors. We show that nitrate reduces the abundance of DELLAs by increasing GA contents through activation of GA metabolism gene expression. Consistently, the growth restraint conferred by nitrate deficiency is partially rescued in global-DELLA mutant that lacks all DELLAs. At the cellular level, we show that nitrate enhances both cell proliferation and elongation in a DELLA-dependent and -independent manner, respectively. Our findings establish a connection between nitrate and GA signaling pathways that allow plants to adapt their growth to nitrate availability.
Resurrecting Golgi proteins to grasp Golgi ribbon formation and self-association under stress
Authors: Mendes Luis F. S. , Batista Mariana R. B. , Kava Emanuel , Bleicher Lucas , Micheletto Mariana C. , Costa-Filho Antonio J.
Published: July 2021

The Golgi complex is a membranous organelle located in the heart of the eukaryotic secretory pathway. A subfamily of the Golgi matrix proteins, called GRASPs, are key players in the stress-induced unconventional secretion, the Golgi dynamics during mitosis/apoptosis, and Golgi ribbon formation. The Golgi ribbon is vertebrate-specific and correlates with the appearance of two GRASP paralogs (GRASP55/GRASP65) and two coiled-coil Golgins (GM130/Golgin45), which interact with each otherin vivo. Although essential for the Golgi ribbon formation and the increase in Golgi structural complexity, the molecular details leading to their appearance only in this subphylum are still unknown. Moreover, despite the new functionalities supported by the GRASP paralogy, little is known about the structural and evolutionary differences between these paralogues. In this context, we used ancestor sequence reconstruction and several biophysical/biochemical approaches to assess the evolution of the GRASP structure, flexibility, and how they started anchoring their Golgin partners. Our data showed that the Golgins appeared in evolution and were anchored by the single GRASP ancestor beforegoraspgene duplication and divergence in Metazoans. After thegoraspdivergence, variations inside the GRASP binding pocket determined which paralogue would recruit each Golgin partner (GRASP55 with Golgin45 and GRASP65 with GM130). These interactions are responsible for the protein’s specific Golgi locations and the appearance of the Golgi ribbon. We also suggest that the capacity of GRASPs to form supramolecular structures is a long-standing feature, which likely affects GRASP’s participation as a trigger of the stress-induced secretory pathway.
Functional and comparative genomics reveals conserved noncoding sequences in the nitrogen-fixing clade
Authors: Pereira Wendell J. , Knaack Sara , Conde Daniel , Chakraborty Sanhita , Folk Ryan A. , Triozzi Paolo M. , Balmant Kelly M. , Dervinis Christopher , Schmidt Henry W. , Ané Jean-Michel , Roy Sushmita , Kirst Matias
Published: July 2021

Nitrogen is one of the most inaccessible plant nutrients, but certain species have overcome this limitation by establishing symbiotic interactions with nitrogen-fixing bacteria in the root nodule. This root nodule symbiosis (RNS) is restricted to species within a single clade of angiosperms, suggesting a critical evolutionary event at the base of this clade, which has not yet been determined. While genes implicated in the RNS are present in most plant species (nodulating or not), gene sequence conservation alone does not imply functional conservation – developmental or phenotypic differences can arise from variation in the regulation of transcription. To identify putative regulatory sequences implicated in the evolution of RNS, we aligned the genomes of 25 species capable of nodulation. We detected 3,091 conserved noncoding sequences (CNS) in the nitrogen-fixing clade that are absent from outgroup species. Functional analysis revealed that chromatin accessibility of 452 CNS significantly correlates with the differential regulation of genes responding to lipo-chitooligosaccharides inMedicago truncatula. These included 38 CNS in proximity to 19 known genes involved in RNS. Five such regions are upstream ofMtCRE1,Cytokinin Response Element 1,required to activate a suite of downstream transcription factors necessary for nodulation inM. truncatula. Genetic complementation of aMtcre1mutant showed a significant association between nodulation and the presence of these CNS, when they are driving the expression of a functional copy ofMtCRE1. Conserved noncoding sequences, therefore, may be required for the regulation of genes controlling the root nodule symbiosis inM. truncatula.
Polar accumulation of pyoverdin and exit from stationary phase
Authors: Moreno-Fenoll Clara , Ardré Maxime , Rainey Paul B.
Published: July 2021

Pyoverdin is a water-soluble metal-chelator synthesized by members of the genusPseudomonasand used for the acquisition of insoluble ferric iron. Although freely diffusible in aqueous environments, preferential dissemination of pyoverdin among adjacent cells, fine-tuning of intracellular siderophore concentrations, and fitness advantages to pyoverdin-producing versus nonproducing cells, indicate control of location and release. Here, using time-lapse fluorescence microscopy to track single cells in growing microcolonies ofPseudomonas fluorescensSBW25, we show accumulation of pyoverdin at cell poles. Accumulation occurs on cessation of cell growth, is achieved by cross-feeding in pyoverdin-nonproducing mutants and is reversible. Moreover, accumulation coincides with localization of a fluorescent periplasmic reporter, suggesting that pyoverdin accumulation at cell poles is part of the general cellular response to starvation. Compatible with this conclusion is absence of non-accumulating phenotypes in a range of pyoverdin mutants. Analysis of the performance of pyoverdin-producing and nonproducing cells under conditions promoting polar accumulation shows an advantage to accumulation on resumption of growth after stress. Examination of pyoverdin polar accumulation in a multispecies community and in a range of laboratory and natural species ofPseudomonas, includingP. aeruginosaPAO1 andP. putidaKT2440, confirms that the phenotype is characteristic ofPseudomonas.
Ribosomal protein L23 drives the metastasis of hepatocellular carcinoma via upregulating MMP9
Authors: Yang Minli , Zhou Yujiao , Deng Haijun , Zhou Hongzhong , Cheng Shengtao , Zhang Dapeng , He Xin , Mai Li , Chen Yao , Li Fan , Chen Juan
Published: July 2021

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths globally and tumor metastasis is one of the major causes of high mortality. To identify novel molecules contributing to HCC metastasis is critical to understanding the underlining mechanism of cancer metastasis. Here, combining the analyze based on published database and liver tissues from HCC patients, we identified that RNA binding protein L23 (RPL23) as a tumor metastasis driver in HCC. RPL23 was elevated in HCC and closely related to poor clinical outcomes. Furthermore, RPL23 depletion inhibited HCC cell proliferation, migration and invasion, while RPL23 overexpression promoted HCC cell metastasis. Mechanistically, RPL23 positively regulated MMP9 expression by stabilizing its mRNA. And increased MMP9 is involved in RPL23-mediated HCC metastasis. Importantly, RPL23 silencing reduced tumor growth and metastasis in vivo. In summary, we identified that RPL23 play an important role in HCC metastasis in an MMP9-dependent manner and may be a novel potential therapeutic target for HCC tumorigenesis and metastasis.
Disruption of the TCA cycle reveals an ATF4-dependent integration of redox and amino acid metabolism
Authors: Ryan Dylan G. , Yang Ming , Prag Hiran A. , Blanco Giovanny Rodriguez , Nikitopoulou Efterpi , Segarra-Mondejar Marc , Powell Christopher A. , Young Tim , Burger Nils , Miljkovic Jan Lj. , Minczuk Michal , Murphy Michael P. , von Kriegsheim Alexander , Frezza Christian
Published: July 2021

The Tricarboxylic Acid Cycle (TCA) cycle is arguably the most critical metabolic cycle in physiology and exists as an essential interface coordinating cellular metabolism, bioenergetics, and redox homeostasis. Despite decades of research, a comprehensive investigation into the consequences of TCA cycle dysfunction remains elusive. Here, we targeted two TCA cycle enzymes, fumarate hydratase (FH) and succinate dehydrogenase (SDH), and combined metabolomics, transcriptomics, and proteomics analyses to fully appraise the consequences of TCA cycle inhibition (TCAi) in kidney epithelial cells. Our comparative approach shows that TCAi elicits a convergent rewiring of redox and amino acid metabolism dependent on the activation of ATF4 and the integrated stress response (ISR). Furthermore, we also uncover a divergent metabolic response, whereby acute FHi, but not SDHi, can maintain asparagine levels via reductive carboxylation and maintenance of cytosolic aspartate synthesis. Our work highlights an important interplay between the TCA cycle, redox biology and amino acid homeostasis.

Highlights

TCA cycle inhibition promotes GSH synthesis and impairs de novo aspartate and proline synthesis

Disruption of mitochondrial thiol redox homeostasis phenocopies TCA cycle inhibition by promoting GSH synthesis and impairing proline and aspartate synthesis

Acute FHi, but not SDHi, can maintain asparagine levels via reductive carboxylation and maintenance of cytosolic aspartate synthesis

TCA cycle inhibition mimics an amino acid deprivation-type response and activates ATF4 via the integrated stress response to maintain redox and amino acid homeostasis
Measuring the temporal quality of a biodiversity database
Authors: Underhill Les G
Published: July 2021

In the context of climate change it is important to keep biodiversity databases up-to-date. This priority generates the need for a metric to assess the concept of up-to-dateness. The objective of this paper is to devise a measure of up-to-dateness for atlas-type biodiversity data. The data input into the algorithm consists of the species, date and grid cell allocation of all available records for a taxon in a region. First, for each grid cell in a region, the median of the date of the most recent record of each species is calculated. Secondly, the median of the median dates for each grid cell yields an overall measure of up-to-dateness. The performance of this algorithm is investigated in relation to databases for six taxa in southern Africa. In June 2021, the up-to-dateness of the databases varied from 41 years for the reptile database to two years for the bird database. The quality of a biodiversity database is a multidimensional concept; up-to-dateness is only one of several dimensions. The paper identifies a need to quantify the rate at which the “value” of a record decays as evidence that a species still occurs at a locality, and suggests an experimental process for doing this. The use of the up-to-dateness index to motivate citizen scientists is discussed.
Average stride length and stride rate of Thoroughbreds and Quarter Horses during ‘Sprint’ and ‘Classic’ races
Authors: Vergara-Hernandez Fernando B. , Nielsen Brian D. , Robison Cara I. , Fabus Taylor A. , Kompare Jasmin L. , LeCompte Lasic Rebecca A. , Colbath Aimee C.
Published: July 2021

The main factors influencing speed in athletes are stride length (SL) and stride rate (SR). However, conflict remains whether SL or SR is the key determinant of higher speeds. Quarter Horses (QH) generally reach higher speeds in their races than do Thoroughbreds (TB). However, the influence of SL and SR on this greater speed is unclear. Therefore, the main objective of this study was to compare SL and SR in QH and TB raced in short (sprint) and long (classic) distances. We hypothesized that QH have a higher SR in comparison to TB, and SR decreases as distance increases. Two race distances were analyzed for each breed: QH races of 100.6 and 402.3 m, and TB races of 1,207.0 m and 2,011.7 m. Data from twenty horses were obtained, consisting of five horses from each race distance (10 QH and 10 TB). Five individuals watched recordings of each race three times counting the number of strides taken by each winning horse. The SR was calculated using the average number of strides over a given race duration, and SL was determined by calculating the total number of strides over the distance covered. Speed was calculated dividing the distance by the time of the winning horse. The PROC Mixed Procedure was used to identify statistical differences between breeds, and between distances within the same breed. Results showed that although the SL of the TB was longer in comparison with the QH (P<0.001), the average SR in QH was higher than in TB (2.88 vs 2.34 + 0.03 strides/s; P<0.001). Further, QH classic distance demonstrated a faster speed than TB at either distance (P<0.001). In conclusion, QH achieve a higher SR in comparison to TB (between 14-20% more than TB), confirming the importance of SR in achieving high racing speeds.
Host-symbiont stress response to lack-of-sulfide in the giant ciliate mutualism
Authors: Espada-Hinojosa Salvador , Drexel Judith , Kesting Julia , Kniha Edwin , Pifeas Iason , Schuster Lukas , Volland Jean-Marie , Zambalos Helena C. , Bright Monika
Published: July 2021

The thiotrophic mutualism between the sulfur-oxidizing, chemoautotrophic (thiotrophic) bacterial ectosymbiontCandidatusThiobius zoothamnicola and the giant ciliateZoothamnium niveumthrives in a variety of shallow-water marine environments with highly fluctuating sulfide emission. To persist over time both partners must reproduce and ensure symbiont transmission prior cessation of sulfide, fueling the symbiont’s carbon fixation and host nourishment. We experimentally investigated the response of this mutualism to waning of sulfide. We found that colonies followed the r-strategy and released initially present but also newly produced macrozooids until death. A fraction of middle-sized longer-lived colonies were particularly proficient in producing and releasing swarmers. The symbionts on the colonies proliferated less and became larger and more rod-shaped under oxic conditions compared to symbionts from freshly collected colonies exposed to sulfide and oxygen. The symbiont monolayer was highly disturbed with epigrowth of other microbes and loss of symbionts that were subsequently found in the experimental seawater. We conclude that both partners’ response to cessation of sulfide emission was remarkably fast. The colony experienced death within two days but host reproduction through swarmers carrying the symbiont ensured the continuation of the association.
Perinatal maternal chronic exposure to dibutyl phthalate promotes visceral obesity in adult female offspring
Authors: Zhou Kunyan , Cheng Ran , Yang Meina , Shen Xiaoyang , Luo Xiaoyan , Ma Li , Xu Liangzhi , Zhang Jing
Published: July 2021

Introduction

Maternal exposure to dibutyl phthalate (DBP) may result in glucolipid dysfunction in female offspring. However, the underlying mechanisms remain elusive. We hypothesized that chronic maternal DBP exposure could induce abnormal metabolism of glucolipid.

Materials and methods

Sprague-Dawley rats were intraperitoneally injected with different doses of DBP, estradiol, and corn oil from gestational day 7 until the end of lactation. The weights, visceral fat percentage, serum lipid, insulin and glucose, protein levels of PI3K signal pathway in muscle were detected in F1 female offspring.

Results

Although the birth weight of F1 female offspring was not different among groups, the weights were heavier in DBP groups from postnatal day 7 to adult (P<0.001). The visceral adipose percentage in adult female offspring was increased by perinatal exposure to DBP (P<0.001). Decreased serum levels of triglyceride (P<0.0001), fasting glucose (P=0.004), prolactin (P=0.006), HOMA-IR (P=0.014) were found in female offspring exposed to DBP, but no difference for fasting insulin, total cholesterol, adiponectin. Increased protein levels of p-AKT, but decreased PTEN and GPR30 were observed in muscle of female offspring in DBP group, but without significant difference. None difference was observed for the protein levels of PI3K, AKT, GLUT4, InsR and IRS-1.

Conclusion

Maternal perinatal exposure to DBP induced obesity and accumulation of visceral adipose tissue for the adult female offspring. Serum glucolipid and local signal transduction of PTEN/PI3K/AKT pathway in muscle were not adversely affected by perinatal exposure to DBP for adult female offspring.
Effects of co-incubation of LPS-stimulated RAW 264.7 macrophages on leptin production by 3T3-L1 adipocytes: A method for co-incubating distinct adipose tissue cell lines
Authors: Caldari-Torres Cristina , Beck Jordan
Published: July 2021

Adipose tissue is a major endocrine organ capable of releasing inflammatory adipokines. Inflammatory adipokine release is linked to the changes occurring in adipose tissue in the overfed state, where tissue remodeling results in hypertrophic adipocytes that recruit monocytes to infiltrate the tissue and take on an inflammatory phenotype. As the proportion of inflammatory macrophages increases there is a concurrent increase in release of macrophage-specific inflammatory mediators, further contributing to the inflamed state and setting an inflammatory loop between the macrophages and adipocytes. Although most inflammatory adipokines are released by macrophages, adipocytes can also release immunomodulatory adipokines, such as leptin. The objective of this research was to determine if co-incubation of activated macrophages with mature adipocytes, using Transwell inserts, affected leptin release by mature adipocytes. We also examined if there were differences in the amount of cell-secreted products quantified in cell-conditioned media collected from macrophage-containing (Transwell insert) and adipocyte-containing (well) compartments. Mature adipocytes (differentiated 3T3-L1 murine fibroblasts) were co-incubated with control and lipopolysaccharide-stimulated (0.01 μg/ml) murine macrophages (RAW264.7), and nitric oxide, interleukin-6, and leptin levels were quantified in the cell-conditioned media from the two compartments. Activation status of the macrophages did not affect leptin release by the adipocytes. We observed higher amounts of leptin in wells compared to Transwells. Nitric oxide and interleukin-6 levels were similar between Transwells and wells, suggesting that these adipokines are traveling through the Transwell inserts and reaching equilibrium between the two compartments. There was a weak negative relationship between nitric oxide release by macrophages and leptin release by adipocytes. Our results suggest that co-incubating activated macrophages and adipocytes using Transwell inserts can result in distinct microenvironments in the different cellular compartments and that separate sampling of these compartments is required to detect the subtle signaling dynamics that exist between these cells.
Parallel Implementation of Smith-Waterman Algorithm on FPGA
Authors: de Oliveira Fabio F. , Dias Leonardo A. , Fernandes Marcelo A. C.
Published: July 2021

In bioinformatics, alignment is an essential technique for finding similarities between biological sequences. Usually, the alignment is performed with the Smith-Waterman (SW) algorithm, a well-known sequence alignment technique of high-level precision based on dynamic programming. However, given the massive data volume in biological databases and their continuous exponential increase, high-speed data processing is necessary. Therefore, this work proposes a parallel hardware design for the SW algorithm with a systolic array structure to accelerate the Forward and Backtracking steps. For this purpose, the architecture calculates and stores the paths in the Forward stage for pre-organizing the alignment, which reduces the complexity of the Backtracking stage. The backtracking starts from the maximum score position in the matrix and generates the optimal SW sequence alignment path. The architecture was validated on Field-Programmable Gate Array (FPGA), and synthesis analyses have shown that the proposed design reaches up to 79.5 Giga Cell Updates per Second (GCPUS).
Met-HER3 crosstalk supports proliferation via MPZL3 in MET-amplified cancer cells
Authors: Stern Yaakov E. , Duhamel Stephanie , Al-Ghabkari Abdulhameed , Monast Anie , Fiset Benoit , Aboualizadeh Farzaneh , Yao Zhong , Stagljar Igor , Walsh Logan A. , Park Morag
Published: July 2021

Receptor tyrosine kinases (RTKs) are recognized as targets of precision medicine in human cancer upon their gene amplification or constitutive activation, resulting in increased downstream signal complexity including heterotypic crosstalk with other RTKs. The Met RTK exhibits such reciprocal crosstalk with several members of the human EGFR (HER) family of RTKs when amplified in cancer cells. We show that Met signaling converges on HER3 tyrosine phosphorylation across a panel of seven MET-amplified cancer cell lines and that HER3 is required for cancer cell expansion and oncogenic capacity in-vitro and in-vivo. Gene expression analysis of HER3-depleted cells identified MPZL3, encoding a single-pass transmembrane protein, as a HER3-dependent effector in multiple MET-amplified cancer cell lines. MPZL3 interacts with HER3 and MPZL3 loss phenocopies HER3 loss in MET-amplified cells, while MPZL3 overexpression rescues proliferation upon HER3 depletion. Together, these data support an oncogenic role for a HER3-MPZL3 axis in MET-amplified cancers.
ACTION AFFORDANCE AFFECTS PROXIMAL AND DISTAL GOAL-ORIENTED PLANNING
Authors: Keshava Ashima , Gottschewsky Nina , Balle Stefan , Nezami Farbod Nosrat , Schüler Thomas , König Peter
Published: July 2021

Abstract

Seminal studies on human cognitive behavior have been conducted in controlled laboratory settings, demonstrating that visual attention is mainly goal-directed and allocated based on the action performed. However, it is unclear how far these results generalize to cognition in more naturalistic settings. The present study investigates active inference processes revealed by eye movements during interaction with familiar and novel tools with two levels of realism of the action affordance. We presented participants with 3D tool models that were either familiar or unfamiliar, oriented congruent or incongruent to their handedness, and asked participants to interact with them by lifting or using. Importantly, we used the same experimental design in two setups. In the first experiment, participants interacted with a VR controller in a low realism environment; in the second, they performed the task with an interaction setup that allowed differentiated hand and finger movements in a high realism environment. We investigated the differences in odds of fixations and their eccentricity towards the tool parts before action initiation. The results show that participants fixate more on the tool’s effector part before action initiation for the use task for unfamiliar tools. Furthermore, with more realistic action affordances, subjects fixate more on the tool’s handle as a function of the tool’s orientation, well before the action was executed. Secondly, the spatial viewing bias on the tool reveals early fixations are influenced by the task and the familiarity of the tools. In contrast, later fixations are associated with the manual planning of the interaction. In sum, the findings from the experiments suggest that fixations are made in a task-oriented way to plan the intended action well before action initiation. Further, with more realistic action affordances, fixations are made towards the proximal goal of optimally planning the grasp even though the perceived action on the tools is identical for both experimental setups. Taken together, proximal and distal goal-oriented planning is contextualized to the realism of action/interaction afforded by an environment.
ANTH domains within CALM, HIP1R, and Sla2 recognize ubiquitin internalization signals
Authors: Pashkova Natalya , Gakhar Lokesh , Yu Liping , Schnicker Nicholas J. , Minard Annabel Y. , Winistorfer Stanley , Johnson Ivan E. , Piper Robert C.
Published: July 2021

Ubiquitin (Ub) serves as a signal for clathrin-mediated endocytosis (CME) by engaging Ub-binding proteins with the internalization apparatus. Ub is a versatile internalization signal because it can be added to a wide variety of membrane proteins, expanding the capacity of cells to use a variety of regulatory mechanisms to specify the conditions under which a particular protein will be internalized. Several candidate adaptors that can recognize ubiquitinated membrane proteins have been identified that work in endocytic processes that are both clathrin-dependent and independent. These include Epsin and Eps15, which bind and help sort Ub-cargo into internalization sites. Here we identify additional components of the endocytosis apparatus that bind Ub. The N-terminal ANTH domains found in CALM, AP180, HIP1R and yeast Sla2 all bind monoubiquitin with µM affinity. ANTH domains belong to a larger superfamily of domains including ENTH and VHS domains, many of which have Ub-binding regions outside of their VHS/ENTH/ANTH domains that enable them to mediate Ub-dependent sorting events throughout the cell. Solution NMR studies combined with a crystal structure of the CALM ANTH domain in a complex with Ub show that Ub binds to a C-terminal region of the ANTH domain that is not present in ENTH domains. Combined loss of Ub-binding by ANTH-domain proteins and other Ub-binding domains within the internalization apparatus of yeast caused defects in the Ub-dependent internalization of the GPCR Ste2 but had no effect on internalization of Ste2 via other internalization signals. These studies define new components of the internalization machinery that work collectively with Epsin and Eps15 to specify recognition of Ub as an internalization signal.
Phosphate starvation response precedes abscisic acid response under progressive mild drought in plants
Authors: Nagatoshi Yukari , Ikazaki Kenta , Kobayashi Yasufumi , Mizuno Nobuyuki , Sugita Ryohei , Takebayashi Yumiko , Kojima Mikiko , Sakakibara Hitoshi , Kobayashi Natsuko I. , Tanoi Keitaro , Fujii Kenichiro , Baba Junya , Ogiso-Tanaka Eri , Ishimoto Masao , Yasui Yasuo , Oya Tetsuji , Fujita Yasunari
Published: July 2021

Drought severely damages crop production, even under conditions so mild that the leaves show no signs of wilting. However, it is unclear how field-grown plants respond to mild drought. Here, we show through 6 years of field trials that ridges are a useful experimental tool to mimic mild drought stress in the field. Mild drought reduces inorganic phosphate levels in the leaves to activate the phosphate starvation response in soybean plants in the field. UsingArabidopsis thalianaand its mutant plants grown in pots under controlled environments, we demonstrate that phosphate starvation response (PSR) occurs before abscisic acid response under progressive mild drought and that PSR plays a crucial role in plant growth under mild drought. Our observations in the field and laboratory using model crop and experimental plants provide insight into the molecular response to mild drought in field-grown plants and the relationship between nutrition and drought stress response.
Upregulation of breathing rate during running exercise by central locomotor circuits
Authors: Hérent Coralie , Diem Séverine , Fortin Gilles , Bouvier Julien
Published: July 2021

While respiratory adaptation to exercise is compulsory to cope with the increased metabolic supply to body tissues and with the necessary clearing of metabolic waste, the neural apparatus at stake remains poorly identified. Using viral tracing, ex vivo and in vivo optogenetic and chemogenetic interference strategies in mice, we unravel interactive locomotor and respiratory networks’ nodes that mediate the respiratory rate increase that accompanies a running exercise. We show that the mesencephalic locomotor region (MLR) and the lumbar spinal locomotor pattern generator (lumbar CPG), which respectively initiate and execute the locomotor behavior, access the respiratory network through distinct entry points. The MLR directly projects onto the inspiratory rhythm generator, the preBötzinger complex (preBötC), and can trigger a moderate increase of respiratory frequency, prior to, or even in the absence of, locomotion. In contrast, the lumbar CPG projects onto the retrotrapezoid nucleus (RTN) that in turn contacts the preBötC to enforce, during effective locomotion, higher respiratory frequencies. These data expand, on the one hand, the functional implications of the MLR beyond locomotor initiation to a bona fide respiratory modulation. On the other hand, they expand the adaptive respiratory ambitions of the RTN beyond chemoception to “locomotor- ception”.
Data and model considerations for estimating time-varying functional connectivity in fMRI
Authors: Ahrends C , Stevner A , Pervaiz U , Kringelbach ML , Vuust P , Woolrich M , Vidaurre D
Published: July 2021

Functional connectivity (FC) in the brain has been shown to exhibit subtle but reliable modulations within a session. One way of estimating time-varying FC is by using state-based models that describe fMRI time series as temporal sequences of states, each with an associated, characteristic pattern of FC. However, the estimation of these models from data sometimes fails to capture changes in a meaningful way, such that the model estimation assigns entire sessions (or the largest part of them) to a single state, therefore failing to capture within-session state modulations effectively; we refer to this phenomenon as the model becoming static, or model stasis. Here, we aim to quantify how the nature of the data and the choice of model parameters affect the model’s ability to detect temporal changes in FC using both simulated fMRI time courses and resting state fMRI data. We show that large between-subject FC differences can overwhelm subtler within-session modulations, causing the model to become static. Further, the choice of parcellation can also affect the model’s ability to detect temporal changes. We finally show that the model often becomes static when the number of free parameters that need to be estimated is high and the number of observations available for this estimation is low in comparison. Based on these findings, we derive a set of practical recommendations for time-varying FC studies, in terms of preprocessing, parcellation and complexity of the model.

Highlights

Time-varying FC models sometimes fail to detect temporal changes in fMRI data

Between- and within-subject FC variability affect model stasis

The choice of parcellation affects model stasis in real fMRI data

The number of observations and free parameters critically affect model stasis Keywords: fMRI; time-varying FC; Hidden Markov Model (HMM); resting state
SARS-CoV-2 Lambda variant exhibits higher infectivity and immune resistance
Authors: Kimura Izumi , Kosugi Yusuke , Wu Jiaqi , Yamasoba Daichi , Butlertanaka Erika P , Tanaka Yuri L , Liu Yafei , Shirakawa Kotaro , Kazuma Yasuhiro , Nomura Ryosuke , Horisawa Yoshihito , Tokunaga Kenzo , Takaori-Kondo Akifumi , Arase Hisashi ,   The Genotype to Phenotype Japan (G2P-Japan) Consortium, Saito Akatsuki , Nakagawa So , Sato Kei
Published: July 2021

SARS-CoV-2 Lambda, a new variant of interest, is now spreading in some South American countries; however, its virological features and evolutionary trait remain unknown. Here we reveal that the spike protein of the Lambda variant is more infectious and it is attributed to the T76I and L452Q mutations. The RSYLTPGD246-253N mutation, a unique 7-amino-acid deletion mutation in the N-terminal domain of the Lambda spike protein, is responsible for evasion from neutralizing antibodies. Since the Lambda variant has dominantly spread according to the increasing frequency of the isolates harboring the RSYLTPGD246-253N mutation, our data suggest that the insertion of the RSYLTPGD246-253N mutation is closely associated with the massive infection spread of the Lambda variant in South America.

Highlights

Lambda S is highly infectious and T76I and L452Q are responsible for this property

Lambda S is more susceptible to an infection-enhancing antibody

RSYLTPGD246-253N, L452Q and F490S confer resistance to antiviral immunity

Graphical Abstract
Unearthing Shifts in Microbial Communities Across a Soil Disturbance Gradient
Authors: Seitz Taylor J. , Schütte Ursel M. E. , Drown Devin M.
Published: July 2021

Permafrost, an important source of soil disturbance, is particularly vulnerable to climate change in Alaska where 85% of the land is underlain with discontinuous permafrost. Boreal forests, home to plants integral to subsistence diets of many Alaska Native communities, are not immune to the effects of climate change. Soil disturbance events such as permafrost thaw, wildfires, and land use change can influence abiotic conditions which can then affect active layer soil microbial communities. Previously, we found negative effects on boreal plants inoculated with microbes impacted by soil disturbance compared to plants inoculated with microbes from undisturbed soils. Here, we identify the key shifts in microbial inoculant communities altered by soil disturbance using 16S rRNA amplicon sequencing as well as changes in potential functional mechanisms that influence plant growth using long read metagenomics. Across our soil disturbance gradient, microbial communities differ significantly based on the level of soil disturbance. Consistent with previous results, the family Acidobacteriaceae, which consists of known plant promoters, was abundant in undisturbed soil, but practically absent in most disturbed soil. In contrast, Comamonadaceae, a family with known agricultural pathogens, was overrepresented in most disturbed soil communities compared to undisturbed. Within our metagenomic data, we found that soil disturbance level drives differences in microbial community function. These results indicate that a decrease in plant growth can be linked to changes in the community and functional composition driven by soil disturbance and climate change. Together these results build a genomic understanding of how shifting soil microbiomes may affect plant productivity and ecosystem health as the Arctic warms.
SARS-CoV-2 in the Republic of Guinea: Fragment and Whole-Genome Sequencing, Phylogenetic Analysis
Authors: Kritsky A.A. , Krasnov Ya.M. , Keita M. , Keita S. , Fedorov A.V. , Shevtsova A.P. , Guseva N.P. , Kazorina E.V. , Sosedova E.A. , Katyshev A.D. , Naryshkina E.A. , Kolomoets E.V. , Shcherbakova S.A. , Popova A.Yu. , Kutyrev V.V.
Published: July 2021

Genetic diversity of SARS-CoV-2 isolates circulating in the Republic of Guinea in May and June 2020, as well as in March 2021, has been demonstrated using fragment (S gene) and whole genome sequencing of 14 strains. Analysis of nucleotide sequences and phylogenetic constructs make it possible to divide the studied strains into 3 groups. Comparison of the obtained data with the already available epidemiological data proves the initial importation of COVID-19 from Western European countries, and also demonstrates four independent import routes in two time periods (March 2020 and no later than March 2021).
T helper cell-licensed mast cells promote inflammatory Th17 cells
Authors: Leveque Edouard , Joulia Régis , Petitfils Camille , Mas-Orea Xavier , Payros Gaelle , Laurent Camille , Gaudenzio Nicolas , Dietrich Gilles , Valitutti Salvatore , Cenac Nicolas , Espinosa Eric
Published: July 2021

CD4+ T helper cells (Th) infiltrate sites of inflammation and orchestrate the immune response by instructing local leukocytes. Mast cells (MCs) are tissue sentinel cells particularly abundant in skin and mucosa. Here, we analyzed the interplay between human MCs and Th cells and, through the application of RNAseq and functional assays, showed that Th cells induced a specific transcriptomic program in helped MCs (named here MCTH) driving them toward an inflammatory phenotype. The gene signature of MCTH indicated that MCs helped by Th cell acquired in turn the capacity to regulate effector T cell response through wide-range of soluble and membrane ligands. Accordingly, we showed that MCTH promoted Th17 cells and notably an inflammatory subset of Th17, producing both IFN-γ and GM-CSF, through a PGE2 and IL-1β axis. Our findings demonstrate that activated effector/memory CD4+ T cells activate and instruct resting MCs toward a specific differentiated pro-inflammatory phenotype endowed with the capacity to speak back to effector T cells and to mold their functions.
Navigating a diversity of turbulent plumes is enhanced by sensing complementary temporal features of odor signals
Authors: Jayaram Viraaj , Kadakia Nirag , Emonet Thierry
Published: July 2021

We and others have shown that during odor plume navigation, walking Drosophila melanogaster bias their motion upwind in response to both the frequency of their encounters with the odor (Demir et al., 2020), and the intermittency of the odor signal, i.e. the fraction of time the signal is above a detection threshold (Alvarez-Salvado et al., 2018). Here we combine and simplify previous mathematical models that recapitulated these data to investigate the benefits of sensing both of these temporal features, and how these benefits depend on the spatiotemporal statistics of the odor plume. Through agent-based simulations, we find that navigators that only use frequency or intermittency perform well in some environments – achieving maximal performance when gains are near those inferred from experiment – but fail in others. Robust performance across diverse environments requires both temporal modalities. However, we also find a steep tradeoff when using both sensors simultaneously, suggesting a strong benefit to modulating how much each sensor is weighted, rather than using both in a fixed combination across plumes.
Filopodia powered by class X myosin promote fusion of mammalian myoblasts
Authors: Hammers David W. , Hart Cora C. , Matheny Michael K. , Heimsath Ernest G. , Lee Young il , Hammer John A. , Cheney Richard E. , Sweeney H. Lee
Published: July 2021

Skeletal muscle fibers are multinucleated cellular giants formed by the fusion of mononuclear myoblasts. Several molecules involved in myoblast fusion have been discovered, and finger-like projections coincident with myoblast fusion have also been implicated in the fusion process. The role of these cellular projections in muscle cell fusion was investigated herein. We demonstrate that these projections are filopodia generated by class X myosin (Myo10), an unconventional myosin motor protein specialized for filopodia. We further show that Myo10 is highly expressed by differentiating myoblasts, and Myo10 ablation inhibits both filopodia formation and myoblast fusion in vitro. In vivo, Myo10 labels regenerating muscle fibers associated with Duchenne muscular dystrophy and acute muscle injury. Conditional loss of Myo10 from muscle-resident stem cells, known as satellite cells, severely impairs postnatal muscle regeneration. Furthermore, the muscle fusion proteins Myomaker and Myomixer are detected in myoblast filopodia. These data demonstrate that Myo10-driven filopodia facilitate multi-nucleated mammalian muscle formation.
Cryo-EM reconstructions of inhibitor-bound SMG1 kinase reveal an autoinhibitory state dependent on SMG8
Authors: Langer Lukas M. , Bonneau Fabien , Gat Yair , Conti Elena
Published: July 2021

The PI3K-related kinase (PIKK) SMG1 monitors progression of metazoan nonsense-mediated mRNA decay (NMD) by phosphorylating the RNA helicase UPF1. Previous work has shown that the activity of SMG1 is impaired by small molecule inhibitors, is reduced by the SMG1 interactors SMG8 and SMG9, and is downregulated by the so-called SMG1 insertion domain. However, the molecular basis for this complex regulatory network has remained elusive. Here, we present cryo-electron microscopy reconstructions of human SMG1-9 and SMG1-8-9 complexes bound to either a SMG1 inhibitor or a non-hydrolyzable ATP analogue at overall resolutions ranging from 2.8 to 3.6 Å. These structures reveal the basis with which a small molecule inhibitor preferentially targets SMG1 over other PIKKs. By comparison with our previously reported substrate-bound structure (Langer et al. 2020), we show that the SMG1 insertion domain can exert an autoinhibitory function by directly blocking the substrate binding path as well as overall access to the SMG1 kinase active site. Together with biochemical analysis, our data indicate that SMG1 autoinhibition is stabilized by the presence of SMG8. Our results explain the specific inhibition of SMG1 by an ATP-competitive small molecule, provide insights into regulation of its kinase activity within the NMD pathway, and expand the understanding of PIKK regulatory mechanisms in general.
Ifenprodil Intracerebrally Offers Neuroprotection against 6-OHDA-Induced Toxicity in SD-Rats via Enhancing Autophagy Function
Authors: Zhao Xinyu , Tian Fugang , Guo Chunmin , Yu Xin
Published: July 2021

The progressive decline of dopamine neurons in the substantia nigra is the main pathogenic change in Parkinson’s disease (PD). Studies have found that excessive excitement of glutamatergic neurons causes intracellular calcium overload and induces autophagy impairment, which is one of the main mechanisms of dopamine neuron damage. The neuroprotective effect of Ifenprodil against 6-OHDA-injured mice was studied in this study. Ifenprodil was administered intraperitoneally (i.p.) or intracerebrally to rats who had a nigral-striatum pathway lesioned by 6-OHDA stereotactic brain injection. The ability to move was evaluated. The survival of dopamine neurons in the nigral was determined using HE staining, while TH-positive expression was measured using immunohistochemistry. Western Blot was used to examine the expression of CaM protein and light chain 3 (LC3), Beclin-1, BNIP3LNix, and p62. The results revealed that Ifenprodil improves motor function in 6-OHDA rats, and intracerebral injection is more effective than systemic administration. The same results also found in HE and IHC. Ifenprodil enhanced LC3II, BNIP3LNix, and Beclin-1 while decreasing p62, p-CaMKII, and β-Ca expression. In addition, Ifenprodil reduced the activation of microglia caused by 6-OHDA. Overall, the findings imply that Ifenprodil intracerebrally may protect against Parkinson’s disease via modulating autophagy-related proteins during 6-OHDA-induced toxicity.
Conformational changes of loops highlight a potential binding site in Rhodococcus equi VapB
Authors: Geerds Christina , Haas Albert , Niemann Hartmut H.
Published: July 2021

Virulence-associated proteins (Vaps) contribute to the virulence of the pathogen Rhodococcus equi, but their mode of action has remained elusive. All Vaps share a conserved core of about 105 amino acids that folds into a compact eight-stranded antiparallel β-barrel with a unique topology. At the top of the barrel, four loops connect the eight β-strands. Previous Vap structures did not show concave surfaces that might serve as a ligand-binding site. Here, the structure of VapB in a new crystal form was determined at 1.71 Å resolution. The asymmetric unit contains two molecules. In one of them, the loop regions at the top of the barrel adopt a different conformation from other Vap structures. An outward movement of the loops results in the formation of a hydrophobic cavity that might act as a ligand-binding site. This lends further support to the hypothesis that the structural similarity between Vaps and avidins suggests a potential binding function for Vaps.
Organisational change capacity and performance: the moderating effect of coercive pressure
Authors: Sukoco Badri Munir , Supriharyanti Elisabeth , Sabar  , Susanto Ely , Nasution Reza Ashari , Daryanto Arief
Published: July 2021

Purpose

To examine three dimensions of organisational change capacity (OCC) which have been proposed sequentially in the following order: OCC for change will affect process capacity for change and develop context capacity for change. Specifically, this study explores the moderating effects of coercive pressure.

Design/methodology/approach

To test the proposed hypotheses, this study conducted survey among middle-level leaders of the 11 top universities (autonomous higher education institutions – AHEIs) in Indonesia. This study used a sample of 92 respondents, deans 21 and vice deans 71 of 11 top Indonesian universities. To test data processing using the SmartPLS 3.0 tool.

Findings

The findings indicate that learning capacity for change is the starting point of OCC, and it influences process capacity and context capacity for change. Coercive pressure strengthens the relationship between learning capacity and context capacity for change. Further, context capacity for change determines organisational performance.

Originality/value

This study empirically examines the OCC construction mechanism as follows: learning capacity for change influences process capacity for change and then has an effect on the OCC for change, which ultimately affects organisational performance.
The impact of changes in regulations on Malaysian IPOs
Authors: Mohd-Rashid Rasidah , Tajuddin Ahmad Hakimi , Khaw Karren Lee-Hwei , Ong Chui Zi
Published: July 2021

Purpose

This study aims to examine the changes in equity guidelines and initial returns in the Malaysian initial public offering (IPO) market.

Design/methodology/approach

The study uses cross-sectional data over 16 years from 2000 to 2016. It uses ordinary least squares for the baseline model and incorporates an interaction term, quantile regression, quadratic term, break test and logit regression model for further analysis.

Findings

The results support the propositions that lockup provisions signal commitment and demand increase initial returns. The revision in the Bumiputera equity requirement means that issuers no longer need to discount offer prices to entice investors. Finally, the revised Sharīʿah-compliance screening requirement ensures that stocks are better in quality and more transparent, leading to a higher demand that drives prices upwards.

Research limitations/implications

This study’s findings provide insights into how issuers can secure good subscriptions. Besides, policymakers should ensure that firms disclose the required information in their prospectuses.

Originality/value

This study adds to the body of knowledge on whether and how the regulatory requirements affect IPO initial returns.