bluuebunny/crossref_metadata_2025_split huggingface dataset:
Small proteins modulate ion channel-like ACD6 to regulate immunity inArabidopsis thaliana
Authors: Chen Junbin , Li Lei , Kim Jong Hum , Neuhäuser Benjamin , Wang Mingyu , Thelen Michael , Hilleary Richard , Chi Yuan , Wei Luyang , Venkataramani Kavita , Exposito-Alonso Moises , Liu Chang , Keck Jakob , Barragan A. Cristina , Schwab Rebecca , Lutz Ulrich , Pei Zhen-Ming , He Sheng-Yang , Ludewig Uwe , Weigel Detlef , Zhu Wangsheng 
Published: January 2021

SUMMARYACCELERATED CELL DEATH 6 (ACD6) mediates a trade-off between growth and defense inArabidopsis thaliana. However, the precise biochemical mechanism by which ACD6 and related proteins in plants act remains enigmatic. Here, we identified two loci,MODULATOR OF HYPERACTIVE ACD6 1(MHA1) and its paralogMHA1-LIKE(MHA1L), that code for ∼7 kDa proteins that differentially interact with specific ACD6 variants. MHA1L enhances accumulation of an ACD6 complex, thereby increasing activity of theACD6standard allele for regulating plant growth and defenses. ACD6 is a multipass transmembrane protein with intracellular ankyrin repeats that are structurally similar to those found in mammalian ion channels. Several lines of evidence link increased ACD6 activity to enhanced calcium influx, likely mediated by ACD6 itself and with MHA1L as a direct regulator of ACD6.
Shifts in marine invertebrate bacterial assemblages associated with tissue necrosis during a heatwave
Authors: Rubio-Portillo Esther , Ramos Esplá Alfonso A. , Antón Josefa 
Published: January 2021

AbstractMarine heatwaves (MHWs) are periods of extremely high seawater temperature that affect marine ecosystems in several ways. Anthozoans (corals and gorgonians) and Porifera (sponges) are usually among the taxa most affected by MHWs. Both are holobiont entities that form complex interactions with a wide range of microbes, which are an essential part of these organisms and play key roles in their health status. Here, we determine microbial community changes suffered in two corals (Cladocora caespitosaandOculina patagonica), one gorgonian (Leptogorgia sarmentosa), and one sponge (Sarcotragus fasciculatus) during the 2015 MHW. The microbial communities were different among hosts and displayed shifts related to host health status, with a higher abundance in necrosed tissues ofRuegeriaspecies or of potential pathogens likeVibrio.We also carry out a meta-analysis using 93 publicly accessible 16S rRNA gene libraries fromO. patagonica,C. caespitosaandL. sarmentosato establish a Mediterranean core microbiome in these species. We have identified oneRuegeriaOTU that maintained a stable and consistent association with these species, which was also related with tissue necrosis in their hosts. Therefore,Ruegeriasp. could play an important and still underexplored role in the health status of its hosts.
Longitudinal analysis of humoral immunity against SARS-CoV-2 Spike in convalescent individuals up to 8 months post-symptom onset
Authors: Anand Sai Priya , Prévost Jérémie , Nayrac Manon , Beaudoin-Bussières Guillaume , Benlarbi Mehdi , Gasser Romain , Brassard Nathalie , Laumaea Annemarie , Gong Shang Yu , Bourassa Catherine , Brunet-Ratnasingham Elsa , Medjahed Halima , Gendron-Lepage Gabrielle , Goyette Guillaume , Gokool Laurie , Morrisseau Chantal , Bégin Philippe , Martel-Laferrière Valérie , Tremblay Cécile , Richard Jonathan , Bazin Renée , Duerr Ralf , Kaufmann Daniel E. , Finzi Andrés 
Published: January 2021

AbstractFunctional and lasting immune responses to the novel coronavirus (SARS-CoV-2) are currently under intense investigation as antibody titers in plasma have been shown to decline during convalescence. Since the absence of antibodies does not equate to absence of immune memory, we sought to determine the presence of SARS-CoV-2-specific memory B cells in COVID-19 convalescent patients. In this study, we report on the evolution of the overall humoral immune responses on 101 blood samples obtained from 32 COVID-19 convalescent patients between 16 and 233 days post-symptom onset. Our observations indicate that anti-Spike and anti-RBD IgM in plasma decay rapidly, whereas the reduction of IgG is less prominent. Neutralizing activity in convalescent plasma declines rapidly compared to Fc-effector functions. Concomitantly, the frequencies of RBD-specific IgM+ B cells wane significantly when compared to RBD-specific IgG+ B cells, which increase over time, and the number of IgG+ memory B cells which remain stable thereafter for up to 8 months after symptoms onset. With the recent approval of highly effective vaccines for COVID-19, data on the persistence of immune responses are of central importance. Even though overall circulating SARS-CoV-2 Spike-specific antibodies contract over time during convalescence, we demonstrate that RBD-specific B cells increase and persist up to 8 months post symptom onset. We also observe modest increases in RBD-specific IgG+ memory B cells and importantly, detectable IgG and sustained Fc-effector activity in plasma over the 8-month period. Our results add to the current understanding of immune memory following SARS-CoV-2 infection, which is critical for the prevention of secondary infections, vaccine efficacy and herd immunity against COVID-19.
Electrophysiological evidence of synergistic auxin transport by interacting Arabidopsis ABCB4 and PIN2 proteins
Authors: Deslauriers Stephen D. , Spalding Edgar P. 
Published: January 2021

AbstractTo understand why both ATP-binding cassette B (ABCB) and PIN-FORMED (PIN) proteins are required for polar auxin transport through tissues, even though only the latter is polarly localized, we biophysically studied their transport characteristics separately and together by whole-cell patch clamping. ABCB4 and PIN2 fromArabidopsis thalianaexpressed in human embryonic kidney cells displayed electrogenic activity when CsCl-based electrolytes were used. Current-voltage (I-V) analysis of the activities and modeling the effects of adding the auxin anion (IAA−) as a potential substrate with the Goldman-Hodgkin-Katz equation, demonstrated that ABCB4 and PIN2 were 9-fold and 10-fold more selective for IAA−than Cl−, respectively. Thus, these proteins directly transport IAA−, which was not unequivocally established by previous auxin retention assays. Co-expression of ABCB4 and PIN2 produced an especially significant result. Co-expression synergistically doubled the selectivity for IAA−. An area of two-fold higher selectivity for IAA−that this result indicates will occur in cells with asymmetric PIN2 and symmetric ABCB4 matches what early models found to be necessary to create observed levels of polar auxin transport through tissues. Thus, the requirement for two different proteins appears to be explained by a synergistic effect on selectivity. More substrate details and important pharmacological results are reported.
Neuronal post-developmentally acting SAX-7S/L1CAM can function as cleaved fragments to maintain neuronal architecture inC. elegans
Authors: Desse V.E. , Blanchette C.R. , Perrat P. , Bénard C.Y. 
Published: January 2021

ABSTRACTWhereas remarkable advances have uncovered mechanisms that drive nervous system assembly, the processes responsible for the lifelong maintenance of nervous system architecture remain poorly understood. Subsequent to its establishment during embryogenesis, neuronal architecture is maintained throughout life in the face of the animal’s growth, maturation processes, the addition of new neurons, body movements, and aging. TheC. elegansprotein SAX-7, homologous to the vertebrate L1 protein family, is required for maintaining the organization of neuronal ganglia and fascicles after their successful initial embryonic development. To dissect the function ofsax-7in neuronal maintenance, we generated a null allele andsax-7S-isoform-specific alleles. We find that the nullsax-7(qv30)is, in some contexts, more severe than previously described mutant alleles, and that the loss ofsax-7Slargely phenocopies the null, consistent withsax-7Sbeing the key isoform in neuronal maintenance. Using a sfGFP::SAX-7S knock-in, we observesax-7Sto be predominantly expressed across the nervous system, from embryogenesis to adulthood. Yet, its role in maintaining neuronal organization is ensured by post-developmentally acting SAX-7S, as larval transgenicsax-7S(+) expression alone is sufficient to profoundly rescue the null mutants’ neuronal maintenance defects. Moreover, the majority of the protein SAX-7 appears to be cleaved, and we show that these cleaved SAX-7S fragments together, not individually, can fully support neuronal maintenance. These findings contribute to our understanding of the role of the conserved protein SAX-7/L1CAM in long-term neuronal maintenance, and may help decipher processes that go awry in some neurodegenerative conditions.
Profiling transcription factor sub-networks in type I interferon signaling and in response to SARS-CoV-2 infection
Authors: Ramana Chilakamarti V. 
Published: January 2021

AbstractType I interferons (IFN α/β) play a central role in innate immunity to respiratory viruses, including coronaviruses. Genetic defects in type I interferon signaling were reported in a significant proportion of critically ill COVID-19 patients. Extensive studies on interferon-induced intracellular signal transduction pathways led to the elucidation of the Jak-Stat pathway. Furthermore, advances in gene expression profiling by microarrays have revealed that type I interferon rapidly induced multiple transcription factor mRNA levels. In this study, transcription factor profiling in the transcriptome was used to gain novel insights into the role of inducible transcription factors in response to type I interferon signaling in immune cells and in lung epithelial cells after SARS-CoV-2 infection. Modeling the interferon-inducible transcription factor mRNA data in terms of distinct sub-networks based on biological functions such as antiviral response, immune modulation, and cell growth revealed enrichment of specific transcription factors in mouse and human immune cells. The evolutionarily conserved core type I interferon gene expression consists of the inducible transcriptional factor mRNA of the antiviral response sub-network and enriched in granulocytes. Analysis of the type I interferon-inducible transcription factor sub-networks as distinct protein-protein interaction pathways revealed insights into the role of critical hubs in signaling. Interrogation of multiple microarray datasets revealed that SARS-CoV-2 induced high levels of IFN-beta and interferon-inducible transcription factor mRNA in human lung epithelial cells. Transcription factor mRNA of the three major sub-networks regulating antiviral, immune modulation, and cell growth were differentially regulated in human lung epithelial cell lines after SARS-CoV-2 infection and in the tissue samples of COVID-19 patients. A subset of type I interferon-inducible transcription factors and inflammatory mediators were specifically enriched in the lungs and neutrophils of COVID-19 patients. The emerging complex picture of type I IFN transcriptional regulation consists of a rapid transcriptional switch mediated by the Jak-Stat cascade and a graded output of the inducible transcription factor activation that enables temporal regulation of gene expression.
The CXCR6/CXCL16 axis links inflamm-aging to disease severity in COVID-19 patients
Authors: Payne Daniel J. , Dalal Surita , Leach Richard , Parker Richard , Griffin Stephen , McKimmie Clive S. , Cook Graham P. , Richards Stephen J. , Hillmen Peter , Munir Talha , Arnold Louise , Riley Kathryn , McKinley Claire , Place Sandra , Baretto Richard L. , Newton Darren J. 
Published: January 2021

AbstractAdvancing age and chronic health conditions, significant risk factors for severe COVID-19, are associated with a pro-inflammatory state, termed inflamm-aging. CXCR6+T cells are known to traffic to the lung and have been reported to increase with age. The ligand of CXCR6, CXCL16, is constitutively expressed in the lung and upregulated during inflammatory responses and the CXCR6/CXCL16 axis is associated with severe lung disease and pneumonia. Genome-wide association studies have also recently identified 3p21.31, encompassing theCXCR6gene, as a susceptibility locus for severe COVID-19. We assessed numbers T cells expressing the chemokine receptor CXCR6 and plasma levels of CXCL16, in control and COVID-19 patients. Results demonstrated that circulating CD8+CXCR6+T cells were significantly elevated with advancing age, yet virtually absent in patients with severe COVID-19. Peripheral levels of CXCL16 were significantly upregulated in severe COVID-19 patients compared to either mild COVID-19 patients or SARS-CoV-2 negative controls. This study supports a significant role of the CXCR6/CXCL16 axis in the immunopathogenesis of severe COVID-19.
Excitable axonal domains adapt to sensory deprivation in the olfactory system
Authors: George Nicholas M , Macklin Wendy B , Restrepo Diego 
Published: January 2021

AbstractThe axon initial segment, nodes of Ranvier, and the oligodendrocyte-derived myelin sheath have significant influence on the firing patterns of neurons and the faithful, coordinated transmission of action potentials to downstream brain regions. In the olfactory bulb, olfactory discrimination tasks lead to adaptive changes in cell firing patterns, and the output signals must reliably travel large distances to other brain regions along highly myelinated tracts. Whether myelinated axons adapt to facilitate olfactory sensory processing is unknown. Here, we investigate the morphology and physiology of mitral cell axons in the adult olfactory system, and show that unilateral sensory deprivation causes system-wide adaptations in axons. Mitral cell spiking patterns and action potentials also adapted to sensory deprivation. Strikingly, both axonal morphology and mitral cell physiology were altered on both the deprived and non-deprived sides, indicating system level adaptations to reduced sensory input. Our work demonstrates a previously unstudied mechanism of plasticity in the olfactory system.
Global connectivity fingerprints predict the domain generality of multiple-demand regions
Authors: Schultz Douglas H. , Ito Takuya , Cole Michael W. 
Published: January 2021

AbstractA set of distributed cognitive control networks are known to contribute to diverse cognitive demands, yet it is unclear how these networks gain this domain-general capacity. We hypothesized that this capacity is largely due to the particular organization of the human brain’s intrinsic network architecture. Specifically, we tested the possibility that each brain region’s domain generality is reflected in its level of global (hub-like) intrinsic connectivity, as well as its particular global connectivity pattern (connectivity fingerprint). Consistent with prior work, we found that cognitive control networks exhibited domain generality, as they represented diverse task context information covering sensory, motor response, and logic rule domains. Supporting our hypothesis, we found that the level of global intrinsic connectivity (estimated with resting-state fMRI) was correlated with domain generality during tasks. Further, using a novel information fingerprint mapping approach, we found that each cognitive control region’s unique rule response profile (information fingerprint) could be predicted based on its unique intrinsic connectivity fingerprint and the information content in non-cognitive control regions. Together these results suggest that the human brain’s intrinsic network architecture supports its ability to represent diverse cognitive task information, largely via the location of multiple-demand regions within the brain’s global network organization.
Factors that affect protein abundance of the bZIP transcription factor ABRE-BINDING FACTOR 2 (ABF2), a positive regulator of abscisic acid signaling
Authors: Linden Katrina J , Chen Yi-Tze , Kyaw Khin , Schultz Brandan , Callis Judy 
Published: January 2021

ABSTRACTMost members of bZIP transcription factor (TF) subgroup A play important roles as positive effectors in abscisic acid (ABA) signaling during germination and/or in vegetative stress responses. In multiple plant species, one member, ABA INSENSITIVE 5 (ABI5), is a major transcription factor that promotes seed maturation and blocks early seeding growth in response to ABA. Other members, referred to as either ABRE-Binding Factors (ABFs), ABRE-Binding proteins (AREBs), or D3 PROTEIN BINDING FACTORS (DPBFs), are implicated as major players in stress responses during vegetative growth. Studies on the proteolytic regulation of ABI5, ABF1, and ABF3 inArabidopsis thalianahave shown that the proteins have moderate degradation rates and accumulate in the presence of the proteasome inhibitor MG132. Exogenous ABA slows their degradation and the ubiquitin E3 ligase called KEEP ON GOING (KEG) is important for their degradation. However, there are some reported differences in degradation among subgroup A members. The conserved C-terminal sequences (referred to as the C4 region) enhance degradation of ABI5 but stabilize ABF1 and ABF3. To better understand the proteolytic regulation of the ABI5/ABFs and determine whether there are differences between vegetative ABFs and ABI5, we studied the degradation of an additional family member, ABF2, and compared itsin vitrodegradation to that of ABI5. As previously seen for ABI5, ABF1, and ABF3, epitope-tagged constitutively expressed ABF2 degrades in seedlings treated with cycloheximide and is stabilized following treatment with the proteasome inhibitor MG132. Tagged ABF2 protein accumulates when seedlings are treated with ABA but its mRNA levels do not increase, suggesting that the protein is stabilized in the presence of ABA. ABF2 is also anin vitroubiquitination substrate of the E3 ligase KEG and recombinant ABF2 is stable inkeglysates. ABF2 with a C4 deletion degrades more quicklyin vitrothan full-length ABF2, as previously observed for ABF1 and ABF3, suggesting that the conserved C4 region contributes to its stability. In contrast to ABF2 and consistent with previously published work, ABI5 with C terminal deletions including an analogous C4 deletion is stabilizedin vitrocompared to full length ABI5.In vivoexpression of an ABF1 C4 deletion protein appears to have reduced activity compared to equivalent levels of full length ABF1. Additional group A family members show similar proteolytic regulation by MG132 and ABA. Altogether, these results together with other work on ABI5 regulation suggest that the vegetative ABFs share proteolytic regulatory mechanisms that are not completely shared with ABI5.
Elevated HScore is Associated with Poor Clinical Outcomes in COVID-19, Even in the Absence of Secondary Hemophagocytic Lymphohistiocytosis
Authors: Benavente Rafael , Peña Camila , Cid Allyson , Cabello Nicolás , Bustamante Pablo , Álvarez Marco , Henríquez Elizabeth , Soto Andrés , Rubilar Erika 
Published: January 2021

AbstractIntroductionPatients with Coronavirus Disease 2019 (COVID-19) frequently experience a hyperinflammatory syndrome, that leads to unfavorable outcomes. This condition resembles Secondary Hemophagocytic Lymphohistiocytosis (sHLH) described in neoplastic, rheumatic and other infectious diseases. However, it has not been prospectively studied on these patients. A scoring system (HScore) has been validated for sHLH, and recently proposed to evaluate hyperinflammation in COVID-19.Methods143 patients aged ≥18 years admitted because of COVID-19 were enrolled in a prospective, single-center, cohort study. HScore was calculated within the 72 hours since admission. The incidence of sHLH during hospitalization was evaluated. Additionally, the relationship between HScore ≥130 points and either the requirement of mechanical ventilation or 60-days mortality was explored.ResultsThe median age of enrolled patients was 57 (21-100), and 63.6% were male. The median HScore was 96 (33-169). One patient was diagnosed with sHLH (incidence 0,7%), due to a HScore of 169. After adjusting for age, sex, comorbidities and obesity, HScore ≥130 was independently associated with the composite clinical outcome (HR 2.13, p=0.022).ConclusionsHLH is not frequent among COVID-19 patients. HScore can efficiently predict the risk for poor outcomes.
Estimation of the SARS-CoV-2 infection fatality rate in Germany
Authors: Dimpfl Thomas , Sönksen Jantje , Bechmann Ingo , Grammig Joachim 
Published: January 2021

ABSTRACTAssessing the infection fatality rate (IFR) of SARS-CoV-2 is one of the most controversial issues during the pandemic. Due to asymptomatic or mild courses of COVID-19, many infections remain undetected. Reported case fatality rates – COVID-19-associated deaths divided by number of detected infections – are therefore poor estimates of the IFR. Endogenous changes of the population at risk of a SARS-CoV-2 infection, changing test practices and an improved understanding of the pathogenesis of COVID-19 further exacerbate the estimation of the IFR. Here, we propose a strategy to estimate the IFR of SARS-CoV-2 in Germany that combines official data on reported cases and fatalities supplied by the Robert Koch Institute (RKI) with data from seroepidemiological studies in two infection hotspots, the Austrian town Ischgl and the German municipality Gangelt, respectively. For this purpose, we use the law of total probability to derive an approximate formula for the IFR that is based on a set of assumptions regarding data quality and test specificity and sensitivity. The resulting estimate of the IFR in Germany of 0.83% (95% CI: [0.69%; 0.98%]) that is based on a combination of the RKI and Ischgl data is notably higher than the IFR estimate reported in the Gangelt study (0.36% [0.29%; 0.45%]). It is closer to the consolidated estimate based on a meta-analysis (0.68% [0.53%; 0.82%]), where the difference can be explained by Germany’s disadvantageous age structure. As a result of virus mutations, vaccination strategies, and improved therapy, a re-estimation of the IFR will eventually be mandated; the proposed method is able to account for such developments.
Connectional Asymmetry of the Inferior Parietal Lobule Shapes Hemispheric Specialization in Humans, Chimpanzees, and Rhesus Macaques
Authors: Cheng Luqi , Zhang Yuanchao , Li Gang , Wang Jiaojian , Sherwood Chet C. , Gong Gaolang , Fan Linzhong , Jiang Tianzi 
Published: January 2021

AbstractThe inferior parietal lobule (IPL) is one of the most expanded cortical regions in humans relative to other primates. It is also among the most structurally and functionally asymmetric regions in the human cerebral cortex. Whether the structural and connectional asymmetries of IPL subdivisions differ across primate species and how this relates to functional asymmetries remain unclear. We identified IPL subregions that exhibited positive allometric in both hemispheres, scaling across rhesus macaque monkeys, chimpanzees, and humans. The patterns of IPL subregions asymmetry were similar in chimpanzees and humans, but no IPL asymmetries were evident in macaques. Among the comparative sample of primates, humans showed the most widespread asymmetric connections in the frontal, parietal, and temporal cortices, constituting leftward asymmetric networks that may provide an anatomical basis for language and tool use. Unique human asymmetric connectivity between the IPL and primary motor cortex might be related to handedness. These findings suggest that structural and connectional asymmetries may underlie hemispheric specialization of the human brain.