bluuebunny/crossref_metadata_2025_split huggingface dataset:
SIX1 Reprograms Myogenic Transcription Factors to Maintain the Rhabdomyosarcoma undifferentiated state
Authors: Hsu Jessica Y. , Danis Etienne P. , Nance Stephanie , O’Brien Jenean , Wessells Veronica M. , Goodspeed Andrew E. , Talbot Jared C. , Amacher Sharon L. , Jedlicka Paul , Black Joshua C. , Costello James C. , Durbin Adam D. , Artinger Kristin B. , Ford Heide L. 
Published: April 2021

SummaryRhabdomyosarcoma (RMS) is a pediatric skeletal muscle sarcoma characterized by the expression of the myogenic-lineage transcription factors (TF) MYOD1 and MYOG. Despite high expression of these TFs, RMS cells fail to terminally differentiate, suggesting the presence of factors that alter their function. Here, we demonstrate that the developmental TF, SIX1, is highly expressed in RMS and is critical to maintain a muscle progenitor-like state. SIX1 loss induces terminal differentiation of RMS cells into myotube-like cells and dramatically impedes tumor growthin vivo. We show that SIX1 maintains the RMS undifferentiated state by controlling enhancer activity and MYOD1 occupancy at loci more permissive to tumor growth over terminal muscle differentiation. Finally, we demonstrate that a gene signature derived from SIX1 loss correlates with differentiation status in RMS and predicts RMS progression in human disease. Our findings demonstrate a master regulatory role for SIX1 in the repression of RMS differentiation via genome-wide alterations in MYOD1-mediated transcription.HighlightsSIX1 prevents differentiation in RMS while it promotes differentiation during normal developmentFN-RMS are highly dependent on SIX1 for growth in both zebrafish and mouse xenograft modelsLoss of SIX1 alters the transcriptional landscape of RMS cells, inducing a growth to differentiation switchSIX1 knockdown in FN-RMS causes reduced super enhancer-based activity at stem-related genes and enhanced MYOD1 binding to differentiation loci, resulting in the activation of a myogenic differentiation programA gene signature derived from SIX1 loss strongly correlates with myogenic differentiation status and is predictive of advanced RMS.
Geraniol Enhances Inhibitory Inputs to Paraventricular Thalamic Nucleus and Induces Sedation in Mice
Authors: Xu Ling , Wang Yan , Yang Ya-Yue , Hua Xiao-Xiao , Du Li-Xia , Zhu Jian-Yu , Huang Li-Na , Fang Fang , Liu Ming-Zhe , Zhang Rui , Li Jin-Bao , Wang Yan-Qing , Zhang Ling , Mi Wen-Li , Mu Di 
Published: April 2021

AbstractGeraniol (GE), a plant-derived acyclic monoterpene, shows a wide variety of beneficial effects. Notably, recent studies have reported the potential sedative effects of GE in fish and rats. However, the mechanisms of GE in sedation remain elusive. Here, we found that GE reduced locomotion, relieved pentylenetetrazol (PTZ)-induced seizures, altered the electroencephalogram (EEG), and facilitated general anesthesia in mice. Meanwhile, GE decreased c-Fos expression and suppressed the calcium activity in the paraventricular thalamic nucleus (PVT). Microinjection of GE into the PVT reduced locomotion and facilitated propofol-induced anesthesia. Furthermore, the electrophysiology results showed that GE-induced dramatic membrane hyperpolarization and suppressed the neuronal activity of PVT neurons, mainly by prolonging spontaneous inhibitory postsynaptic currents and inducing tonic inhibitory currents via GABAAreceptors. Our study revealed that GE enhances inhibitory inputs to PVT neurons and induces sedation in mice. These findings provide a potential candidate for further development of sedatives and anesthetics.Graphic Summary
Task-independent metrics of computational hardness predict human cognitive performance
Authors: Franco Juan P. , Doroc Karlo , Yadav Nitin , Bossaerts Peter , Murawski Carsten 
Published: April 2021

AbstractThe survival of human organisms depends on our ability to solve complex tasks in the face of limited cognitive resources. However, little is known about the factors that drive the complexity of those tasks. Here, building on insights from computational complexity theory, we quantify the computational hardness of cognitive tasks using a set of task-independent metrics related to the computational resource requirements of individual instances of a task. We then examine the relation between those metrics and human behavior and find that they predict both time spent on a task as well as accuracy in three canonical cognitive tasks. Our findings demonstrate that performance in cognitive tasks can be predicted based on generic metrics of their inherent computational hardness.TeaserThe ability of humans to solve cognitive tasks is affected by generic mathematical properties of problems related to their computational complexity.
Single cell response landscape of graded Nodal signaling in zebrafish explants
Authors: Cheng Tao , Xing Yan-Yi , Li Yun-Fei , Liu Cong , Huang Ying , Zhang Ying-Jie , Megason Sean G. , Xu Peng-Fei 
Published: April 2021

AbstractNodal, as a morphogen, plays important roles in cell fate decision, pattern formation and organizer function. But because of the complex contextin vivoand technology limitations, systematic studying of genes, cell types and patterns induced by Nodal alone is still missing. Here, by using a relatively simplified model, the zebrafish blastula animal pole explant avoiding additional instructive signals and prepatterns, we constructed a single cell response landscape of graded Nodal signaling, identified 105 Nodal immediate targets and depicted their expression patterns. Our results show that Nodal signaling is sufficient to induce anterior-posterior patterned axial mesoderm and head structure. Surprisingly, the endoderm induced by Nodal alone is mainly the anterior endoderm which gives rise to the pharyngeal pouch only, but not internal organs. Among the 105 Nodal targets, we identified 14 genes carrying varying levels of axis induction capability. Overall, our work provides new insights for understanding of the Nodal function and a valuable resource for future studies of patterning and morphogenesis induced by it.
Analysis of viral RNA-host protein interactomes enables rapid antiviral drug discovery
Authors: Zhang Shaojun , Huang Wenze , Ren Lili , Ju Xiaohui , Gong Mingli , Rao Jian , Sun Lei , Li Pan , Ding Qiang , Wang Jianwei , Zhang Qiangfeng Cliff 
Published: April 2021

AbstractRNA viruses including SARS-CoV-2, Ebola virus (EBOV), and Zika virus (ZIKV) constitute a major threat to global public health and society. The interactions between viral genomes and host proteins are essential in the life cycle of RNA viruses and thus provide targets for drug development. However, viral RNA-host protein interactions have remained poorly characterized. Here we applied ChIRP-MS to profile the interactomes of human proteins and the RNA genomes of SARS-CoV-2, EBOV, and ZIKV in infected cells. Integrated interactome analyses revealed interaction patterns that reflect both common and virus-specific host responses, and enabled rapid drug screening to target the vulnerable host factors. We identified Enasidenib as a SARS-CoV-2 specific antiviral agent, and Trifluoperazine and Cepharanthine as broad spectrum antivirals against all three RNA viruses.One Sentence SummaryInteractome analyses of host proteins and the SARS-CoV-2, EBOV, and ZIKV RNA genomes unveil viral biology and drug targets.
Hypo-osmotic Stress Induces ATP Release via Volume-regulated Anion Channels in Undifferentiated Mammary Cells
Authors: Furuya Kishio , Takahashi Yuko , Hirata Hiroaki , Kobayashi Takeshi , Samsonov Mikhail , Sokabe Masahiro 
Published: April 2021

AbstractThe high interstitial ATP concentration in the cancer microenvironment is a major source of adenosine, which acts as a strong immune suppressor. However, the source of ATP release has not been elucidated. We measured the ATP release during hypotonic stress using a real-time ATP luminescence imaging system in primary cultured mammary cells and in breast cell lines. In primary cultured cells, ATP was intermittently released with transient-sharp peaks, while in breast cell lines ATP was released with a slowly rising diffuse pattern. The diffuse ATP release pattern was changed to a transient-sharp pattern by cholera toxin treatment and the reverse change was induced by transforming growth factor (TGF) β treatment. DCPIB, an inhibitor of volume-regulated anion channels (VRACs), only suppressed the diffuse pattern. The inflammatory mediator sphingosine-1-phosphate (S1P) induced a diffuse ATP release pattern isovolumetrically. The knockdown of A isoform of leucine-rich repeat-containing protein 8 (LRRC8A), the essential molecular entity of VRACs, using shRNA suppressed the diffuse pattern. These results suggest that abundantly expressed VRACs are a conduit of ATP release in undifferentiated cells, including cancer cells.
Identity signaling, identity reception and the evolution of social recognition in a Neotropical frog
Authors: Tumulty James P. , Lange Zachary K. , Bee Mark A. 
Published: April 2021

AbstractAnimals recognize familiar individuals to perform a variety of important social behaviors. Social recognition is often mediated by communication between signalers who produce signals that contain identity information and receivers who categorize these signals based on previous experience. We tested two hypotheses about adaptations in signalers and receivers that enable the evolution of social recognition using two species of closely related territorial poison frogs. Male golden rocket frogs (Anomaloglossus beebei) recognize the advertisement calls of conspecific territory neighbors and display a “dear enemy effect” by responding less aggressively to neighbors than strangers, while male Kai rocket frogs (A. kaiei) do not. Our results did not support the identity signaling hypothesis: both species produced advertisement calls that contain similar amounts of identity information. Our results did support the identity reception hypothesis: both species exhibited habituation of aggression to playbacks simulating the arrival of a new neighbor, but only golden rocket frogs showed renewed aggression when they subsequently heard calls from a different male. These results suggest that an ancestral mechanism of plasticity in aggression common among frogs has been modified through natural selection to be specific to calls of individual males in golden rocket frogs, enabling a social recognition system.
Tetratricopeptide repeat domain 36 protects renal tubular cells from cisplatin-induced apoptosis via maintaining mitochondrial homeostasis
Authors: Yan Xin , Peng Rui , Tian Dayu , Chen Lei , He Qingling , Li Qianyin , Zhou Qin 
Published: April 2021

AbstractThe apoptosis of proximal tubule epithelial cells (PTECs) is a critical event of acute kidney injury (AKI). Tetratricopeptide repeat domain 36 (TTC36) with three tetratricopeptide repeats is evolutionarily conserved across mammals, which functions as a chaperone for heat shock protein 70. We have revealed that TTC36 is specifically expressed in PTECs in our previous work. There are few studies about the role TTC36 played in AKI. Therefore, in this study, we investigated the function of TTC36 in the apoptosis of HK2 cells, which are derived from the human proximal tubule. Firstly, we observed that TTC36 was obviously down-regulated and was negatively related to the kidney damage degree in a mouse model of acute kidney injury established by ischemia/reperfusion. In addition, TTC36 overexpression protected HK2 cells against cisplatin-induced apoptosis. Moreover, we discovered the mechanism that TTC36 mitigated cisplatin-triggered mitochondrial disorder via sustaining the membrane potential of mitochondria and mitochondrial autophagy-related gene expression. Collectively, these results suggested that TTC36 plays a protective role in the cisplatin-induced apoptosis of renal tubular cells through maintaining the mitochondrial potential and mitochondrial autophagy-related gene expression. These observations highlight the essential role of TTC36 in regulating PTEC apoptosis and imply TTC36/mitochondrial homeostasis axis as a potential target for the therapeutic intervention in AKI.
RNA-specific condensation promotes auto-regulation of polyQ RNA-binding protein Whi3
Authors: Gerbich Therese M. , Langdon Erin M. , McLaughlin Grace A. , Stormo Benjamin M. , Yu Blair , Roper Marcus , Gladfelter Amy S. 
Published: April 2021

AbstractRNA-binding proteins are frequently seen to be capable of auto-regulation by binding their own transcripts. In this work, we show that in the multinucleated fungusAshbya gossypii, the phase-separating RNA-binding protein Whi3 binds and regulates its own transcripts in distinct condensates from its other targets. Failure of Whi3 to bind its own transcript leads to a reduction in Whi3 protein level and its inability to properly regulate its other targets, leading to defects in nuclear cycling, polarized growth, and transcription of START-regulated genes. These results present a role for auto-regulation and condensate formation triggered by an RNA-binding protein interacting with its own coding transcript. Given the propensity of RNA-binding proteins to interact with their own coding mRNAs, this may be a wide-spread mechanism of feedback that utilizes biomolecular condensates.
Neural mechanisms of context-dependent segmentation tested on large-scale recording data
Authors: Asabuki Toshitake , Fukai Tomoki 
Published: April 2021

AbstractThe brain performs various cognitive functions by learning the spatiotemporal salient features of the environment. This learning likely requires unsupervised segmentation of hierarchically organized spike sequences, but the underlying neural mechanism is only poorly understood. Here, we show that a recurrent gated network of neurons with dendrites can context-dependently solve difficult segmentation tasks. Dendrites in this model learn to predict somatic responses in a self-supervising manner while recurrent connections learn a context-dependent gating of dendro-somatic current flows to minimize a prediction error. These connections select particular information suitable for the given context from input features redundantly learned by the dendrites. The model selectively learned salient segments in complex synthetic sequences. Furthermore, the model was also effective for detecting multiple cell assemblies repeating in large-scale calcium imaging data of more than 6,500 cortical neurons. Our results suggest that recurrent gating and dendrites are crucial for cortical learning of context-dependent segmentation tasks.
Morph-specific patterns of sex organ positions in species with style length polymorphism
Authors: Ganguly Shatarupa , Barua Deepak 
Published: April 2021

AbstractIn style length polymorphism, morph-specific sequence of encountering male and female sex organs within a flower by pollinators can cause differences in the need to avoid self-pollination and encourage inter-morph pollination. We asked if this difference can lead to disparity in stigma-anther separation (herkogamy) between morphs and spatial match between sex organs of complementary morphs (reciprocity). Further, we tested if herkogamy, and hence the level of selfing, is fairly constant among individuals of a population. Additionally, we examined the relationship between herkogamy and reciprocity among individuals of a population to understand functional interactions between these two morphological traits. Using data on sex organ heights for >200 heterostylous species from the literature, we observed that the short-styled morph had higher herkogamy as compared to the long-styled morph indicating a higher need to avoid selfing. Reciprocity did not show a consistent difference between the upper and lower sex organs implying a strong influence of local ecological factors. In most populations, allometric relationships suggested that herkogamy and hence the level of selfing remains constant. Finally, we observed that herkogamy and reciprocity can be related among individuals of a population, sometimes indicating a potential trade-off between avoidance of self-pollination and facilitation of inter-morph pollination.
A new species of the genusCarlogonus(Spirostreptida: Harpagophoridae) from West Bengal, India
Authors: Bhakat Somnath 
Published: April 2021

AbstractA new species ofCarlogonus, Carlogonus bengalensisis described from West Bengal, India. The adult is blackish brown in colour with a yellowish curved tail, round body with 60 segments, 55 mm in length, 5thsegment of male bears a hump, telopodite of the gonopod long, flat and band like with a single curved antetorsal process, mesal process with a red spine, proplical lobe with a curved orange spine, inner surface of metaplical fold with sigilla, palette spatula like and a few blepharochatae at the apical margin. Male bears white pad on femur and tibia. Comparison was made with the “exaratusgroup” of the genusCarlogonus.
TIC236gain-of-function mutations unveil the link between plastid division and plastid protein import
Authors: Fang Jun , Li Bingqi , Chen Lih-Jen , Dogra Vivek , Luo Shengji , Wang Pengcheng , Hwang Inhwan , Li Hsou-min , Kim Chanhong 
Published: April 2021

SummaryThe chloroplast translocons TOC75 and TIC236 are homologs of the bacterial translocation and assembly module (Tam) A and TamB involved in protein export. Here, we unveil a TIC236-allied component, the chloroplast outer membrane protein CRUMPLED LEAF (CRL), absence of which impairs plastid division and induces autoimmune responses inArabidopsis thaliana. A forward genetic screen aimed at findingcrlsuppressors revealed multipleTIC236gain-of-function mutations (TIC236GFs). Despite the low sequence identity between TIC236 and bacterial TamB, each mutated TIC236GF residue is conserved in TamB. Consistently, atic236- knockdown mutant exhibited multiple lesion phenotypes similar tocrl, indicating a shared functionality of CRL and TIC236. Ensuing reverse genetic analyses revealed genetic interaction between CRL and SP1, a RING-type ubiquitin E3 ligase, as well as with the plastid protease FTSH11, which function in TOC and TIC protein turnover, respectively. Loss of either SP1 or FTSH11 rescuedcrlmutant phenotypes to varying degrees due to increased translocon levels. Consistent with impaired plastid division exhibited by bothcrlandtic236-knockdown mutants, CRL interacts with the transit peptides of proteins essential in plastid division, and TIC236GF mutant proteins reinforce their import via increased TIC236 stability. Overall, our data shed new light on the links between plastid division, plant stress response and plastid protein import. We have also isolated and characterized the first GF mutants exhibiting increased protein import efficiency, which may inspire chloroplast engineering for agricultural advancement.
Clinical analysis of Pseudomonas aeruginosa‐positive and ‐negative green nail syndrome cases: A single center retrospective analysis
Authors: Lee Hanjae , Mun Je‐Ho , Cho Soyun , Park Hyunsun 
Published: April 2021

AbstractGreen nail syndrome (GNS) is a paronychial infection mainly due to Pseudomonas aeruginosa, characterized by green discoloration of the nail plate. Although the diagnosis of GNS may be straightforward with its distinctive color change, the clinical management of the disease can be sometimes confusing, especially when the bacterial culture result is inconsistent. There is, however, a paucity of comprehensive reviews regarding the treatment of GNS in the actual clinical setting. In this retrospective review of 34 patients, we found that GNS mostly occurs on a single digit (79.4%) on the big toe or thumb (85.3%) with frequent concurrent fungal infection (67.6%). The prevalence of inconsistent bacterial culture result with no evidence of P. aeruginosa was unexpectedly high (n = 22, 64.7%), in which case coagulase‐negative staphylococci were most frequently detected. The P. aeruginosa‐negative group did not demonstrate any statistically significant differences compared with the P. aeruginosa‐positive group, and it still responded well to the typical topical and/or oral fluoroquinolone treatment. GNS without the evidence of P. aeruginosa may be a more common occurrence than reported in the literature, and it can be managed successfully with the same strategy employed to treat P. aeruginosa‐positive cases. It may result from the low detection rate of P. aeruginosa due to the limited sensitivity of the test, or inadequate amount and/or contamination of the sample, warranting close scrutiny by clinicians.
Specialists and generalists fulfil important and complementary functional roles in ecological processes
Authors: Dehling D. Matthias , Bender Irene M. A. , Blendinger Pedro G. , Böhning‐Gaese Katrin , Muñoz Marcia C. , Neuschulz Eike L. , Quitián Marta , Saavedra Francisco , Santillán Vinicio , Schleuning Matthias , Stouffer Daniel B. 
Published: April 2021

Abstract

Species differ in their resource use and their interactions with other species and, consequently, they fulfil different functional roles in ecological processes. Species with specialized functional roles (specialists) are considered important for communities because they often interact with species with which few other species interact, thereby contributing complementary functional roles to ecological processes. However, the contribution of specialists could be low if they only interact with a small range of interaction partners. In contrast, species with unspecialized functional roles (generalists) often do not fulfil complementary roles but their contribution to ecological processes could be high because they interact with a large range of species.

To investigate the importance of the functional roles of specialists versus generalists, we tested the relationship between species' degree of specialization and their contribution to functional‐role diversity for frugivorous birds in Andean seed‐dispersal networks. We used two measures for the specialization of birds—one based on the size, and one based on the position of their interaction niche—and measured their effect on the birds' contribution to functional‐role diversity and their functional complementarity, a measure of how much a species' functional role is complementary to those of the other species.

In all networks, there were similar log‐normal distributions of species' contributions to functional‐role diversity and functional complementarity. Contribution to functional‐role diversity and functional complementarity increased with both increasing niche‐position specialization and increasing niche size, indicating that the composition of functional roles in the networks was determined by an interplay between specialization and generalization. There was a negative interaction between niche‐position specialization and niche size in both models, which showed that the positive effect of niche‐position specialization on functional‐role diversity and functional complementarity was stronger for species with a small niche size, and vice versa.

Our results show that there is a continuum from specialized to generalized functional roles in species communities, and that both specialists and generalists fulfil important functional roles in ecological processes. Combining interaction networks with functional traits, as exemplified in this study, provides insight into the importance of an interplay of redundancy and complementarity in species' functional roles for ecosystem functioning.

A free Plain‐Language Summary can be found within the Supporting Information of this article.