bluuebunny/crossref_metadata_2025 huggingface dataset:
TRAF4-mediated nonproteolytic ubiquitination of androgen receptor promotes castration-resistant prostate cancer
Authors: Singh Ramesh , Meng Huan , Shen Tao , Lumahan Lance Edward V. , Nguyen Steven , Shen Hong , Dasgupta Subhamoy , Qin Li , Karri Dileep , Zhu Bokai , Yang Feng , Coarfa Cristian , O’Malley Bert W. , Yi Ping
Published: May 2023

Castration-resistant prostate cancer (CRPC) poses a major clinical challenge with the androgen receptor (AR) remaining to be a critical oncogenic player. Several lines of evidence indicate that AR induces a distinct transcriptional program after androgen deprivation in CRPCs. However, the mechanism triggering AR binding to a distinct set of genomic loci in CRPC and how it promotes CRPC development remain unclear. We demonstrate here that atypical ubiquitination of AR mediated by an E3 ubiquitin ligase TRAF4 plays an important role in this process. TRAF4 is highly expressed in CRPCs and promotes CRPC development. It mediates K27-linked ubiquitination at the C-terminal tail of AR and increases its association with the pioneer factor FOXA1. Consequently, AR binds to a distinct set of genomic loci enriched with FOXA1- and HOXB13-binding motifs to drive different transcriptional programs including an olfactory transduction pathway. Through the surprising upregulation of olfactory receptor gene transcription, TRAF4 increases intracellular cAMP levels and boosts E2F transcription factor activity to promote cell proliferation under androgen deprivation conditions. Altogether, these findings reveal a posttranslational mechanism driving AR-regulated transcriptional reprogramming to provide survival advantages for prostate cancer cells under castration conditions.
Universality in RNA and DNA deformations induced by salt, temperature change, stretching force, and protein binding
Authors: Tian Fu-Jia , Zhang Chen , Zhou Erchi , Dong Hai-Long , Tan Zhi-Jie , Zhang Xing-Hua , Dai Liang
Published: May 2023

Nucleic acid deformations play important roles in many biological processes. The physical understanding of nucleic acid deformation by environmental stimuli is limited due to the challenge in the precise measurement of RNA and DNA deformations and the complexity of interactions in RNA and DNA. Magnetic tweezers experiments provide an excellent opportunity to precisely measure DNA and RNA twist changes induced by environmental stimuli. In this work, we applied magnetic tweezers to measure double-stranded RNA twist changes induced by salt and temperature changes. We observed RNA unwinds when lowering salt concentration, or increasing temperature. Our molecular dynamics simulations revealed the mechanism: lowering salt concentration or increasing temperature enlarges RNA major groove width, which causes twist decrease through twist-groove coupling. Combining these results with previous results, we found some universality in RNA and DNA deformations induced by three different stimuli: salt change, temperature, and stretching force. For RNA, these stimuli first modify the major groove width, which is transduced into twist change through twist-groove coupling. For DNA, these stimuli first modify diameter, which is transduced into twist change through twist-diameter coupling. Twist-groove coupling and twist-diameter coupling appear to be utilized by protein binding to reduce DNA and RNA deformation energy cost upon protein binding.
A new capacity of gut microbiota: Fermentation of engineered inorganic carbon nanomaterials into endogenous organic metabolites
Authors: Cui Xuejing , Wang Xiaoyu , Chang Xueling , Bao Lin , Wu Junguang , Tan Zhiqiang , Chen Jinmei , Li Jiayang , Gao Xingfa , Ke Pu Chun , Chen Chunying
Published: May 2023

Carbon-based nanomaterials (CNMs) have recently been found in humans raising a great concern over their adverse roles in the hosts. However, our knowledge of the in vivo behavior and fate of CNMs, especially their biological processes elicited by the gut microbiota, remains poor. Here, we uncovered the integration of CNMs (single-walled carbon nanotubes and graphene oxide) into the endogenous carbon flow through degradation and fermentation, mediated by the gut microbiota of mice using isotope tracing and gene sequencing. As a newly available carbon source for the gut microbiota, microbial fermentation leads to the incorporation of inorganic carbon from the CNMs into organic butyrate through the pyruvate pathway. Furthermore, the butyrate-producing bacteria are identified to show a preference for the CNMs as their favorable source, and excessive butyrate derived from microbial CNMs fermentation further impacts on the function (proliferation and differentiation) of intestinal stem cells in mouse and intestinal organoid models. Collectively, our results unlock the unknown fermentation processes of CNMs in the gut of hosts and underscore an urgent need for assessing the transformation of CNMs and their health risk via the gut-centric physiological and anatomical pathways.
Supercritical fluid in deep subduction zones as revealed by multiphase fluid inclusions in an ultrahigh-pressure metamorphic vein
Authors: Jin Deshi , Xiao Yilin , Tan Dong-Bo , Wang Yang-Yang , Wang Xiaoxia , Li Wancai , Su Wen , Li Xiaoguang
Published: May 2023

Due to their low viscosity, high mobility, and high element contents, supercritical fluids are important agents in the cycling of elements. However, the chemical composition of supercritical fluids in natural rocks is poorly understood. Here, we investigate well-preserved primary multiphase fluid inclusions (MFIs) from an ultrahigh-pressure (UHP) metamorphic vein of the Bixiling eclogite in Dabieshan, China, thus providing direct evidence for the components of supercritical fluid occurring in a natural system. Via the 3D modeling of MFIs by Raman scanning, we quantitatively determined the major composition of the fluid trapped in the MFIs. Combined with the peak-metamorphic pressure–temperature conditions and the cooccurrence of coesite, rutile, and garnet, we suggest that the trapped fluids in the MFIs represent supercritical fluids in a deep subduction zone. The strong mobility of the supercritical fluids with respect to carbon and sulfur suggests that such fluids have profound effects on global carbon and sulfur cycling.
A proprioceptive feedback circuit drives
Caenorhabditis elegans
locomotor adaptation through dopamine signaling
Authors: Ji Hongfei , Fouad Anthony D. , Li Zihao , Ruba Andrew , Fang-Yen Christopher
Published: May 2023

An animal adapts its motor behavior to navigate the external environment. This adaptation depends on proprioception, which provides feedback on an animal’s body postures. How proprioception mechanisms interact with motor circuits and contribute to locomotor adaptation remains unclear. Here, we describe and characterize proprioception-mediated homeostatic control of undulatory movement in the roundworm
Caenorhabditis elegans
. We found that the worm responds to optogenetically or mechanically induced decreases in midbody bending amplitude by increasing its anterior amplitude. Conversely, it responds to increased midbody amplitude by decreasing the anterior amplitude. Using genetics, microfluidic and optogenetic perturbation response analyses, and optical neurophysiology, we elucidated the neural circuit underlying this compensatory postural response. The dopaminergic PDE neurons proprioceptively sense midbody bending and signal to AVK interneurons via the D2-like dopamine receptor DOP-3. The FMRFamide-like neuropeptide FLP-1, released by AVK, regulates SMB head motor neurons to modulate anterior bending. We propose that this homeostatic behavioral control optimizes locomotor efficiency. Our findings demonstrate a mechanism in which proprioception works with dopamine and neuropeptide signaling to mediate motor control, a motif that may be conserved in other animals.
Imaging of pH distribution inside individual microdroplet by stimulated Raman microscopy
Authors: Gong Kedong , Ao Jianpeng , Li Kejian , Liu Le , Liu Yangyang , Xu Guanjun , Wang Tao , Cheng Hanyun , Wang Zimeng , Zhang Xiuhui , Wei Haoran , George Christian , Mellouki Abdelwahid , Herrmann Hartmut , Wang Lin , Chen Jianmin , Ji Minbiao , Zhang Liwu , Francisco Joseph S.
Published: May 2023

Aerosol microdroplets as microreactors for many important atmospheric reactions are ubiquitous in the atmosphere. pH largely regulates the chemical processes within them; however, how pH and chemical species spatially distribute within an atmospheric microdroplet is still under intense debate. The challenge is to measure pH distribution within a tiny volume without affecting the chemical species distribution. We demonstrate a method based on stimulated Raman scattering microscopy to visualize the three-dimensional pH distribution inside single microdroplets of varying sizes. We find that the surface of all microdroplets is more acidic, and a monotonic trend of pH decreasing is observed in the 2.9-μm aerosol microdroplet from center to edge, which is well supported by molecular dynamics simulation. However, bigger cloud microdroplet differs from small aerosol for pH distribution. This size-dependent pH distribution in microdroplets can be related to the surface-to-volume ratio. This work presents noncontact measurement and chemical imaging of pH distribution in microdroplets, filling the gap in our understanding of spatial pH in atmospheric aerosol.
Upregulation of the ERRγ–VDAC1 axis underlies the molecular pathogenesis of pancreatitis
Authors: Chanda Dipanjan , Thoudam Themis , Sinam Ibotombi Singh , Lim Chae Won , Kim Myeongjin , Wang Jiale , Lee Kyeong-Min , Ma Jing , Saxena Romil , Choi Jinhyuk , Oh Chang Joo , Lee Hoyul , Jeon Yong Hyun , Cho Sung Jin , Jung Hoe-Yune , Park Keun-Gyu , Choi Hueng-Sik , Suh Jae Myoung , Auwerx Johan , Ji Baoan , Liangpunsakul Suthat , Jeon Jae-Han , Lee In-Kyu
Published: May 2023

Emerging evidence suggest that transcription factors play multiple roles in the development of pancreatitis, a necroinflammatory condition lacking specific therapy. Estrogen-related receptor γ (ERRγ), a pleiotropic transcription factor, has been reported to play a vital role in pancreatic acinar cell (PAC) homeostasis. However, the role of ERRγ in PAC dysfunction remains hitherto unknown. Here, we demonstrated in both mice models and human cohorts that pancreatitis is associated with an increase in ERRγ gene expression via activation of STAT3. Acinar-specific ERRγ haploinsufficiency or pharmacological inhibition of ERRγ significantly impaired the progression of pancreatitis both in vitro and in vivo. Using systematic transcriptomic analysis, we identified that voltage-dependent anion channel 1 (VDAC1) acts as a molecular mediator of ERRγ. Mechanistically, we showed that induction of ERRγ in cultured acinar cells and mouse pancreata enhanced VDAC1 expression by directly binding to specific site of the
Vdac1
gene promoter and resulted in VDAC1 oligomerization. Notably, VDAC1, whose expression and oligomerization were dependent on ERRγ, modulates mitochondrial Ca
2+
and ROS levels. Inhibition of the ERRγ–VDAC1 axis could alleviate mitochondrial Ca
2+
accumulation, ROS formation and inhibit progression of pancreatitis. Using two different mouse models of pancreatitis, we showed that pharmacological blockade of ERRγ–VDAC1 pathway has therapeutic benefits in mitigating progression of pancreatitis. Likewise, using PRSS1
R122H
-Tg mice to mimic human hereditary pancreatitis, we demonstrated that ERRγ inhibitor also alleviated pancreatitis. Our findings highlight the importance of ERRγ in pancreatitis progression and suggests its therapeutic intervention for prevention and treatment of pancreatitis.
Plants cultivated for ecosystem restoration can evolve toward a domestication syndrome
Authors: Conrady Malte , Lampei Christian , Bossdorf Oliver , Hölzel Norbert , Michalski Stefan , Durka Walter , Bucharova Anna
Published: May 2023

The UN Decade on Ecosystem Restoration calls for upscaling restoration efforts, but many terrestrial restoration projects are constrained by seed availability. To overcome these constraints, wild plants are increasingly propagated on farms to produce seeds for restoration projects. During on-farm propagation, the plants face non-natural conditions with different selection pressures, and they might evolve adaptations to cultivation that parallel those of agricultural crops, which could be detrimental to restoration success. To test this, we compared traits of 19 species grown from wild-collected seeds to those from their farm-propagated offspring of up to four cultivation generations, produced by two European seed growers, in a common garden experiment. We found that some plants rapidly evolved across cultivated generations towards increased size and reproduction, lower within-species variability, and more synchronized flowering. In one species, we found evolution towards less seed shattering. These trait changes are typical signs of the crop domestication syndrome, and our study demonstrates that it can also occur during cultivation of wild plants, within only few cultivated generations. However, there was large variability between cultivation lineages, and the observed effect sizes were generally rather moderate, which suggests that the detected evolutionary changes are unlikely to compromise farm-propagated seeds for ecosystem restoration. To mitigate the potential negative effects of unintended selection, we recommend to limit the maximum number of generations the plants can be cultivated without replenishing the seed stock from new wild collections.
Branched germline cysts and female-specific cyst fragmentation facilitate oocyte determination in mice
Authors: Ikami Kanako , Shoffner-Beck Suzanne , Tyczynska Weh Malgorzata , Schnell Santiago , Yoshida Shosei , Diaz Miranda Edgar Andres , Ko Sooah , Lei Lei
Published: May 2023

During mouse gametogenesis, germ cells derived from the same progenitor are connected via intercellular bridges forming germline cysts, within which asymmetrical or symmetrical cell fate occurs in female and male germ cells, respectively. Here, we have identified branched cyst structures in mice, and investigated their formation and function in oocyte determination. In fetal female cysts, 16.8% of the germ cells are connected by three or four bridges, namely branching germ cells. These germ cells are preferentially protected from cell death and cyst fragmentation and accumulate cytoplasm and organelles from sister germ cells to become primary oocytes. Changes in cyst structure and differential cell volumes among cyst germ cells suggest that cytoplasmic transport in germline cysts is conducted in a directional manner, in which cellular content is first transported locally between peripheral germ cells and further enriched in branching germ cells, a process causing selective germ cell loss in cysts. Cyst fragmentation occurs extensively in female cysts, but not in male cysts. Male cysts in fetal and adult testes have branched cyst structures, without differential cell fates between germ cells. During fetal cyst formation, E-cadherin (E-cad) junctions between germ cells position intercellular bridges to form branched cysts. Disrupted junction formation in E-cad-depleted cysts led to an altered ratio in branched cysts. Germ cell-specific E-cad knockout resulted in reductions in primary oocyte number and oocyte size. These findings shed light on how oocyte fate is determined within mouse germline cysts.
A single-cell multiomic analysis of kidney organoid differentiation
Authors: Yoshimura Yasuhiro , Muto Yoshiharu , Ledru Nicolas , Wu Haojia , Omachi Kohei , Miner Jeffrey H. , Humphreys Benjamin D.
Published: May 2023

Kidney organoids differentiated from pluripotent stem cells are powerful models of kidney development and disease but are characterized by cell immaturity and off-target cell fates. Comparing the cell-specific gene regulatory landscape during organoid differentiation with human adult kidney can serve to benchmark progress in differentiation at the epigenome and transcriptome level for individual organoid cell types. Using single-cell multiome and histone modification analysis, we report more broadly open chromatin in organoid cell types compared to the human adult kidney. We infer enhancer dynamics by cis-coaccessibility analysis and validate an enhancer driving transcription of
HNF1B
by CRISPR interference both in cultured proximal tubule cells and also during organoid differentiation. Our approach provides an experimental framework to judge the cell-specific maturation state of human kidney organoids and shows that kidney organoids can be used to validate individual gene regulatory networks that regulate differentiation.
Zinc treatment reverses and anti-Zn-regulated miRs suppress esophageal carcinomas in vivo
Authors: Fong Louise Y. , Huebner Kay , Jing Ruiyan , Smalley Karl J. , Brydges Christopher R. , Fiehn Oliver , Farber John L. , Croce Carlo M.
Published: May 2023

Esophageal squamous cell carcinoma (ESCC) is a deadly disease with few prevention or treatment options. ESCC development in humans and rodents is associated with Zn deficiency (ZD), inflammation, and overexpression of oncogenic microRNAs: miR-31 and miR-21. In a ZD-promoted ESCC rat model with upregulation of these miRs, systemic antimiR-31 suppresses the miR-31-EGLN3/STK40-NF-κB–controlled inflammatory pathway and ESCC. In this model, systemic delivery of Zn-regulated antimiR-31, followed by antimiR-21, restored expression of tumor-suppressor proteins targeted by these specific miRs: STK40/EGLN3 (miR-31), PDCD4 (miR-21), suppressing inflammation, promoting apoptosis, and inhibiting ESCC development. Moreover, ESCC-bearing Zn-deficient (ZD) rats receiving Zn medication showed a 47% decrease in ESCC incidence vs. Zn-untreated controls. Zn treatment eliminated ESCCs by affecting a spectrum of biological processes that included downregulation of expression of the two miRs and miR-31-controlled inflammatory pathway, stimulation of miR-21-PDCD4 axis apoptosis, and reversal of the ESCC metabolome: with decrease in putrescine, increase in glucose, accompanied by downregulation of metabolite enzymes ODC and HK2. Thus, Zn treatment or miR-31/21 silencing are effective therapeutic strategies for ESCC in this rodent model and should be examined in the human counterpart exhibiting the same biological processes.
Anterior cingulate cortex orexin signaling mediates early-life stress-induced social impairment in females
Authors: Luo Fei , Deng Jun-yang , Sun Xuan , Zhen Jian , Luo Xiao-dan
Published: May 2023

Early-life stress has long-term impacts on the structure and function of the anterior cingulate cortex (ACC), and raises the risk of adult neuropsychiatric disorders including social dysfunction. The underlying neural mechanisms, however, are still uncertain. Here, we show that, in female mice, maternal separation (MS) during the first three postnatal weeks results in social impairment accompanied with hypoactivity in pyramidal neurons (PNs) of the ACC. Activation of ACC PNs ameliorates MS-induced social impairment. Neuropeptide Hcrt, which encodes hypocretin (orexin), is the top down-regulated gene in the ACC of MS females. Activating ACC orexin terminals enhances the activity of ACC PNs and rescues the diminished sociability observed in MS females via an orexin receptor 2 (OxR2)-dependent mechanism. Our results suggest orexin signaling in the ACC is critical in mediating early-life stress-induced social impairment in females.
CDYL reinforces male gonadal sex determination through epigenetically repressing
Wnt4
transcription in mice
Authors: Okashita Naoki , Maeda Ryo , Tachibana Makoto
Published: May 2023

In mammals, male and female gonads initially develop from bipotential progenitor cells, which can differentiate into either testicular or ovarian cells. The decision to adopt a testicular or ovarian fate relies on robust genetic forces, i.e., activation of the testis-determining gene
Sry
, as well as a delicate balance of expression levels for pro-testis and pro-ovary factors. Recently, epigenetic regulation has been found to be a key element in activation of
Sry
. Nevertheless, the mechanism by which epigenetic regulation controls the expression balance of pro-testis and pro-ovary factors remains unclear. Chromodomain Y-like protein (CDYL) is a reader protein for repressive histone H3 methylation marks. We found that a subpopulation of
Cdyl
-deficient mice exhibited XY sex reversal. Gene expression analysis revealed that the testis-promoting gene
Sox9
was downregulated in XY
Cdyl
-deficient gonads during the sex determination period without affecting
Sry
expression. Instead, we found that the ovary-promoting gene
Wnt4
was derepressed in XY
Cdyl
-deficient gonads prior to and during the sex-determination period.
Wnt4
heterozygous deficiency restored
SOX9
expression in
Cdyl
-deficient XY gonads, indicating that derepressed
Wnt4
is a cause of the repression of
Sox9
. We found that CDYL directly bound to the
Wnt4
promoter and maintained its H3K27me3 levels during the sex-determination period. These findings indicate that CDYL reinforces male gonadal sex determination by repressing the ovary-promoting pathway in mice.
Carbon isotope fractionation by an ancestral rubisco suggests that biological proxies for CO
2
through geologic time should be reevaluated
Authors: Wang Renée Z. , Nichols Robert J. , Liu Albert K. , Flamholz Avi I. , Artier Juliana , Banda Doug M. , Savage David F. , Eiler John M. , Shih Patrick M. , Fischer Woodward W.
Published: May 2023

The history of Earth’s carbon cycle reflects trends in atmospheric composition convolved with the evolution of photosynthesis. Fortunately, key parts of the carbon cycle have been recorded in the carbon isotope ratios of sedimentary rocks. The dominant model used to interpret this record as a proxy for ancient atmospheric CO
2
is based on carbon isotope fractionations of modern photoautotrophs, and longstanding questions remain about how their evolution might have impacted the record. Therefore, we measured both biomass (ε
p
) and enzymatic (ε
Rubisco
) carbon isotope fractionations of a cyanobacterial strain (
Synechococcus elongatus
PCC 7942) solely expressing a putative ancestral Form 1B rubisco dating to ≫1 Ga. This strain, nicknamed ANC, grows in ambient pCO
2
and displays larger ε
p
values than WT, despite having a much smaller ε
Rubisco
(17.23 ± 0.61‰ vs. 25.18 ± 0.31‰, respectively). Surprisingly, ANC ε
p
exceeded ANC ε
Rubisco
in all conditions tested, contradicting prevailing models of cyanobacterial carbon isotope fractionation. Such models can be rectified by introducing additional isotopic fractionation associated with powered inorganic carbon uptake mechanisms present in Cyanobacteria, but this amendment hinders the ability to accurately estimate historical pCO
2
from geological data. Understanding the evolution of rubisco and the CO
2
concentrating mechanism is therefore critical for interpreting the carbon isotope record, and fluctuations in the record may reflect the evolving efficiency of carbon fixing metabolisms in addition to changes in atmospheric CO
2
.
The DedA superfamily member PetA is required for the transbilayer distribution of phosphatidylethanolamine in bacterial membranes
Authors: Roney Ian J. , Rudner David Z.
Published: May 2023

The sorting of phospholipids between the inner and outer leaflets of the membrane bilayer is a fundamental problem in all organisms. Despite years of investigation, most of the enzymes that catalyze phospholipid reorientation in bacteria remain unknown. Studies from almost half a century ago in
Bacillus subtilis
and
Bacillus megaterium
revealed that newly synthesized phosphatidylethanolamine (PE) is rapidly translocated to the outer leaflet of the bilayer [Rothman & Kennedy,
Proc. Natl. Acad. Sci. U.S.A.
74
, 1821–1825 (1977)] but the identity of the putative PE flippase has eluded discovery. Recently, members of the DedA superfamily have been implicated in flipping the bacterial lipid carrier undecaprenyl phosphate and in scrambling eukaryotic phospholipids in vitro. Here, using the antimicrobial peptide duramycin that targets outward-facing PE, we show that
Bacillus subtilis
cells lacking the DedA paralog PetA (formerly YbfM) have increased resistance to duramycin. Sensitivity to duramycin is restored by expression of
B. subtilis
PetA or homologs from other bacteria. Analysis of duramycin-mediated killing upon induction of PE synthesis indicates that PetA is required for efficient PE transport. Finally, using fluorescently labeled duramycin we demonstrate that cells lacking PetA have reduced PE in their outer leaflet compared to wildtype. We conclude that PetA is the long-sought PE transporter. These data combined with bioinformatic analysis of other DedA paralogs argue that the primary role of DedA superfamily members is transporting distinct lipids across the membrane bilayer.
Circular RNA vaccine induces potent T cell responses
Authors: Amaya Laura , Grigoryan Lilit , Li Zhijian , Lee Audrey , Wender Paul A. , Pulendran Bali , Chang Howard Y.
Published: May 2023

Circular RNAs (circRNAs) are a class of RNAs commonly found across eukaryotes and viruses, characterized by their resistance to exonuclease-mediated degradation. Their superior stability compared to linear RNAs, combined with previous work showing that engineered circRNAs serve as efficient protein translation templates, make circRNA a promising candidate for RNA medicine. Here, we systematically examine the adjuvant activity, route of administration, and antigen-specific immunity of circRNA vaccination in mice. Potent circRNA adjuvant activity is associated with RNA uptake and activation of myeloid cells in the draining lymph nodes and transient cytokine release. Immunization of mice with engineered circRNA encoding a protein antigen delivered by a charge-altering releasable transporter induced innate activation of dendritic cells, robust antigen-specific CD8 T cell responses in lymph nodes and tissues, and strong antitumor efficacy as a therapeutic cancer vaccine. These results highlight the potential utility of circRNA vaccines for stimulating potent innate and T cell responses in tissues.
Detecting the exponential relaxation spectrum in glasses by high-precision nanocalorimetry
Authors: Song Lijian , Gao Yurong , Zou Peng , Xu Wei , Gao Meng , Zhang Yan , Huo Juntao , Li Fushan , Qiao Jichao , Wang Li-Min , Wang Jun-Qiang
Published: May 2023

Nonexponential relaxations are universal characteristics for glassy materials. There is a well-known hypothesis that nonexponential relaxation peaks are composed of a series of exponential events, which have not been verified. In this Letter, we discover the exponential relaxation events during the recovery process using a high-precision nanocalorimetry, which are universal for metallic glasses and organic glasses. The relaxation peaks can be well fitted by the exponential Debye function with a single activation energy. The activation energy covers a broad range from
α
relaxation to
β
relaxation and even the fast
γ/β′
relaxation. We obtain the complete spectrum of the exponential relaxation peaks over a wide temperature range from 0.63
T
g
to 1.03
T
g
, which provides solid evidence that nonexponential relaxation peaks can be decomposed into exponential relaxation units. Furthermore, the contribution of different relaxation modes in the nonequilibrium enthalpy space is measured. These results open a door for developing the thermodynamics of nonequilibrium physics and for precisely modulating the properties of glasses by controlling the relaxation modes.
The RPA–RNF20–SNF2H cascade promotes proper chromosome segregation and homologous recombination repair
Authors: Li Jimin , Zhao Jingyu , Gan Xiaoli , Wang Yanyan , Jiang Donghao , Chen Liang , Wang Fangwei , Xu Jingyan , Pei Huadong , Huang Jun , Chen Xuefeng
Published: May 2023

The human tumor suppressor Ring finger protein 20 (RNF20)-mediated histone H2B monoubiquitination (H2Bub) is essential for proper chromosome segregation and DNA repair. However, what is the precise function and mechanism of RNF20–H2Bub in chromosome segregation and how this pathway is activated to preserve genome stability remain unknown. Here, we show that the single-strand DNA-binding factor Replication protein A (RPA) interacts with RNF20 mainly in the S and G2/M phases and recruits RNF20 to mitotic centromeres in a centromeric R-loop-dependent manner. In parallel, RPA recruits RNF20 to chromosomal breaks upon DNA damage. Disruption of the RPA–RNF20 interaction or depletion of RNF20 increases mitotic lagging chromosomes and chromosome bridges and impairs BRCA1 and RAD51 loading and homologous recombination repair, leading to elevated chromosome breaks, genome instability, and sensitivities to DNA-damaging agents. Mechanistically, the RPA–RNF20 pathway promotes local H2Bub, H3K4 dimethylation, and subsequent SNF2H recruitment, ensuring proper Aurora B kinase activation at centromeres and efficient loading of repair proteins at DNA breaks. Thus, the RPA–RNF20–SNF2H cascade plays a broad role in preserving genome stability by coupling H2Bub to chromosome segregation and DNA repair.
The
Chlamydia trachomatis
type III-secreted effector protein CteG induces centrosome amplification through interactions with centrin-2
Authors: Steiert Brianna , Icardi Carolina M. , Faris Robert , McCaslin Paige N. , Smith Parker , Klingelhutz Aloysius J. , Yau Peter M. , Weber Mary M.
Published: May 2023

The centrosome is the main microtubule organizing center of the cell and is crucial for mitotic spindle assembly, chromosome segregation, and cell division. Centrosome duplication is tightly controlled, yet several pathogens, most notably oncogenic viruses, perturb this process leading to increased centrosome numbers. Infection by the obligate intracellular bacterium
Chlamydia trachomatis
(
C.t.
) correlates with blocked cytokinesis, supernumerary centrosomes, and multipolar spindles; however, the mechanisms behind how
C.t.
induces these cellular abnormalities remain largely unknown. Here we show that the secreted effector protein, CteG, binds to centrin-2 (CETN2), a key structural component of centrosomes and regulator of centriole duplication. Our data indicate that both CteG and CETN2 are necessary for infection-induced centrosome amplification, in a manner that requires the C-terminus of CteG. Strikingly, CteG is important for in vivo infection and growth in primary cervical cells but is dispensable for growth in immortalized cells, highlighting the importance of this effector protein to chlamydial infection. These findings begin to provide mechanistic insight into how
C.t.
induces cellular abnormalities during infection, but also indicate that obligate intracellular bacteria may contribute to cellular transformation events. Centrosome amplification mediated by CteG–CETN2 interactions may explain why chlamydial infection leads to an increased risk of cervical or ovarian cancer.
Vertebrate-tropism of a cressdnavirus lineage implicated by poxvirus gene capture
Authors: Kinsella Cormac M. , van der Hoek Lia
Published: May 2023

Among cressdnaviruses, only the family
Circoviridae
is recognized to infect vertebrates, while many others have unknown hosts. Detection of virus-to-host horizontal gene transfer is useful for solving such virus–host relationships. Here, we extend this utility to an unusual case of virus-to-virus horizontal transfer, showing multiple ancient captures of cressdnavirus
Rep
genes by avipoxviruses—large dsDNA pathogens of birds and other saurians. As gene transfers must have occurred during virus coinfections, saurian hosts were implied for the cressdnavirus donor lineage. Surprisingly, phylogenetic analysis revealed that donors were not members of the vertebrate-infecting
Circoviridae
, instead belonging to a previously unclassified family that we name
Draupnirviridae
. While draupnirviruses still circulate today, we show that those in the genus
Krikovirus
infected saurian vertebrates at least 114 Mya, leaving endogenous viral elements inside snake, lizard, and turtle genomes throughout the Cretaceous Period. Endogenous krikovirus elements in some insect genomes and frequent detection in mosquitoes imply that spillover to vertebrates was arthropod mediated, while ancestral draupnirviruses likely infected protists before their emergence in animals. A modern krikovirus sampled from an avipoxvirus-induced lesion shows that their interaction with poxviruses is ongoing. Captured
Rep
genes in poxvirus genomes often have inactivated catalytic motifs, yet near-total presence across the
Avipoxvirus
genus, and evidence of both expression and purifying selection on them suggests currently unknown functions.
A dual-action antibiotic that kills
Clostridioides difficile
vegetative cells and inhibits spore germination
Authors: Janardhanan Jeshina , Kim Choon , Qian Yuanyuan , Yang Jingdong , Meisel Jayda E. , Ding Derong , Speri Enrico , Schroeder Valerie A. , Wolter William R. , Oliver Allen G. , Mobashery Shahriar , Chang Mayland
Published: May 2023

Clostridioides difficile
infection (CDI) is the most lethal of the five CDC urgent public health treats, resulting in 12,800 annual deaths in the United States alone [
Antibiotic Resistance Threats in the United States, 2019
(2019), 
www.cdc.gov/DrugResistance/Biggest-Threats.html
]. The high recurrence rate and the inability of antibiotics to treat such infections mandate discovery of new therapeutics. A major challenge with CDI is the production of spores, leading to multiple recurrences of infection in 25% of patients [C. P. Kelly, J. T. LaMont, 
N. Engl. J. Med.
359
, 1932–1940 (2008)], with potentially lethal consequence. Herein, we describe the discovery of an oxadiazole as a bactericidal anti-
C. difficile
agent that inhibits both cell-wall peptidoglycan biosynthesis and spore germination. We document that the oxadiazole binds to the lytic transglycosylase SleC and the pseudoprotease CspC for prevention of spore germination. SleC degrades the cortex peptidoglycan, a critical step in the initiation of spore germination. CspC senses germinants and cogerminants. Binding to SleC is with higher affinity than that to CspC. Prevention of spore germination breaks the nefarious cycles of CDI recurrence in the face of the antibiotic challenge, which is a primary cause of therapeutic failure. The oxadiazole exhibits efficacy in a mouse model of recurrent CDI and holds promise in clinical treatment of CDI.
Interpreting Covid-related memes
Authors: Yus Francisco , Maíz-Arévalo Carmen
Published: May 2023

One of the sources of relief, entertainment and
socialisation during the Covid pandemic lockdown was the massive
exchange of memes on social media and messaging applications. The
objective of this chapter is to analyse and categorise 150
Peninsular Spanish memes collected from different interactive
channels online (mainly social media and the messaging app WhatsApp)
during the strict 2020 Covid lockdown in Spain (March-May 2020). The
sample was then analysed under “incongruity-resolution theory” and
categorized with the following research questions in mind:
(a) what inferential strategies the internet user is expected
to perform to interpret these Covid memes correctly; (b) what
role text and image play in the eventual derivation of humorous
effects from these memes; and (c) what kind of contextual
information the internet user is expected to have access to for
successful comprehension. Answering these research questions will
eventually allow for a differentiation between Covid memes and
non-Covid ones, as already intuitively felt by most users.
Political-electoral memes and interactional humour on
Twitter
Authors: Pano Alamán Ana , Rueda Ana Mancera
Published: May 2023

This chapter presents the results of a qualitative study
of a corpus of replies to humoristic memes, which were published and
viralised on Twitter during the Spanish general elections campaign
held on November 2019. Based on the General Theory of Verbal Humour
and on its adaptation to multimodal humour, this study aims at
establishing whether and how memes made up of a single image or a
combination of an image and a caption may generate humorous effects
on the imagined audience on Twitter and encourage responses that
entail continued humour. The results show that most of the memes
analysed convey recognition, understanding, appreciation, and
agreement among Twitter users, whose responses express laughter
using different multimodal affordances, or replicate the humorous
contents of the meme by producing new memes. Moreover, humour
created by these memes enables producer users and recipients to
challenge the political power, while nurturing in-group
solidarity.
From mode adoption to saluting
a dead kitten
Authors: Bischetti Luca , Attardo Salvatore
Published: May 2023

There has been some research in what can be broadly
described as humor performance in the reactions to humorous turns
(be they punch lines or jab lines). Two areas that have received
particular attention are (1) the reactions to irony, which have been
shown to range from mode adoption (i.e., when the respondent adopts
the ironical mode and responds with irony to the irony) to treating
the irony as a “literal” statement and reacting to it ignoring its
ironical intention; and (2) failed humor, in which the range of
reactions is much broader, from laughter to open expression of
displeasure.

Much less has been written on reactions in online
discourse and this case study of one humorous tweet by comedian
Ricky Gervais, mocking the Academy Award ceremony (the Oscars), will
be examined to examine the differences between a corpus of 200+
tweets as responses to Gervais’ original tweet, and proviso studies.
We will also consider how much the exchange can be quantified as to
its viral nature.
Communicative strategies in interactional male humour
Authors: Alvarado Ortega M. Belén
Published: May 2023

This paper will present an analysis of male interactional
humour in Spanish conversation. Humour can appear in such
conversations as a strategy to show (im)politeness between
participants in the interaction. Focussing in particular on
politeness strategies, we will seek to identify the different types
of humour that arise in conversations between men. To this end, we
will draw on Brown and Levinson’s theory of politeness ([1978] 1987: 213), which
lists a number of strategies that aim to produce politeness and, at
the same time, calculates the estimated risk of losing face that
arises from an individual’s conversational behaviour. In the
analysis we will also consider Spencer-Oatey’s (2000, 2007) proposal of a set of factors that can
affect rapport management strategies. Our aim is to show that humour
as expressed between men in conversational utterances, involves
conversational strategies that are used to elicit respect for both
listener and speaker, or to save the negative and positive face of
these, according to politeness criteria. To this end, the
VALESCO.HUMOR corpus is used, which comprises 148 ironic-humorous
sequences extracted from 67 colloquial conversations.
Humour at the opening and closing phases of service encounters in
small cafeterias and bars in Seville
Authors: Padilla Cruz Manuel
Published: May 2023

In an interactive context like service encounters, humour
becomes essential because of the positive feelings that it
generates. These contribute to an amicable ambiance and tighten
bonds of union. Hence, humour greatly impacts customer satisfaction,
revisit intention and, ultimately, customer loyalty. Although
individual skills and sense of humour come into play, awareness of
the role of humour often prompts many baristas and customers to use
it in their transactions. Its various forms and functions in
distinct service encounters have already received some attention,
but its use at the opening and closing phases of these encounters
with a phatic purpose still remains an underexplored issue. This
chapter will compare data from two previous studies in order to
determine the types of humour wherewith such encounters were opened
and closed at small establishments in Seville. It aims to ascertain
how humorous tokens achieved proximity and strengthened social
relationships, and to elucidate whether their use to create phatic
communion was affected by factors like the interlocutors’ age and
the time segment when the encounters took place.
Digital Simulation of Projective Non-Abelian Anyons with 68 Superconducting Qubits
Authors: Xu Shibo , Sun Zheng-Zhi , Wang Ke , Xiang Liang , Bao Zehang , Zhu Zitian , Shen Fanhao , Song Zixuan , Zhang Pengfei , Ren Wenhui , Zhang Xu , Dong Hang , Deng Jinfeng , Chen Jiachen , Wu Yaozu , Tan Ziqi , Gao Yu , Jin Feitong , Zhu Xuhao , Zhang Chuanyu , Wang Ning , Zou Yiren , Zhong Jiarun , Zhang Aosai , Li Weikang , Jiang Wenjie , Yu Li-Wei , Yao Yunyan , Wang Zhen , Li Hekang , Guo Qiujiang , Song Chao , Wang H. , Deng Dong-Ling
Published: May 2023

Non-Abelian anyons are exotic quasiparticle excitations hosted by certain topological phases of matter. They break the fermion-boson dichotomy and obey non-Abelian braiding statistics: their interchanges yield unitary operations, rather than merely a phase factor, in a space spanned by topologically degenerate wavefunctions. They are the building blocks of topological quantum computing. However, experimental observation of non-Abelian anyons and their characterizing braiding statistics is notoriously challenging and has remained elusive hitherto, in spite of various theoretical proposals. Here, we report an experimental quantum digital simulation of projective non-Abelian anyons and their braiding statistics with up to 68 programmable superconducting qubits arranged on a two-dimensional lattice. By implementing the ground states of the toric-code model with twists through quantum circuits, we demonstrate that twists exchange electric and magnetic charges and behave as a particular type of non-Abelian anyons, i.e., the Ising anyons. In particular, we show experimentally that these twists follow the fusion rules and non-Abelian braiding statistics of the Ising type, and can be explored to encode topological logical qubits. Furthermore, we demonstrate how to implement both single- and two-qubit logic gates through applying a sequence of elementary Pauli gates on the underlying physical qubits. Our results demonstrate a versatile quantum digital approach for simulating non-Abelian anyons, offering a new lens into the study of such peculiar quasiparticles.
Induced mutation on Indonesian black orchid (Coelogyne pandurata Lindley) in-vitro culture by gamma irradiation
Authors: Widiarsih S , Dwimahyani I
Published: May 2023

The black orchid (Coelogyne pandurata Lindley) is one of the native Indonesian orchid species. In its natural habitat, its existence is threatened by continuous forest exploitation. Coveted in the global market for hybridization purposes, the black orchid is still considered difficult to be grown in cultivation and may take years to flower. Its conservation and breeding may be carried out through a combination of tissue culture and mutagen application, as induced mutation may increase genetic variation. This experiment aims to investigate the effects of different levels of gamma irradiation on black orchid plantlets. The research design used is a complete random design, utilizing six levels of gamma irradiation (0, 5, 10, 15, 20, and 25 Gy). The observation was carried out for survival rate, number of leaves, number of roots, number of shoots, leaf color, and plantlet type. Plantlets of 10 Gy have the best survival rate and the number of new shoots, but the only number of leaves in the 5 Gy dose is significantly higher than the control. Plantlet growth of 25 Gy is nearly all stagnated. Root growth is also significantly reduced in plantlets of 15 Gy and above. The largest morphological changes are found in 10 and 15 Gy, therefore this range is recommended for future mutation breeding research of black orchids.
Optimization of annealing temperature for amplification of the exon one region of the HPPD gene in HA1 accession sunflowers
Authors: Yunita R , Rosadi F N , Jamsari  , Azizah A
Published: May 2023

The HPPD gene is one of the genes that is actively involved in the biosynthesis of tocopherol, which is the main component of Vitamin E. Sunflower is raw materials for natural medicine since their oil contains vitamin E. To obtain complete information regarding the whole sequences of the 4-Hydroxyphenylpyruvate Dioxygenase (HPPD) gene in sunflower accession HA1, the exon one region needs to be identified using a PCR-based method. One factor affecting the success rate of PCR is the annealing temperature. The optimum annealing temperature will produce specific target gene products. This study aimed to determine the optimal temperature for amplifying the exon 1 region of the HPPD gene using the PCR method. This research began with primer design activities, followed by in vitro amplification (PCR), then optimization of annealing temperature using gradient PCR. The results showed that the optimum temperature for amplifying fragment one was an annealing temperature of 53 °C, fragment two was at an annealing temperature of 45 °C, and fragment three had an annealing temperature of 57 °C with the expected size of PCR products are 306 bp, 506 bp, and 534 bp respectively.
Study of Flowering Phenology of West Sumatera Local Jamblang (Syzygium cumini (L.) Skeels)
Authors: Al-Hamda H M , Swasti E , Satria B
Published: May 2023

The flower of the jamblang plant (Syzygium cumini (L.) Skeels) is a type of compound flower. The jamblang flowers have a panicle like shape with branches that are far apart. The phenology study has practical importance for planning the plant breeding program, including if there will be the development of superior jamblang varieties. The purpose of this study was to determine the development and biological characteristics of jamblang flowers. The observation was conducted on the duration of the flower initiation phase, the small bud phase, the large bud phase, and the complete blooming phase (anthesis), and also flower biological characteristics. This research was carried out in Padang City from February to May 2022 using a survey method with purposive sampling. There are three of plant genotypes that were used as object in this study. The development of jamblang flowers in each phase has a different time for each flower genotype. The characteristics of flowers have similarities in each of their genotypes. Jamblang plant is classified as plants that have a complete flower structure and a perfect flower because it has two penitals on one flower.
Field Emergence Test in Relation to Laboratory Seed Quality Tests of Sweet Corn Seed
Authors: Wulansari R , Farhana B , Fajrina N
Published: May 2023

High quality seeds of sweet corn will lead to high productivity. The quality of seeds can be known through germination testing. The field emergence test is one of seed quality testing with approach to a new method of quality testing in the field. The aims to study seed testing with the approach of field emergence method and finds out its relationship with the germination and vigor tests. This research used randomized complete block design (RCBD) with seven replications on each variety. Field emergence test was carried out by observing the number of open leaves and plant height while laboratory seed quality tests were assessed using standard germination test and accelerated ageing (AA) vigor test. The result showed that the field emergence test observed at 14 days after planting (DAP) gave a clear distinction of normal and abnormal plants, with a criteria normal plant had a criterion 3-4 open leaves and 16.9 ± 2.9 cm in plant height while abnormal had less than 3 leaves and short plant height. Field emergence percentage was calculated by the number of normal plants. There was a correlation at each time of observation of field emergence with germination and vigor tests result.