bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced loss of retinoic acid network genes in Xenopus laevis achieves a tighter signal regulation
Authors: Abbou Tali , Bendelac-Kapon Liat , Sebag Audeliah , Fainsod Abraham 
Published: January 2022

AbstractRetinoic acid (RA) is a major regulatory signal during embryogenesis produced from vitamin A (retinol) by an extensive, autoregulating metabolic and signaling network to prevent fluctuations that result in developmental malformations. Xenopus laevis is an allotetraploid hybrid frog species whose genome includes L (long) and S (short) chromosomes from the originating species. Evolutionarily, the X. laevis subgenomes have been losing either L or S homoeologs in about 43% of genes to generate singletons. In the RA network, out of the 47 genes, about 46% have lost one of the homoeologs, like the genome average. In contrast, RA metabolism genes from storage (retinyl esters) to retinaldehyde production exhibit enhanced gene loss with 75% singletons out of 28 genes. The effect of this gene loss on RA signaling autoregulation was studied. Employing transient RA manipulations, homoeolog gene pairs were identified in which one homeolog exhibits enhanced responses or looser regulation than the other, while in other pairs both homoeologs exhibit similar RA responses. CRISPR /Cas9 targeting of individual homoeologs to reduce their activity supports the hypothesis where the RA metabolic network gene loss results in tighter network regulation and more efficient RA robustness responses to overcome complex regulation conditions.
Heterogeneity of social cognition in temporo-parietal junction: Overlapping yet distinct representation between visual perspective-taking and theory of mind
Authors: Ogawa Kenji , Matsuyama Yuiko 
Published: January 2022

AbstractVisual perspective taking (VPT), particularly level 2 VPT (VPT2), which allows an individual to understand that the same object can be seen differently by others, is related to the theory of mind (ToM), because both functions require a decoupled representation from oneself. Although previous neuroimaging studies have shown that VPT and ToM activate the temporo-parietal junction (TPJ), it is unclear whether common neural substrates are involved in VPT and ToM. To clarify this point, the present study directly compared the TPJ activation patterns of individual participants performing VPT2 and ToM tasks using functional magnetic resonance imaging and within-subjects design. VPT2-induced activations were compared with activations observed during a mental rotation task as a control task, whereas ToM-related activities were identified with a standard ToM localizer using false-belief stories. A whole-brain analysis revealed that VPT2 and ToM activated overlapping areas in the posterior part of the TPJ. By comparing the activations induced by VPT2 and ToM in individual participants, we found that the peak voxels induced by ToM were located significantly more anteriorly and dorsally within the bilateral TPJ than those measured during the VPT2 task. We further confirmed that these activity areas were spatially distinct from the nearby extrastriate body area (EBA), visual motion area (MT+), and the posterior superior temporal sulcus (pSTS) using independent localizer scans. Our findings revealed that VPT2 and ToM have distinct representations, albeit partially overlapping, indicating the functional heterogeneity of social cognition within the TPJ.Significance StatementThe temporo-parietal junction (TPJ) is consistently activated by social cognitive tasks such as visual perspective taking (VPT) and theory of mind (ToM) tasks. The present study investigated whether VPT and ToM have the same neural substrates within the TPJ using functional magnetic resonance imaging (fMRI) with a within-subjects design. While VPT and ToM tasks activated overlapping areas in the posterior part of the TPJ, the individual peak voxels induced by ToM were located significantly more anteriorly and dorsally compared with those observed during the VPT task. Moreover, they were spatially distinct from the nearby functional modules, such as the extrastriate body area, visual motion area, and posterior superior temporal sulcus. Our findings reveal the heterogeneity of social cognition representation within the TPJ.
Gene expression profiles of some prognostic markers in a human breast cell line (MCF7) exposed to Curcumin nanoparticles and nanocapsules
Authors: Shaker Emad S. , Nasr Ghada M. , Moawad Mahmoud 
Published: January 2022

1.ABSTRACTIntroductionWorldwide, cancer is a significant public health problem. Curcumin exhibits anti-inflammatory, antiproliferative, and anticancer properties when used in medicine. Investigated study for Curcumin’s chemopreventive mechanism against human malignancies, this research examined the cellular and molecular alterations generated by curcumin modified compound in breast cancer (MCF-7) cell lines. Oncogenic EGFR and VEGFR2 mutations lead to the formation, invasion, and maintenance of malignant phenotypes in humans, including breast cancer. Studied prognostic markers such as C-myc and Ki67 in breast cancer, and the apoptotic gene as Caspase-3 have been done.Aim of the workThe purpose of this study is to determine the therapeutic efficacy of curcumin nanoparticles and nanocapsules in breast cancer cell lines (MCF7).Materials and methodsWe used real-time PCR to assess the expression of the C-myc, Ki67, EGFR, VEGFR2, and Caspase-3 genes in MCF7 cells treated with Curcumin nanoparticles and nanocapsules.ResultsCurcumin nanoparticles and nanocapsules boosted apoptotic cell populations considerably regardless of the nanotechnology used. Additionally, the mRNA expression analysis results indicated that the mechanism activated by curcumin nanocapsules involved the upregulation of the oncogenes EGFR and VEGFR2. In comparison to curcumin nanoparticles, curcumin nanocapsules significantly reduced the expression of Ki67 and c-myc mRNAs in breast cancer cells. The mRNA expression study revealed that curcumin nanocapsules produce an increase in the apoptotic Caspase-3 gene production compared to cells treated with curcumin nanoparticles.ConclusionThis work demonstrates that curcumin nanoparticles created using a novel mechanical process can be employed successfully as an anticancer agent. These findings add to our understanding of the molecular mechanisms behind curcumin nanocapsules’ anticancer activity in breast cancer.
Transglutaminase mediated asprosin oligomerization allows its tissue storage as fibers
Authors: Morcos Yousef A.T. , Pryymachuk Galyna , Lütke Steffen , Gerken Antje , Godwin Alan R. F. , Jowitt Thomas A. , Piekarek Nadin , Hoffmann Thorben , Niehoff Anja , Odenthal Margarete , Drebber Uta , Grisk Olaf , Ladilov Yury , Bloch Wilhelm , Callewaert Bert , Paulsson Mats , Hucklenbruch-Rother Eva , Baldock Clair , Sengle Gerhard 
Published: January 2022

AbstractAsprosin, the C-terminal furin cleavage product of profibrillin-1, was reported to act as a hormone that circulates at nanomolar levels and is recruited to the liver where it induces G protein-coupled activation of the cAMP-PKA pathway and stimulates rapid glucose release into the circulation. Although derived upon C-terminal cleavage of fibrillin-1, a multidomain extracellular matrix glycoprotein with a ubiquitous distribution in connective tissues, little is known about the mechanisms controlling the bioavailability of asprosin in tissues. In the current view, asprosin is mainly produced by white adipose tissue from where it is released into the blood in monomeric form. Here, by employing newly generated specific asprosin antibodies we monitored the distribution pattern of asprosin in human and murine connective tissues such as placenta, and muscle. Thereby we detected the presence of asprosin positive extracellular fibers. Further, by screening established cell lines for asprosin synthesis we found that most cells derived from musculoskeletal tissues render asprosin into an oligomerized form. Our analyses show that asprosin already multimerizes intracellularly, but that stable multimerization via covalent bonds is facilitated by transglutaminase activity. Further, asprosin fiber formation requires an intact fibrillin-1 fiber network for proper linear deposition. Our data suggest a new extracellular storage mechanism of asprosin in an oligomerized form which may regulate its cellular bioavailability in tissues.
Proximity labeling reveals spatial regulation of the anaphase-promoting complex/cyclosome by a microtubule adaptor
Authors: Cao Xiaofu , Shah Adnan Shami , Sanford Ethan J. , Smolka Marcus B. , Baskin Jeremy M. 
Published: January 2022

SUMMARYThe anaphase-promoting complex/cyclosome (APC/C) coordinates advancement through mitosis via temporally controlled polyubiquitination of effector proteins. Despite the long-appreciated spatial organization of key events in mitosis mediated largely by cytoskeletal networks, the spatial regulation of APC/C, the major mitotic E3 ligase, is poorly understood. Here, we describe a microtubule-resident protein, PLEKHA5, as an interactor of APC/C and spatial regulator of its activity in mitosis. PLEKHA5 knockdown delayed mitotic progression, causing accumulation of APC/C substrates dependent upon the PLEKHA5–APC/C interaction. To assess the spatial importance of this interaction, we developed microtubule-localized proximity biotinylation tools, which revealed that depletion of PLEKHA5 decreased the extent of APC/C association with the microtubule cytoskeleton. This decreased APC/C microtubule-localization in turn prevented efficient loading of APC/C with its co-activator CDC20, leading to defects in E3 ligase catalytic activity. We propose that PLEKHA5 functions as an adaptor of APC/C that promotes its subcellular localization to microtubules and facilitates its activation by CDC20, thus ensuring the timely turnover of key mitotic APC/C substrates and proper progression through mitosis.
GWAS and functional studies implicate a role for altered DNA repair in the evolution of drug resistance in Mycobacterium tuberculosis
Authors: Naz Saba , Paritosh Kumar , Sanyal Priyadarshini , Khan Sidra , Singh Yogendra , Varshney Umesh , Nandicoori Vinay Kumar 
Published: January 2022

AbstractThe emergence of drug resistance in Mycobacterium tuberculosis (Mtb) is alarming and demands in-depth knowledge for timely diagnosis. We performed genome-wide association analysis (GWAS) using 2237 clinical strains of Mtb to identify novel genetic factors that evoke drug resistance. In addition to the known direct targets, for the first time, we identified a strong association between the mutations in the DNA repair genes and the multidrug-resistant phenotype. To evaluate the impact of variants identified in the clinical samples in the evolution of drug resistance, we utilized knockouts and complemented strains in Mycobacterium smegmatis (Msm) and Mtb. Results show that variant mutations abrogated the function of MutY and UvrB. MutY variant showed enhanced survival compared with wild-type (Rv) when the Mtb strains were subjected to multiple rounds of ex vivo antibiotic stress. Notably, in an in vivo Guinea pig infection model, the MutY variant outcompeted the wild-type strain. Collectively, we show that novel variant mutations in the DNA repair genes abrogate their function and contribute to better survival under antibiotic/host stress conditions.
Multivalent interactions drive the Toxoplasma AC9:AC10:ERK7 complex to concentrate ERK7 in the apical cap
Authors: Back Peter S. , O’Shaughnessy William J. , Moon Andy S. , Dewangan Pravin S. , Reese Michael L. , Bradley Peter J. 
Published: January 2022

ABSTRACTThe Toxoplasma inner membrane complex (IMC) is a specialized organelle that is crucial for the parasite to establish an intracellular lifestyle and ultimately cause disease. The IMC is composed of both membrane and cytoskeletal components, further delineated into the apical cap, body, and basal subcompartments. The apical cap cytoskeleton was recently demonstrated to govern the stability of the apical complex, which controls parasite motility, invasion, and egress. While this role was determined by individually assessing the apical cap proteins AC9, AC10, and the MAP kinase ERK7, how the three proteins collaborate to stabilize the apical complex is unknown. In this study, we use a combination of deletion analyses and yeast-2-hybrid experiments to establish that these proteins form an essential complex in the apical cap. We show that AC10 is a foundational component of the AC10:AC9:ERK7 complex and demonstrate that the interactions among them are critical to maintain the apical complex. Importantly, we identify multiple independent regions of pairwise interaction between each of the three proteins, suggesting that the AC9:AC10:ERK7 complex is organized by multivalent interactions. Together, these data support a model in which multiple interacting domains enable the oligomerization of the AC9:AC10:ERK7 complex and its assembly into the cytoskeletal IMC, which serves as a structural scaffold that concentrates ERK7 kinase activity in the apical cap.IMPORTANCEThe phylum Apicomplexa consists of obligate, intracellular parasites including the causative agents of toxoplasmosis, malaria, and cryptosporidiosis. Hallmarks of these parasites are the IMC and the apical complex, both of which are unique structures that are conserved throughout the phylum and required for parasite survival. The apical cap portion of the IMC has previously been shown to stabilize the apical complex. Here, we expand on those studies to determine the precise protein-protein interactions of the apical cap complex that confer this essential function. We describe the multivalent nature of these interactions and show that the resulting protein oligomers likely tether ERK7 in the apical cap. This study represents the first description of the architecture of the apical cap at a molecular level, expanding our understanding of the unique cell biology that drives Toxoplasma infections.
An Antioxidant Polysaccharide from Ganoderma lucidum Induces Apoptotic Activity in Breast Cancer Cell Line
Authors: Uddin Pk Md. Moyen , Pervin Rumana , Biswas Mohammad Shahangir , Rahman Md. Matiar 
Published: January 2022

AbstractThe purpose of this study is to elucidate the apoptotic activity of Ganoderma lucidum polysaccharide (GLP) in a human breast cancer cell line MCF-7 in vitro. According to DPPH assay, GLP showed a good antioxidant (IC50 value is 202.4 μg/mL). Based on MTT assay, the results showed that GLP inhibits MCF-7 cells proliferation in a dose- and time-dependent manner (p<0.001). IC50 values of the cytotoxicity of GLP and doxorubin were 110.907 μg/mL and 58.206 μg/mL respectively. The results from the flow cytometry indicated that GLP could induce apoptotic activity through inducing the up-regulation of the Bax and Caspase-9 and the down-regulation of the BcL-2 in MCF-7 cells. At 2×IC50, GLP increased the early-apoptotic and dead cells of MCF-7 from 18.23% to 34.76% and 8.45% to16.34% respectively. In conclusion, the GLP shows anticancer activity against MCF-7 through preventing the proliferation and inducing the apoptosis of MCF-7 cells. Our data provide the potential molecular targets in cancer prevention and reveal the key barriers in the current anticancer drugs development.
Sequence assignment validation in cryo-EM models with checkMySequence
Authors: Chojnowski Grzegorz 
Published: January 2022

AbstractThe availability of new AI-based protein structure prediction tools radically changed the way cryo-EM maps are interpreted, but it has not eliminated the challenges of map interpretation faced by a microscopist. Models will continue to be locally rebuilt and refined using interactive tools. This inevitably results in occasional errors, among which register-shifts remain one of the most difficult to identify and correct. Here we introduce checkMySequence; a fast, fully automated and parameter-free method for detecting register-shifts in protein models built into cryo-EM maps. We show that the method can assist model building in cases where poorer map resolution hinders visual interpretation. We also show that checkMySequence could have helped avoid a widely discussed sequence register error in a model of SARS-CoV-2 RNA-dependent RNA polymerase that was originally detected thanks to a visual residue-by-residue inspection by members of the structural biology community.SynopsisWe present a new method, checkMySequence, for fast and automated detection of register errors in protein models built into cryo-EM reconstructions.
Embracing enzyme promiscuity with activity-based compressed biosensing
Authors: Holt Brandon Alexander , Lim Hong Seo , Su Melanie , Tuttle McKenzie , Liakakos Haley , Qiu Peng , Kwong Gabriel A. 
Published: January 2022

AbstractGenome-scale activity-based profiling of proteases requires identifying substrates that are specific to each individual protease. However, this process becomes increasingly difficult as the number of target proteases increases because most substrates are promiscuously cleaved by multiple proteases. We introduce a method – Substrate Libraries for Compressed sensing of Enzymes (SLICE) – for selecting complementary sets of promiscuous substrates to compile libraries that classify complex protease samples (1) without requiring deconvolution of the compressed signals and (2) without the use of highly specific substrates. SLICE ranks substrate libraries according to two features: substrate orthogonality and protease coverage. To quantify these features, we design a compression score that was predictive of classification accuracy across 140 in silico libraries (Pearson r = 0.71) and 55 in vitro libraries (Pearson r = 0.55) of protease substrates. We demonstrate that a library comprising only two protease substrates selected with SLICE can accurately classify twenty complex mixtures of 11 enzymes with perfect accuracy. We envision that SLICE will enable the selection of peptide libraries that capture information from hundreds of enzymes while using fewer substrates for applications such as the design of activity-based sensors for imaging and diagnostics.
Hypoxia-Induced Ethanol Production in Arabidopsis Root Apex Cells Affects Endocytic Vesicle Recycling and F-Actin Organisation
Authors: Kagenishi Tomoko , Baluška František , Yokawa Ken 
Published: January 2022

AbstractEthanol (EtOH) is a short-chain alcohol that is abundant in nature. EtOH is endogenously produced by plants under hypoxic conditions, and exogenously applied EtOH improves plant stress tolerance at low concentrations (<1%). However, no direct observations have shown how EtOH affects cellular events in plants. In intact Arabidopsis roots, 0.1% EtOH promoted reactive oxygen species production in root apex cells. EtOH also accelerated exocytic vesicle recycling and altered F-actin organisation, both of which are closely related to cell membrane properties. In addition to exogenous EtOH application, hypoxic treatment resulted in EtOH production in roots and degradation of the cross-wall actin cytoskeleton in root epidermal cells. We conclude that hypoxia-induced EtOH production affects endocytic vesicle recycling and associated signalling pathways.
Mutation in shoot-to-root mobile transcription factor, ELONGATED HYPOCOTYL 5, leads to low nicotine levels in tobacco
Authors: Singh Deeksha , Dwivedi Shambhavi , Sinha Hiteshwari , Singh Nivedita , Trivedi Prabodh Kumar 
Published: January 2022

ABSTRACTTobacco remains one of the most commercially important crops due to the parasympathomimetic alkaloid nicotine used in cigarettes. Most genes involved in nicotine biosynthesis are expressed in root tissues; however, their light-dependent regulation has not been studied. We identified the ELONGATED HYPOCOTYL 5 homolog, NtHY5, fromNicotiana tabacumand demonstrated its role in nicotine biosynthesis. We report the development of CRISPR/Cas9-based mutant plants,NtHY5CR, and show down-regulation of the nicotine biosynthetic pathway, whereas NtHY5 overexpression (NtHY5OX) plants show the opposite effect. Grafting experiments using wild type,NtHY5CR,and NtHY5OX indicated that NtHY5 moves from shoot-to-root to regulate nicotine biosynthesis in the root tissue. We conclude that shoot HY5, directly or through enhancing expression of the HY5 in the root, promotes nicotine biosynthesis. The CRISPR/Cas9-based mutants developed, in this study; with low nicotine accumulation in leaves could help people to overcome their nicotine addiction and the risk of death from tobacco use.
Differential mosquito attraction to humans is associated with skin-derived carboxylic acid levels
Authors: De Obaldia Maria Elena , Morita Takeshi , Dedmon Laura C. , Boehmler Daniel J. , Jiang Caroline S. , Zeledon Emely V. , Cross Justin R. , Vosshall Leslie B. 
Published: January 2022

SUMMARYFemaleAedes aegyptimosquitoes feed on human blood, which they use to develop their eggs. It has been widely noted that some people are more attractive to mosquitoes than others, but the mechanistic basis of this phenomenon is poorly understood. Here we tested mosquito attraction to skin odor collected from human subjects and identified people who are exceptionally attractive or unattractive to mosquitoes. Notably, these preferences were stable over several years, indicating consistent longitudinal differences in skin odor between subjects. We carried out gas chromatography/quadrupole time of flight-mass spectrometry to analyze the chemical composition of human skin odor in these subjects and discovered that highly attractive people produce significantly increased levels of carboxylic acids. Mosquitoes could reliably distinguish a highly attractive human from their weakly attractive counterparts unless we substantially diluted the odor of the “mosquito magnet.” This is consistent with the hypothesis that odor concentration is a major driver of differential attraction, rather than the less-favored skin odor blend containing repellent odors, although these are not mutually- exclusive. Mosquitoes detect carboxylic acids with a large family of odor-gated ion channels encoded by the Ionotropic Receptor gene superfamily. Mutant mosquitoes lacking any of the Ionotropic Receptor (IR) co-receptorsIr8a, Ir25a,andIr76b,were severely impaired in attraction to human scent but retained the ability to differentiate highly and weakly attractive people. The link between elevated carboxylic acids in “mosquito-magnet” human skin odor and phenotypes of genetic mutations in carboxylic acid receptors suggests that such compounds contribute to differential mosquito attraction. Understanding why some humans are more attractive than others provides insights into what skin odorants are most important to the mosquito and could inform the development of more effective repellents.