Biology subjects

Hu, K.

Publications and source records attributed to Hu, K..

108 records · Page 6Linked to original sources

bioRxiv2020

Assessment of whether published non-Cochrane systematic reviews of nursing follow the review protocols registered in the International Prospective Register of Systematic Reviews (PROSPERO): A comparative study

Purpose We compare published non-Cochrane reviews of nursing with their pre-registered protocols on PROSPERO to quantify the prevalence of differences and the extent to which the differences were explained.Methods We searched for protocols and their corresponding reviews in PROSPERO’s nursing group that were “completed and published” from inception to September 8th, 2019. Two authors independently identified differences and classified the difference as none, partial, or complete, and determined if the existed differences had been explained. Frequency (n), percentage (%), median, and inter-quartile ranges were used to analyze the extent of differences and explanations.Results We identified 22 pre-registered protocols and their reviews. All 22 pairs (100%) exhibited differences. Eighteen pairs (82%) showed differences in at least six methodological sections, while 21 pairs (95%) involved completed difference in at least one section. The median number of differences per review was 8.00 (upper quartile = 6.00, lower quartile = 9.75). The differences involved all 13 compared methodology-related sections. Only 5 (3%) of all differences were explained in the systematic reviews.Conclusions We observed widespread differences between non-Cochrane reviews of nursing and their protocols recorded in PROSPERO, with relatively few explanations for the changes. Measures including establishing a new item in the reporting guideline of systematic reviews to guide reporting and explaining the reasons for differences between protocols and systematic reviews or even requiring authors to do so at the Journal’s author guideline are recommended to improve transparency.View Full Text

scientific communication and education↗

bioRxiv2020

Profiling of the reprogramome and quantification of fibroblast reprogramming to pluripotency

Pluripotent state can be established via reprogramming of somatic nuclei by factors within an oocyte or by ectopic expression of a few transgenes. Considered as being extensive and intensive, the full complement of genes to be reprogrammed, however, has never been defined, nor has the degree of reprogramming been determined quantitatively. Here, we propose a new concept of reprogramome, which is defined as the full complement of genes that need to be reprogrammed to the expression levels found in pluripotent stem cells (PSCs). This concept in combination with RNA-seq enables us to precisely profile reprogramome and sub-reprogramomes, and study the reprogramming process with the help of other available tools such as GO analyses. With reprogramming of human fibroblasts into PSCs as an example, we have defined the full complement of the human fibroblast-to-PSC reprogramome. Furthermore, our analyses of the reprogramome revealed that WNT pathways and genes with roles in cellular morphogenesis have to be extensively and intensely reprogrammed for the establishment of pluripotency. We further developed the first mathematical model to quantitate the overall reprogramming, as well as reprogramming in a specific cellular feature such as WNT signaling pathways and genes regulating cellular morphogenesis. We anticipate that our concept and mathematical model may be applied to study and quantitate other reprogramming (pluripotency reprogramming from other somatic cells, and lineage reprogramming), as well as transcriptional and epigenetic differences between any two types of cells including cancer cells and their normal counterparts.

cell biology↗

bioRxiv2019

Dynamic changes in rhythmic and arrhythmic neural signatures in the subthalamic nucleus induced by anaesthesia and intubation

BackgroundSubcortical structures including the basal ganglia have been proposed to be crucial for arousal, consciousness, and behavioural responsiveness. However, how basal ganglia contributes to the loss and recovery of consciousness during anaesthesia has not been well characterized.\n\nMethodsIn this study, using local field potentials (LFPs) from subthalamic nucleus (STN) and scalp electroencephalogram in 12 Parkinsons disease patients, we investigate STN neural signatures during propofol general anaesthesia and during intubation as an arousal intervention in anaesthesia.\n\nResultsPropofol-induced anaesthesia resulted in changes in multiple frequency bands in STN LFPs, including increased low-frequency activities (slow-wave oscillation, delta, theta, and alpha bands) and decreased higher-frequency activities. This was also accompanied by increased STN-frontal cortical coherence in alpha frequency band. Beta and high-gamma activities in the STN temporally increased during intubation compared to the status of loss of consciousness. We also show that the dynamic changes in the high frequency activities (80-180 Hz) in STN LFPs induced by propofol and intubation correlated with power-law exponent in the power spectra between 2 and 80 Hz.\n\nConclusionsOur findings suggest that anaesthesia and intubation induced changes in the STN LFPs in multiple frequency bands. They are also consistent with the hypothesis that the power-law exponent in the power spectra between 2 and 80 Hz reflect the excitation/inhibition balance in the STN, which is modulated by anaesthesia and intubation, and further modulate the high frequency activity.

neuroscience↗

bioRxiv2019

EuRBPDB: a comprehensive resource for annotation, functional and oncological investigation of eukaryotic RNA binding proteins (RBPs)

RNA binding proteins (RBPs) are a large protein family that plays important roles at almost all levels of gene regulation through interacting with RNAs, and contributes to numerous biological processes. However, the complete list of eukaryotic RBPs including human is still unavailable. In this study, we systematically identified RBPs in 162 eukaryotic species based on both computational analysis of RNA binding domains (RBDs) and large-scale RNA binding proteomic (RBPome) data, and established a comprehensive eukaryotic RBP database, EuRBPDB (http://EuRBPDB.syshospital.org:8081). We identified a total of 311,571 RBPs with RBDs and 3,639 non-canonical RBPs without known RBDs. EuRBPDB provides detailed annotations for each RBP, including basic information and functional annotation. Moreover, we systematically investigated RBPs in the context of cancer biology based on published literatures and large-scale omics data. To facilitate the exploration of the clinical relevance of RBPs, we additionally designed a cancer web interface to systematically and interactively display the biological features of RBPs in various types of cancers. EuRBPDB has a user-friendly web interface with browse and search functions, as well as data downloading function. We expect that EuRBPDB will be a widely-used resource and platform for the RNA biology community.

bioinformatics↗

bioRxiv2019

The methodological quality of animal studies: A cross-sectional study based on the SYRCLEs risk of bias tool

ObjectiveTo assess the methodological quality of animal studies published in China and abroad using the SYRCLEs risk of bias tool, and to provide references to improve the methodological quality of animal studies to encourage high quality preclinical studies.\n\nMethodsAn electronic search was performed in the Chinese Scientific Citation Database (CSCD) and Web of Science from 2014 to October 2018. Document screening and data extraction were performed independently by four researchers. The methodological quality of the included studies was assessed using the SYRCLEs risk of bias tool. Statistical analysis was performed using SPSS23.\n\nResultsA total of 2764 animal studies were included. Of the studies, 984 were published in English and 1780 were in Chinese. The citation frequency of more than 90% of the included studies was less than 5. The results of methodological quality assessment showed that 36.36% (8/22) of the sub-items were rated as \"low risk\" in more than 50% of the included studies, of which 75% (6/8) were rated as \"low risk\" in more than 80% of the included studies. A total of 59.09% (13/22) of the sub-items were rated as \"low risk\" in less than 30% of the included studies, of which 92.31% (12/13) were rated as \"low risk\" in less than 10% of the included studies. The incidence of \"low risk\" Chinese studies regarding performance bias, detection bias and reporting bias were lower than English studies. For foreign studies, more attention should be paid to selection bias, attrition bias, and reporting bias.\n\nConclusionWe identified limitations in the methodological quality of animal experiment studies published in China and abroad. We therefore suggest that it is necessary to take targeted measures to popularize the SYRCLEs risk of bias tool to effectively improve the design and implementation of animal experiments, and guide study development.

scientific communication and education↗

bioRxiv2019

Massively parallel kinetic profiling of natural and engineered CRISPR nucleases

Engineered Streptococcus pyogenes (Sp) Cas9s and Acidaminococcus sp. (As) Cas12a (formerly Cpf1) improve cleavage specificity in human cells. However, the fidelity, enzymatic mechanisms, and cleavage products of emerging CRISPR nucleases have not been profiled systematically across partially mispaired off-target DNA sequences. Here, we describe NucleaSeq-- nuclease digestion and deep sequencing--a massively parallel platform that measures cleavage kinetics and captures the time-resolved identities of cleaved products for more than ten thousand DNA targets that include mismatches, insertions, and deletions relative to the guide RNA. The binding specificity of each enzyme is measured on the same DNA library via the chip-hybridized association mapping platform (CHAMP). Using this integrated cleavage and binding platform, we profile four SpCas9 variants and AsCas12a. Engineered Cas9s retain wtCas9-like off-target binding but increase cleavage specificity; Cas9-HF1 shows the most dramatic increase in cleavage specificity. Surprisingly, wtCas12a--reported as a more specific nuclease in cells--has cleavage specificity similar to wtCas9 in vitro. Initial cleavage position and subsequent end-trimming vary across nucleases, guide RNA sequences, and position and base identity of mispairs in target DNAs. Using these large datasets, we develop a biophysical model that reveals mechanistic insights into off-target cleavage activities by these nucleases. More broadly, NucleaSeq enables rapid, quantitative, and systematic comparison of the specificities and cleavage products of engineered and natural nucleases.

molecular biology↗

bioRxiv2019

A doublecortin-domain protein of Toxoplasma and its orthologues bind to and modify the structure and organization of tubulin polymers

TgDCX is a doublecortin-domain protein associated with the conoid fibers, a set of strongly curved non-tubular tubulin-polymers in Toxoplasma. TgDCX deletion impairs conoid structure and parasite invasion. TgDCX contains two tubulin-binding domains: a partial P25-alpha and the DCX/doublecortin domain. Orthologues are found in apicomplexans and their free-living relatives Chromera and Vitrella. We report that isolated TgDCX-containing conoid fibers retain their pronounced curvature, but loss of TgDCX destabilizes the fibers. We crystallized and determined the 3D-structure of the DCX-domain, which is similar to those of human doublecortin and well-conserved among TgDCX orthologues. However, the orthologues vary widely in targeting to the conoid in Toxoplasma and in modulating microtubule organization in Xenopus cells. Several orthologues bind to microtubules in Xenopus cells, but only TgDCX generates short, strongly curved microtubule arcs. EM analysis shows microtubules decorated with TgDCX bundled into rafts, often bordered on one edge by a "C"-shaped incomplete tube. A Chromera orthologue closely mimics TgDCX targeting in Toxoplasma and binds to microtubules in Xenopus cells, but does not generate arcs or "C"-shaped tubes, and fails to rescue the defects of the TgDCX-knockout parasite. These observations suggest that species-specific features of TgDCX enable it to generate strongly curved tubulin-polymers to support efficient host-cell invasion.

cell biology↗

bioRxiv2019

Modular tissue-specific regulation of doublesex underpins sexually dimorphic development in Drosophila

The ability of a single genome to produce distinct and often dramatically different male and female forms is one of the wonders of animal development. In most animals, sex-specific phenotypes are shaped by interactions between a sex determination pathway and spatial patterning gene networks. In Drosophila melanogaster, most sexually dimorphic traits are controlled by sex-specific isoforms of the doublesex (dsx) transcription factor, and dsx expression is mostly limited to cells that give rise to sexually dimorphic traits. However, it is unknown how this mosaic of \"sex-naive\" and \"sex-aware\" tissues arises. Here, we characterize the cis-regulatory sequences that control dsx expression in the foreleg, which contains multiple types of sex-specific sensory organs. We find that separate modular enhancers are responsible for dsx expression in each sexually dimorphic organ. Expression of dsx in the sex comb is co-regulated by two enhancers with distinct spatial and temporal specificities that are separated by a genitalia-specific enhancer. Thus, the mosaic of sexually dimorphic and monomorphic organs depends on modular regulation of dsx transcription by dedicated cell type-specific enhancers.\n\nSummary StatementWe identify the modular cis-regulatory elements that direct expression of doublesex in sexually dimorphic structures in Drosophila legs and genitalia. This regulatory landscape provides insight into how cells obtain their sex-specific identity.

developmental biology↗

bioRxiv2019

Cell type-specific monoclonal antibody cross-reactivity screening in non-human primates and development of comparative immunophenotyping panels for CyTOF

Monoclonal antibodies are a critical tool for immunologists, with applications including immunomicroscopy and cytometry, and non-human primates are essential models for drug development. Very few antibodies are raised against non-human primate antigens; instead, researchers typically use anti-human antibodies that are found to be cross-reactive with non-human primates. The NIH maintains a valuable database of cross-reactivity, but its coverage is not complete, especially for less common species. Furthermore, the database only indicates the presence or absence of staining and does not indicate if a different cell population is stained in the NHP species than in humans. We screened 332 antibodies in five immune cell populations in blood from cynomologus macaques (Macaca fascicularis), rhesus macaques (Macaca mulatta), African green monkeys (Chlorocebus aethiops) and olive/yellow baboons (Papio hamadryas anubis x Papio hamadryas cynocephalus), thereby generating a comprehensive cross-reactivity catalog that includes cell type-specificity. We subsequently used this catalog to help create large CyTOF mass cytometry panels for three of those species and humans. The curated dataset containing the primary data for each antibody has been deposited as a browsable resource at https://immuneatlas.org and https://flowrepository.org/id/FR-FCM-Z2Z7.

immunology↗

bioRxiv2019

Evaluating Invasive EEG Implantations in Medically Refractory Epilepsy with Functional Scalp EEG Recordings and Structural Imaging Data

Seizures in patients with medically refractory epilepsy (MRE) epilepsy cannot be controlled with drugs. For focal MRE, seizures originate in the epileptogenic zone (EZ), which is the minimum amount of cortex that must be treated to be seizure free. Localizing the EZ is often a laborious process wherein clinicians first inspect scalp EEG recordings during several seizure events, and then formulate an implantation plan for subsequent invasive monitoring. The goal of implantation is to place electrodes into the brain region covering the EZ. Then, during invasive monitoring, clinicians visually inspect intracranial EEG recordings to more precisely localize the EZ. The EZ is then surgically removed. Unfortunately surgical success rates average at 50%. Such grim outcomes call for analytical assistance in creating more accurate implantation plans from scalp EEG. In this paper, we introduce a method that combines imaging data (CT and MRI scans) with scalp EEG to derive an implantation distribution. Specifically, scalp EEG data recorded over a seizure event is converted into a time-gamma frequency map, which is then processed to derive a spectrally annotated implantation distribution (SAID). The SAID represents a distribution of gamma power in each of the eight cortical lobe/hemisphere partitions. We applied this method to 4 MRE patients who underwent treatment, and found that the SAID distribution overlapped more with clinical implantations in success cases than in failed cases. These preliminary findings suggest that the SAID may help in improving EZ localization accuracy and surgical outcomes.

neuroscience↗

bioRxiv2019

Frequency of mutations in 21 hereditary breast and ovarian cancer susceptibility genes among high-risk Chinese individuals

PurposeTo determine the prevalence and clinical prediction factors associated with deleterious mutations among 882 high-risk Chinese individuals who underwent multigene panel testing for hereditary breast and ovarian cancer (HBOC) risk assessment.\n\nExperimental DesignSubjects were selected from individuals referred for genetic testing using a 21-gene panel (Oseq-BRCA) between January 2015 and March 2018. The distribution and prevalence of deleterious mutations were analyzed for the full cohort as well as subtypes.\n\nResultsOverall, 176 deleterious mutations were observed in 19.50% (n = 172) individuals. Of these, 26 mutations are not reported in public databases and literatures. In the ovarian cancer only subgroup, 115 deleterious mutations were identified in 429 patients (48.6%). Patients with ovarian cancer with mutations were enriched for a family history of breast or ovarian cancers (p < 0.05). In the breast cancer only subgroup, 31 deleterious mutations were identified in 261 patients. Most mutations occurred in BRCA1 (8; 25.8%) and BRCA2 (11; 35.5%). An additional 12 deleterious mutations (38.7%) were found in 7 other susceptibility genes. An increased frequency of mutation rate (57.9%) was observed in the subgroup of subjects with histories of both breast and ovarian cancer.\n\nConclusions19.50% of individuals carried a deleterious mutation in HBOC susceptibility genes in our cohort. Subgroup of subjects with histories of both breast and ovarian cancer had the highest prevalence of mutations. Our results highlighted the genetic heterogeneity of HBOC and the efficiency of multigene panel in performing risk assessment.

cancer biology↗

bioRxiv2018

TgCentrin2 is required for invasion and replication in the human parasite Toxoplasma gondii

Centrins are EF-hand containing proteins ubiquitously found in eukaryotes and are key components of centrioles/basal bodies as well as certain contractile fibers. We previously identified three centrins in the human parasite Toxoplasma gondii, all of which localized to the centrioles. However, one of them, TgCentrin2 (CEN2), is also targeted to ring-shaped structures at the apical and basal ends of the parasite, as well as to multiple annuli at the junction between the apical cap and the rest of the membrane cortex. The role(s) that TgCentrin2 plays in these locations was unknown. Here we report the functional characterization of TgCentrin2 in the parasite lytic cycle. After multiple unsuccessful attempts to knock out or knock down the TgCentrin2 gene with existing tools, we designed a new conditional knockdown method that combines transcriptional and protein stability control to achieve tight regulation of TgCentrin2 levels in the parasite. We discovered that under knockdown conditions, there was an ordered loss of TgCentrin2 from its four compartments, due to differences in incorporation kinetics and structural inheritance over successive generations. This was correlated with the development of major invasion deficiency at early stages of CEN2 knockdown, and replication defects at later stages. These results indicate that TgCentrin2 is incorporated into multiple cytoskeletal structures to serve distinct functions in T. gondii that are required for parasite survival.

cell biology↗

bioRxiv2018

Structure of a novel dimeric SET domain methyltransferase regulating cell motility

Lysine methyltransferases (KMTs) were initially associated with transcriptional control through their methylation of histones and other nuclear proteins, but have since been found to regulate many other cellular activities. The apical complex lysine (K) methyltransferase (AKMT) of the human parasite Toxoplasma gondii was recently shown to play a critical role in regulating cellular motility. Here we report a 2.1-[A] resolution crystal structure of the conserved and functional C-terminal portion (aa289-709) of T. gondii AKMT. AKMT dimerizes via a unique intermolecular interface mediated by the C-terminal TPR (tetratricopeptide repeat)-like domain together with a specific zinc-binding motif that is absent from all other KMTs. Disruption of AKMT dimerization impaired both its enzyme activity and parasite egress from infected host cells in vivo. Structural comparisons reveal that AKMT is related to the KMTs in the SMYD family, with, however, a number of distinct structural features in addition to the unusual dimerization interface. These features are conserved among the apicomplexan parasites and their free-living relatives, but not found in any known KMTs in animals. AKMT therefore is the founding member of a new subclass of KMT that has important implications for the evolution of the apicomplexans.

biochemistry↗

bioRxiv2018

Proteasome Substrate Capture and Gate Activation by Mycobacterium tuberculosis PafE

In all domains of life, proteasomes are gated chambered proteases that require opening by activators in order to facilitate protein degradation. Twelve proteasome accessory factor E (PafE) monomers assemble into a single, dodecameric ring to promote proteolysis that is required for the full virulence of the human bacterial pathogen Mycobacterium tuberculosis. While the best characterized proteasome activators use ATP to deliver proteins into a proteasome, PafE does not require ATP. In order to understand the mechanism of PafE-mediated protein targeting and proteasome activation, we studied the interactions of PafE with native substrates, including a newly identified proteasome substrate, Rv3213c, and with proteasome core particles. We characterized the function of a highly conserved feature conserved in bacterial proteasome activator proteins: a glycine-glutamine-tyrosine-leucine or \"GQYL\" motif at their carboxyl-termini that is essential to stimulate proteolysis. Using cryo-electron microscopy, we found that the GQYL motif of PafE interacts with specific residues in the -subunits of the proteasome core particle to trigger gate opening and degradation. Finally, we found that PafE rings have 40-[A] openings lined with hydrophobic residues that form a chamber for capturing substrates prior to the onset of degradation. This result suggests PafE has a previously unrecognized chaperone activity. Collectively, our data provide new insights on the mechanistic understanding of ATP-independent proteasome degradation in bacteria.

biochemistry↗

bioRxiv2017

Modeling the schizophrenias: subunit-specific NMDAR antagonism dissociates oscillatory signatures of frontal hypofunction and hippocampal hyperfunction

NMDAR antagonism alters mesolimbic, hippocampal, and cortical function, acutely reproducing the positive, cognitive, and negative symptoms of schizophrenia. These physiological and behavioral effects may depend differentially on NMDAR subtype-and region-specific effects. The dramatic electrophysiological signatures of NMDAR blockade in rodents include potentiated high frequency oscillations (HFOs, ~140 Hz), likely generated in mesolimbic structures, and increased HFO phase-amplitude coupling (PAC), a phenomenon related to goal-directed behavior and dopaminergic tone. This study examined the impact of subtype-specific NMDAR antagonism on HFOs and PAC. We found that positive-symptom-associated NR2A-preferring antagonism (NVP-AAM077), but not NR2B-specific antagonism (Ro25-6985) or saline control, replicated increases in HFO power seen with nonspecific antagonism (MK-801). However, PAC following NR2A-preferring antagonism was distinct from all other conditions. While{theta} -HFO PAC was prominent or potentiated in other conditions, NVP-AAM077 increased{delta} -HFO PAC and decreased{theta} -HFO PAC. Furthermore, active wake epochs exhibiting narrowband frontal{delta} oscillations, and not broadband sleep-associated{delta} , selectively exhibited{delta} -HFO coupling, while paradoxical sleep epochs having a high CA1{theta} to frontal{delta} ratio selectively exhibited{theta} -HFO coupling. Our results suggest: (1) NR2A-preferring antagonism induces oscillopathies re[fl]ecting frontal hyperfunction and hippocampal hypofunction; and (2) HFO PAC indexes cortical vs. hippocampal control of mesolimbic circuits.

neuroscience↗

bioRxiv2017

Sleeping Beauty transposon integrates into non-TA dinucleotides via an alternative mechanism

Sleeping Beauty transposon (SB) is an important genetic tool for generating mutations in vertebrates. It is well known that SB exclusively integrates into TA dinucleotides. However, this \"TA law\" has never been strictly tested in large number of insertion sites after next generation sequencing was widely utilized. In this study, we analyzed 600 million pairs of Illumina sequence reads and identified 28 thousand SB insertions in non-TA sites. We recovered some non-TA sites using PCR and confirmed that at least parts of the insertions at non-TA sites are real integrations. The consensus sequence of these non-TA sites showed an asymmetric pattern distinct from the symmetric pattern of the canonical TA sites. The right side of the consensus sequence is exactly the same as the sequence of SB transposon ends, indicating interaction between the transposon DNA and the target DNA. Based on these results we suggested that SB has an alternative integration mechanism besides the canonical one to integrate its DNA into non-TA sites.\n\nHighlights[~] For the first time, we proved that Sleeping Beauty transposon can integrate into non-TA dinucleotides.\n\n [~]For the first time, we provided evidence that transposon DNA can directly interact with target DNA.\n\n [~]And for the first time, we found that a transposon can have two independent integration mechanisms.

molecular biology↗

bioRxiv2017

Metabolomic profiling reveals effects of marein on energy metabolism in HepG2 cells

Previous studies have suggested that Coreopsis tinctoria improves insulin resistance in rats fed with high-fat diet. But little is known about the antidiabetic effects of marein which is the main component of C. tinctoria. This study investigated the effects of ethyl acetate extract of C. tinctoria (AC) on insulin resistance (IR) in rats fed a high-fat diet. High glucose and fat conditions cause a significant increase in blood glucose, insulin, serum TC,TG and LDL-C, leading to an abnormal IR in rats. However, treatment with AC protects against HFD-induced IR by improving fasting serum glucose and lipid homeostasis. High glucose conditions cause a significant decrease in glycogen synthesis and increases PEPCK and G6Pase protein levels and Krebs-cycle-related enzymes levels, leading to an abnormal metabolic state in HepG2 Cells. However, treatment with Marein improves IR by increasing glucose uptake and glycogen synthesis and by downregulating PEPCK and G6Pase protein levels. The statistical analysis of HPLC/MS data demonstrates that Marein restores the normal metabolic state. The results show that AC ameliorates IR in rats and Marein has the potential effect in improving IR by ameliorating glucose metabolic disorders.\n\nAbbreviations

pharmacology and toxicology↗

bioRxiv2017

Stability and function of a putative microtubule organizing center in the human parasite Toxoplasma gondii

The organization of the microtubule cytoskeleton is dictated by microtubule nucleators or organizing centers. Toxoplasma gondii, an important human parasite, has an array of 22 regularly spaced cortical microtubules stemming from a hypothesized organizing center, the apical polar ring. Here, we examine the functions of the apical polar ring by characterizing two of its components, KinesinA and APR1, and discovered that its putative role in templating can be separated from its mechanical stability. Parasites that lack both KinesinA and APR1 ({Delta}kinesinA{Delta}apr1) are capable of generating 22 cortical microtubules. However, the apical polar ring is fragmented in live{Delta} kinesinA{Delta}apr1 parasites, and is undetectable by electron microscopy after detergent extraction. Disintegration of the apical polar ring results in the detachment of groups of microtubules from the apical end of the parasite. These structural defects are linked to a diminished ability of the parasite to move and to invade host cells, as well as decreased secretion of effectors important for these processes. Together, the findings demonstrate the importance of the structural integrity of the apical polar ring and the microtubule array in the Toxoplasma lytic cycle, which is responsible for massive tissue destruction in acute toxoplasmosis.

cell biology↗