Processing of fearful faces exhibits characteristics of subcortical functions.

A subcortical pathway is thought to have evolved to facilitate fear information transmission, but direct evidence for its existence in humans is lacking. In recent years, rapid, preattentive, and preconscious fear processing has been demonstrated, providing indirect support for the existence of the subcortical pathway by challenging the necessity of canonical cortical pathways in fear processing. However, direct support also requires evidence for the involvement of subcortical regions in fear processing. To address this issue, here we investigate whether fear processing reflects the characteristics of the subcortical structures in the hypothesized subcortical pathway. Using a monocular/dichoptic paradigm, Experiment 1 demonstrated a same-eye advantage for fearful but not neutral face processing, suggesting that fear processing relied on monocular neurons existing mainly in the subcortex. Experiments 2 and 3 further showed insensitivity to short-wavelength stimuli and a nasal-temporal hemifield asymmetry in fear processing, both of which were functional characteristics of the superior colliculus, a key hub of the subcortical pathway. Furthermore, all three experiments revealed a low spatial frequency selectivity of fear processing, consistent with magnocellular input via subcortical neurons. These results suggest a selective involvement of subcortical structures in fear processing, which, together with the indirect evidence for automatic fear processing, provides a more complete picture of the existence of a subcortical pathway for fear processing in humans. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Mechanistic study of C5F10O-induced lung toxicity in rats: An eco-friendly insulating gas alternative to SF6.

The global warming and other environmental problems caused by SF6 emissions can be reduced due to the widespread use of eco-friendly insulating gas, perfluoropentanone (C5F10O). However, there is an exposure risk to populations in areas near C5F10O equipment, so it is important to clarify its biosafety and pathogenesis before large-scale application. In this paper, histopathology, transcriptomics, 4D-DIA proteomics, and LC-MS metabolomics of rats exposed to 2000 ppm and 6000 ppm C5F10O are analyzed to reveal the mechanisms of toxicity and health risks. Histopathological shows that inflammatory cell infiltration, epithelial cell hyperplasia, and alveolar atrophy accompanied by alveolar wall thickening are present in both low-dose and high-dose groups. Analysis of transcriptomic and 4D-DIA proteomic show that Cell cycle and DNA replication can be activated by both 2000 ppm and 6000 ppm C5F10O to induce cell proliferation. In addition, it also leads to the activation of pathways such as Antigen processing and presentation, Cell adhesion molecules and Complement and coagulation cascades, T cell receptor signal path, Th1 and T cell receptor signal path, Th1 and Th2 cell differentiation, complement and coagulation cascades. Finally, LC-MS metabolomics analysis confirms that the metabolic pathways associated with glycerophospholipids, arachidonic acid, and linoleic acid are disrupted and become more severe with increasing doses. The mechanism of lung toxicity caused by C5F10O is systematically expounded based on the multi-omics analysis and provided biosafety references for further promotion and application of C5F10O.

Quorum sensing N-acyl homoserine lactones-SdiA enhances the biofilm formation of E. coli by regulating sRNA CsrB expression.

As an important virulence phenotype of Escherichia coli, the regulation mechanism of biofilm by non-coding RNA and quorum sensing system has not been clarified. Here, by transcriptome sequencing and RT-PCR analysis, we found CsrB, a non-coding RNA of the carbon storage regulation system, was positively regulated by the LuxR protein SdiA. Furthermore, ß-galactosidase reporter assays showed that SdiA enhanced promoter transcriptional activity of csrB. The consistent dynamic expression levels of SdiA and CsrB during Escherichia coli growth were also detected. Moreover, curli assays and biofilm assays showed sdiA deficiency in Escherichia coli SM10λπ or BW25113 led to a decreased formation of biofilm, and was significantly restored by over-expression of CsrB. Interestingly, the regulations of SdiA on CsrB in biofilm formation were enhanced by quorum sensing signal molecules AHLs. In conclusion, SdiA plays a crucial role in Escherichia coli biofilm formation by regulating the expression of non-coding RNA CsrB. Our study provides new insights into SdiA-non-coding RNA regulatory network involved in Escherichia coli biofilm formation.

Invisible social grouping facilitates the recognition of individual faces.

Emerging evidence suggests a specialized mechanism supporting perceptual grouping of social entities. However, the stage at which social grouping is processed is unclear. Through four experiments, here we showed that participants' recognition of a visible face was facilitated by the presence of a second facing (thus forming a social grouping) relative to a nonfacing face, even when the second face was invisible. Using a monocular/dichoptic paradigm, we further found that the social grouping facilitation effect occurred when the two faces were presented dichoptically to different eyes rather than monocularly to the same eye, suggesting that social grouping relies on binocular rather than monocular neural channels. The above effects were not found for inverted face dyads, thereby ruling out the contribution of nonsocial factors. Taken together, these findings support the unconscious influence of social grouping on visual perception and suggest an early origin of social grouping processing in the visual pathway.

Bilateral eye movements disrupt the involuntary perceptual representation of trauma-related memories.

Bilateral eye movement (EM) is a critical component in eye movement desensitization and reprocessing (EMDR), an effective treatment for post-traumatic stress disorder. However, the role of bilateral EM in alleviating trauma-related symptoms is unclear. Here we hypothesize that bilateral EM selectively disrupts the perceptual representation of traumatic memories. We used the trauma film paradigm as an analog for trauma experience. Nonclinical participants viewed trauma films followed by a bilateral EM intervention or a static Fixation period as a control. Perceptual and semantic memories for the film were assessed with different measures. Results showed a significant decrease in perceptual memory recognition shortly after the EM intervention and subsequently in the frequency and vividness of film-related memory intrusions across one week, relative to the Fixation condition. The EM intervention did not affect the explicit recognition of semantic memories, suggesting a dissociation between perceptual and semantic memory disruption. Furthermore, the EM intervention effectively reduced psychophysiological affective responses, including the skin conductance response and pupil size, to film scenes and subjective affective ratings of film-related intrusions. Together, bilateral EMs effectively reduce the perceptual representation and affective response of trauma-related memories. Further theoretical developments are needed to elucidate the mechanism of bilateral EMs in trauma treatment.

CircVAPA contributes to hyper-proliferation and inflammation of keratinocytes through miR-125b-5p/sirt6 axis in psoriasis.

Psoriasis is an autoimmune skin disease with abnormal keratinocyte hyperproliferation. The important roles of circular RNAs (circRNAs) in various inflammatory diseases have been revealed. The present study aimed to investigate the roles of circVAPA and its molecular mechanisms in psoriasis. Quantitative real-time polymerase chain reaction was performed to measure the RNA expression. Enzyme-linked immunosorbent assays were employed to examine the production of inflammatory factors. Cell-counting kit-8, EDU and flow cytometry assay were conducted to examine the cell viability, proliferation and apoptosis respectively. Dual-luciferase reporter assay and ribonucleoprotein immunoprecipitation (RIP) were conducted to verify the target relationship between miR-125b-5p and circVAPA or Sirt6. Herein our findings showed increased expression of circVAPA and Sirt6 and decreased level of miR-125b-5p in psoriatic lesional tissues and M5-stimulated keratinocytes. Mechanistically, circVAPA knockdown significantly suppressed the promotion of M5 on cell viability, proliferation, and inflammation of HaCaT cells. circVAPA was verified to interact with miR-125b-5p, while inhibition of miR-125b-5p counteracted circVAPA knockdown-mediated effects in M5-stimulated HaCaT cells. Sirt6 was confirmed as a target of miR-125b-5p, and miR-125b-5p overexpression inhibited cell growth and inflammation partly by targeting Sirt6 in M5-stimulated HaCaT cells. Moreover, circVAPA was featured as a competing endogenous RNA by directly sponging miR-125b-5p to up-regulate the expression of Sirt6. CircVAPA participate in the progression of psoriasis through miR-125b-5p/sirt6 axis by regulating proliferation and inflammation of keratinocytes, highlighting a potential therapeutic target for psoriasis.

Successful colonoscopic removal of a foreign body that caused sigmoid colon perforation: a case report.

Large bowel perforation is an acute abdominal emergency requiring rapid diagnosis for proper treatment. The high mortality rate associated with large bowel perforation underlines the importance of an accurate and timely diagnosis. Computed tomography is useful for diagnosis of ingested foreign bodies, and endoscopic repair using clips can be an effective treatment of colon perforations. We herein describe a 78-year-old man with sigmoid colon perforation caused by accidental swallowing of a jujube pit. The jujube pit had become stuck in the wall of the sigmoid colon and was successfully removed by colonoscopy, avoiding an aggressive surgery. As a result of developments in endoscopic techniques, endoscopic closure has become a feasible option for the management of intestinal perforation.

SdiA Improves the Acid Tolerance of E. coli by Regulating GadW and GadY Expression.

The acid tolerance mechanism is important for Escherichia coli to resist acidic conditions encountered in mammalian host digestive tract environment. Here, we explored how the LuxR protein SdiA influenced E. coli acid tolerance ability in the context of the glutamate- and glutamine-dependent acid resistance system (AR2). First, using a growth and acid shock assay under different acid stresses, we demonstrated that the deletion of sdiA in SM10λpir or BW25113 led to impaired growth under the acidic environment of pH 3-6, which was restored by complementary expression of SdiA. Next, transcriptome sequencing and qPCR disclosed that the expression of glutamate decarboxylase W (GadW) and GadY, the key members of the AR2 system, were regulated by SdiA. Further, ß-galactosidase reporter assays showed that the promoter activity of gadW and gadY was positively regulated by SdiA. Moreover, qPCR and ß-galactosidase reporter assays confirmed that the regulation of SdiA on GadW, but not GadY, could be enhanced by quorum sensing (QS) signal molecules AHLs. Collectively, these data suggest that SdiA plays a crucial role in acid tolerance regulation of E. coli. Our findings provide new insights into the important contribution of quorum sensing system AHLs-SdiA to the networks that regulate acid tolerance.

The effects of dihydroartemisinin on inflammatory bowel disease-related bone loss in a rat model.

Bone loss is one of the important extra-intestinal manifestations in patients with inflammatory bowel diseases (IBDs). Compounds derived from natural products have been used to treat IBDs. However, the role of natural products on IBD-induced bone loss is not completely clarified. In the present study, we observed the effects of dihydroartemisinin (DHA), an antimalaria drug, on IBD and IBD-induced bone loss in a rat model. Chronic IBD model was established in Sprague-Dawley rats by giving them 2.5% dextran sodium sulfate in drinking water. DHA was given by intraperitoneal injection. Blood, colon, and bone samples were collected for biomarker assay and histological analysis. There was an obvious increase in tumor necrotic factor (TNF) α and receptor activator of nuclear factor (NF)-kB ligand (RANKL), and decrease in procollagen type 1 N-terminal propeptide (P1NP) level in IBD groups compared with the normal control (p < 0.05). The disease activity score of IBD rats was significantly higher than the control (p < 0.01). Obvious decrease in disease activity score, TNFα, and RANKL level and increase in P1NP were observed in DHA-treated IBD rats. Bone loss, shown as the decrease in bone mineral density, bone volume fraction, and trabecular number and increase in trabecular separation were observed in IBD rats compared with control (p < 0.01). DHA treatment obviously abolished the bone loss, in particular in the high-dose group (p < 0.05). DHA treatment also inhibited the excessive osteoclast formation; RANKL protein expression; and RANK, TRAF6, Fra-1, NFATc1 mRNA expression induced by IBD. Our data indicated that DHA may be a potential therapeutic agent for IBD and IBD-induced bone loss. Impact statement Bone loss is one of the important extra-intestinal manifestations in patients with inflammatory bowel diseases (IBDs). Studies have shown that compounds derived from natural products are useful in the treatment of IBDs. However, few studies have investigated the role of compounds derived from natural products in treatment of osteoporosis in IBDs. The current study aimed to show the effects of dihydroartemisinin (DHA), antimalaria drug, on bone loss in a rat model of IBD. The findings showed that DHA intervention dose dependently protected against bone loss in IBD rats by inhibiting tumor necrotic factor α production and osteoclast formation. These findings highlights that DHA may be beneficial for bone health in those patients with IBD.

Tenascin-c renders a proangiogenic phenotype in macrophage via annexin II.

Tenascin-c is an extracellular matrix glycoprotein, the expression of which relates to the progression of atherosclerosis, myocardial infarction and heart failure. Annexin II acts as a cell surface receptor of tenascin-c. This study aimed to delineate the role of tenascin-c and annexin II in macrophages presented in atherosclerotic plaque. Animal models with atherosclerotic lesions were established using ApoE-KO mice fed with high-cholesterol diet. The expression of tenascin-c and annexin II in atherosclerotic lesions was determined by qRT-PCR, Western blot and immunohistochemistry analysis. Raw 264.7 macrophages and human primary macrophages were exposed to 5, 10 and 15 µg/ml tenascin-c for 12 hrs. Cell migration as well as the proangiogenic ability of macrophages was examined. Additionally, annexin II expression was delineated in raw 264.7 macrophages under normal condition (20% O2 ) for 12 hrs or hypoxic condition (1% O2 ) for 6-12 hrs. The expression of tenascin-c and annexin II was markedly augmented in lesion aorta. Tenascin-c positively regulated macrophage migration, which was dependent on the expression of annexin II in macrophages. VEGF release from macrophages and endothelial tube induction by macrophage were boosted by tenascin-c and attenuated by annexin II blocking. Furthermore, tenascin-c activated Akt/NF-κB and ERK signalling through annexin II. Lastly, hypoxia conditioning remarkably facilitates annexin II expression in macrophages through hypoxia-inducible factor (HIF)-1α but not HIF-2α. In conclusion, tenascin-c promoted macrophage migration and VEGF expression through annexin II, the expression of which was modulated by HIF-1α.

Microtubules acquire resistance from mechanical breakage through intralumenal acetylation.

Eukaryotic cells rely on long-lived microtubules for intracellular transport and as compression-bearing elements. We considered that long-lived microtubules are acetylated inside their lumen and that microtubule acetylation may modify microtubule mechanics. Here, we found that tubulin acetylation is required for the mechanical stabilization of long-lived microtubules in cells. Depletion of the tubulin acetyltransferase TAT1 led to a significant increase in the frequency of microtubule breakage. Nocodazole-resistant microtubules lost upon removal of acetylation were largely restored by either pharmacological or physical removal of compressive forces. In in vitro reconstitution experiments, acetylation was sufficient to protect microtubules from mechanical breakage. Thus, acetylation increases mechanical resilience to ensure the persistence of long-lived microtubules.

Tubulin acetylation protects long-lived microtubules against mechanical ageing.

Long-lived microtubules endow the eukaryotic cell with long-range transport abilities. While long-lived microtubules are acetylated on Lys40 of α-tubulin (αK40), acetylation takes place after stabilization and does not protect against depolymerization. Instead, αK40 acetylation has been proposed to mechanically stabilize microtubules. Yet how modification of αK40, a residue exposed to the microtubule lumen and inaccessible to microtubule-associated proteins and motors, could affect microtubule mechanics remains an open question. Here we develop FRET-based assays that report on the lateral interactions between protofilaments and find that αK40 acetylation directly weakens inter-protofilament interactions. Congruently, αK40 acetylation affects two processes largely governed by inter-protofilament interactions, reducing the nucleation frequency and accelerating the shrinkage rate. Most relevant to the biological function of acetylation, microfluidics manipulations demonstrate that αK40 acetylation enhances flexibility and confers resilience against repeated mechanical stresses. Thus, unlike deacetylated microtubules that accumulate damage when subjected to repeated stresses, long-lived microtubules are protected from mechanical ageing through their acquisition of αK40 acetylation. In contrast to other tubulin post-translational modifications that act through microtubule-associated proteins, motors and severing enzymes, intraluminal acetylation directly tunes the compliance and resilience of microtubules.

Clinical significance of integrin ß6 as a tumor recurrence factor in follicular thyroid carcinoma.

BACKGROUND: Overexpression of integrin ß6 plays an important role in a variety of malignant tumor invasion and metastasis. METHODS: The expression levels of integrin ß6, matrix metalloproteinase (MMP)-2 and MMP-9 were analyzed by immunohistochemistry with human follicular thyroid carcinomas. Then we investigated their correlation with clinical outcomes parameters, relationship, and the survival time. RESULTS: The integrin ß6 staining was expressed in cellular membrane and cytoplasm of follicular thyroid carcinoma cells. The MMP-2 and MMP-9 expressions were mainly found in cellular cytoplasm. In correlation with the clinical outcome parameters of 60 patients, there were significant statistical differences of integrin ß6, MMP-2, and MMP-9 expression levels in different size of tumor. Integrin ß6 and MMP-9 expressions have significant statistical differences in T classifications. MMP-2 and MMP-9 expressions have significant statistical differences in different M classification. Other clinical outcome parameters had no significant statistical differences. CONCLUSION: Integrin ß6 expression correlated significantly with MMP-9 expression, and may be a valuable recurrence indicator for follicular thyroid carcinomas.

A monoclonal antibody against PMEL.

PMEL, also known as Pmel17 or gp100, is a melanocyte-specific glycoprotein that is essential for the formation of stage II melanosomes. As it has a highly restricted expression pattern in normal tissues and a transient presence on the cell surface, PMEL is believed to be a potential target for antibody drug conjugate therapy in some pigmentary diseases. The production of a high specificity and high affinity monoclonal antibody against human PMEL was helpful for the antibody drug conjugate therapy study. In the present study, monoclonal antibodies (MAbs) against PMEL were obtained by immunizing BALB/c mice with the recombinant PMEL-GST fusion protein. Three mAbs (A3F, G11B, and J7E) with a titer of 1:6000, 1:10,000, and 1:3000, respectively, were obtained. Immunoglobulin subclass assay revealed that A3F was IgG2b, G11B was IgG1, and J7E was IgG2a. Specificity analysis by Western blotting demonstrated that A3F and J7E cross-reacted with GPNMB or LAMP; however, G11B reacted with PMEL only. Immunohistochemistry experiments showed that G11B could bind human PMEL antigen in normal skin. Flow cytometry assay demonstrated that G11B could bind to the surface of PMEL positive melanoma cells but not PMEL negative cells. Taken together, these results show that this G11B provides a useful tool for the antibody drug conjugate therapy study in some pigmentary diseases.

A non-stimulatory monoclonal antibody against the inhibitory immunoreceptor LAIR-1.

The human leukocyte-associated Ig-like receptor (LAIR) family contains two members: LAIR-1 (CD305) and LAIR-2 (CD306). Among them, LAIR-1 is a transmembrane glycoprotein bearing two intracellular immunoreceptor tyrosine-based inhibition motifs (ITIM) and LAIR-2 is soluble. Both molecules bind collagen and LAIR-2 has higher affinity than LAIR-1. LAIR-1 can mediate strong inhibitory signal but the functions of leukocytes expressing LAIR-1 are unclear because of the absence of an effective method to isolate them with resting status. In this study, we generated a monoclonal antibody (MAb) by immunizing BALB/c mice with the recombinant LAIR-2-GST fusion protein, which we termed 3G4. The subclass of 3G4 was identified as IgG1. Specificity analysis by Western blotting demonstrated 3G4 could react with both LAIR-1 and LAIR-2. Unlike another LAIR-1-specific MAb (9.1C3), 3G4 did not inhibit the lysis of target cells P815 by NK cells in a redirected cytotoxicity assay. Preincubation of LAIR-1-transfected K562 cells with 3G4 mildly prevented the binding of LAIR-1 to collagens I and III in a dose-dependent manner. Taken together, the novel MAb 3G4 provides a useful tool to isolate LAIR-1-positive cells without changing their resting state for further application.

Post-operative pericardial effusion following treatment of small hepatocellular carcinoma with radiofrequency ablation: A case report.

Radiofrequency ablation (RFA) is a minimally invasive technique used to treat liver tumors. The current study presents the case of a patient with hepatocellular carcinoma who suffered from post-operative pericardial effusion following RFA treatment. We hypothesize that RFA thermal conduction may damage the diaphragm and pericardium, leading to local edema in the pericardium. RFA is a minimally invasive technique, however, adequate preparatory work must be performed prior to surgery, including a comprehensive assessment of the patient. During surgery, the location and extent of the region to receive RFA must be determined precisely in order to reduce the range of damage and to avoid post-operative complications. This study describes a case of pericardial effusion caused by RFA of liver cancer. We analyzed the causes and preventive measures for pericardial effusion in order to contribute to the prevention pericardial effusion that is complicated by RFA of liver cancer.

GPNMB enhances bone regeneration by promoting angiogenesis and osteogenesis: potential role for tissue engineering bone.

Bone regeneration is a coordinated process involving the connection between blood vessels and bone cells. Glycoprotein non-metastatic melanoma protein B (GPNMB) is known to be vital in bone formation. However, the effect of GPNMB on bone regeneration and the underlying molecular mechanism are still undefined. Fibroblast growth factor receptor (FGFR)-mediating signaling is pivotal in bone formation and angiogenesis. Therefore, we assessed GPNMB function as a communicating molecule between osteoblasts and angiogenesis, and the possible correlation with FGFR-1 signaling. Recombinant GPNMB dose-dependently increased the differentiation of human bone marrow stromal cells (hBMSCs) into osteoblasts, as well as the mRNA levels of osteoblasts marker alkaline phosphatase (ALP) and osteocalcin (OCN). Furthermore, these increases depended on the activation of FGFR-1 signaling, as pretreatment with FGFR-1 siRNA or its inhibitor SU5402 dramatically dampened GPNMB-induced osteogenesis. Additionally, GPNMB triggered dose-dependently the proliferation and migration of human umbilical vein endothelial cells (hUVECs), FGFR-1 phosphorylation, as well as capillary tube and vessels formation in vitro and in vivo. Blocking FGFR-1 signaling dampened GPNMB-induced angiogenic activity. Following construction of a rodent cranial defect model, scaffolds delivering GPNMB resulted in an evident increase in blood vessels and new bone formation; however, combined delivery of GPNMB and SU5402 abated these increase in defect sites. Taken together, these results suggest that GPNMB stimulates bone regeneration by inducing osteogenesis and angiogenesis via regulating FGFR-1 signaling. Consequently, our findings will clarify a new explanation about how GPNMB induces bone repair, and provide a potential target for bone regeneration therapeutics and bone engineering.

[Chuzhen therapy for sub-health: a randomized controlled study].

OBJECTIVE: To observe the effect on intervention of sub-health with pestle needle (Chuzhen). METHOD: Randomized controlled trail was adopted for this research. One hundred and fifty-three cases were randomly divided into two groups of a Chuzhen group (79 cases) and a massage group (74 cases). Acupoint of Bazhen (Baihui Bazhen, Shendao Bazhen, Zhiyang Bazhen, Mingmen Bazhen, Yaoyangguan Bazhen), Hechelu on the head, the neck and the lumbar area were adopted in Chuzhen group. While regular whole-body massage was applied in the massage group. The human sub-health score, the cornell medical index (CMI) and thermal texture maps system (TTM) technology of the two groups before and after the intervention were observed. RESULTS: 1) After treatment, sub-health condition score, the CMI score, the M-R score and the TTM index were all increased in both groups (all P<0.01) 2) Comparison of D-value of the two groups before and after the intervention: the level of the sub-health score, the total score of CMI, and the index of sleep, pressure, Governor Vessel, Hukou (first web), blood lipid, viscosity of blood, microcirculation of TTM index of the Chuzhen group changed more obvious (all P<0.01), but there was no statistic significances in the M-R score and blood sugar of the TTM (both P>0.05). 3) The sub-health condition score in Chuzhen group was higher than that in the massage group (P<0.01). CONCLUSION: Chuzhen therapy has definite effect on intervention of sub-health, which is better than regular general massage.

The chromosomal passenger complex activates Polo kinase at centromeres.

The coordinated activities at centromeres of two key cell cycle kinases, Polo and Aurora B, are critical for ensuring that the two sister kinetochores of each chromosome are attached to microtubules from opposite spindle poles prior to chromosome segregation at anaphase. Initial attachments of chromosomes to the spindle involve random interactions between kinetochores and dynamic microtubules, and errors occur frequently during early stages of the process. The balance between microtubule binding and error correction (e.g., release of bound microtubules) requires the activities of Polo and Aurora B kinases, with Polo promoting stable attachments and Aurora B promoting detachment. Our study concerns the coordination of the activities of these two kinases in vivo. We show that INCENP, a key scaffolding subunit of the chromosomal passenger complex (CPC), which consists of Aurora B kinase, INCENP, Survivin, and Borealin/Dasra B, also interacts with Polo kinase in Drosophila cells. It was known that Aurora A/Bora activates Polo at centrosomes during late G2. However, the kinase that activates Polo on chromosomes for its critical functions at kinetochores was not known. We show here that Aurora B kinase phosphorylates Polo on its activation loop at the centromere in early mitosis. This phosphorylation requires both INCENP and Aurora B activity (but not Aurora A activity) and is critical for Polo function at kinetochores. Our results demonstrate clearly that Polo kinase is regulated differently at centrosomes and centromeres and suggest that INCENP acts as a platform for kinase crosstalk at the centromere. This crosstalk may enable Polo and Aurora B to achieve a balance wherein microtubule mis-attachments are corrected, but proper attachments are stabilized allowing proper chromosome segregation.

Use of DT40 conditional-knockout cell lines to study chromosomal passenger protein function.

The CPC [chromosomal passenger complex; INCENP (inner centromere protein), Aurora B kinase, survivin and borealin] is implicated in many mitotic processes. In the present paper we describe how we generated DT40 conditional-knockout cell lines for incenp1 and survivin1 to better understand the role of these CPC subunits in the control of Aurora B kinase activity. These lines enabled us to reassess current knowledge of survivin function and to show that INCENP acts as a rheostat for Aurora B activity.