A nuclear pore complex-associated regulation of SUMOylation in meiosis.

The nuclear pore complex (NPC) provides a permeable barrier between the nucleoplasm and cytoplasm. In a subset of NPC constituents that regulate meiosis in the fission yeast Schizosaccharomyces pombe, we found that nucleoporin Nup132 (homolog of human Nup133) deficiency resulted in transient leakage of nuclear proteins during meiosis I, as observed in the nup132 gene-deleted mutant. The nuclear protein leakage accompanied the liberation of the small ubiquitin-like modifier (SUMO)-specific ubiquitin-like protease 1 (Ulp1) from the NPC. Ulp1 retention at the nuclear pore prevented nuclear protein leakage and restored normal meiosis in a mutant lacking Nup132. Furthermore, using mass spectrometry analysis, we identified DNA topoisomerase 2 (Top2) and RCC1-related protein (Pim1) as the target proteins for SUMOylation. SUMOylation levels of Top2 and Pim1 were altered in meiotic cells lacking Nup132. HyperSUMOylated Top2 increased the binding affinity at the centromeres of nup132 gene-deleted meiotic cells. The Top2-12KR sumoylation mutant was less localized to the centromeric regions. Our results suggest that SUMOylation of chromatin-binding proteins is regulated by the NPC-bound SUMO-specific protease and is important for the progression of meiosis.

The Phosphoprotein Synapsin Ia Regulates the Kinetics of Dense-Core Vesicle Release.

Common fusion machinery mediates the Ca2+-dependent exocytosis of synaptic vesicles (SVs) and dense-core vesicles (DCVs). Previously, Synapsin Ia (Syn Ia) was found to localize to SVs, essential for mobilizing SVs to the plasma membrane through phosphorylation. However, whether (or how) the phosphoprotein Syn Ia plays a role in regulating DCV exocytosis remains unknown. To answer these questions, we measured the dynamics of DCV exocytosis by using single-vesicle amperometry in PC12 cells (derived from the pheochromocytoma of rats of unknown sex) overexpressing wild-type or phosphodeficient Syn Ia. We found that overexpression of phosphodeficient Syn Ia decreased the DCV secretion rate, specifically via residues previously shown to undergo calmodulin-dependent kinase (CaMK)-mediated phosphorylation (S9, S566, and S603). Moreover, the fusion pore kinetics during DCV exocytosis were found to be differentially regulated by Syn Ia and two phosphodeficient Syn Ia mutants (Syn Ia-S62A and Syn Ia-S9,566,603A). Kinetic analysis suggested that Syn Ia may regulate the closure and dilation of DCV fusion pores via these sites, implying the potential interactions of Syn Ia with certain DCV proteins involved in the regulation of fusion pore dynamics. Furthermore, we predicted the interaction of Syn Ia with several DCV proteins, including Synaptophysin (Syp) and soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins. By immunoprecipitation, we found that Syn Ia interacted with Syp via phosphorylation. Moreover, a proximity ligation assay (PLA) confirmed their phosphorylation-dependent, in situ interaction on DCVs. Together, these findings reveal a phosphorylation-mediated regulation of DCV exocytosis by Syn Ia.SIGNIFICANCE STATEMENT Although they exhibit distinct exocytosis dynamics upon stimulation, synaptic vesicles (SVs) and dense-core vesicles (DCVs) may undergo co-release in neurons and neuroendocrine cells through an undefined molecular mechanism. Synapsin Ia (Syn Ia) is known to recruit SVs to the plasma membrane via phosphorylation. Here, we examined whether Syn Ia also affects the dynamics of DCV exocytosis. We showed that Syn Ia regulates the DCV secretion rate and fusion pore kinetics during DCV exocytosis. Moreover, Syn Ia-mediated regulation of DCV exocytosis depends on phosphorylation. We further found that Syn Ia interacts with Synaptophysin (Syp) on DCVs in a phosphorylation-dependent manner. Thus, these results suggest that Syn Ia may regulate the release of DCVs via phosphorylation.

7-Epitaxol induces apoptosis in cisplatin-resistant head and neck squamous cell carcinoma via suppression of AKT and MAPK signalling.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Although cisplatin-based chemotherapy is commonly used in HNSCC, frequent development of cisplatin resistance is a potential cause of poor HNSCC prognosis. In the present study, we investigated the anticancer efficacy of a major paclitaxel metabolite namely 7-Epitaxol in cisplatin-resistant HNSCC. The findings revealed that 7-Epitaxol exerts cytotoxic effects in cisplatin-resistant HNSCC cell lines by inducing cell cycle arrest and intrinsic and extrinsic apoptotic pathways. Specifically, 7-Epitaxol increased Fas, TNF-R1, DR5, DcR3 and DcR2 expressions, reduced Bcl-2 and Bcl-XL (anti-apoptotic proteins) expressions, and increased Bid and Bim L/S (pre-apoptotic proteins) expressions, leading to activation of caspase-mediated cancer cell apoptosis. At the upstream cell signalling level, 7-Epitaxol reduced the phosphorylation of AKT, ERK1/2 and p38 to trigger apoptosis. In vivo results showed that animals treated with 7-Epitaxol show antitumor growth compared to control animals. Taken together, the study demonstrates the potential anticancer efficacy of 7-Epitaxol in inducing apoptosis of cisplatin-resistant HNSCC cells through the suppression of AKT and MAPK signalling pathways.

Successful management of tumor necrosis factor-alpha inhibitor-induced Sweet syndrome in a patient with ulcerative colitis: A case report.

Tumor necrosis factor (TNF) α inhibitors are widely used to treat inflammatory bowel disease (IBD); however, some patients have unexpected inflammatory episodes during anti-TNF therapy. The objective of our research was to highlight a paradoxical case of anti-TNF-agent-induced Sweet syndrome compared with Sweet syndrome treated by anti-TNF agents. We describe a 62-year-old male with a history of ulcerative colitis presenting with multiple polymorphic indurated skin macules and plaques after 2 months of adalimumab therapy. Neutrophilic dermatosis was diagnosed based on the clinical presentation and skin biopsy and may have resulted from extraintestinal manifestations of a flare-up of IBD or been induced by adalimumab therapy. We conclude that when facing this dilemma, adalimumab should be discontinued, and the dose of prednisolone should be increased before determining the definitive cause. Based on drug hypersensitivity syndrome (DHS) risk assessment in the 10-D assessment system, this case was classified as grade 1 (no risk). Finally, we review the molecular and cellular mechanisms connecting cytokine dysregulation to Sweet syndrome.

Asymmetrical localization of Nup107-160 subcomplex components within the nuclear pore complex in fission yeast.

The nuclear pore complex (NPC) forms a gateway for nucleocytoplasmic transport. The outer ring protein complex of the NPC (the Nup107-160 subcomplex in humans) is a key component for building the NPC. Nup107-160 subcomplexes are believed to be symmetrically localized on the nuclear and cytoplasmic sides of the NPC. However, in S. pombe immunoelectron and fluorescence microscopic analyses revealed that the homologous components of the human Nup107-160 subcomplex had an asymmetrical localization: constituent proteins spNup132 and spNup107 were present only on the nuclear side (designated the spNup132 subcomplex), while spNup131, spNup120, spNup85, spNup96, spNup37, spEly5 and spSeh1 were localized only on the cytoplasmic side (designated the spNup120 subcomplex), suggesting the complex was split into two pieces at the interface between spNup96 and spNup107. This contrasts with the symmetrical localization reported in other organisms. Fusion of spNup96 (cytoplasmic localization) with spNup107 (nuclear localization) caused cytoplasmic relocalization of spNup107. In this strain, half of the spNup132 proteins, which interact with spNup107, changed their localization to the cytoplasmic side of the NPC, leading to defects in mitotic and meiotic progression similar to an spNup132 deletion strain. These observations suggest the asymmetrical localization of the outer ring spNup132 and spNup120 subcomplexes of the NPC is necessary for normal cell cycle progression in fission yeast.

Presynaptic SNAP-25 regulates retinal waves and retinogeniculate projection via phosphorylation.

Patterned spontaneous activity periodically displays in developing retinas termed retinal waves, essential for visual circuit refinement. In neonatal rodents, retinal waves initiate in starburst amacrine cells (SACs), propagating across retinal ganglion cells (RGCs), further through visual centers. Although these waves are shown temporally synchronized with transiently high PKA activity, the downstream PKA target important for regulating the transmission from SACs remains unidentified. A t-SNARE, synaptosome-associated protein of 25 kDa (SNAP-25/SN25), serves as a PKA substrate, implying a potential role of SN25 in regulating retinal development. Here, we examined whether SN25 in SACs could regulate wave properties and retinogeniculate projection during development. In developing SACs, overexpression of wild-type SN25b, but not the PKA-phosphodeficient mutant (SN25b-T138A), decreased the frequency and spatial correlation of wave-associated calcium transients. Overexpressing SN25b, but not SN25b-T138A, in SACs dampened spontaneous, wave-associated, postsynaptic currents in RGCs and decreased the SAC release upon augmenting the cAMP-PKA signaling. These results suggest that SN25b overexpression may inhibit the strength of transmission from SACs via PKA-mediated phosphorylation at T138. Moreover, knockdown of endogenous SN25b increased the frequency of wave-associated calcium transients, supporting the role of SN25 in restraining wave periodicity. Finally, the eye-specific segregation of retinogeniculate projection was impaired by in vivo overexpression of SN25b, but not SN25b-T138A, in SACs. These results suggest that SN25 in developing SACs dampens the spatiotemporal properties of retinal waves and limits visual circuit refinement by phosphorylation at T138. Therefore, SN25 in SACs plays a profound role in regulating visual circuit refinement.

Centriole distal appendages promote membrane docking, leading to cilia initiation.

The distal appendages (DAPs) of centrioles have been proposed to anchor cilia to the plasma membrane, but their molecular composition, assembly, and exact function in ciliogenesis remain poorly understood. Using quantitative centrosome proteomics and superresolution microscopy, we identified five DAP components, including one previously described (CEP164), one partially characterized (CEP89 [ccdc123]), and three novel (CEP83 [ccdc41], SCLT1, and FBF1) DAP proteins. Analyses of DAP assembly revealed a hierarchy. CEP83 recruits both SCLT1 and CEP89 to centrioles. Subsequent recruitment of FBF1 and CEP164 is independent of CEP89 but mediated by SCLT1. All five DAP components are essential for ciliogenesis; loss of CEP83 specifically blocks centriole-to-membrane docking. Undocked centrioles fail to recruit TTBK2 or release CP110, the two earliest modifications found on centrioles prior to cilia assembly, revealing centriole-to-membrane docking as a temporal and spatial cue promoting cilia initiation.

5-hydroxytryptophan attenuates imiquimod-induced psoriasiform dermatitis probably through inhibition of IL-17A production and keratinocyte activation.

Psoriasis is a chronic autoimmune disease with keratinocyte activation and lymphocyte infiltration in the skin. Our previous study found that 5-hydroxytryptophan (5(OH)Trp), a tryptophan metabolite, alleviated collagen-induced arthritis and suppressed cytokine production. In this study, we evaluated the effects of 5(OH)Trp in a mouse model for psoriasiform dermatitis, induced by imiquimod (IMQ). We showed that 5(OH)Trp significantly reduced the cumulative scores, epidermal thickness and ki-67 expression in the skin. In addition, 5(OH)Trp decreased local and systemic inflammation. Moreover, 5(OH)Trp significantly inhibited keratinocyte activation with decrease in IL-6 production and p-Erk1/2 and p-STAT3 expression. 5(OH)Trp also inhibited the differentiation of IFN-γ- and IL-17A-expressing CD4+ T cells and related cytokine production (TNF-α, IL-6, IL-17A and IFN-γ) in splenocytes. In conclusion, 5(OH)Trp can inhibit imiquimod-induced psoriasiform dermatitis in mice and inhibit activation in keratinocytes and splenocytes.

Implant volume estimation in direct-to-implant breast reconstruction after nipple-sparing mastectomy.

BACKGROUND: Nipple-sparing mastectomy (NSM) is an increasingly popular alternative to more traditional mastectomy approaches. However, estimating the implant volume during direct-to-implant (DTI) reconstruction following NSM is difficult for surgeons with little-to-moderate experience. We aimed to provide a fast, easy to use, and accurate method to aid in the estimation of implant size for DTI reconstruction using the specimen weight and breast volume. METHODS: A retrospective analysis was performed using data from 145 NSM patients with specific implant types. Standard two-dimensional digital mammograms were obtained in 118 of the patients. Breast morphological factors (specimen weight, mammographic breast density and volume, and implant size and type) were recorded. Curve-fitting and linear regression models were used to develop formulas predicting the implant volume, and the prediction performance of the obtained formulas was evaluated using the prospective data set. RESULTS: Two formulas to estimate the implant size were obtained, one using the specimen weight and one using the breast volume. The coefficients of correlation (R2) in these formulas were over 0.98 and the root mean squared errors were approximately 13. CONCLUSIONS: These implant volume estimate formulas benefit surgeons by providing a preoperative implant volume assessment in DTI reconstruction using the breast volume and an intraoperative assessment using the specimen weight. The implant size estimation formulas obtained in the present study may be applied in a majority of patients.

Applying the transtheoretical model to promote functional fitness of community older adults participating in elastic band exercises.

AIMS: The transtheoretical model was applied to promote behavioural change and test the effects of a group senior elastic band exercise programme on the functional fitness of community older adults in the contemplation and preparation stages of behavioural change. BACKGROUND: Forming regular exercise habits is challenging for older adults. The transtheoretical model emphasizes using different strategies in various stages to facilitate behavioural changes. DESIGN: Quasi-experimental design with pre-test and post-tests on two groups. METHODS: Six senior activity centres were randomly assigned to either the experimental or control group. The data were collected during 2011. A total of 199 participants were recruited and 169 participants completed the study (experimental group n = 84, control group n = 85). The elastic band exercises were performed for 40 minutes, three times per week for 6 months. The functional fitness of the participants was evaluated at baseline and at the third and sixth month of the intervention. Statistical analyses included a two-way mixed design analysis of variance, one-way repeated measures analysis of variance and an analysis of covariance. RESULTS: All of the functional fitness indicators had significant changes at post-tests from pre-test in the experimental group. The experimental group had better performances than the control group in all of the functional fitness indicators after three months and 6 months of the senior elastic band exercises. CONCLUSION: The exercise programme provided older adults with appropriate strategies for maintaining functional fitness, which improved significantly after the participants exercising regularly for 6 months.

Do nurses have worse pregnancy outcomes than non-nurses?

BACKGROUND: Nurses encounter multiple occupational exposures at work which may harm their reproductive health. The purpose of the study was to compare pregnancy complications and outcomes including cesarean deliveries, tocolysis, miscarriage, and preterm labor between female nurses and comparable women who were not nurses in Taiwan. METHODS: This nationwide population-based study was performed using the National Health Insurance Research Database from 1997 to 2008. We identified 3,656 pregnancies among 2,326 nurses and 111,889 pregnancies among 74,919 non-nurses. A generalized estimating equation was used to compare risks between the two groups. RESULTS: The rates of tocolysis (28.6 vs 22.3%), miscarriage (6.0 vs 5.3%), and preterm labor (8.1 vs 4.4%) were significantly higher among nurses than non-nurses. After adjustment for background differences, nurses had significantly higher risks for cesarean section (adjusted OR 1.12 [95% confidence interval (CI) 1.03-1.22]), tocolysis (OR 1.18 [95% CI 1.09-1.29]), and preterm labor (OR 1.46 [95% CI 1.28-1.67]) than non-nurses. CONCLUSIONS: Nurses are at higher risk for cesarean section, tocolysis, and preterm labor than non-nurses. Occupational exposure related to these adverse pregnancy outcomes should be examined. Strategies to decrease the risks should be developed to improve reproductive health among nurses.

Inhibitory effects of scutellarein on proliferation of human lung cancer A549 cells through ERK and NFκB mediated by the EGFR pathway.

High expression levels of cyclooxygenase-2 (COX-2) contribute a strong proliferative ability to human lung cancer cells, and this function is link to the epidermal growth factor receptor (EGFR) pathway, which was mediated by extracellular-signal-regulated kinase (ERK) and nuclear factor kappa B (NFκB). In this study, scutellarein, a flavonoid compound, was screened for proliferation inhibition at different concentrations (0, 5, 25 and 50 µM) at 24 h or 48 h in human lung cancer cell line A549. Results showed that A549 cell proliferation was inhibited by 50 µM scutellarein treatment in 24 h and 48 h of treatment. The expression levels of phosphorylated EGFR, phosphorylated ERK, phosphorylated NFκB and COX-2 were reduced in a dose-dependent manner after 24 h scutellarein treatments at different concentrations. Further, ERK inhibitor U0126 and NFκB inhibitor MG132 also inhibited A549 cell proliferation similar to 50 κM scutellarein treatment from 24 h to 48 h. The experimental results showed that scutellarein could inhibit proliferation of the human lung cancer cell line A549 through ERK and NFκB mediated by the EGFR pathway.

Chronic radiation dermatitis induced by cardiac catheterization: a case report and literature review.

Fluoroscopy-induced chronic radiation dermatitis (FICRD) is an uncommon but increasing complication that is challenging to diagnose due to its varied symptoms and delayed onset, usually from months to years after radiation exposure. For patients undergoing cardiac catheterization, high-risk factors for radiodermatitis include obesity, the presence of complex or chronic total occlusion lesions, the use of a fixed large beam angulation, and a procedure time of more than 2 hours. We present an individual with FICRD that had an indurated plaque on his back for 7 years to familiarize physicians with high-risk groups and early recognition of the disease.

Worsening Quality of Life in Young Adult, Highly Educated, and Married Female Patients with Vitiligo: A Hospital-Based Case Control Study in Taiwan.

Vitiligo is an acquired chronic depigmentation disorder that can have a negative impact on the quality of life (QoL). This is especially true for patients with non-white skin. Only few studies have investigated the QoL of Asian patients with vitiligo. We aimed to investigate the QoL in Taiwanese vitiligo patients and identify the factors that influence their QoL. The cross-sectional study recruited 100 vitiligo patients and 100 controls with general skin diseases in the Department of Dermatology of Changhua Christian Hospital. Data were obtained using a structured questionnaire for demographic information and modified Skindex-21 instruments. The QoL was not significantly different between vitiligo patients and controls. Among the vitiligo patients, adults exhibited deteriorated emotional levels and total QoL as compared with non-adults. Married females reported greater levels of emotional disturbance than the unmarried ones. A higher educational level and shorter history of disease were associated with greater emotional impacts. The patients with a generalized type of vitiligo suffered more in total QoL. After multivariate adjustment, the young adult patients aged 20-39 were associated with poorer total QoL. It is suggested that vitiligo patients who are aged between 20 and 39, are married females, are highly educated, have a shorter disease history, and suffer from the generalized type of this disease demonstrate more deterioration in their life quality compared with other vitiligo patients. Care providers should tailor the psychological counseling and treatment accordingly.

The effects of hydrogen treatment in a cigarette smoke solution-induced chronic obstructive pulmonary disease-like changes in an animal model.

Background: Molecular hydrogen, with its antioxidant and anti-inflammatory properties, may be suitable for the prevention and treatment of chronic obstructive pulmonary disease (COPD). This study aims to investigate the therapeutic efficacy of hydrogen-oxygen (H2/O2) treatment in cigarette smoke solution (CSS)-induced COPD-like injury in a female BALB/c mouse model. Methods: Thirty mice were randomly assigned to three groups: Control (n=8), COPD (n=10), and COPD + H2/O2 (n=12). CSS was administered by intraperitoneal (IP) injection twice weekly for 6 weeks during the COPD induction phase. Simultaneously, the COPD + H2/O2 group started received 75 minutes of inhalation therapy (42% H2) delivered by the Oxy-Hydrogen Generator twice daily for 9 weeks. Mice body weights and survival were measured throughout the study period. Neutrophil elastase (NE) activity and lung histopathological changes were also evaluated. Results: The results showed a higher survival rate in the COPD + H2/O2 group compared to the COPD group (100% vs. 80%) during the induction phase. Slight decreases in body weight gains were observed in the COPD and COPD + H2/O2 groups during the first 15 days of the induction phase, but there was no significant difference in mean body weights among the three groups throughout the study period. NE activity was numerically lower in the COPD + H2/O2 group compared to the COPD group. The histopathological evaluation showed significant improvements in the H2/O2-treated mice with respect to mean linear intercept (MLI) and lesion (inflammation and emphysema) scores. Improvements in goblet cell hypertrophy and hyperplasia of airway epithelium were not significant. Conclusions: A 9-week H2/O2 inhalation therapy delivered by the Oxy-Hydrogen Generator to CSS-induced COPD-like injury in mice showed improvement in survival rate, alveolar structural changes, and histopathological lesion scores of the lung.

Characterization of Collapsin Response Mediator Protein 2 in Colorectal Cancer Progression in Subjects with Diabetic Comorbidity.

BACKGROUND: Common demographic risk factors are identified in colorectal cancer (CRC) and type 2 diabetes mellitus (DM), nevertheless, the molecular link and mechanism for CRC-DM comorbidity remain elusive. Dysregulated glycogen synthase kinase-3 beta under metabolic imbalance is suggested to accelerate CRC pathogenesis/progression via regulating collpasin response mediator protein-2 (CRMP2). Accordingly, roles of CRMP2 in CRC and CRC-DM patients were investigated for elucidating the molecular convergence of CRC and DM. METHODS: CRMP2 profile in tumor tissues from CRC and CRC-DM patients was investigated to explore the link between CRC and DM etiology. Meanwhile, molecular mechanism of glucose to regulate CRMP2 profile and CRC characteristics was examined in vitro and in vivo. RESULTS: CRMP2 was significantly lower in tumor lesions and associated with advanced tumor stage in CRC-DM patients. Physiological hyperglycemia suppressed CRMP2 expression/activity and augmented malignant characteristics of CRC cells. Hyperglycemia promotes actin de-polymerization, cytoskeleton flexibility and cell proliferation/metastasis by downregulating CRMP2 profile and thus contributes to CRC disease progression. CONCLUSIONS: This study uncovers molecular evidence to substantiate and elucidate the link between CRC and T2DM, as well as characterizing the roles of CRMP2 in CRC-DM. Accordingly, altered metabolic adaptations are promising targets for anti-diabetic and cancer strategies.

Motivation theory-based physical activity programme for older adults in residential care facility: A modified Delphi and single-group pretest-posttest study.

BACKGROUND: Physical inactivity exposes older adults living in long-term care institutions to a high risk of health deterioration. Developing effective behaviour change interventions based on a theoretical framework is a pressing concern. AIMS: This study developed an 'Easy Walking' intervention programme based on the Wheel of Motivation and aimed to: (1) develop the intervention programme for promoting self-efficacy of older adults living in long-term care facilities; and (2) examine the perceived helpfulness of the intervention programme for encouraging walking behaviours. METHODS: This study consisted of two stages. In the first stage, a three-round modified Delphi process was conducted with ten experts to rate the eight motivators in the Wheel of Motivation. The Easy Walking programme was designed accordingly. In the second stage, a single-group pretest-posttest study design was employed to evaluate the Easy Walking programme. Structured questionnaires were used to collect data on the changes in self-efficacy and on the perceived helpfulness regarding the programme. RESULTS: The Easy Walking intervention programme features eight factors that influence motivation. Thirty older adults participated in and evaluated the programme. The results showed a significant difference in self-efficacy (t = -7.02, p < .001) of the older adults. Regarding the perceived usefulness of the intervention, the mean scores for each item ranged from 3.73 to 4.93 points. 'Safe environment' was perceived to be the most helpful factor for encouraging walking behaviours. CONCLUSION: The Easy Walking programme enhanced the self-efficacy of institutionalised older adults and was perceived as helpful in physical activity engagement. Nursing professionals in long-term care institutions could implement the Easy Walking programme to be part of daily nursing activities.

Risk of cancer development in patients with keloids.

Keloid is a skin disease characterized by exaggerated scar formation, excessive fibroblast proliferation, and excessive collagen deposition. Cancers commonly arise from a fibrotic microenvironment; e.g., hepatoma arises from liver cirrhosis, and oral cancers arise from submucosal fibrosis. As keloids are a prototypic fibroproliferative disease, this study investigated whether patients with keloids have an increased cancer risk. In a matched, population-based study, first 17,401 patients treated for keloids during 1998-2010 with 69,604 controls without keloids at a ratio of 1:4 were evaluated. The association between keloids and risk of cancer was estimated by logistic regression or Cox proportional hazard regression models after adjustment of covariates. In total, 893 first-time cases of cancer were identified in the 17,401 patients with keloids. The overall cancer risk was 1.49-fold higher in the keloids group compared to controls. Regarding specific cancers, the keloids group, had a significantly higher risk of skin cancer compared to controls (Relative risk = 1.73). The relative risk for skin cancer was even higher for males with keloids (Relative risk = 2.16). Further stratified analyses also revealed a significantly higher risk of developing pancreatic cancer in female patients with keloids compared to controls (Relative risk = 2.19) after adjustment for known pancreatic cancer risk factors. This study indicates that patients with keloids have a higher than normal risk for several cancer types, especially skin cancers (both genders) and pancreatic cancer (females). Therefore, patients with keloids should undergo regular skin examinations, and females with keloids should regularly undergo abdominal ultrasonography.

Caenorhabditis elegans TLK-1 controls cytokinesis by localizing AIR-2/Aurora B to midzone microtubules.

Defects in chromosome condensation, segregation or cytokinesis during mitosis disrupt genome integrity and cause organismal death or tumorigenesis. The conserved kinase AIR-2/Aurora B is required for normal execution of all these important mitotic events in Caenorhabditis elegans. TLK-1 has been recently shown to be a substrate and activator of AIR-2 in the presence of another AIR-2 activator ICP-1/INCENP, and to cooperate with AIR-2 to ensure proper mitotic chromosome segregation. However, whether TLK-1 may contribute to chromosome condensation or cytokinesis is unclear. A time-lapse microscopy analysis showed that tlk-1 mutants are defective in chromosome condensation and cytokinesis, in addition to chromosome segregation, during mitosis. Our data indicate that TLK-1 contributes to chromosome condensation and segregation, at least in part, in a manner that is distinct from the ICP-1-mediated mechanism and does not involve loading AIR-2 or condensin proteins to mitotic chromosomes. Moreover, TLK-1 functions in cytokinesis by localizing AIR-2 to the midzone microtubules. The localization pattern of TLK-1 is different from those of ICP-1 and AIR-2, revealing differences in dynamic regulation and association of TLK-1 and ICP-1 towards AIR-2 in vivo. Interestingly, human TLK2 could functionally substitute for tlk-1, suggesting that the mitotic roles of TLK members might be evolutionarily conserved.

Transient Breakage of the Nucleocytoplasmic Barrier Controls Spore Maturation via Mobilizing the Proteasome Subunit Rpn11 in the Fission Yeast Schizosaccharomyces pombe.

Forespore membrane (FSM) closure is a process of specialized cytokinesis in yeast meiosis. FSM closure begins with the contraction of the FSM opening and finishes with the disassembly of the leading-edge proteins (LEPs) from the FSM opening. Here, we show that the FSM opening starts to contract when the event of virtual nuclear envelope breakdown (vNEBD) occurs in anaphase II of the fission yeast Schizosaccharomyces pombe. The occurrence of vNEBD controls the redistribution of the proteasomal subunit Rpn11 from the nucleus to the cytosol. To investigate the importance of Rpn11 re-localization during vNEBD, Rpn11 was sequestered at the inner nuclear membrane by fusion with the transmembrane region of Bqt4 (Rpn11-GFP-INM). Remarkably, in the absence of endogenous rpn11+, the cells carrying Rpn11-GFP-INM had abnormal or no spore formation. Live-cell imaging analysis further reveals that the FSM opening failed to contract when vNEBD occurred, and the LEP Meu14 was persistently present at the FSM in the rpn11-gfp-INM cells. The results suggest that the dynamic localization of Rpn11 during vNEBD is essential for spore development.