Hornerin mediates phosphorylation of the polo-box domain in Plk1 by Chk1 to induce death in mitosis.

The centrosome assembles a bipolar spindle for faithful chromosome segregation during mitosis. To prevent the inheritance of DNA damage, the DNA damage response (DDR) triggers programmed spindle multipolarity and concomitant death in mitosis through a poorly understood mechanism. We identified hornerin, which forms a complex with checkpoint kinase 1 (Chk1) and polo-like kinase 1 (Plk1) to mediate phosphorylation at the polo-box domain (PBD) of Plk1, as the link between the DDR and death in mitosis. We demonstrate that hornerin mediates DDR-induced precocious centriole disengagement through a dichotomous mechanism that includes sequestration of Sgo1 and Plk1 in the cytoplasm through phosphorylation of the PBD in Plk1 by Chk1. Phosphorylation of the PBD in Plk1 abolishes the interaction with Sgo1 and phosphorylation-dependent Sgo1 translocation to the centrosome, leading to precocious centriole disengagement and spindle multipolarity. Mechanistically, hornerin traps phosphorylated Plk1 in the cytoplasm. Furthermore, PBD phosphorylation inactivates Plk1 and disrupts Cep192::Aurora A::Plk1 complex translocation to the centrosome and concurrent centrosome maturation. Remarkably, hornerin depletion leads to chemoresistance against DNA damaging agents by attenuating DDR-induced death in mitosis. These results reveal how the DDR eradicates mitotic cells harboring DNA damage to ensure genome integrity during cell division.

Preoperative acute pancreatitis and hyperenzymemia are associated with poor prognosis in patients with nonfunctional pancreatic neuroendocrine tumors.

BACKGROUND: We aimed to investigate the prevalence of acute pancreatitis (AP) and hyperenzymemia as well as their clinical impact on postoperative survival outcomes in patients with pancreatic neuroendocrine tumors (PNETs). METHODS: A retrospective cohort study of 218 patients who underwent radical surgical resection for nonfunctional PNETs (NF-PNETs) was conducted. Multivariate survival analysis was performed by the Cox proportional hazard model, with results expressed as hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Of the 151 patients who met the inclusion criteria, the incidences of preoperative AP and hyperenzymemia were 7.9% (12/152) and 23.2% (35/151), respectively. The mean recurrence-free survival (RFS, 95% CI) for patients in control, AP, and hyperenzymemia groups was 136 (127-144), 88 (74-103), and 90 (61-122) months, with a 5-year RFS rate of 86.5%, 58.3%, and 68.9%, respectively. In the multivariable-adjusted Cox hazard model that included tumor grade and lymph node status, the adjusted HR of AP and hyperenzymemia for recurrence was 2.58 (95% CI: 1.47-7.86, p = 0.008) and 2.43 (95% CI: 1.08-7.06, p = 0.040). CONCLUSION: Preoperative AP and hyperenzymemia are associated with poor RFS following radical surgical resection in NF-PNETs patients.

Long Term Outcomes of No-Touch Isolation Principles Applied in Pancreaticoduodenectomy for Treatment of Pancreatic Adenocarcinoma: A Multicenter Retrospective Study with Propensity Score Matching.

Background: The recurrence and liver metastasis rates are still high in pancreatic head cancer with curative surgical resection. A no-touch isolation principle in pancreaticoduodenectomy (PD) may improve this situation, however, the exact advantages and efficacy of these principles have not been confirmed. Materials and methods: Among 370 patients who underwent PD, three centers were selected and classified into two groups: the no-touch PD group (n = 70) and the conventional PD group (n = 300). Propensity score matching was used to control for selection bias at a ratio of 1:1. The confounding variables were age, sex, body mass index, adjuvant chemotherapy, carbohydrate antigen 19-9, tumor size and tumor differentiation. Results: Patients in the no-touch PD group had better overall survival (OS) and disease-free survival (DFS) than those in the conventional PD group (OS: 17 vs. 13 months, p = 0.0035, DFS: 15 vs. 12 months, p = 0.087), with lower 1- and 2-year disease-related mortality rates (1-year: 32.9% vs. 47%, p = 0.032; 2-year: 42.5% vs. 82% p = 0.000) and recurrence and liver metastasis rates (1-year: 30.0% vs. 43.3%, p = 0.041; 2-year: 34.3% vs. 48.7%, p = 0.030). Compared with the matched conventional PD group, the no-touch PD group also had a better OS (17 vs. 12 months, p = 0.032). Conclusions: Our study showed the no-touch isolation principle may be a better choice to improve long-term survival for pancreatic cancer patients.

p Components of Cluster-Lag Consensus for Second-Order Multiagent Systems With Adaptive Controller on Cooperative-Competitive Networks.

The consensus tracking problem means that a group of followers tracks the desired trajectory with local communication. In this article, partial components of cluster consensus have been considered. In this scenario, the p components of the followers in different clusters track the leader at different lag times, while p components of each agent in the same cluster reach a consensus, which is called p components of cluster-lag (PCCL) consensus. By using a seminorm ||xi||2,p and a Lyapunov-Krasovskii functional, PCCL consensus for second-order multiagent systems with homogeneous nonlinear systems on cooperative-competitive networks has been considered. For the case that the communication network graph is undirected, a decentralized adaptive controller, which is based on the exchanged neighbors' information from the same cluster, is designed such that all the agents reach PCCL consensus. For the directed graph case, an adaptive protocol based on the intracoupling strength is constructed for each cluster to achieve PCCL consensus. Finally, two simulation examples are illustrated to show the effectiveness of the proposed control protocols.

Laparoscopic Cholecystectomy in a Patient With Situs Inversus Totalis Presenting With Cholelithiasis: A Case Report.

Laparoscopic cholecystectomy is the standard treatment for cholelithiasis. A very rare condition named situs inversus should not be considered as a contraindication for laparoscopic cholecystectomy. Here, we reported a case of successful laparoscopic cholecystectomy in a patient with situs inversus totalis. We also described the technical advantages of this treatment and reviewed the literature.

Distributed H∞ Estimation in Sensor Networks With Two-Channel Stochastic Attacks.

This paper is concerned with the distributed estimation problem in sensor networks subjected to unknown attacks. Network attacks are considered to exist in two classes of channels: 1) communication channels from the plant to sensors and 2) communication channels among sensors. The status of an attack is viewed as a stochastic phenomenon, and the transmitted information will be affected when the attacker successfully carries out an attack on the related data packet. Based on the sensors' own measurements and their neighbors' local information, a novel distributed estimation model against two-channel stochastic attacks is presented. A sufficient condition on the existence of the desired distributed H ∞ estimators is derived and the distributed estimator gains are designed by solving a linear matrix inequality. Two illustrative examples are provided to demonstrate the effectiveness of the new design techniques.

Set-Membership Estimation for Complex Networks Subject to Linear and Nonlinear Bounded Attacks.

This paper is concerned with the set-membership estimation problem for complex networks subject to unknown but bounded attacks. Adversaries are assumed to exist in the nonsecure communication channels from the nodes to the estimators. The transmitted measurements may be modified by an attack function with added noise that is determined by the adversary but unknown to the estimators. A novel set-membership estimation model against unknown but bounded attacks is presented. Two sufficient conditions are derived to guarantee the existence of the set-membership estimators for the cases that the attack functions are linear and nonlinear, respectively. Two strategies for the design of the set-membership estimator gains are presented. The effectiveness of the proposed estimator design method is verified by two simulation examples.

Deblurring traffic sign images based on exemplars.

Motion blur appearing in traffic sign images may lead to poor recognition results, and therefore it is of great significance to study how to deblur the images. In this paper, a novel method for deblurring traffic sign is proposed based on exemplars and several related approaches are also made. First, an exemplar dataset construction method is proposed based on multiple-size partition strategy to lower calculation cost of exemplar matching. Second, a matching criterion based on gradient information and entropy correlation coefficient is also proposed to enhance the matching accuracy. Third, L0.5-norm is introduced as the regularization item to maintain the sparsity of blur kernel. Experiments verify the superiority of the proposed approaches and extensive evaluations against state-of-the-art methods demonstrate the effectiveness of the proposed algorithm.

Duodenum and ventral pancreas preserving subtotal pancreatectomy for low-grade malignant neoplasms of the pancreas: An alternative procedure to total pancreatectomy for low-grade pancreatic neoplasms.

AIM: To describe the indications, technique and outcomes of the novel surgical procedure of duodenum and ventral pancreas preserving subtotal pancreatectomy (DVPPSP). METHODS: Data collected retrospectively from 43 patients who underwent DVPPSP and TP between 2009 and 2015 in our single centre were analysed. For enrolment, only patients with low-grade pancreatic neoplasms, such as pancreatic neuroendocrine tumors, intraductal papillary mucinous neoplasms (IPMNs), and solid pseudo-papillary tumors, were included. Ten DVPPSP (group 1) and 13 TP (group 2) patients were selected in this study. RESULTS: There were no significant differences in age, gender, comorbidities, preoperative symptoms, American Society of Anesthesiologists score or indications for surgery between the two groups. The most common indication was IPMN for DVPPSP and TP (60% vs 85%, P = 0.411). Compared with the TP group, the DVPPSP group had comparable postoperative morbidities (P = 0.405) and mortalities (both nil), but significantly shorter operative time (232 ± 19.6 min vs 335 ± 32.3 min, P < 0.001). DVPPSP preserved better long-term pancreatic function with less supplementary therapy (P < 0.001) and better quality of life (QoL) after surgery, including better scores in social (P = 0.042) and global health (P = 0.047) on functional scales and less appetite loss (P = 0.049) on the symptom scale. CONCLUSION: DVPPSP is a feasible and safe procedure that could be an alternative to TP for low-grade neoplasms arising from the body and tail region but across the neck region of the pancreas; DVPPSP had better metabolic function and QoL after surgery.

Multisensor-Based Periodic Estimation in Sensor Networks With Transmission Constraint and Periodic Mixed Storage.

In this paper, we consider a periodic estimation problem in sensor networks with a shared communication channel. The transmission constraint is inevitable in a single-channel-based sensor network if the sensors are heterogeneous or deployed far away from each other. A novel stochastic competitive transmission strategy is presented to deal with the transmission constraint, such that the sensors communicate with the fusion center (FC) in a strict asynchronous manner. A periodic mixed storage strategy combing the zero-input and the hold-input mechanisms is presented to describe periodic updating of the stored information in the sensors' buffers. A recursive Kalman filtering algorithm is derived for the FC to periodically generate estimates of state variables describing an object by using a linear continuous-time stochastic model. Two simulation examples are presented to show the effectiveness of the proposed results.

DDA3 and Mdp3 modulate Kif2a recruitment onto the mitotic spindle to control minus-end spindle dynamics.

Active turnover of spindle microtubules (MTs) for the formation of a bi-orientated spindle, chromosome congression and proper chromosome segregation is regulated by MT depolymerases such as the kinesin-13 family and the plus-end-tracking proteins (+TIPs). However, the control mechanisms underlying the spindle MT dynamics that are responsible for poleward flux at the minus end of MTs are poorly understood. Here, we show that Mdp3 (also known as MAP7D3) forms a complex with DDA3 (also known as PSRC1) and controls spindle dynamics at the minus end of MTs by inhibiting DDA3-mediated Kif2a recruitment to the spindle. Aberrant Kif2a activity at the minus end of spindle MTs in Mdp3-depleted cells decreased spindle stability and resulted in unaligned chromosomes in metaphase, lagging chromosomes in anaphase, and chromosome bridges in telophase and cytokinesis. Although they play opposing roles in minus-end MT dynamics, acting as an MT destabilizer and an MT stabilizer, respectively, DDA3 and Mdp3 did not affect the localization of each other. Thus, the DDA3 complex orchestrates MT dynamics at the MT minus end by fine-tuning the recruitment of Kif2a to regulate minus-end MT dynamics and poleward MT flux at the mitotic spindle.

Ska1 cooperates with DDA3 for spindle dynamics and spindle attachment to kinetochore.

Spindle microtubules (MTs) capture kinetochores (KTs) on the centromere sequence of sister chromatids to align at the mitotic equator and segregate toward spindle poles during mitosis. For efficient chromosome capture, KTs initially attach to the lateral surface of a MT, providing a considerably larger contact surface than the MT tip. A sequential change of KT composition upon spindle attachment enables a conversion from lateral to stable end-on attachment. However, the molecular link between spindle dynamics and KT composition is not fully understood. Here, we report that Ska1 and DDA3 act as molecular linkers in the interplay between KTs and spindle dynamics. After recruitment of Kif2a onto the mitotic spindle by DDA3, Ska1 targets Kif2a to the minus-end of spindle MTs and facilitates spindle dynamics. Furthermore, DDA3 targets Ska1 to KTs to stabilize end-on attachment. Thus, our findings identified a definite regulatory mechanism of the search and capture process for stable spindle attachment through cross-talk between spindle dynamics and KT composition mediated by DDA3 and Ska1.

DDA3 targets Cep290 into the centrosome to regulate spindle positioning.

The centrosome is an important cellular organelle which nucleates microtubules (MTs) to form the cytoskeleton during interphase and the mitotic spindle during mitosis. The Cep290 is one of the centrosomal proteins and functions in cilia formation. Even-though it is in the centrosome, the function of Cep290 in mitosis had not yet been evaluated. In this study, we report a novel function of Cep290 that is involved in spindle positioning. Cep290 was identified as an interacting partner of DDA3, and we confirmed that Cep290 specifically localizes in the mitotic centrosome. Depletion of Cep290 caused a reduction of the astral spindle, leading to misorientation of the mitotic spindle. MT polymerization also decreased in Cep290-depleted cells, suggesting that Cep290 is involved in spindle nucleation. Furthermore, DDA3 stabilizes and transports Cep290 to the centrosome. Therefore, we concluded that DDA3 controls astral spindle formation and spindle positioning by targeting Cep290 to the centrosome.