Primary Nuclei Research Articles

Cosmic ray e± at high energy

There is a commonly expressed opinion in the literature, that cosmic-ray (CR) e+ come from a primary source, which could be dark matter or pulsars. In these proceedings we review some evidence to the contrary: namely, that e+ come from secondary production due to CR nuclei scattering on interstellar matter. We show that recent measurements of the total e± flux at E ≲ 3 TeV are in good agreement with the predicted flux of secondary e±, that would be obtained if radiative energy losses during CR propagation do not play an important role. If the agreement between data and secondary prediction is not accidental, then the requirement of negligible radiative energy losses implies a very short propagation time for high energy CRs: tesc ≲. 105 yr at rigidities R ≳ 3 TV. Such short propagation history may imply that a recent, near-by source dominates the CRs at these energies. We review independent evidence for a transition in CR propagation, based on the spectral hardening of primary and secondary nuclei around R ~ 100 GV. The transition rigidity of the nuclei matches the rigidity at which the e+ flux saturates its secondary upper bound.

Refinement of Primary Silicon Grains in Semi-Solid Al-25%Si Hypereutectic Aluminum Alloy Slurry

s: The semi-solid slurry of Al-25%Si hypereutectic aluminum alloy was prepared through a copper serpentine pouring channel, the effect of pouring temperature and numbers of channel bend on the slurry microstructure was investigated. The results show that the primary silicon grains in Al-25%Si hypereutectic alloy solidified at a traditional condition are very large and the average silicon grain size is about 65.3μm, however, when the liquid Al-25%Si alloy is poured through a copper serpentine pouring channel, the primary silicon grains are fined obviously. If the channel has three bends and the pouring temperature is 747°C,the average silicon grain size in the slurry is about 33.7μm. If the channel has four bends and the pouring temperature is 747°C, the average silicon grain size in the slurry is about 30.9μm. If the channel has seven bends and the pouring temperature is 747°C, the average silicon grain size in the slurry is about 28.6μm. The analysis shows that the chilling effect of the inner channel wall precipitates primary silicon nuclei, and so the primary silicon grains of Al-25%Si alloy are fined greatly. Meanwhile, the subsequent washing of the alloy melt also promotes the separation of primary silicon grains from the inner wall and the primary silicon grains are further fined. The above research work demonstrates eventually that the copper serpentine pouring channel process is a good method for fining the primary silicon grains in hypereutectic Al-25%Si alloy rather than using chemical fining agent phosphorus as in traditional process.

Towards a better estimation of energy and species of primary cosmic rays in the knee region with the Tibet hybrid experiment: Utilization of refined EAS lateral distributions

A new hybrid experiment (YAC-II+Tibet-III+MD) located at Yangbajing has started to improve the capability of explicit measurements of the cosmic-ray components (P, He, CNO, Fe, etc) at the knee energy region since 2014. Considering the different features of air shower development for different primary cosmic-ray nuclei, using a full Monte Carlo simulation, we modified the lateral distribution functions for proton-induced, helium-induced and iron-induced air showers, respectively. The results show that the air shower size of different nuclei obtained by the modified Nishimura-Kamata-Greisen function is consistent with the true shower size within 5% systematic errors. Furthermore, we studied the Extensive Air Shower age parameter determination from the lateral distribution functions of charged particles near the air shower core with the Tibet hybrid experiment. The derived age parameter can be well used to estimate the particle type of the incident primary cosmic rays.

Preparation of Al-Zn-Mg-Cu alloy semisolid slurry through a water-cooled serpentine pouring channel

The semisolid slurry of Al-Zn-Mg-Cu alloy was prepared through a self-designed water-cooled copper serpentine pouring channel (WSPC) machine. Influences of pouring temperature, the number of turns and the cooling water flow rate on the microstructure of the semisolid Al-Zn-Mg-Cu alloy slurry were investigated. The results show that the semisolid Al-Zn-Mg-Cu alloy slurry with satisfactory quality can be generated by the WSPC when the pouring temperature is in the range between 680 oC and 700 oC. At a given pouring temperature, the average grain size of primary α-Al decreases and the shape factor increases with the increase of the number of turns. When the cooling water flow rate is 450 L·h-1, the obtained semisolid slurry is optimal. During the preparation of the semisolid Al-Zn-Mg-Cu alloy slurry with low superheat pouring, the alloy melt has mixed inhibition and convection flow characteristics by “self-stirring”. When the alloy melt flows through the serpentine channel, the chilling effect of the inner wall of the channel, the convection and mixed inhibition of the alloy melt greatly promote the heterogeneous nucleation and grain segregation. This effect destroys the dendrite growth mode under traditional solidification conditions, and the primary nuclei gradually evolve into spherical or nearspherical grains.

The endosperm development and the variations of structures of embryo sacs: unravelling the low fecundity of Zephyranthes candida (Amaryllidaceae)

To unravel a low fecundity in Zephyranthes candida (Lindl.) Herb., the development of the endosperm was studied using conventional paraplast section technique. The results show that the endosperm develops normally and comprises four major stages viz. syncytial, cellularization, differentiation and maturation. Both proliferation of antipodal cells and their close contact with the primary endosperm nucleus were observed, which should favor transportation of nutrients and accelerate development of embryo and endosperm. In Z. candida, at least four events of nuclear migration occurred during the course of embryogenesis and endosperm development. The 12.7% structurally and functionally abnormal ovules, along with the 22.3% collapsed and aborted ovules observed accounts for the low fecundity to some extent.

Nivel de conocimientos de las enfermeras y el médico de la familia sobre la visita al hogar y los cuidados paliativos domiciliarios

En la visita al hogar se presta una atención integral, continuada y personalizada a los pacientes y su familia, es el lugar donde se alimentan, descansan, ocupan el tiempo de ocio, y se relacionan con su núcleo primario y es donde deben existir las mejores condiciones para satisfacer las necesidades biológicas, psicológicas, espirituales, sociales y culturales. Siendo necesario que las enfermeras/os y médicos de la atención primaria de salud, cuenten con las herramientas necesarias para atender tanto personas sanas como a pacientes tributarios de cuidados paliativos. Objetivo: El objetivo de este trabajo es determinar el nivel de conocimientos de las enfermeras y médicos de familia sobre la visita al hogar y los cuidados paliativos domiciliarios. Metodología: Se realizó un estudio descriptivo de corte transversal en el periodo comprendido de febrero a septiembre del año 2016, en el Policlínico Vedado. El universo estuvo formado por todos los médicos y enfermeras/os de los 40 consultorios que conforman nuestro policlínico, y te tomó una muestra de 40 enfermeras y 18 médicos a los que se les aplicó una encuesta con preguntas abiertas y cerradas. Resultados: Se constata que las enfermeras y los médicos deben trabajar aún más sobre los aspectos relacionados con al paciente y los cuidados al final de la vida. Conclusiones: Se concluye que se debe trabajar más sobre los aspectos relacionados con el paciente y los cuidados paliativos domiciliarios

Revisiting the Spatially Dependent Propagation Model with the Latest Observations of Cosmic-Ray Nuclei

Abstract Recently the AMS-02 collaboration published detections of light cosmic-ray nuclei, including lithium, beryllium, boron, carbon, and oxygen. Combined with the released energy spectra of proton and helium, both primary and secondary spectra have a prominent hardening above ∼200 GV. In particular, the spectral variation of secondary cosmic rays is greater than the primary ones. One of the plausible interpretations for the above anomalies is the spatial-dependent diffusion model. It has successfully described various observational phenomena, e.g., hardening of primary nuclei, diffuse gamma-ray distribution and cosmic-ray anisotropy, etc. In this work, we apply the spatial-dependent propagation model to the latest observations, including both primary and secondary nuclei. Apart from the primary components, the spectra of secondary nuclei can be properly reproduced as well, especially the upturn above 200 GV. We also calculate the ratios of both secondary-to-primary and secondary-to-secondary. We find that except for the Be/B ratio, the computations of the spatial-dependent propagation model are in good agreement with the current data.

Application of New Approximations of the Lateral Distribution of EAS Cherenkov Light in the Atmosphere

A new knee-like approximation of the lateral distribution function (LDF) of EAS Cherenkov light in the 30–3000 TeV energy range was proposed and tested with simulated showers in our earlier studies. This approximation fits the LDFs of individual showers accurately for all types of primary particles gamma-rays, protons, and nuclei) and is suitable for reconstructing the shower core, determining the energy, and separating gamma-induced showers from hadron-induced ones. In the present study, the knee-like fitting function is used to determine the parameters of real showers detected by TAIGA-HiSCORE. It is demonstrated that this approximation characterizes properly all types of individual LDFs of experimental events in the 300–1000 TeV range. The accuracy of fit is governed by fluctuations intrinsic to the process of measurement of the Cherenkov photon density. The probability density function of these fluctuations was reconstructed and introduced into simulations. Certain useful methodical applications of the knee-like approximation are con-sidered, and the possibility of shower sorting into nuclei groups is examined. The extensive statistical coverage and detailed LDF measurement data of HiSCORE have provided the first opportunity to examine in depth the LDF of Cherenkov radiation in the 300–1000 TeV range.

The molecular origins and pathophysiological consequences of micronuclei: New insights into an age-old problem.

Micronuclei (MN), the small nucleus-like bodies separated from the primary nucleus, can exist in cells with numerical and/or structural chromosomal aberrations in apparently normal tissues and more so in tumors in humans. While MN have been observed for over 100 years, they were merely and constantly considered as passive indicators of chromosome instability (CIN) for a long time. Relatively little is known about the molecular origins and biological consequences of MN. Rapid technological advances are helping to close these gaps. Very recent studies provide exciting evidence that MN act as key platform for chromothripsis and a trigger of innate immune response, suggesting that MN could affect cellular functions by both genetic and nongenetic means. These previously unappreciated findings have reawakened widespread interests in MN. In this review, the diverse mechanisms leading to MN generation and the complex fate profiles of MN are discussed, together with the evidence for their contribution to CIN, inflammation, senescence and cell death. Moreover, we put this knowledge together into a speculative perspective on how MN may be responsible for cancer development and how their presence may influence the choice of treatment. We suggest that the heterogeneous responses to MN may function physiological to ensure the arrestment, elimination and immune clearance of damaged cells, but pathologically, may enable the survival and oncogenic transformation of cells bearing CIN. These insights not only underscore the complexity of MN biology, but also raise a host of new questions and provide fertile ground for future research.

Preparation of Curcuma Longa L. Extract Nanoparticles Using Supercritical Solution Expansion

Nanoparticles of Curcuma longa Linn (turmeric) rhizome extract were prepared using supercritical carbon dioxide (SC-CO2). The SC-CO2 was used for sample pre-treatment, including lipophilic compounds removal and extraction, as well as particle production. The particle formation process was based on the expansion of supercritical solution of plant extract into a secondary chamber. In the course of the expansion of supercritical solution process, the herbal extract changed from dissolved mode at higher pressures to precipitated mode at lower pressures, as long as the pressures were higher than the critical pressure. The particle growth via coagulation was limited by a large number of unsuccessful collisions between CO2 molecules and primary nuclei due to the presence of pressurized CO2 molecules where the particle formation occurs. The presence of curcumin derivatives in nanoparticles was confirmed by liquid chromatography-mass spectrometry results. Irregular to quasi-spherical particles with average diameter of 47 ± 20 nm (n = 300) were prepared at a pre-expansion pressure of 35 MPa, pressure drop of 24 MPa, temperature of 50°C, equilibration time of 30 min, collection time of 60 min, extract volume of 30 μL, and feeding solution concentration of 2 mg mL−1.

Planos e propostas institucionais da Universidade de Brasília sobre o uso e a ocupação do Campus Universitário Darcy Ribeiro

A Universidade de Brasília tem o seu principal campus localizado junto ao núcleo original da cidade. O primeiro planejamento do Campus Universitário foi realizado por Lucio Costa em 1960. As demais propostas foram desenvolvidas majoritariamente por profissionais das áreas de arquitetura e urbanismo da própria instituição, tanto docentes quanto técnico-administrativos. Nem toda a documentação que se originou dessas iniciativas foi amplamente disponibilizada junto à comunidade universitária. O presente artigo, escrito com base em pesquisa nos acervos do Centro de Planejamento Oscar Niemeyer, Prefeitura do Campus, Faculdade de Arquitetura e Urbanismo, e Arquivo Central da Universidade de Brasília, teve como objetivo compilar as propostas e planos relacionados ao planejamento físico do Campus Universitário Darcy Ribeiro. O texto apresenta informações chave sobre o Campus Universitário; elenca e descreve brevemente vinte documentos criados no âmbito administrativo da universidade; e avalia e correlaciona esses documentos a fim de constituir um panorama da produção técnica que diz respeito ao planejamento físico do Campus. O resgate e a divulgação da documentação que contém o planejamento físico do Campus estende a historiografia sobre o tema.

Bone morphogenetic protein 2 alleviated intervertebral disc degeneration through mediating the degradation of ECM and apoptosis of nucleus pulposus cells via the PI3K/Akt pathway.

The present study aimed to explore the underlying mechanisms of bone morphogenetic protein 2 (BMP2) in alleviating intervertebral disc degeneration (IDD). A rat puncture IDD model was constructed, and the rats were randomly divided into six groups: Control; IDD (model); IDD+PBS [containing 1010 adeno‑associated virus serotype 2 (AAV)]; and IDD + AAV2‑BMP2 (106, 108 and 1010). IL‑1β was used to treat primary nucleus pulposus (NP) cells to mimic IDD in vitro. The effects of BMP2 in IDD were determined by magnetic resonance imaging (MRI), hematoxylin and eosin staining and Alcian Blue staining in vivo. The levels of collagen II, aggrecan, transcription factor SOX9 (SOX9) and matrix metalloproteinase 13 (MMP‑13) were examined using western blot analysis and reverse transcription quantitative polymerase chain reaction (RT‑qPCR) in NP tissues and cells. The expression of C‑telopeptide of type II collagen (CTX‑II) in the sera or cell supernatants was determined by ELISA. In addition, the levels of phosphorylation of phosphoinositide 3‑kinase (PI3K) and protein kinase B (Akt), and the levels of apoptosis‑associated proteins and apoptosis ratio of NP cells were also determined by western blot analysis and flow cytometry, respectively. LY29400, an inhibitor of PI3K, was used to additionally confirm the signal pathway mechanism of BMP2 treatment in IDD. BMP2 significantly extended the interval between discs and alleviated the fibrous ring rupture and the decrease in the levels of glycoproteins in IDD rats, as determined by MRI and histological staining. Additionally, BMP2 treatment significantly upregulated the levels of collagen II, aggrecan and SOX9, but downregulated the levels of MMP‑13 and CTX‑II in IDD rats and NP cells in a dose‑dependent manner. Concurrently, recombinant human (rh)BMP2 pretreatment also significantly decreased the apoptosis ratio of interleukin (IL)‑1β‑treated NP cells via downregulating the level of cleaved caspase‑3 and upregulating the level of uncleaved poly (adenosine 5'‑diphosphate‑ribose) polymerase. It was demonstrated that rhBMP2 also significantly decreased the inflammatory response in NP tissues and cells, based on levels of IL‑6, TNF‑α and IL‑10. In addition, rhBMP2 inhibited cell apoptosis via upregulating the phosphorylation levels of the PI3K/Akt signaling pathway, and LY29400 pretreatment inhibited the effects of BMP2 in IL‑1β treated NP cells. BMP2 alleviated IDD via the PI3K/Akt signaling pathway by inhibiting NP cell apoptosis and decreasing the levels of matrix proteins.

Potential therapeutic role of Co-Q10 in alleviating intervertebral disc degeneration and suppressing IL-1β-mediated inflammatory reaction in NP cells

Coenzyme Q10 (Co-Q10) is extraordinarily popular and has been used in abundant interventions as an antioxidant reagent that participates in numerous oxidation reactions. According to substantial evidence previously reported, interleukin-1β (IL-1β) is deemed to be one of the chief orchestrator molecules in the degeneration of intervertebral disc (IVD). However, it is unknown whether Co-Q10 is able to protect against IVD degeneration. In the current study, mouse-derived IVDs as well as primary human nucleus pulposus (NP) cells were isolated and cultured. NP cells were stimulated with IL-1β, with or without selective addition of Co-Q10 to investigate the therapeutic effect of Co-Q10 on IVD degeneration. Levels of IL-1β-induced inflammatory biomarkers including TNF-α, COX-2, IL-6 and iNOS were reduced by Co-Q10, which was possibly associated with inhibition of NF-κB signaling activation. Furthermore, Co-Q10 maintained the production of anabolic biomarkers in NP cells such as collagen 2, aggrecan and Sox-9 and altered the enhanced catabolism induced by IL-1β. Moreover, the therapeutic role of Co-Q10 in sustaining IVD tissue-enhanced anabolism is potentially dependent on activation of the Akt signaling pathway. In summary, Co-Q10 may potentially represent an available molecular target that may shed light on approaches to the prevention and treatment of IVD degeneration in the future.

Altered nuclear envelope structure and proteasome function of micronuclei

Micronuclei are extra-nuclear bodies containing whole chromosomes that were not incorporated into the nucleus after cell division or damaged chromosome fragments. Even though the link between micronuclei and DNA damage is described for a long time, little is known about the functional organization of micronuclei and their contribution to tumorigenesis. We showed fusions between micronuclear membranes and lysosomes by electron microscopy and linked lysosome function to DNA damage levels in micronuclei. In addition, micronuclei drastically differ from primary nuclei in nuclear envelope composition, with a significant increase in the relative amount of nuclear envelope proteins LBR and emerin and a decrease in nuclear pore proteins. Strikingly, micronuclei lack active proteasomes, as the processing subunits and other factors of the ubiquitin proteasome system. Moreover, micronuclear chromatin shows a higher degree of compaction as compared to primary nuclei. The specific aberrations identified in micronuclei and the potential functional consequences of these defects may contribute to the role of micronuclei in catastrophic genomic rearrangements.

Distinction Between Variability-Based Modulation and Mean-Based Activation Revealed by BOLD-fMRI and Eyes-Open/Eyes-Closed Contrast

Recent BOLD-fMRI studies have revealed spatial distinction between variability- and mean-based between-condition differences, suggesting that BOLD variability could offer complementary and even orthogonal views of brain function with traditional activation. However, these findings were mainly observed in block-designed fMRI studies. As block design may not be appreciate for characterizing the low-frequency dynamics of BOLD signal, the evidences suggesting the distinction between BOLD variability and mean are less convincing. Based on the high reproducibility of signal variability modulation between continuous eyes-open (EO) and eyes-closed (EC) states, here we employed EO/EC paradigm and BOLD-fMRI to compare variability- and mean-based EO/EC differences while the subjects were in light. The comparisons were made both on block-designed and continuous EO/EC data. Our results demonstrated that the spatial patterns of variability- and mean-based EO/EC differences were largely distinct with each other, both for block-designed and continuous data. For continuous data, increases of BOLD variability were found in secondary visual cortex and decreases were mainly in primary auditory cortex, primary sensorimotor cortex and medial nuclei of thalamus, whereas no significant mean-based differences were observed. For the block-designed data, the pattern of increased variability resembled that of continuous data and the negative regions were restricted to medial thalamus and a few clusters in auditory and sensorimotor networks, whereas activation regions were mainly located in primary visual cortex and lateral nuclei of thalamus. Furthermore, with the expanding window analyses we found variability results of continuous data exhibited a rather slower dynamical process than typically considered for task activation, suggesting block design is less optimal than continuous design in characterizing BOLD variability. In sum, we provided more solid evidences that variability-based modulation could represent orthogonal views of brain function with traditional mean-based activation.

Dissolution Behavior and Changes in the Surface Morphology of Pt-Cu Nanoparticles

Platinum (Pt) nanoparticles is used as cathode catalyst in polymer electrolyte fuel cell (PEFC) to enhance oxygen reduction reaction, however high cost of Pt is preventing popularization of PEFC. Therefore, Pt-transition metal (M) alloy is expected to be used as cathode catalyst instead of Pt in order to lower the amount of Pt usage in PEFC. Both Pt and M dissolution under PEFC operating condition is one of the biggest problem, because their dissolutions lead to performance loss of PEFC. In this study, we selected Cu as additive elements, and the dissolutions and the consequent surface morphological changes of Pt-Cu nanoparticles were investigated by inductively coupled plasma mass spectroscopy (ICP-MS), and field emission-scanning electron microscopy (FE-SEM). Plating bath was prepared by mixing 6 mM K2PtCl4, 6 mM CuSO4·5H2O, and 0.5 M Na2SO4, and pH of the bath was adjusted to 2.0 by adding H2SO4. Pt-Cu nanoparticles were pulse-electroplated on glassy carbon substrate in this bath. Electroplated nanoparticles were fully dissolved by aqua regia, and then tested aqua regia was analyzed with ICP-MS for determining chemical composition of the nanoparticles. Chemical composition was also investigated by using FE-SEM-energy dispersive X-ray spectroscopy, and was determined to be Pt-35 at. % Cu (Pt-35Cu). Pt-35Cu was subjected to potential cycling in 0.5 M H2SO4 at 298 K. A total of 5,000 cycles of potential cycling were applied between 0.05 V and 1.4 V vs. standard hydrogen electrode at 100 mV s-1. Potential cycling was interrupted at the 50th, 200th, and 500th cycles, and every 500 cycles thereafter, and the test solutions were sampled for quantitative ICP-MS analysis of both Pt and Cu ions dissolved from Pt-35Cu. Furthermore, surface morphologies before and after potential cycling were observed by FE-SEM at identical location. Before potential cycling, electroplated Pt-35Cu was composed of numerous Pt-Cu nuclei (less than 3 nm in diameter) that agglomerated to form larger secondary particles (30–50 nm). The surfaces of Pt-35Cu were rapidly flattened with increasing cycle number. After 1,000 cycles of potential cycling, the fine structure of primary nuclei completely vanished and reconstructed to form flattened surface. During this potential cycling, both Pt and Cu dissolved from Pt-35Cu, and the amount of dissolved Cu ions was much larger than the amount of dissolved Pt ions. Especially during the initial potential cycling, Cu was selectively dissolved from Pt-35Cu, and Pt-enriched layer was consequently formed on its surface. Cu dissolution was thereafter suppressed by Pt-enriched layer formation. Even the large Cu dissolution in the initial stage doesn’t affect to surface morphology change. Accordingly, surface morphology change during potential cycling is not likely due to Cu dissolution, but is likely due to Pt surface diffusion and/or Pt dissolution and re-deposition. The authors acknowledge Ookayama Materials Analysis Division, Tokyo Institute of Technology, for assistance with the FE-SEM, and ICP-MS analysis.

Age-related morphometrical peculiarities of Lithuanian women\u2019s primordial ovarian follicles

BackgroundFor the first time, thorough morphometrical measurements of primordial ovarian follicles were performed and their age-related changes were investigated in Lithuanian women of the reproductive age.MethodsOvaries of dead women (n = 30) were divided into six age groups: 15–20 years old, 21–25 years old, 26–30 years old, 31–35 years old, 36–40 years old and 41–46 years old. Histological slides of left and right ovaries were stained using haematoxylin-eosin and periodic acid–Schiff (PAS) staining methods. The morphometrical measurements of 10 primordial ovarian follicles of the left and right ovary of each woman were made from microphotographs.ResultsThe diameter of primordial ovarian follicles increased in groups of women from 15 years old to 35 years old and decreased in the groups from 36 years old to 46 years old. The area of primordial ovarian follicles increased in the groups of women until 35 years old. It decreased in the groups of women older than 36 years. The follicular basement membrane thickened from 1.29 ± 0.11 μm to 1.43 ± 0.18 μm with increasing age of women. The diameter of primary oocytes enlarged until 35 years and then began to decrease. The area of primary oocytes increased in women until 35 years. It decreased in groups of women aged 36–40 and 41–46 years old. The diameter and the area of primary oocytes nuclei increased in women aged 15–30 years old; later, it began to decrease. The length of follicular cells varied from 8.56 ± 0.43 μm to 8.72 ± 0.27 μm (p > 0.05). The height of follicular cells varied from 2.59 ± 0.27 μm to 2.7 ± 0.21 μm (p > 0.05).The diameter, the area and the basement membrane thickness of primordial ovarian follicles and the diameter and the area of primary oocytes and their nuclei differed insignificantly in left and right ovaries in all age groups of women (p > 0.5). The length and height of follicular cells were similar in left and right ovaries of the same age group (p > 0.5).ConclusionsThe age decreasing of morphometrical parameters begins in primordial ovarian follicles and their primary oocytes in Lithuanian women older than 35 years. The thickness of the follicular basement membrane increased with increasing age of women. No significant differences were found in the morphometrical parameters in primordial follicles of left and right ovaries in the same age group of women.

Progranulin Is Positively Associated with Intervertebral Disc Degeneration by Interaction with IL-10 and IL-17 Through TNF Pathways.

Progranulin (PGRN) is a widely expressed growth factor that effectively inhibits tumor necrosis factor α (TNFα)-mediated inflammatory response. TNFα is involved in intervertebral disc degeneration (IDD) and plays a key role. This study aims to determine the role of PGRN in the intervertebral disc degeneration process. We collected intervertebral discs (IVDs) from humans and mice with different genetic backgrounds. We examined the expression of PGRN in IVD tissues by immunohistochemistry staining and Western blotting assay. We examined the peripheral serum level of PGRN by ELISA assay. Murine IVD tissue samples were taken to undergo safranin O, HE, and immunohistochemistry staining. Primary human nucleus pulposus cells were used for ELISA and RT-PCR assays. PGRN as well as interlukin-10 (IL-10) and interlukin-17 (IL-17) expressions were elevated in degenerative discs and peripheral blood sera. Loss of PGRN led to accelerated disc degeneration in the animal model, along with decreased expression of IL-10 and increased expression of IL-17. Additionally, the PGRN level was positively related to levels of IL-10 and IL-17. In vitro study suggested that PGRN protected against disc degeneration by inducing IL-10 and reducing IL-17. PGRN is associated with intervertebral disc degeneration through interfering with IL-10 and IL-17; thus, PGRN could be an interesting biomarker for diagnosis and a potential treatment target.

TGF-β Initiates β-Catenin-Mediated CTGF Secretory Pathway in Old Bovine Nucleus Pulposus Cells: A Potential Mechanism for Intervertebral Disc Degeneration.

ABSTRACTWe have recently demonstrated that overexpression of Smurf2 under the control of type II collagen alpha 1 (Col2a1) promoter induces an intervertebral disc degeneration phenotype in Col2a1‐Smurf2 transgenic mice. The chondrocyte‐like cells that express type II collagen and Smurf2 in the transgenic mouse discs are prone to degenerate. However, how the chondrocyte‐like cells contribute to disc degeneration is not known. Here, we utilized primary old bovine nucleus pulposus (NP) cells as substitutes for the chondrocyte‐like cells in Col2a1‐Smurf2 transgenic mouse discs to identify mechanism. We found that 35% of the cells were senescent; TGF‐β treatment of the cells induced a rapid moderate accumulation of β‐catenin, which interacted with connective tissue growth factor (CTGF/CCN2) in the cytoplasm and recruited it to the membrane for secretion. The TGF‐β‐initiated β‐catenin‐mediated CTGF secretory cascade did not occur in primary young bovine NP cells; however, when Smurf2 was overexpressed in young bovine NP cells, the cells became senescent and allowed this cascade to occur. These results suggest that Smurf2‐induced disc degeneration in Col2a1‐Smurf2 transgenic mice occurs through activation of CTGF secretory pathway in senescent disc cells. © 2018 The Authors JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Chromosomes trapped in micronuclei are liable to segregation errors.

ABSTRACTDNA in micronuclei is likely to get damaged. When shattered DNA from micronuclei gets reincorporated into the primary nucleus, aberrant rearrangements can take place, a phenomenon referred to as chromothripsis. Here, we investigated how chromatids from micronuclei act in subsequent divisions and how this affects their fate. We observed that the majority of chromatids derived from micronuclei fail to establish a proper kinetochore in mitosis, which is associated with problems in chromosome alignment, segregation and spindle assembly checkpoint activation. Remarkably, we found that, upon their formation, micronuclei already display decreased levels of important kinetochore assembly factors. Importantly, these defects favour the exclusion of the micronucleus over the reintegration into the primary nucleus over several divisions. Interestingly, the defects observed in micronuclei are likely overcome once micronuclei are reincorporated into the primary nuclei, as they further propagate normally. We conclude that the formation of a separate small nuclear entity represents a mechanism for the cell to delay the stable propagation of excess chromosome(s) and/or damaged DNA, by inducing kinetochore defects.