Nuclear Spheres Research Articles

Non-spherical nucleon clusters in the mantle of a neutron star: CLDM based on Skyrme-type forces

Neutron stars are superdense compact astrophysical objects. The central region of the neuron star (the core) consists of locally homogeneous nuclear matter, while in the outer region (the crust) nucleons are clustered. In the outer crust these nuclear clusters represent neutron-rich atomic nuclei and all nucleons are bound within them. Whereas in the inner crust some neutrons are unbound, but nuclear clusters still keeps generally spherical shape. Here we consider the region between the crust and the core of the star, so-called mantle, where non-spherical nuclear clusters may exist. We apply compressible liquid drop model to calculate the energy density for several shape types of nuclear clusters. It allows us to identify the most energetically favorable configuration as function of baryon number density. Employing four Skyrme-type forces (SLy4 and BSk24, BSk25, BSk26), which are widely used in the neutron star physics, we faced with strong model dependence of the ground state composition. In particular, in agreement with previous works within liquid drop model, mantle is absent for SLy4 (nuclear spheres directly transit into homogeneous nuclear matter; exotic nuclear shapes do not appear).

Extensive nuclear sphere generation in the human Alzheimer's brain

Nuclear spheres are protein aggregates consisting of FE65, TIP60, BLM, and other yet unknown proteins. Generation of these structures in the cellular nucleus is putatively modulated by the amyloid precursor protein (APP), either by its cleavage or its phosphorylation. Nuclear spheres were preferentially studied in cell culture models and their existence in the human brain had not been known. Existence of nuclear spheres in the human brain was studied using immunohistochemistry. Cell culture experiments were used to study regulative mechanisms of nuclear sphere generation. The comparison of human frontal cortex brain samples from Alzheimer's disease (AD) patients to age-matched controls revealed a dramatically and highly significant enrichment of nuclear spheres in the AD brain. Costaining demonstrated that neurons are distinctly affected by nuclear spheres, but astrocytes never are. Nuclear spheres were predominantly found in neurons that were negative for threonine 668 residue in APP phosphorylation. Cell culture experiments revealed that JNK3-mediated APP phosphorylation reduces the amount of sphere-positive cells. The study suggests that nuclear spheres are a new APP-derived central hallmark of AD, which might be of crucial relevance for the molecular mechanisms in neurodegeneration.

Membrane tethering of APP c-terminal fragments is a prerequisite for T668 phosphorylation preventing nuclear sphere generation

A central molecular hallmark of Alzheimer's disease (AD) is the β- and γ-secretase-mediated cleavage of the amyloid precursor protein (APP), which causes the generation of different c-terminal fragments like C99, AICD57, or AICD50 that fully or in part contain the APP transmembrane domain. In this study, we demonstrate that membrane-tethered C99 is phosphorylated by JNK3A at residue T668 (APP695 numbering) to a higher extent than AICD57, whereas AICD50 is not capable of being phosphorylated. The modification decreases the turnover of APP, while the blockade of APP cleavage increases APP phosphorylation. Generation of nuclear spheres, complexes consisting of the translocated AICD, FE65 and other proteins, is significantly reduced as soon as APP c-terminal fragments are accessible for phosphorylation. This APP modification, which we identified as significantly reduced in high plaque-load areas of the human brain, is linearly dependent on the level of APP expression. Accordingly, we show that APP abundance is likewise capable of modulating nuclear sphere generation. Thus, the precise and complex regulation of APP phosphorylation, abundance, and cleavage impacts the generation of nuclear spheres, which are under discussion of being of relevance in neurodegeneration and dementia. Future pharmacological manipulation of nuclear sphere generation may be a promising approach for AD treatment.

Friends in Need…

China's rise to prominence in Asia has been both dramatic and seemingly inexorable. The country has significantly expanded its economic and diplomatic involvement and considerably extended its military reach. However, despite growing hard power and greater global presence, Beijing feels vulnerable and has very few reliable partners. Within this context China's close and enduring friendship with Pakistan stands out. Indeed, as Andrew Small astutely observes in the opening sentence of The China-Pakistan Axis: Asia's New Geopolitics, Beijing's ties with Islamabad have run closer than most formal alliances (p. 1). In this impressive book, Small outlines in considerable detail the main contours of this fascinating and secretive relationship.While all states are dysfunctional to some degree, China and Pakistan appear to be defined by the extreme nature of their respective dysfunctionalities. In addition, judging from Small's analysis, their relationship is itself highly dysfunctional. In psychology, codependency is defined as a pathological relationship where two parties are dependent on each other to an unhealthy degree. Each party has feelings of extreme insecurity and fears being alone. This condition appears to have defined the China-Pakistan relationship since the 1960s. Both Beijing and Islamabad suffer from high anxiety and believe they have a dearth of trustworthy friends in other capitals. Accordingly, each side views this partnership as essential to maintaining its own national security. Implicit in The China-Pakistan Axis is the idea that codependency is an apt diagnosis of the partnership's dysfunctionality, or at least that significant elements of this condition apply. Whether the author concurs with this characterization, it does seem consistent with his reference to Chinese and Pakistani pathologies in their foreign relationships (p. 7).China has enjoyed a warm relationship with Pakistan since the 1960s, with the leaders of both countries often referring to the bilateral relationship as an all-weather friendship. It considers Pakistan a pivotal state that will decisively influence the course of events in surrounding countries, notably Afghanistan. Moreover, Beijing also thinks of Islamabad as a longtime but deeply troubled ally on a geostrategic fault line between South and Central Asia-a region where China has had few friends. Yet Beijing's support has become more restrained than in the past as Pakistan has gradually declined in overall geopolitical significance. Although Pakistan is still an important partner and a major arms market for Chinese defense firms, its value as a conduit to the Islamic world or facilitator on the global stage has been greatly reduced. In the 21st century, China has robust relationships with every country in the Middle East and globally has full diplomatic ties with all but 22 microstates. In particular, India looms ever larger as a major economic partner for China. As a result, China's interests in Pakistan are increasingly regional and aimed at restraining Islamabad. And yet despite these developments, Islamabad continues to be Beijing's key capital in South Asia precisely because it is a counterweight to New Delhi.Labeling the China-Pakistan relationship an axis is controversial. Yet Small's meticulous research suggests the term is appropriate to characterize this rather unique partnership. At least in terms of cooperative relationships, China has maintained few enduring friendships. After all, the country has tended to not play well with others. Formal alliances, such as with the Soviet Union, ended badly, and China's relationship with its sole remaining official treaty ally-North Korea-has been extremely tumultuous across the decades. Beijing's ties to another erstwhile Communist comrade in arms-Vietnam-have also been characterized by considerable turmoil, leading to extended border unpleasantries and outright war in 1979. By contrast, Beijing's ties with Islamabad have been remarkably steady, with high levels of security cooperation in the conventional and nuclear spheres. …

Deterrence in Indo-Pak Context: A Critical Appraisal

It was an imbalance in the conventional power that forced Pakistan to see nuclear weapons' capability, as a deterrence against India, after the war of 1971 that resulted in separation of former East Pakistan. This is the context of ‘deterrence’ in today's South Asia. The only solution to the dilemmas created by the region's nuclearization is to engage seriously and constructively to build a better understanding of each other's conventional and nuclear policies, doctrines, and postures, and meaningful CBMs both in nuclear and conventional military spheres to build trust and confidence. Both India and Pakistan have to maintain rational decision-making to ensure the credibility of their deterrence and to achieve the objective of maintaining stability.

Nuclear spheres modulate the expression of BEST1 and GADD45G

Nuclear spheres are composed of FE65, TIP60, BLM and other yet unknown proteins. The amyloid precursor protein plays a central role for the generation of these highly toxic aggregates in the nucleus of cells. Thus, nuclear spheres might play a crucial role in Alzheimer's disease (AD). However, studies are hampered by the elevated cell death, once spheres are generated. In this work, we established for the first time a stable nuclear sphere model based on the inductive expression of FE65 and TIP60 following Doxycycline stimulation. We studied hitherto controversially discussed target genes, give clues for the reason of controversy, and moreover report new highly reliable targets bestrophin 1 and growth arrest and DNA-damage-inducible protein gamma. qPCR studies further revealed that the regulation of these targets strongly depends on the generation of nuclear spheres, but not on the induction of FE65 or TIP60 alone. As the bestrophin 1 ion channel was recently described to be involved in the abnormal release of GABA, our study might reveal the missing link between AD associated neurotransmitter changes and the amyloid precursor protein.

Образ города в повести Дины Рубиной «Высокая вода венецианцев»

In the article an attempt is made to analyze the peculiarity of the structure of space in Dina Rubina’s novel «High Water Venetians». Venice is viewed as a field with a nuclear and peripheral spheres. Field analysis of language components allows to see a live, evolving image of the city directly linked to the internal state of the main character.

India and Space Weaponization: Why Space Debris Trumps Kinetic Energy Antisatellite Weapons as the Principal Threat to Satellites

Since China tested a Kinetic-Energy Anti-Satellite (KE-ASAT) weapon in 2007, evidence has surfaced that India may have initiated a similar program. This article makes an anticipatory policy intervention against the development of KE-ASAT weapons. It presents data to show that space debris, and not KE-ASAT weapons, pose the highest risk for the safe operation of Indian satellites. It models a KE-ASAT weapons exchange between India and China in three different scenarios to demonstrate that use of such weapons even on a limited scale would produce an exponential increase in space debris. The latter would threaten the safe operation of satellites for all countries concerned. These data suggest that the concept of deterrence as understood in conventional and nuclear spheres is not easily transportable to the domain of space weapons, which threaten the physical destruction of satellites. If weaponization of space becomes inevitable, policy makers would be better off investing in weapons that disable but do not physically destroy satellites.

FE65 regulates and interacts with the Bloom syndrome protein in dynamic nuclear spheres – potential relevance to Alzheimer's disease

The intracellular domain of the amyloid precursor protein (AICD) is generated following cleavage of the precursor by the γ-secretase complex and is involved in membrane to nucleus signaling, for which the binding of AICD to the adapter protein FE65 is essential. Here we show that FE65 knockdown causes a downregulation of the protein Bloom syndrome protein (BLM) and the minichromosome maintenance (MCM) protein family and that elevated nuclear levels of FE65 result in stabilization of the BLM protein in nuclear mobile spheres. These spheres are able to grow and fuse, and potentially correspond to the nuclear domain 10. BLM plays a role in DNA replication and repair mechanisms and FE65 was also shown to play a role in DNA damage response in the cell. A set of proliferation assays in our work revealed that FE65 knockdown in HEK293T cells reduced cell replication. On the basis of these results, we hypothesize that nuclear FE65 levels (nuclear FE65/BLM containing spheres) may regulate cell cycle re-entry in neurons as a result of increased interaction of FE65 with BLM and/or an increase in MCM protein levels. Thus, FE65 interactions with BLM and MCM proteins may contribute to the neuronal cell cycle re-entry observed in brains affected by Alzheimer's disease.

Abstract 5354: Nuclear spheres in developmental biology and diagnosis

Abstract Introduction: The nuclear content of individual spheres with identical luminal diameters in buccal mucosa cells of patients with a malignant neoplasm at a distant site was first described by the author in 1962. Their biologic etiology remains unknown however. Recent studies revealed data on their correlation with nuclear spheres of cancer stem cells in asymmetric division. Materials and Methods: Observation of nuclear micro spheres was made by means of the highest magnification of the light microscope using a 100x objective and 10x ocular with a microscopic tube length of 1.25. The hematoxylin-eosin stain was applied for histological sections and cytological specimens. Buccal mucosa spreads of 145 cases were examined in correlation with cancer stem cells. Nuclear spheres in buccal mucosa cells were compared to those in self-renewal daughter cells of cancer stem cells in asymmetric division. Results: In asymmetric division of cancer stem cells the self-renewal daughter cell nucleus consisted entirely of spheres with identical luminal diameters of 0.33 to 0.5 µm. The other daughter cell was well differentiated with a nucleus devoid of spheres. In the buccal mucosa specimens with a distant malignant neoplasm, the nuclear content of spheres with luminal diameters of < 0.5 µm were noted in 112 of 145 cases with a sensitivity of 77% and specificity of 86%. The primary tumors were diverse in type and location. Discussion: The scientific literature is silent as to the rationale for nuclear spheres that appear with their identical luminal diameters in the buccal mucosa cells distant from a primary malignant neoplasm and identical to those of self-renewal daughter cells in asymmetric stem cell division. Nuclear spheres in cells distant from the primary tumor may occur as a result of circulating blood DNA or through blood cell migration to the buccal mucosa. The systemic manifestation of nuclear spheres at distant sites from a primary tumor is in keeping with the systemic involvement of cancer described by numerous investigators including the teams led by M. Us-Krasovic and B. Palcic (2005) and D.S. Alberts and P.H. Bartels (2007). The identification of nuclear spheres as a result of an overt or occult cancer offers the potential of a non-invasive cancer test. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5354. doi:1538-7445.AM2012-5354

Regions of the Haptoglobin 5' Flanking Gene Sequence Show Different Binding Affinities to Nuclear Matrix Proteins during the Acute Phase Response

The effect of the acute phase response on the affinity of binding between nuclear matrix proteins and the rat haptoglobin (Hp) gene region was examined. Nuclear matrices isolated from acute phase livers were enriched with the 5' Hp gene flanking region (-705/+159), but not with the spliced, protein-coding sequence. Reassociation experiments with isolated nuclear protein matrix spheres and end-labeled fragments I (-146/+156), II (-146/-541), and III (-541/-705) revealed that the matrix proteins displayed an increased binding potential during the acute phase response for all of the examined regions, this being most pronounced for fragment II. BAL 31 digestion of fragment II showed that the sequence element that was responsible for the increased association with nuclear matrix proteins during the acute phase response was a tract of 38 adenine bases. The DNA region established stable associations with nuclear lamin B (67 kDa, pI 5.7) in the controls, and with lamins A (69 kDa, pI 7.0), B, isoforms of lamin C (62 kDa, pI 6.55-6.95), and a 55-kDa (pI 5.9) polypeptide during the acute phase response. Sequence ABC (-165/-56), which overlaps fragments I and II and represents the Hp cis-acting element, did not bind to the non-histone nuclear matrix proteins.

Lamellate bodies in the nuclei of dragonfly (Odonata) oocytes.

Concentrically lamellate spherical bodies have been observed in the oocyte nuclei of the anisopterous dragonflyCordulia aenea. In their ultrastructure, these bodies resemble the “cortical granules” reported from the cytoplasm of the sea urchin oocytes. The lamellate bodies ofCordulia are compared with other lamellate systems known to exist in nuclei. It is suggested that the nuclear lamellate spheres ofCordulia may be homologous with the somewhat less regular lamellate bodies described from maize microspores.

Histological and Histogenetic Studies on the Pars Intermedia of the Pituitary in the Hamster

The author, using 235 hamsters of both sexes of various ages raging from birth to 300 days, made the histological and histogenetic study of the pars intermedia of the hypophysis of the hamsters. The results obtained were as follows1. The pars intermedia is composed of epithelial parenchymatous cells, border layer cells which lie along the hypophyseal cleft, connective tissues and very few blood vessels, but do not contain nerve fibers.2. In the intermedis cells, the mitoses are most numerous in number at the 3th day, and always found throughout life, although they are rare in adult.3. In adult the parenchymatoua cells are large and shaped variously. The cytoplasm is abundant and granular, staining basophilic, and the cell boundaries are not always clear. The parenchymatous cells are stained positively with GOMORI's aldehyde-fuchsin and periodic acid-SCHIFF reaction. The nuclei, irregularly shaped, generally contain one or two acidophilic nucleoli.4. The author confirms that nuclear spheres derived from nucleoli, discharge the contents, and thus that the nuclei become irregularly shaped, showing incisures and folds.5. In earlier stages of life, the parenchymatous cells are grouped very densely, and then they become larger. At the 30th day the nuclear sphere first appears, and at the 40th day a small number of cells show the nuclei with incisures and folds.6. In adult, the border layer cells have scanty cytoplasm with ovoid, cylindrical or flatt nuclei. These cells are seen at 7th day for the first time and then gradually increase in number. These cells differenciate from the parenchymatous cells.7. The connective tissues are scanty in the pars intermedia.