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Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Zinc supplementation to cancer cells counteracts hypoxia-induced inhibition of HIPK2, suppresses HIF-1alpha activity and restores p53Ser46-dependent drug response
No full textRegulation of p53 activity by HIPK2: molecular mechanisms and therapeutical implications in human cancer cells.
No full textThe p53 protein is the most studied tumor suppressor and the p53 pathway has been shown to mediate cellular stress responses that are disrupted when cancer develops. After DNA damage, p53 is activated as transcription factor to directly induce the expression of target genes involved in cell-cycle arrest, DNA repair, senescence and, importantly, apoptosis. Post-translational modifications of p53 are essential for the activation of p53 and for selection of target genes. The tumor suppressor homeodomain-interacting protein kinase-2 (HIPK2) is a crucial regulator of p53 apoptotic function by phosphorylating its N-terminal serine 46 (Ser46) and facilitating Lys382 acetylation at the C-terminus. HIPK2 is activated by numerous genotoxic agents and can be deregulated in tumors by several conditions including hypoxia. Recent findings suggest that HIPK2 active/inactive protein can affect p53 function in multiple and unexpected ways. This makes p53 as well as HIPK2 interesting targets for cancer therapy. Hence, understanding the role of HIPK2 as p53 activator may provide important insights in the process of tumor progression, and may also serve as the crucial point in the diagnostic and therapeutical aspects of cancer
The immunocompromised district: a unifying concept for lymphoedematous, herpes-infected and otherwise damaged sites
No full textSystemic immunodeficiency is known to facilitate the onset of opportunistic infections, tumours and immune disorders
in any district of the body. There are clinical events, such as chronic lymphoedema, herpetic infections, vaccinations and
heterogeneous physical injuries which can selectively damage and immunologically mark the cutaneous district they act
upon. After the causing event has disappeared, the affected district may appear clinically normal, but its immune
behaviour is often compromised forever. An immunocompromised district becomes a site which is particularly
susceptible to subsequent outbreaks of opportunistic infections, tumours and immune disorders confined to the
district itself.
In this review, there is an ample case-report collection of opportunistic disorders (infectious, neoplastic, immune) which
appeared in immunocompromised districts. The cases have been grouped according to the clinical settings responsible
for the local immune imbalance: regional chronic lymphoedema; herpes-infected sites, which feature the well-known
Wolf’s isotopic response; and otherwise damaged areas, comprising sites of vaccination, ionizing or UV radiation, thermal
burns and traumas.
Whatever the immunocompromising factor, a common denominator which facilitates the occurrence of tumours,
infections and dysimmune reactions in an immunocompromised district may reside in locally hampered lymph drainage
and/or locally altered neuromediator signalling. In fact, any obstacle to the normal trafficking of immunocompetent cells
through lymphatic channels or any interference with the signals that the neuropeptides and neurotransmitters released
by peripheral nerves send to cell membrane receptors of immunocompetent cells, can significantly alter the local immune
response, thus paving the way for heterogeneous opportunistic disorders in the immunocompromised district
Blockade of HIPK2 apoptotic function is involved in chemoresistance to cisplatin in ovarian cancer cells
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Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Overexpression of HIPK2 circumvents the blockade of apoptosis in chemoresistant ovarian cancer cells.
Get PDFObjective. Chemoresistance, due to inhibition of apoptotic response, is the major reason for the failure of anticancer therapies. HIPK2 regulates
p53-apoptotic function via serine-46 (Ser46) phosphorylation and activation of p53 is a key determinant in ovarian cancer cell death. In this study
we determined whether HIPK2 overexpression restored apoptotic response in chemoresistant cancer cells.
Methods. Using cisplatin chemosensitive (2008) and chemoresistant (2008C13) ovarian cancer cell lines we compared drug-induced activation
of the HIPK2/p53Ser46 apoptotic pathway. The levels of HIPK2, Ser46 phosphorylation, and PARP cleavage were detected by Western blotting.
The p53Ser46 apoptotic commitment was evaluated by luciferase assay using the Ser46 specific AIP1 target gene promoter. The apoptotic
pathway was detected by caspase-3, -8, and -9 activities.
Results. HIPK2 was expressed differently in sensitive versus chemoresistant cells in response to different chemotherapeutic drugs (i.e., cisplatin
and adriamycin), though the p53Ser46 apoptotic pathway was not defective in chemoresistant 2008C13 cells. Thus, 2008C13 cells were resistant to
cisplatin but sensitive to adriamycin-induced apoptosis through activation of the HIPK2/p53Ser46 pathway. HIPK2 knock-down inhibited the
adriamycin-induced apoptosis in 2008C13 cells. Exogenous HIPK2 triggered apoptosis in chemoresistant cells, associated with induction of
p53Ser46-target gene AIP1.
Conclusions. HIPK2 is an important regulator of p53 activity in response to a chemotherapeutic drug. These results suggest that different drugactivated
pathways may regulate HIPK2 and that HIPK2/p53Ser46 deregulation is involved in chemoresistance. Exogenous HIPK2 might
represent a novel therapeutic approach to circumvent inhibition of apoptosis in treatment of chemoresistant ovarian cancers with wtp53
Combination therapy strategies in HIPK2 knockdown tumor cells require Sirt1 inhibitor to activate p53 apoptotic transcription
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