scholarly journals Mechanisms underlying melanoma invasion as a consequence of MLK3 loss

2021 ◽  
Author(s):  
Henriette U. Balinda ◽  
Alanna Sedgwick ◽  
Crislyn D’Souza-Schorey
Keyword(s):  
Cell Invasion ◽  
Critical Role ◽  
Jnk Signaling ◽  
Erk Activation ◽  
Aggressive Form ◽  
Melanoma Invasion ◽  
High Incidence ◽  
Hsp90 Activity ◽  
Critical Insight ◽  
Insight Into

AbstractInvasive melanoma is an aggressive form of skin cancer with high incidence of mortality. The process of invasion is a crucial primary step in the metastatic cascade, yet the mechanisms involved are still under investigation. Here we document a critical role for MLK3 (MAP3K11) in the regulation of melanoma cell invasion. We report that cellular loss of MLK3 in melanoma cells promotes cell invasion. Knock down of MLK3 expression results in the hyperactivation of ERK, which is linked to the formation of a BRAF/Hsp90/Cdc37 protein complex. ERK hyperactivation leads to enhanced phosphorylation and inactivation of GSK3β and the stabilization of c-Jun and JNK activity. Blocking of ERK and JNK signaling as well as Hsp90 activity downstream of MLK3-silencing significantly reduces melanoma invasion. Furthermore, our studies show that ERK activation in the aforementioned context is coupled to MT1-MMP transcription as well as the TOM1L1-dependent localization of the membrane protease to invadopodia at the invasive front. These studies provide critical insight into the mechanisms that couple MLK3 loss with BRAF hyperactivation and its consequence on melanoma invasion.

Importance of the Intersection of Library and Information Sciences with Systems Theory

2017 ◽  
Vol 1 (1) ◽  
Author(s):  
Hannah Lee
Keyword(s):  
System Theory ◽  
General System ◽  
General System Theory ◽  
Von Bertalanffy ◽  
Meta Level ◽  
Professional Field ◽  
The Subject ◽  
Critical Insight ◽  
Insight Into ◽  
Information Sciences

This paper is the attempt to show how system theory could provide critical insight into the transdisciplinary field of library and information sciences (LIS). It begins with a discussion on the categorization of library and information sciences as an academic and professional field (or rather, the lack of evidence on the subject) and what is exactly meant by system theory, drawing upon the general system theory established by Ludwig von Bertalanffy. The main conversation of this paper focuses on the inadequacies of current meta-level discussions of LIS and the benefits of general system theory (particularly when considering the exponential rapidity in which information travels) with LIS.

Intimacy as Transgression and the Problem of Freedom

2018 ◽  
Vol 1 (1) ◽  
pp. 18
Author(s):  
Kym Maclaren
Keyword(s):  
Intimate Relationships ◽  
Critical Analysis ◽  
Mutual Recognition ◽  
Public Institutions ◽  
The Other ◽  
Social Forces ◽  
Critical Insight ◽  
Insight Into ◽  
What Matters

“To consent to love or be loved,” said Merleau-Ponty, “is to consent also to influence someone else, to decide to a certain extent on behalf of the other.” This essay explicates that idea through a meditation on intimacy. I propose, first, that, on Merleau-Ponty’s account, we are always transgressing into each other’s experience, whether we are strangers or familiars; I call this “ontological intimacy.” Concrete experiences of intimacy are based upon this ontological intimacy, and can take place at two levels: (1) at-this-moment (such that we can experience intimacy even with strangers, by sharing a momentary but extra-ordinary mutual recognition) and (2) in shared interpersonal institutions, or habitual, enduring, and co-enacted visions of who we are, how to live, and what matters. Through particular examples of dynamics within these layers of intimacy (drawing upon work by Berne and by Russon), I claim that we are always, inevitably, imposing an “unfreedom” upon our intimate others. Freedom, then, can only develop from within and by virtue of this “unfreedom.” Thus, what distinguishes empowering or emancipating relationships from oppressive ones is not the removal of transgressive normative social forces; it is rather the particular character of those transgressive forces. Some transgressions upon others’ experience—some forms of “unfreedom”—will tend to promote freedom; others will tend to hinder it. This amounts to a call for promoting agency and freedom not only through critical analysis of public institutions, practices and discourses, but also through critical insight into and transformation of our most private and intimate relationships.

Critical Insight into the Attributes of Emerging Novel Coronavirus (COVID-19) in India and Across the World

Coronaviruses ◽  
2020 ◽  
Vol 1 (1) ◽  
pp. 49-56
Author(s):  
Gaurav M. Doshi ◽  
Hemen S. Ved ◽  
Ami P. Thakkar
Keyword(s):  
Review Article ◽  
World Health ◽  
Effective Vaccine ◽  
Human Contact ◽  
The World ◽  
Critical Insight ◽  
Novel Coronavirus ◽  
Health Organization ◽  
Insight Into ◽  
Old Drugs

The World Health Organization (WHO) has recently announced the spread of novel coronavirus (nCoV) globally and has declared it a pandemic. The probable source of transmission of the virus, which is from animal to human and human to human contact, has been established. As per the statistics reported by the WHO on 11th April 2020, data has shown that more than sixteen lakh confirmed cases have been identified globally. The reported cases related to nCoV in India have been rising substantially. The review article discusses the characteristics of nCoV in detail with the probability of potentially effective old drugs that may inhibit the virus. The research may further emphasize and draw the attention of the world towards the development of an effective vaccine as well as alternative therapies. Moreover, the article will help to bridge the gap between the new researchers since it’s the current thrust area of research.

scholarly journals Renal Manifestations of Covid-19: Physiology and Pathophysiology

2021 ◽  
Vol 10 (6) ◽  
pp. 1216
Author(s):  
Zaher Armaly ◽  
Safa Kinaneh ◽  
Karl Skorecki
Keyword(s):  
Viral Replication ◽  
Virus Disease ◽  
Multiorgan Failure ◽  
Critical Role ◽  
Kidney Injury ◽  
Small Sample ◽  
Renal Physiology ◽  
High Morbidity ◽  
Enzymatic Production ◽  
High Incidence

Corona virus disease 2019 (COVID-19) imposes a serious public health pandemic affecting the whole world, as it is spreading exponentially. Besides its high infectivity, SARS-CoV-2 causes multiple serious derangements, where the most prominent is severe acute respiratory syndrome as well as multiple organ dysfunction including heart and kidney injury. While the deleterious impact of SARS-CoV-2 on pulmonary and cardiac systems have attracted remarkable attention, the adverse effects of this virus on the renal system is still underestimated. Kidney susceptibility to SARS-CoV-2 infection is determined by the presence of angiotensin-converting enzyme 2 (ACE2) receptor which is used as port of the viral entry into targeted cells, tissue tropism, pathogenicity and subsequent viral replication. The SARS-CoV-2 cellular entry receptor, ACE2, is widely expressed in proximal epithelial cells, vascular endothelial and smooth muscle cells and podocytes, where it supports kidney integrity and function via the enzymatic production of Angiotensin 1-7 (Ang 1-7), which exerts vasodilatory, anti-inflammatory, antifibrotic and diuretic/natriuretic actions via activation of the Mas receptor axis. Loss of this activity constitutes the potential basis for the renal damage that occurs in COVID-19 patients. Indeed, several studies in a small sample of COVID-19 patients revealed relatively high incidence of acute kidney injury (AKI) among them. Although SARS-CoV-1 -induced AKI was attributed to multiorgan failure and cytokine release syndrome, as the virus was not detectable in the renal tissue of infected patients, SARS-CoV-2 antigens were detected in kidney tubules, suggesting that SARS-CoV-2 infects the human kidney directly, and eventually induces AKI characterized with high morbidity and mortality. The mechanisms underlying this phenomenon are largely unknown. However, the fact that ACE2 plays a crucial role against renal injury, the deprivation of the kidney of this advantageous enzyme, along with local viral replication, probably plays a central role. The current review focuses on the critical role of ACE2 in renal physiology, its involvement in the development of kidney injury during SARS-CoV-2 infection, renal manifestations and therapeutic options. The latter includes exogenous administration of Ang (1-7) as an appealing option, given the high incidence of AKI in this ACE2-depleted disorder, and the benefits of ACE2/Ang1-7 including vasodilation, diuresis, natriuresis, attenuation of inflammation, oxidative stress, cell proliferation, apoptosis and coagulation.

scholarly journals Lessons from the study of plant mating systems for exploring the causes and consequences of inbreeding in marine invertebrates

2021 ◽  
Vol 168 (3) ◽  
Author(s):  
Kevin C. Olsen ◽  
Will H. Ryan ◽  
Ellen T. Kosman ◽  
Jose A. Moscoso ◽  
Don R. Levitan ◽  
...  
Keyword(s):  
Mating Systems ◽  
Marine Invertebrates ◽  
Reproductive Traits ◽  
Theory And Practice ◽  
Costs And Benefits ◽  
Life History Variation ◽  
Invertebrate Animals ◽  
Plant Mating Systems ◽  
Critical Insight ◽  
Insight Into

AbstractMany benthic marine invertebrates resemble plants in being modular and either sessile or sedentary, and by relying on an external vector to disperse their gametes. These shared features, along with recent evidence of inbreeding in these taxa, suggest that theory and practice bearing on the evolutionary costs and benefits of inbreeding for plants could advance our understanding of the ecology and evolution of invertebrate animals. We describe how the theory for the evolution of inbreeding and outbreeding could apply to benthic invertebrates, identify and compare techniques used to quantify inbreeding in plants and animals, translate relevant botanical concepts and empirical patterns to their zoological equivalents, and articulate predictions for how inbreeding might be associated with major axes of variation in sessile and sedentary marine invertebrates. The theory of inbreeding and outbreeding provides critical insight into major patterns of life-history variation in plants and holds similar promise as a complementary perspective on the evolution of reproductive traits, lifespan, ecological strategies, and dispersal in marine invertebrates. Extending what we have learned from plants to marine invertebrates promises to broaden the general study of mating systems.

Why Does He Do It? What Explanations Resonate During Counseling for Women in Understanding Their Partner’s Abuse?

2021 ◽  
pp. 088626052198985
Author(s):  
Sally Marsden ◽  
Cathy Humphreys ◽  
Kelsey Hegarty
Keyword(s):  
Partner Violence ◽  
Research Question ◽  
Critical Role ◽  
Mental Health Research ◽  
Individual Characteristics ◽  
Clinical Group ◽  
Structured Interviews ◽  
Women’S Perceptions ◽  
Ipv Perpetration ◽  
Insight Into

Intimate partner violence (IPV) is a complex and multifaceted problem gaining increasing attention within mental health research and practice. IPV explanations focus on both individual and systemic levels; however, it is increasingly acknowledged that a single level explanation may not be sufficient. The practices of clinical disciplines may, however, still privilege an explanation at one level over another, which will influence how they work with clients. It is likely that one such clinical group, psychologists, may play a critical role in helping victim-survivors to understand and explain their experiences of IPV. However, we were unable to find any studies focusing on women’s perceptions of psychologists’ role in this. Additionally, we know little about women victim-survivors’ perceptions of why their partners use IPV. To address these gaps, the research question for this study was: What explanations resonate during counseling for women in understanding their partner’s abuse? To explore this question, 20 women who had seen psychologists after experiencing IPV participated in semi-structured interviews. The interviews were analyzed using reflexive thematic analysis and three themes constructed from the data. The first two themes, narcissist description was helpful and not all bad all the time, showed that the women found it powerful in their healing processes when psychologists offered the opportunity to discuss their partners individual characteristics as explanations for their use of IPV. The third theme, structural explanations, showed that some of the women also reflected on wider structural contexts. Implications for clinical practice include the potential healing effect when practitioners can move along a continuum of explanation levels, covering both the inner and outer worlds. Implications for research into IPV perpetration are that women hold expertise and insight into individual perpetrators and could make valuable contributions to this field.

scholarly journals Human immunity against EBV—lessons from the clinic

2017 ◽  
Vol 214 (2) ◽  
pp. 269-283 ◽  
Author(s):  
Stuart G. Tangye ◽  
Umaimainthan Palendira ◽  
Emily S.J. Edwards
Keyword(s):  
Immune Cell ◽  
Underlying Disease ◽  
Lymphoproliferative Disease ◽  
Barr Virus ◽  
Ebv Infection ◽  
Human Immunity ◽  
Critical Insight ◽  
Epstein Barr ◽  
Mammalian Immune System ◽  
Insight Into

The mammalian immune system has evolved over many millennia to be best equipped to protect the host from pathogen infection. In many cases, host and pathogen have coevolved, each acquiring sophisticated ways of inducing or protecting from disease. Epstein-Barr virus (EBV) is a human herpes virus that infects >90% of individuals. Despite its ubiquity, infection by EBV is often subclinical; this invariably reflects the necessity of the virus to preserve its host, balanced with sophisticated host immune mechanisms that maintain viral latency. However, EBV infection can result in various, and often fatal, clinical sequelae, including fulminant infectious mononucleosis, hemophagocytic lymphohistiocytosis, lymphoproliferative disease, organomegaly, and/or malignancy. Such clinical outcomes are typically observed in immunosuppressed individuals, with the most extreme cases being Mendelian primary immunodeficiencies (PIDs). Although these conditions are rare, they have provided critical insight into the cellular, biochemical, and molecular requirements for robust and long-lasting immunity against EBV infection. Here, we review the virology of EBV, mechanisms underlying disease pathogenesis in PIDs, and developments in immune cell–mediated therapy to treat disorders associated with or induced by EBV infection.

Science and Theology for Everyone: How Climate Science is Shaping Christianity in the UK

2021 ◽  
Vol 62 (2) ◽  
pp. 147-157
Author(s):  
Caleb Gordon ◽  
Hannah Malcolm
Keyword(s):  
Critical Role ◽  
Climate Science ◽  
Significant Shift ◽  
Christian Life ◽  
Ethical Problems ◽  
Technical Leadership ◽  
Science And Theology ◽  
The Uk ◽  
Insight Into

This article analyses the growing participation of UK Christians in climate initiatives over the last five years. In many cases, climate science is cited as a necessary consideration for the fulfilment of already-existing Christian commitments. This represents a significant shift in the ways UK Christians understand the role of dialogue between theology and the sciences; previous science and theology dialogue has usually been treated as an area of expert concern, primarily offering insight into apologetics or specific ethical problems. By contrast, the dialogue between climate science and theology has seen the emergence of non-technical leadership amid the expectation that climate science plays a critical role in re-examining the meaning of Christian life, both for individuals and as communities.

Paclitaxel Promotes Cell Apoptosis in Uterine Leiomyomas

Pharmacology ◽  
2017 ◽  
Vol 100 (5-6) ◽  
pp. 246-252 ◽  
Author(s):  
Haiping Liu ◽  
Jianye Wang ◽  
Lianbing Sheng ◽  
Yan Zhang ◽  
Ning Tang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Critical Role ◽  
Estradiol Benzoate ◽  
Uterine Leiomyomas ◽  
Health Concern ◽  
Major Health ◽  
Gynecological Tumors ◽  
Dose Limiting Toxicity ◽  
Insight Into ◽  
Apoptosis Level

Uterine leiomyomas are common clinical gynecological tumors, which are a major health concern for many women. In the current study, we aimed to investigate the effect of paclitaxel (PTX) on uterine leiomyomas. A mouse model of uterine leiomyomas was established by estradiol benzoate, followed by treatment with increasing doses of PTX. PTX showed no dose-limiting toxicity that affected the survival of mice, and was able to restore the apoptosis level of uterus tissues of the model mice to normal levels. In this study, we discovered that PTX played a critical role in promoting apoptosis in the mouse model of uterine leiomyomas, which provides a new insight into the therapy of uterine leiomyomas.

Platelets in tissue repair: control of apoptosis and interactions with regenerative cells

Blood ◽  
2013 ◽  
Vol 122 (15) ◽  
pp. 2550-2554 ◽  
Author(s):  
Meinrad Gawaz ◽  
Sebastian Vogel
Keyword(s):  
Cell Survival ◽  
Tissue Repair ◽  
Molecular Mechanisms ◽  
Healing Process ◽  
Critical Role ◽  
Cellular Migration ◽  
Tissue Repair And Regeneration ◽  
Primary Hemostasis ◽  
Regenerative Cells ◽  
Insight Into

Abstract Besides mediating primary hemostasis and thrombosis, platelets play a critical role in tissue repair and regeneration. They regulate fundamental mechanisms involved in the healing process including cellular migration, proliferation, and angiogenesis. Control of apoptosis/cell survival and interaction with progenitor cells, which are clinically relevant but poorly understood aspects of platelets in tissue repair, will be highlighted in this review. Gaining deeper insight into the less well-characterized molecular mechanisms is necessary to develop new therapeutic platelet-based options.

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