The struggle of a good friend getting old:cellular senescence in viral responses and therapy

Cellular senescence is a state of stable cell cycle arrest associated with macromolecular alterations and secretion of pro-inflammatory cytokines and molecules. Senescence-associated phenotypes restrict damage propagation and activate immune responses, two essential processes involved in response to viral infections. However, excessive accumulation and persistence of senescent cells can become detrimental and promote pathology and dysfunctions. Various pharmacological interventions, including antiviral therapies, lead to aberrant and premature senescence. Here, we review the molecular mechanisms by which viral infections and antiviral therapy induce senescence. We highlight the importance of these processes in attenuating viral dissemination and damage propagation, but also how prematurely induced senescent cells can promote detrimental adverse effects in humans. We describe which sequelae due to viral infections and treatment can be partly due to excessive and aberrant senescence. Finally, we propose that pharmacological strategies which eliminate senescent cells or suppress their secretory phenotype could mitigate side effects and alleviate the onset of additional morbidities. These strategies can become extremely beneficial in patients recovering from viral infections or undergoing antiviral therapy

How human papillomavirus replication and immune evasion strategies take advantage of the host DNA damage repair machinery

The DNA damage response (DDR) is a complex signalling network activated when DNA is altered by intrinsic or extrinsic agents. DDR plays important roles in genome stability and cell cycle regulation, as well as in tumour transformation. Viruses have evolved successful life cycle strategies in order to ensure a chronic persistence in the host, virtually avoiding systemic sequelae and death. This process promotes the periodic shedding of large amounts of infectious particles to maintain a virus reservoir in individual hosts, while allowing virus spreading within the community. To achieve such a successful lifestyle, the human papilloma virus (HPV) needs to escape the host defence systems. The key to understanding how this is achieved is in the virus replication process that provides by itself an evasion mechanism by inhibiting and delaying the host immune response against the viral infection. Numerous studies have demonstrated that HPV exploits both the ataxia-telangiectasia mutated (ATM) and ataxia-telangiectasia and rad3-related (ATR) DDR pathways to replicate its genome and maintain a persistent infection by downregulating the innate and cell-mediated immunity. This review outlines how HPV interacts with the ATM-and ATR-dependent DDR machinery during the viral life cycle to create an environment favourable to viral replication, and how the interaction with the signal transducers and activators of transcription (STAT) protein family and the deregulation of the Janus kinase (JAK)-STAT pathways may impact the expression of interferon-inducible genes and the innate immune responses

$1.00 per RT #BostonMarathon #PrayForBoston: analyzing fake content on Twitter

This study found that 29% of the most viral content on Twitter during the Boston bombing crisis were rumors and fake content.AbstractOnline social media has emerged as one of the prominent channels for dissemination of information during real world events. Malicious content is posted online during events, which can result in damage, chaos and monetary losses in the real world. We analyzed one such media i.e. Twitter, for content generated during the event of Boston Marathon Blasts, that occurred on April, 15th, 2013. A lot of fake content and malicious profiles originated on Twitter network during this event. The aim of this work is to perform in-depth characterization of what factors influenced in malicious content and profiles becoming viral. Our results showed that 29% of the most viral content on Twitter, during the Boston crisis were rumors and fake content; while 51% was generic opinions and comments; and rest was true information. We found that large number of users with high social reputation and verified accounts were responsible for spreading the fake content. Next, we used regression prediction model, to verify that, overall impact of all users who propagate the fake content at a given time, can be used to estimate the growth of that content in future. Many malicious accounts were created on Twitter during the Boston event, that were later suspended by Twitter. We identified over six thousand such user profiles, we observed that the creation of such profiles surged considerably right after the blasts occurred. We identified closed community structure and star formation in the interaction network of these suspended profiles amongst themselves

Time-delayed model of immune response in plants

In the studies of plant infections, the plant immune response is known to play an essential role. In this paper we derive and analyse a new mathematical model of plant immune response with particular account for post-transcriptional gene silencing (PTGS). Besides biologically accurate representation of the PTGS dynamics, the model explicitly includes two time delays to represent the maturation time of the growing plant tissue and the non-instantaneous nature of the PTGS. Through analytical and numerical analysis of stability of the steady states of the model we identify parameter regions associated with recovery and resistant phenotypes, as well as possible chronic infections. Dynamics of the system in these regimes is illustrated by numerical simulations of the model

The essential role of mitochondrial dynamics in antiviral immunity.

Viruses alter cellular physiology and function to establish cellular environment conducive for viral proliferation. Viral immune evasion is an essential aspect of viral persistence and proliferation. The multifaceted mitochondria play a central role in many cellular events such as metabolism, bioenergetics, cell death, and innate immune signaling. Recent findings accentuate that viruses regulate mitochondrial function and dynamics to facilitate viral proliferation. In this review, we will discuss how viruses exploit mitochondrial dynamics to modulate mitochondria-mediated antiviral innate immune response during infection. This review will provide new insight to understanding the virus-mediated alteration of mitochondrial dynamics and functions to perturb host antiviral immune signaling

Information spreading during emergencies and anomalous events

The most critical time for information to spread is in the aftermath of a serious emergency, crisis, or disaster. Individuals affected by such situations can now turn to an array of communication channels, from mobile phone calls and text messages to social media posts, when alerting social ties. These channels drastically improve the speed of information in a time-sensitive event, and provide extant records of human dynamics during and afterward the event. Retrospective analysis of such anomalous events provides researchers with a class of "found experiments" that may be used to better understand social spreading. In this chapter, we study information spreading due to a number of emergency events, including the Boston Marathon Bombing and a plane crash at a western European airport. We also contrast the different information which may be gleaned by social media data compared with mobile phone data and we estimate the rate of anomalous events in a mobile phone dataset using a proposed anomaly detection method.Comment: 19 pages, 11 figure

TREX1 DNA exonuclease deficiency, accumulation of single stranded DNA and complex human genetic disorders

Aicardi-Goutieres syndrome (AGS) is an unusual condition that clinically mimics a congenital viral infection. Several genes have recently been implicated in the aetiology of this disorder. One of these genes encodes the DNA exonuclease TREX1. Recent work from Yang, Lindahl and Barnes has provided insight into the cellular consequence of TREX1-deficiency. They found that TREX1-deficiency resulted in the intracellular accumulation of single stranded DNA resulting in chronic activation of the DNA damage response network, even in cells from Trex1-mutated AGS patients. Here, I summarise their findings and discuss them in context with the other AGS causative genes which encode subunits of the RNase H2 complex. I describe mechanisms by which the inappropriate intracellular accumulation of nucleic acid species might deleteriously impact upon normal cell cycle progression. Finally, using the example of Systemic Lupus Erythematosus (SLE), I also summarise the evidence suggesting that the failure to process intermediates of nucleic acid metabolism can result in the activation of uncontrolled autoimmunity

Possible attenuation of the G2 DNA damage cell cycle checkpoint in HeLa cells by extremely low frequency (ELF) electromagnetic fields

BACKGROUND: The issue remains unresolved as to whether low frequency magnetic fields can affect cell behaviour, with the possibility that they may be in part responsible for the increased incidence of leukaemia in parts of the population exposed to them. METHODS: Combined treatment of HeLa cells with gamma-irradiation (1, 3 and 5 Grays) and extra low frequency magnetic fields of ~50 Hz was carried out under rigorously controlled conditions. RESULTS: Synchronised cells progressing from S-phase arrived at mitosis on average marginally ahead of irradiation controls not exposed to ELF. In no instance out of a total of twenty separate experiments did this "double-insult" further delay entry of cells into mitosis, as had been anticipated. CONCLUSION: This apparently "non-genotoxic" agent (ELF) appears to be capable of affecting cells that would normally arrest for longer in G2, suggesting a weakening of the stringency of the late cycle (G2) checkpoint