Da remiziramo...

Dobra vijest o imunitetu od covida-19: Oni koji su preboljeli koronu sigurni su barem 6 mjeseci
Rijetki slučajevi ponovne zaraze stvorili su zabrinutost da bi imunitet mogao biti kratkog roka, ali istraživanje Oxforda to opovrgava

https://www.jutarnji.hr/vijesti/svijet/dobra-vijest-o-imunitetu-od-covida-19-oni-koji-su-preboljeli-koronu-sigurni-su-barem-6-mjeseci-15006456

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Na primjeru "Bergamo" se može vidjeti da je imunost(zaštita) do sada barem 8 mjeseci.
I jučer su imali 3x manje novozaraženih od ostatka regije Lombardia.

na tvojem primjeru vidi se da svatko može natipkati i ostati živ.

ne komentiraš mihine upise od cca d-10 ili čak d-7.

ne?

kaj si ono pisao?

kaj je on pisao?

a, radi se o desetak dana.

odi patke hranit, korisnije je.

Sve što ovi idioti koji "upravljaju" s ovim je da pokušavaju dovoljno otupiti ljude da im postane dobar dan kad ima ispod 40 mrtvih. A da oni mogu i dalje svirati kurcu i izbjegavati ikakve ozbiljnije poteze i mjere. Pišam se i na zemlju ovakvu i na ove koji ju vode.

Stiže cjepivo strpite se i ne gubite živce još mjesec dva.

epikur37 wrote:Stiže cjepivo strpite se i ne gubite živce još mjesec dva.

za dvije nedjelje

epikur37 wrote:Stiže cjepivo strpite se i ne gubite živce još mjesec dva.

žuna, žuna, žuna

stiso pakšu gaće?

sada više nije prehladica, šmrklići i sl?

ima nekih novih otkrića...nisam siguran da će ovo itko čitati ali ipak stavit ću:

The PANoptosome: A Deadly Protein Complex Driving Pyroptosis, Apoptosis, and Necroptosis (PANoptosis)

Front. Cell. Infect. Microbiol., 03 June 2020

Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, United States

Programmed cell death is regulated by evolutionarily conserved pathways that play critical roles in development and the immune response. A newly recognized pathway for proinflammatory programmed cell death called PANoptosis is controlled by a recently identified cytoplasmic multimeric protein complex named the PANoptosome. The PANoptosome can engage, in parallel, three key modes of programmed cell death—pyroptosis, apoptosis, and necroptosis. The PANoptosome components have been implicated in a wide array of human diseases including autoinflammatory diseases, neurodegenerative diseases, cancer, microbial infections, and metabolic diseases.
Here, we review putative components of the PANoptosome and present a phylogenetic analysis of their molecular domains and interaction motifs that support complex assembly. We also discuss genetic data that suggest PANoptosis is coordinated by scaffolding and catalytic functions of the complex components and propose mechanistic models for PANoptosome assembly. Overall, this review presents potential mechanisms governing PANoptosis based on evolutionary analysis of the PANoptosome components.

Introduction
Programmed cell death (PCD) is an evolutionarily conserved process that plays central roles in maintaining organismal homeostasis. Three key PCD pathways have been studied in great detail—pyroptosis (inflammasome-dependent PCD executed by gasdermin family members), apoptosis (PCD mediated by the apoptosome and executioner caspases), and necroptosis (PCD mediated by RIPK3 and the downstream effector MLKL). Previous studies have provided a foundation for us to understand the active and extensive crosstalk between the inflammasome/pyroptosis and apoptosis and necroptosis (Lamkanfi et al., 2008; Malireddi et al., 2010, 2018, 2020; Gurung et al., 2014, 2016a; Lukens et al., 2014; Kuriakose et al., 2016; Zheng et al., 2020). Some pathogenic challenges, such as influenza A virus (IAV) infection (Kuriakose et al., 2016), inhibition of the homeostasis-regulating transforming growth factor β-activated kinase 1 (TAK1) (Malireddi et al., 2018, 2020), and functional alterations in receptor-interacting serine/threonine-protein kinase (RIPK) 1 (Dannappel et al., 2014; Dillon et al., 2014; Kaiser et al., 2014; Rickard et al., 2014a; Dondelinger et al., 2019; Newton et al., 2019a; Lalaoui et al., 2020), can induce pyroptosis, apoptosis, and necroptosis together. These observations raised a question about regulation of PCD in these cases—are the three pathways activated independently of each other, or is a single cell death-inducing complex controlling all three? Studies using mice lacking Tak1 in myeloid cells and small molecule inhibitors of TAK1 kinase activity suggested the latter (Malireddi et al., 2019, 2020). This evidence led to the identification of a single cell death-inducing complex that is assembled to induce a PCD phenomenon called PANoptosis (Malireddi et al., 2019, 2020). The complex has subsequently been named the PANoptosome (Figure 1A) (Christgen et al., 2020). The PANoptosome was initially shown to contain RIPK1, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing 3 (NLRP3), and caspase (CASP) 8 (Malireddi et al., 2020). A subsequent study determined that RIPK3, CASP6, Z-DNA-binding protein 1 (ZBP1), and CASP1 are also components of the PANoptosome that is assembled in response to IAV infection (Zheng et al., 2020). Collectively, these studies showed that the PANoptosome contains molecules critical for pyroptosis, apoptosis, and necroptosis and is able to activate all three to execute proinflammatory cell death (Christgen et al., 2020). Therefore, PANoptosis provides a mechanism for the host to activate alternative cell death defense mechanisms if one or more of the PCD pathways are compromised by a pathogen or other blockade. In this review, we will discuss PANoptosis and the molecular components of the PANoptosome complex, including their domain structures and functions, and use evolutionary analyses to contextualize the interactions between these molecules.

Established Mechanisms of PANoptosis
Pathogen sensing by the innate immune system activates intracellular signaling cascades to induce a proinflammatory immune response. Many innate sensors also trigger PCD either by directly interacting with mediators of cell death or through the downstream effects of secreted cytokines. One pathogen that elicits proinflammatory immune responses and PCD is IAV. Yearly seasonal flu outbreaks are caused by IAV strains, but hypervirulent strains sporadically emerge and can result in catastrophic pandemics, such as the 1918 Spanish flu, which killed approximately 50 million people worldwide (Johnson and Mueller, 2002). One feature that made the Spanish flu so deadly was its ability to initiate a dramatic host inflammatory response to the virus, culminating in a rapid “cytokine storm,” severe lung tissue damage, and death. The NLRP3 inflammasome was shown to be a major antiviral host defense mechanism controlling lung inflammation during IAV infection (Kanneganti et al., 2006a,b; Thomas et al., 2009). However, the PCD induced by IAV is not entirely dependent on the NLRP3 inflammasome. The loss of a component essential for just one PCD pathway does not protect the cells from IAV-induced cell death (Kuriakose et al., 2016). Cells lacking the ability to induce pyroptosis, apoptosis, and necroptosis collectively due to genetic loss of Ripk3 and Casp8 (or Fadd) are protected (Kuriakose et al., 2016). Combinatorial pharmacological inhibition of these three PCD pathways also protects the cells. IAV-induced PCD is also dependent on type I interferon signaling, as cells lacking interferon alpha and beta receptor subunit 1 (IFNAR1) are resistant to IAV-induced cell death (Kuriakose et al., 2016). These findings suggest the existence of upstream regulator(s) controlled by type I interferon signaling. The search for the upstream molecules responsible for NLRP3 inflammasome activation and PCD identified ZBP1—cells lacking Zbp1 are completely protected from PCD (Kuriakose et al., 2016). Later studies provided additional confirmation that ZBP1 is responsible for RIPK3-dependent cell death during IAV infection (Thapa et al., 2016; Kesavardhana et al., 2017). These observations led to the first description of PANoptosis (Malireddi et al., 2019). Mechanistically, ZBP1 drives PANoptosis by recruiting RIPK3 and CASP8 to the PANoptosome upon sensing IAV infection (Kuriakose et al., 2016; Kesavardhana et al., 2017; Kuriakose and Kanneganti, 2017; Zheng et al., 2020).

Although the ZBP1 PANoptosome promotes PANoptosis to shape the immune response against viral infections, its role in maintaining organismal homeostasis is increasingly being appreciated. Lethality in mice caused by the Ripk1RHIM mutation can be rescued by concomitantly deleting ZBP1 or mutating the RHIM domain in ZBP1 (Lin et al., 2016; Newton et al., 2016; Jiao et al., 2020), suggesting that RIPK1 inhibits the aberrant induction of PANoptosis by ZBP1. This evidence extends the concept of PANoptosis beyond the context of infection and shows that it can also regulate fundamental organismal processes such as development.

Further evidence for the role of PANoptosis in organismal processes can be seen from studies with RIPK1. The regulation of PANoptosis by RIPK1 is essential for homeostasis, cell death, and inflammatory immune responses. The scaffolding function of RIPK1 promotes cell survival signaling via the assembly of complex-I, which blocks both early and late cell death checkpoints downstream of TNFR1 signaling (Gerlach et al., 2011; Vince et al., 2012; Dondelinger et al., 2013; Peltzer et al., 2016, 2018; Ting and Bertrand, 2016; Taraborrelli et al., 2018), while RIPK1's kinase activity or receptor-interacting protein homotypic interaction motif (RHIM) function enables PCD (Dillon et al., 2014; Kaiser et al., 2014; Rickard et al., 2014b; Dowling et al., 2015; Newton et al., 2019a; Lalaoui et al., 2020; Tao et al., 2020). Deletion of RIPK1 in mice is embryonically lethal, which may be caused by the activation of RIPK3-regulated PANoptosis-like cell death through CASP8 and Fas-associated protein with a death domain (FADD) leading to systemic inflammation (Kelliher et al., 1998; Zhang et al., 2011; Dillon et al., 2014). In addition, mutations inactivating CASP8 catalytic activity lead to embryonic lethality in mice mediated by PANoptosis through the activation of RIPK1, RIPK3-MLKL, and CASP1 (Fritsch et al., 2019; Newton et al., 2019b). Mutating the CASP8 cleavage site in RIPK1, which is essential to regulate RIPK1 activity, also causes embryonic lethality and inflammation (Newton et al., 2019a; Lalaoui et al., 2020; Tao et al., 2020). Collectively, these studies provide evidence for the regulation of PANoptosis by RIPK1 and CASP8.

Another key regulator of PANoptosis was identified through a study of the complex-I component TAK1 (Malireddi et al., 2018). TAK1 was found to play an important role in NLRP3 inflammasome activation and to also modulate RIPK1 activity to regulate PANoptosis (Malireddi et al., 2019). In the absence of TAK1 activity due to pharmacological inhibition or genetic loss, RIPK1 activates PANoptosis and inflammation through its kinase activity (Malireddi et al., 2018; Orning et al., 2018; Sarhan et al., 2018). A follow up study discovered RIPK1 kinase-independent activation of PANoptosis, questioning the dogma that RIPK1 kinase function is required for PCD (Malireddi et al., 2020). These studies suggest that loss of function or deregulation of RIPK1 homeostasis can engage PANoptosis and affect organismal development and immune responses.

The discovery of PANoptosis in the contexts of IAV infection and organismal homeostasis led us to revisit autoinflammatory diseases in which components of the PCD machinery have been implicated to determine whether PANoptosis also plays a role here. A mutation in the Pstpip2 gene (Pstpip2cmo) causes autoinflammation via CASP8- and NLRP3/CASP1-regulated PCD. Combined deletion of Ripk3, Casp1, and Casp8, which blocks all three arms of PANoptosis (pyroptosis, apoptosis, and necroptosis), rescued the mice from the autoinflammatory condition, while inhibition of a single arm was not sufficient for rescue (Lukens et al., 2014; Gurung et al., 2016a), suggesting the involvement of PANoptosis in mediating the autoinflammatory condition. Another example of PANoptosis in autoinflammation can be seen in mice with a mutation in Sharpin (Sharpincpdm). The inflammation in Sharpincpdm mice can be rescued by deletion of TNF or expression of kinase-dead RIPK1 (Gerlach et al., 2011; Berger et al., 2014). It can also be rescued by hemizygous deletion of CASP8 along with the loss of RIPK3 (Rickard et al., 2014b). Skin inflammation can also be delayed by the loss of Nlrp3 or the inflammasome-dependent cytokine IL-1β (Berger et al., 2014; Douglas et al., 2015; Gurung et al., 2016b). Involvement of the three arms of PANoptosis suggests a role for PCD and the inflammatory cytokines released by PANoptotic cells in driving inflammation in Sharpincpdm mice.

Several other proteins associated with autoinflammation with dual roles in cell survival and inflammatory immune signaling pathways have been implicated in PANoptosis. In addition to RIPK1, deletion of other complex-I molecules, including HOIP, HOIL-1, and A20, also leads to embryonic lethality and autoinflammatory diseases, suggesting they may have a role in regulating PANoptosis (Gerlach et al., 2011; Vince et al., 2012; Dondelinger et al., 2013; Vande Walle et al., 2014; Peltzer et al., 2016; Ting and Bertrand, 2016; Taraborrelli et al., 2018; Zhang et al., 2019).

Whether it is induced in response to infection, during organismal homeostasis, or in the context of autoinflammation, PANoptosis is executed by a molecular complex called the PANoptosome that integrates apoptotic, necroptotic, and inflammasome components. Downstream cytokines such as IL-1β and IL-18 and damage-associated molecular patterns (DAMPs) released by PANoptotic cells act as alarmins initiating and amplifying the inflammatory response. Overall, the PANoptosome is responsible for driving this inflammatory form of cell death, and defects in PANoptosome components have been implicated in a host of human diseases including autoinflammatory and neurodegenerative diseases, cancer, and susceptibility to pathogenic infections (Figure 1B, Table 1)

https://www.frontiersin.org/articles/10.3389/fcimb.2020.00238/full

veberu prvo u debelo meso :D

KRAJ KORONA AGONIJE?
Iz Pfizera zatražili hitno odobrenje cjepiva protiv Covida-19, Fauci euforičan: ‘Pomoć je na putu‘
Pfizer je procijenio da bi do kraja godine mogao imati na raspolaganju 50 milijuna doza cjepiva

https://www.jutarnji.hr/vijesti/svijet/iz-pfizera-zatrazili-hitno-odobrenje-cjepiva-protiv-covida-19-fauci-euforican-pomoc-je-na-putu-15032383

Varaždinska županija ima najstrože mjere

Nacionalni stožer prihvatio je prijedloge Stožera civilne zaštite Varaždinske županije koja je postala najkritičnija regija u EU prema broju zaraženih i donio Odluku. U Varaždinskoj županiji zatvaraju se ugostiteljski objekti. Zabranjuju se sportska događanja u kojima se ostvaruje bliski kontakt. Privremeno se obustavlja i rad sportskih centara i terena za sportove u kojima dolazi do fizičkog kontakta. Donesena je zabrana održavanja svih javnih okupljanja na otvorenom s više od 20 ljudi, zabrana svih okupljanja u zatvorenim prostorima, privremeno se obustavljaju umjetnički programi, kinoprojekcije, sajmovi, izložbe... Više o Odluci o izmjenama i dopuni Odluke o uvođenju nužnih epidemioloških mjera za područje Varaždinske županije pročitajte OVDJE.

Pročitajte više na: https://www.vecernji.hr/vijesti/sto-se-mijenja-od-nedjelje-pogledajte-nove-mjere-u-borbi-protiv-koronavirusa-1447630 - www.vecernji.hr

Lockdowns hurt the economy, which in turn can cause many problems. Unemployment, psychological distress, and long-term economic harm need to be considered when deciding how to act.

This is absolutely true. There are more factors at play here than just the physical health of individuals and communities.
However, having economic interruptions which last for several weeks is a historically validated response strategy that is as old as history. A short, hard lockdown saves both the economy and the health of the population. If the lockdown is not doing the job very well, and new cases will not slow down, the strategy would be to strengthen the lockdown, rather than lift it.
The price a country pays for reopening too early can be incredibly high. Massive amounts of deaths, a collapsed healthcare system, and having multiple lockdowns would cause massive amounts of damage, and must be avoided.

https://www.endcoronavirus.org/countries

epikur37 wrote:veberu prvo u debelo meso :D

čuj te eufemizme.

neka ti safet u debelo meso, prvo.
kasnije možete žlundrice sisat.

epikur37 wrote:veberu prvo u debelo meso :D

Ne troši svoje vrijeme uzalud.

Eroo wrote:

epikur37 wrote:veberu prvo u debelo meso :D

Ne troši svoje vrijeme uzalud.

Ma ok je, samo ga treba pelcovat :D

Eroo wrote:

Lockdowns hurt the economy, which in turn can cause many problems. Unemployment, psychological distress, and long-term economic harm need to be considered when deciding how to act.

This is absolutely true. There are more factors at play here than just the physical health of individuals and communities.
However, having economic interruptions which last for several weeks is a historically validated response strategy that is as old as history. A short, hard lockdown saves both the economy and the health of the population. If the lockdown is not doing the job very well, and new cases will not slow down, the strategy would be to strengthen the lockdown, rather than lift it.
The price a country pays for reopening too early can be incredibly high. Massive amounts of deaths, a collapsed healthcare system, and having multiple lockdowns would cause massive amounts of damage, and must be avoided.

https://www.endcoronavirus.org/countries

Neki dan si ti pisao da je lockdown odlicno rjesenje da se u Izraelu rijesilo da ovo da ono.

Sad kad Vili & Plenkovic to ne zele napraviti sad je to 10 zala egipta. Bah neda mi se vise nista. Ljudi vidimo se kad se vidimo.

epikur37 wrote:

Eroo wrote:

epikur37 wrote:veberu prvo u debelo meso :D

Ne troši svoje vrijeme uzalud.

Ma ok je, samo ga treba pelcovat :D

bum vas spelcal.
kamenom

veber wrote:

epikur37 wrote:

Eroo wrote:

epikur37 wrote:veberu prvo u debelo meso :D

Ne troši svoje vrijeme uzalud.

Ma ok je, samo ga treba pelcovat :D

bum vas spelcal.
kamenom

Tko tebe kamenom ti njega kruhom...kod nas kršćana je tako ;)

Ja sam 15 godina mlađi od tebe pa nije red da te ja učim a ero je 15 godina stariji od tebe...pa :p

Lockdown svakako nije rješenje problema nego "kupovanje vremena" dok se ne nađe lijek ili cjepivo, ali i pokušaj usporavanja širenja zaraze kako ne bi došlo do preopterećenosti zdravstvenih ustanova. 

Mi sad imamo drugi lockdown, ali ga se nitko više ne pridržava. Igrališta su prepuna djece, ljudi su u grupama, posjećuju se. 
Roditelji šalju djecu u vrtić iako nisu zaposleni (jer im je dosadno bez prijatelja)...

Samim time ovo zadnje zaključavanje je bilo totalno besmisleno i nema nikakvih rezultata osim što je napravilo veliko opterećenje za proračun. 
A maska...
Svima je mrska i teška prvenstveno zato jer ne štitit nas, nego druge (ukoliko smo sami zaraženi), pa samim time nitko nije motiviran nositi je u svim zatvorenim prostorima. 
Naravno, govorim o našem mentalitetu, ne o Japancima ili Fincima.

epikur37 wrote:Ja sam 15 godina mlađi od tebe pa nije red da te ja učim a ero je 15 godina stariji od tebe...pa :p

to ne mijenja činjenicu da ste sančosi.