2 : The Kiss Of Death
The kiss of death (Italian: Il bacio della morte) is the sign given by a mafioso boss or caporegime that signifies that a member of the crime family has been marked for death, usually as a result of some perceived betrayal.[1] It is unclear how much is based on fact and how much on the imagination of authors, but it remains a cultural meme[2][3] and appears in literature and films. Illustrative is the scene in the film The Valachi Papers when Vito Genovese (Lino Ventura) gives the kiss of death to Joe Valachi (Charles Bronson) to inform him that his betrayal of "the family" is known, and that he will be executed.
2 : The Kiss of Death
The exact origin is unknown, but an Italian source identifies the bacio della morte as the kiss given to the assassin delegated to "execute" a death sentence, as if to seal the solemn judgment and to wish success on the assignment. Some believe it refers to the kiss of Judas which was given to Jesus to betray him to the soldiers seeking him out.[4] Its use goes back to at least the early 19th century in Sicily.[5]
Triatoma bites are associated with a variety of other adverse reactions, which can range from mild localized inflammation to a severe, systemic, anaphylactic reaction. Allergic reactions following bites from five different Triatoma species have been reported. The majority of allergic reactions have been attributed to Triatoma protracta, which is found in California; and Triatoma rubida, which is found predominately in Arizona. The other three species associated with reported adverse reactions are Triatoma gerstaeckeri, Triatoma sanguisuga, and Triatoma rubrofasciata.2,4 One death following an anaphylactic reaction secondary to a Triatoma bite was reported in Arizona in 2004, though that case report did not delineate the species.5
As the kissing bug is a nocturnal insect capable of flight, outside lights should be turned off or away from the home so as not to attract them to the area. Other avoidance strategies include use of approved indoor pesticides as well as use of bed nets. The floor of the bedroom should be kept free of clutter and bed linens should not touch the floor. In high incidence areas, examination of bed sheets prior to getting into bed may be helpful. As the insect rarely bites covered skin, wearing pajamas with long sleeves and long pants is reasonable, as is spraying insect repellent on uncovered skin prior to bed.2
By now, those in the non-gamer community enjoying HBO's The Last of Us adaptation should be taking the hint: with two major character deaths over the course of just two episodes, no one is guaranteed a happy ending on this show.
Following the loss of Joel's daughter Sarah (Nico Parker) in the premiere, Anna Torv's Tess met her end in the second episode, which premiered Sunday night. Her death, however, played out differently than it does in the Last of Us game. Series creators Craig Mazin and Neil Druckmann confirm there's a good reason for that.
A runner spots Tess and instead of violently charging her as we've seen infected do before, it calmly walks over and gives her an open-mouthed kiss to allow tendrils of the evolved cordyceps fungi to pass into her.
Male textile workers: 2,390 deaths of textile mills. 525 died from tuberculosis. In other words, 22 per cent of deaths among male textile workers is due to tuberculosis. 47 per cent of deaths in the age period 25 to 34 years, is from tuberculosis.
Portraits of Squad 13's members flash across the screen, with their details, in the order: Ichigo, Goro, Miku, Zorome, Kokoro, Futoshi, Ikuno and Mitsuru. Next, Zero Two licks the honey off her lips, then a shot of honey being poured is shown. Zero Two holds Hiro's face and kisses him. Following this, Hiro is shot backwards, then catapulted into the air. During this, the background transitions from red to the sky. Strelizia in stampede mode catches him, then evolves to form Strelizia's iron maiden form. Strelizia flies closer to the point of view, then lands to the left of Delphinium, Argentea, Genista and Chlorophytum.
Tumor immunosurveillance, a mechanism to protect immunocompetent hosts against the emergence of spontaneous tumors, mainly relies on the initial recognition of stressed cells by natural killer (NK) cells and the subsequent triggering of tumor-specific cytotoxic T lymphocyte (CTL) responses.1 While both NK cells and CTLs are responsible for killing tumor cells via direct contacts, unlike CTLs, NK cells exhibit killing without prior sensitization.2 CTLs are CD8+ T lymphocytes that recognize tumor-associated antigens (TAAs) as processed peptides bound to major histocompatibility complex (MHC) class I (MHC-I) molecules. Their priming requires concomitant triggering of CD4+ T helper (Th) lymphocytes.3 Although in certain circumstances tumor cells can directly present TAAs to CTLs,4 it is commonly assumed that this direct presentation is mostly tolerogenic.5 Indeed, professional antigen-presenting cells (APCs), particularly dendritic cells (DCs), remain the principal initiators of CD4+ and CD8+ T cell-mediated immune responses.6 DCs are broadly distributed in peripheral tissues, and function as scavenger cells that continuously sample antigens to subsequently vehicle them to the lymphoid organs, the exclusive site of naïve lymphocyte priming.6 The cardinal role of DCs in the development of the antitumor immune response resides in their unique abilities to engulf dying tumor cells, a principal source of TAAs, and cross-present TAAs to CD8+ T cells in the lymph nodes (LNs).7, 8 Indeed, the presence of DCs in human carcinomas has been largely documented9 and certain studies associated the quality and/or quantity of tumor-infiltrating DCs to a favorable prognosis for the patient.10, 11, 12, 13 It is traditionally believed that apoptotic bodies or necrotic debris are generated as a result of direct killing of tumor cells by NK cells and CTLs.1 However, there is growing evidence that conventional DCs or certain DC subsets are endowed with a direct tumoricidal property by delivering cell death signals to pre-malignant/malignant cells, and also by providing signals required for their own maturation into immunostimulatory APCs. The vision that DCs can detect tumor cells, directly kill them to sample antigens and alert the immune system, would challenge the textbook picture of the traditional NK/DC/T-cell cooperation in tumor immunosurveillance. Here, we review the cell death pathways mediated by NK cells and CTLs on tumor cells, the recent findings on killer properties of DCs, and their implications in tumor immunosurveillance and future development in cancer immunotherapies.
There are numerous mechanisms for cell death and each pathway differentially influences immunogenicity (for review see Zitvogel et al.14). Classically, cell death was subdivided into programmed cell death and necrosis or accidental cell death.15 Programmed cell death is a finely regulated physiologic process triggered by diverse forms of cellular stress and leading to nucleus fragmentation, whereas necrotic cell death results from a rapid loss of integrity of the plasma membrane with no energy consumption.15
Among GZM family members, GZM A and B are the most abundant in mice and humans.19 GZM A and K are tryptic proteases that cleave substrates after Arg or Lys residues. Their activity targets the endoplasmic reticulum-associated protein complex (SET complex), resulting in the release of GZM A-activated DNAse and its translocation to the nucleus and single-strand DNA nicks20 (Figure 1). GZM A and K also trigger a rapid release of reactive oxygen species (ROS) and mitochondrial transmembrane potential loss.19 GZM B, the most active GZM, is a caspase-like serine protease with a unique specificity for Asp residues to cleave its substrate.19 GZM B causes a double-stranded DNA fragmentation in both caspase-dependent and -independent pathways (Figure 1). In caspase-dependent cell death, caspase-3 and -8 are cleaved by GZM B, subsequently engaging the cellular apoptotic cascade. In the caspase-independent pathway, GZM B disrupts mitochondrial function through activation of the proapoptotic Bcl2-family member BH3-interacting domain death agonist (Bid), which recruits the proteins Bcl2-associated X protein (Bax) and Bcl2-antagonist/killer (Bak) to change mitochondrial membrane permeability. This causes the release of ROS and cytochrome c. In addition, it has been recently shown that GZM B directly cleaves the inhibitor of the caspase-activated deoxynuclease (ICAD), allowing caspase-independent DNA fragmentation.21 GZM C and M induce cell death when delivered by PFR in vitro.19 Different subsets of cytotoxic cells have been proposed to express different combinations and amounts of PFR and GMZ, which influence the mechanism of targeted cell death.22 GZMs, even though triggering specific pathways, are somewhat functionally redundant, and can complement the lack of other GZM activity according to the nature of the target and/or the invader. For instance, cytotoxic lymphocytes from GZM A or B-deficient mice maintain their ability to kill target cells, including tumor cells, by granule exocytosis, although this is less efficient when compared to those of wild-type mice.19
TRAIL/Apo2L and FasL are homotrimeric type II transmembrane proteins, which belong to the TNF superfamily.23, 24 Their extracellular portion can be cleaved for release as a soluble form. The mechanism by which FasL and TRAIL induce apoptosis are similar, involving recruitment of their receptor in the death-inducing signaling complex (DISC), and activation of caspases and downstream triggering of the same pro-apoptotic cascade of events (Figure 1; and for review see ref Nagata23 and Schaefer et al.24).
TRAIL and FasL pro-apoptotic effects rely on a distinct set of receptors. Contrary to FasL, which acts through the ligation of its only receptor Fas,23 TRAIL interacts with a complex system of receptors that belong to the TNF receptor family.25 In humans, five binding receptors (TRAIL-Rs) have been identified. Both the TRAIL-R1/death receptor (DR4) and TRAIL-R2/TRICK2 (DR5) contain a functional death domain (DD) and mediate apoptosis. TRAIL-R3/decoy receptor 1 (DcR)1/TRID/LIT and TRAIL-R4/DcR2/TRUNDD are generally referred to as DcRs that inhibit TRAIL-induced death when overexpressed. TRAIL-R4 possesses a truncated cytoplasmic tail lacking a DD, and TRAIL-R3 exists as a GPI-linked protein. TRAIL also binds with a low affinity to osteoprotegerin, an inhibitor of the osteoclasts function. In mice, only one death-inducing receptor, mDR5, has been identified along with two DcRs, mDcTRAIL-1 and mDCTRAIL-2L, distantly functionally similar to the human TRAIL-R3 and -R4, respectively. 041b061a72