Platelets express adaptor proteins of the extrinsic apoptosis pathway and can activate caspase-8

Background Apoptotic pathways in platelets are important for their survival and function. Platelet apoptosis may be involved in the pathogenesis of immune thrombocytopenia (ITP), an autoimmune-mediated disease. In contrast to the intrinsic apoptosis pathway, not much is known about the extrinsic pathway mechanisms in platelets. Objectives To investigate the expression of proteins involved in the extrinsic apoptosis pathway, including the death receptors, adaptor and regulator proteins in human platelets. To determine a possible trigger of the extrinsic apoptosis pathway in platelets. Methods To investigate the expression of key markers of the extrinsic pathway we used targeted immunofluorescence and flow cytometry assays. To study their expression and interaction we performed Western blotting and co-immunoprecipitation. Treated platelets with different apoptosis triggers were subjected to flow cytometry. Results We could identify the protein expression of the pro-apoptotic proteins TRADD (Tumor Necrosis Factor Receptor type 1- Associated DEATH Domain protein), TRAF2/5, (TNF Associated Factor) and DEDAF (Death Effector Domain- Associated Factor), FADD (Fas-Associated protein with death domain) as well as the anti-apoptotic proteins DJ-1 (Deglycase 1) and c-FLIP in human platelets. ABT-737 treatment induced a disruption in the co-localization of DJ-1 with FADD. Platelets treated with ABT-737 showed an activation in caspase-3 and -8. The exposure to TNF (Tumor Necrosis Factor), FasL (Fas ligand), and TWEAK or to plasma derived from ITP patients, did not lead to changes in caspase-3 and -8 activation in platelets. Conclusions Human platelets express some proteins of the extrinsic apoptosis pathway which can be modulated only by ABT-737 treatment. However so far, no other apoptosis trigger or interaction with an external receptor have been yet identified

MxB is an interferon-induced restriction factor of human herpesviruses

The type I interferon (IFN) system plays an important role in controlling herpesvirus infections, but it is unclear which IFN-mediated effectors interfere with herpesvirus replication. Here we report that human myxovirus resistance protein B (MxB, also designated Mx2) is a potent human herpesvirus restriction factor in the context of IFN. We demonstrate that ectopic MxB expression restricts a range of herpesviruses from the Alphaherpesvirinae and Gammaherpesvirinae, including herpes simplex virus 1 and 2 (HSV-1 and HSV-2), and Kaposi's sarcoma-associated herpesvirus (KSHV). MxB restriction of HSV-1 and HSV-2 requires GTPase function, in contrast to restriction of lentiviruses. MxB inhibits the delivery of incoming HSV-1 DNA to the nucleus and the appearance of empty capsids, but not the capsid delivery to the cytoplasm or tegument dissociation from the capsid. Our study identifies MxB as a potent pan-herpesvirus restriction factor which blocks the uncoating of viral DNA from the incoming viral capsid

Cell cycle-dependent expression of AAV2 Rep in HSV-1 co-infections gives rise to a mosaic of cells replicating either AAV2 or HSV-1

Adeno-associated virus 2 (AAV2) depends on the simultaneous presence of a helper virus such as herpes simplex virus 1 (HSV-1) for productive replication. At the same time, AAV2 efficiently blocks the replication of HSV-1, which would eventually limit its own replication by diminishing the helper virus reservoir. This discrepancy begs the question of how AAV2 and HSV-1 can coexist in a cell population. Here we show that in coinfected cultures, AAV2 DNA replication takes place almost exclusively in S/G(2)-phase cells, while HSV-1 DNA replication is restricted to G(1) phase. Live microscopy revealed that not only wild-type AAV2 (wtAAV2) replication but also reporter gene expression from both single-stranded and double-stranded (self-complementary) recombinant AAV2 vectors preferentially occurs in S/G(2)-phase cells, suggesting that the preference for S/G(2) phase is independent of the nature of the viral genome. Interestingly, however, a substantial proportion of S/G(2)-phase cells transduced by the double-stranded but not the single-stranded recombinant AAV2 vectors progressed through mitosis in the absence of the helper virus. We conclude that cell cycle-dependent AAV2 rep expression facilitates cell cycle-dependent AAV2 DNA replication and inhibits HSV-1 DNA replication. This may limit competition for cellular and viral helper factors and, hence, creates a biological niche for either virus to replicate. IMPORTANCE Adeno-associated virus 2 (AAV2) differs from most other viruses, as it requires not only a host cell for replication but also a helper virus such as an adenovirus or a herpesvirus. This situation inevitably leads to competition for cellular resources. AAV2 has been shown to efficiently inhibit the replication of helper viruses. Here we present a new facet of the interaction between AAV2 and one of its helper viruses, herpes simplex virus 1 (HSV-1). We observed that AAV2 rep gene expression is cell cycle dependent and gives rise to distinct time-controlled windows for HSV-1 replication. High Rep protein levels in S/G(2) phase support AAV2 replication and inhibit HSV-1 replication. Conversely, low Rep protein levels in G(1) phase permit HSV-1 replication but are insufficient for AAV2 replication. This allows both viruses to productively replicate in distinct sets of dividing cells

Atrial function after the atrial switch operation for transposition of the great arteries: comparison with arterial switch and normals by cardiovascular magnetic resonance

OBJECTIVES: The atria serve as reservoir, conduit, and active pump for ventricular filling. The performance of the atrial baffles after atrial switch repair for transposition of the great arteries may be abnormal and impact the function of the systemic right ventricle. We sought to assess atrial function in patients after atrial repair in comparison to patients after arterial switch repair (ASO) and to controls. METHODS: Using magnetic resonance imaging, atrial volumes and functional parameters were measured in 17 patients after atrial switch repair, 9 patients after ASO and 10 healthy subjects. RESULTS: After the atrial switch operation, the maximum volume of the pulmonary venous atrium was significantly enlarged, but not of the systemic venous atrium. In both patients groups, independently from the surgical technique used, the minimum atrial volumes were elevated, which resulted in a decreased total empting fraction compared with controls (P < .01). The passive empting volume was diminished for right atrium, but elevated for left atrium after atrial switch and normal for left atrium after ASO; however, the passive empting fraction was diminished for both right atrium and left atrium after both operations (P < .01). The active empting volume was the most affected parameter in both atria and both groups and active empting fractions were highly significantly reduced compared with controls. CONCLUSION: Atrial function is abnormal in all patients, after atrial switch and ASO repair. The cyclic volume changes, that is, atrial filling and empting, are reduced when compared with normal subjects. Thus, the atria have lost part of their capacity to convert continuous venous flow into a pulsatile ventricular filling. The function of the pulmonary venous atrium, acting as preload for the systemic right ventricle, after atrial switch is altered the most

Laboratory diagnosis of ruminant abortion in Europe

Abortion in ruminants is a major cause of economic loss worldwide, and the management and control of outbreaks is important in limiting their spread, and in preventing zoonotic infections. Given that rapid and accurate laboratory diagnosis is central to controlling abortion outbreaks, the submission of tissue samples to laboratories offering the most appropriate tests is essential. Direct antigen and/or DNA detection methods are the currently preferred methods of reaching an aetiological diagnosis, and ideally these results are confirmed by the demonstration of corresponding macroscopic and/or histopathological lesions in the fetus and/or the placenta. However, the costs of laboratory examinations may be considerable and, even under optimal conditions, the percentage of aetiological diagnoses reached can be relatively low. This review focuses on the most commonly occurring and important abortifacient pathogens of ruminant species in Europe highlighting their epizootic and zoonotic potential. The performance characteristics of the various diagnostic methods used, including their specific advantages and limitations, are discussed

Nuclear modification factor of neutral pions in the forward and backward regions in ppPb collisions

The nuclear modification factor of neutral pions is measured in proton-lead collisions collected at a center-of-mass energy per nucleon of $8.16$ TeV with the LHCb detector. The $\pi^0$ production cross section is measured differentially in transverse momentum ($p_{T}$) for 1.5π0 production cross section is measured differentially in transverse momentum (pT) for 1.5<pT<10.0  GeV and in center-of-mass pseudorapidity (ηc.m.) regions 2.5<ηc.m.<3.5 (forward) and -4.0<ηc.m.<-3.0 (backward) defined relative to the proton beam direction. The forward measurement shows a sizable suppression of π0 production, while the backward measurement shows the first evidence of π0 enhancement in proton-lead collisions at the LHC. Together, these measurements provide precise constraints on models of nuclear structure and particle production in high-energy nuclear collisions.The nuclear modification factor of neutral pions is measured in proton-lead collisions collected at a center-of-mass energy per nucleon of 8.16~{\rm TeV}$with the LHCb detector. The$\pi^0$production cross section is measured differentially in transverse momentum ($p_{\rm T}$) for$1.5<p_{\rm T}<10.0~{\rm GeV}$and in center-of-mass pseudorapidity ($\eta_{\rm c.m.}$) regions$2.5<\eta_{\rm c.m.}<3.5$(forward) and$-4.0<\eta_{\rm c.m.}<-3.0$(backward) defined relative to the proton beam direction. The forward measurement shows a sizable suppression of$\pi^0$production, while the backward measurement shows the first evidence of$\pi^0$ enhancement in proton-lead collisions at the LHC. Together, these measurements provide precise constraints on models of nuclear structure and particle production in high-energy nuclear collisions

Search for the rare hadronic decay Bs0→ppˉB_s^0\to p \bar{p}

A search for the rare hadronic decay Bs0→pp¯ is performed using proton-proton collision data recorded by the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 6  fb-1. No evidence of the decay is found and an upper limit on its branching fraction is set at B(Bs0→pp¯)&lt;4.4(5.1)×10-9 at 90% (95%) confidence level; this is currently the world’s best upper limit. The decay mode B0→pp¯ is measured with very large significance, confirming the first observation by the LHCb experiment in 2017. The branching fraction is determined to be B(B0→pp¯)=(1.27±0.15±0.05±0.04)×10-8, where the first uncertainty is statistical, the second is systematic and the third is due to the external branching fraction of the normalization channel B0→K+π-. The combination of the two LHCb measurements of the B0→pp¯ branching fraction yields B(B0→pp¯)=(1.27±0.13±0.05±0.03)×10-8.A search for the rare hadronic decay $B_s^0\to p \bar{p}$ is performed using proton-proton collision data recorded by the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 6 fb$^{-1}$. No evidence of the decay is found and an upper limit on its branching fraction is set at ${\cal B}(B_s^0\to p \bar{p}) < 4.4~(5.1) \times 10^{-9}$ at 90% (95%) confidence level; this is currently the world's best upper limit. The decay mode $B^0\to p \bar{p}$ is measured with very large significance, confirming the first observation by the LHCb experiment in 2017. The branching fraction is determined to be ${\cal B}(B^0\to p \bar{p}) = \rm (1.27 \pm 0.15 \pm 0.05 \pm 0.04) \times 10^{-8}$, where the first uncertainty is statistical, the second is systematic and the third is due to the external branching fraction of the normalization channel $B^0\to K^+\pi^-$. The combination of the two LHCb measurements of the $B^0\to p \bar{p}$ branching fraction yields ${\cal B}(B^0\to p \bar{p}) = \rm (1.27 \pm 0.13 \pm 0.05 \pm 0.03) \times 10^{-8}$