See related research by Mirouse et al., https://ccforum.biomedcentral.com/articles/10.1186/s13054-017-1731-0 This comment refers to the article available at: https://doi.org/10.1186/s13054-017-1731-0.
The violation of Bell inequalities with two entangled and spatially separated quantum two-level systems (TLSs) is often considered as the most prominent demonstration that nature does not obey local ...realism. Under different but related assumptions of macrorealism--which macroscopic systems plausibly fulfil--Leggett and Garg derived a similar inequality for a single degree of freedom undergoing coherent oscillations and being measured at successive times. Here, we test such a "Bell's inequality in time", which should be violated by a quantum TLS. Our TLS is a superconducting quantum circuit in which Rabi oscillations are continuously driven while it is continuously and weakly measured. The time correlations present at the detector output agree with quantum-mechanical predictions and violate the Leggett-Garg inequality by five standard deviations. PUBLICATION ABSTRACT
Full text
Available for:
IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Pemphigus is classified as a group of chronic, recurrent, and potentially fatal bullous autoimmune diseases that leads to blisters and skin lesions resulting from IgG antibodies and the loss of ...cellular connections in the epidermis. Human endogenous retrovirus (HERV) sequences and their products (RNA, cytosolic DNA, and proteins) can modulate the immune system and contribute to autoimmunity. The extent to which, HERV-W env copies may be involved in the pathogenesis of pemphigus remains to be elucidated.
This study aimed to comparatively evaluate the relative levels of HERV-W env DNA copy numbers in the peripheral blood mononuclear cells (PBMCs) of pemphigus vulgaris patients and healthy controls.
Thirty-one pemphigus patients and the corresponding age- and sex-matched healthy controls were included in the study. The relative levels of HERV-W env DNA copy numbers were then evaluated by qPCR using specific primers, in the PBMCs of the patients and controls.
Our results indicated that relative levels of HERV-W env DNA copy numbers in the patients were significantly higher than that in the controls (1.67±0.86 vs. 1.17±0.75; p = 0.02). There was also a significant difference between the HERV-W
copies of male and female patients (p = 0.001). Furthermore, there was no relationship between the HERV-W env copy number and disease onset (p = 0.19) . According to the obtained data, we could not find any relationship between the HERV-W
copy number and serum Dsg1(p=0.86) and Dsg3 (p=0.76) levels.
Our results indicated a positive link between the HERV-W env copies and pathogenesis of pemphigus. The association between clinical severity score and HERVW env copies in the PBMCs as a biomarker for pemphigus needs further studies.
Highlights • Important age and sex differences in LPS-induced hypothermia. • Gonadectomy significantly increases hypothermia in males but no in females. • Pubertal mice display more anti-inflammatory ...cytokines than adults after LPS.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
•Peripheral & central immune responses were examined following LPS treatment.•LPS treatment increased plasma cytokine levels and sickness symptoms in all mice.•Peripheral cytokines persisted at 8 & ...24 h after LPS in adult females.•Males expressed greater cytokine mRNA expression in the prefrontal cortex.•There are important region- and time-specific differences after LPS treatment.
Puberty is a critical developmental period that is characterized by significant brain development. Exposure to stress during this time can alter brain functioning setting the stage for long-lasting behavioural outcomes. The objective of this study was to investigate age and sex differences in the peripheral and central immune responses, along with sickness behaviour, following immune stress. The results showed that LPS treatment increased serum cytokine levels and sickness symptoms in all mice. Pubertal males displayed increased IL-1β concentrations at 2 h and increased IL-6 concentrations at 8 h post-treatment whereas increased concentrations of TNFα, IL-10, IL-12, IL-1β, IFNγ, and IL-6 persisted at 8 and 24 h in adult females. Consistent with peripheral cytokines, pubertal males displayed greater IL-1β, TNFα, and IL-6 mRNA expression in the prefrontal cortex at 2 h, whereas adult males expressed more of the aforementioned cytokines at 8 h compared to saline controls. Adult males also displayed greater IL-1β mRNA expression compared to their female counterparts, and adult females displayed greater TNFα mRNA expression compared to their male counterparts. These results not only provide a better understanding of the age and sex differences in acute immune response, but also show important region- and time-specific differences in the response to an immune challenge, and that the peripheral immune response differs from the central response. This highlights the need to examine immune markers in both the periphery and the central nervous system for an accurate depiction of acute immune response following an immune challenge.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
•Pubertal LPS alters gut microbiota and induces anxiety and depression.•LPS treatment during puberty appears to alter TLR4 functioning.•Pubertal probiotic exposure mitigates LPS-induces ...sickness.•Probiotics during puberty promote resilience to stress-induced anxiety and depression.
Puberty/adolescence is a significant period of development and a time with a high emergence of psychiatric disorders. During this period, there is increased neuroplasticity and heightened vulnerability to stress and inflammation. The gut microbiome regulates stress and inflammatory responses and can alter brain chemistry and behaviour. However, the role of the gut microbiota during pubertal development remains largely uninvestigated. The current study examined gut manipulation with probiotics during puberty in CD1 mice on lipopolysaccharide (LPS)-induced immune responses and enduring effects on anxiety- and depression-like behaviours and stress-reactivity in adulthood. Probiotics reduced LPS-induced sickness behaviour at 12 h in females and at 48 h following LPS treatment in males. Probiotics also reduced LPS-induced changes in body weight at 48 h post-treatment in females. Probiotic treatment also prevented LPS-induced increases in pro- and anti-inflammatory peripheral cytokines at 8 h following LPS treatment, reduced central cytokine mRNA expression in the hypothalamus, hippocampus and PFC, and prevented LPS-induced changes to in the gut microbiota. A single exposure to LPS during puberty resulted in enduring depression-like behaviour in female mice, and anxiety-like behaviour in male mice in adulthood. However, pubertal exposure to probiotics prevented enduring LPS-induced depression-like behaviour in females and anxiety-like behaviors in males. Moreover, probiotics altered toll-like receptor-4 activity in the paraventricular nucleus of the hypothalamus (PVN) in males in response to a novel stressor in adulthood. Our results suggest that the gut microbiome plays an important role in pubertal neurodevelopment. These findings indicate that exposure to probiotics during puberty mitigates inflammation and decreases stress-induced vulnerabilities to emotional behaviours later in life, in a sex-specific manner.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The future development of quantum information using superconducting circuits requires Josephson qubits with long coherence times combined with a high-fidelity readout. Significant progress in the ...control of coherence has recently been achieved using circuit quantum electrodynamics architectures, where the qubit is embedded in a coplanar waveguide resonator, which both provides a well-controlled electromagnetic environment and serves as qubit readout. In particular, a new qubit design, the so-called transmon, yields reproducibly long coherence times. However, a high-fidelity single-shot readout of the transmon, desirable for running simple quantum algorithms or measuring quantum correlations in multi-qubit experiments, is still lacking. Here, we demonstrate a new transmon circuit where the waveguide resonator is turned into a sample-and-hold detector-more specifically, a Josephson bifurcation amplifier-which allows both fast measurement and single-shot discrimination of the qubit states. We report Rabi oscillations with a high visibility of 94%, together with dephasing and relaxation times longer than 0.5 μs. By carrying out two measurements in series, we also demonstrate that this new readout does not induce extra qubit relaxation.
Full text
Available for:
IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The immune response is a dynamic system that maintains the integrity of the body, and more specifically fight against infections. However, an unbalanced host immune response is highlighted in many ...diseases. Exacerbated responses lead to autoimmune and allergic diseases, whereas, low or inefficient responses favor opportunistic infections and viral reactivations. Conflicting situations may also occur, such as in sepsis where inflammation and compensatory immunosuppression make it difficult to deploy the appropriate drug treatment. Until the current day, assessing the immune profile of patients remains a challenge. This is especially due to the inter-individual variability-a key feature of the immune system-which hinders precise diagnosis, prognosis, and therapeutic stratification. Our incapacity to practically interpret the host response may contribute to a high morbidity and mortality, such as the annual 6 million worldwide deaths in sepsis alone. Therefore, there is a high and increasing demand to assess patient immune function in routine clinical practice, currently met by Immune Functional Assays. Immune Functional Assays (IFA) hold a plethora of potentials that include the precise diagnosis of infections, as well as prediction of secondary and latent infections. Current available products are devoted to indirect pathogen detection such as Mycobacteria tuberculosis interferon gamma release assays (IGRA). In addition, identifying the status and the underlying factors of immune dysfunction (e.g., in septic patients) may guide immune targeted therapies. Tools to monitor and stratify the immune status are currently being studied but they still have many limitations such as technical standardization, biomarkers relevance, systematic interpretation and need to be simplified, in order to set the boundaries of "healthy," "ill," and "critically ill" responses. Thus, the design of new tools that give a comprehensive insight into the immune functionality, at the bedside, and in a timely manner represents a leap toward immunoprofiling of patients.
Human endogenous retroviruses (HERVs) and mammalian apparent long terminal repeat (LTR) retrotransposons (MaLRs) are retroviral sequences that integrated into germ line cells millions of years ago. ...Transcripts of these LTR retrotransposons are present in several tissues, and their expression is modulated in pathological conditions, although their function remains often far from being understood. Here, we focused on the HERV/MaLR expression and modulation in a scenario of immune system activation. We used a public data set of human peripheral blood mononuclear cells (PBMCs) RNA-Seq from 15 healthy participants to a clinical trial before and after exposure to lipopolysaccharide (LPS), for which we established an RNA-Seq workflow for the identification of expressed and modulated cellular genes and LTR retrotransposon elements.
We described the HERV and MaLR transcriptome in PBMCs, finding that about 8.4% of the LTR retrotransposon loci were expressed and identifying the betaretrovirus-like HERVs as those with the highest percentage of expressed loci. We found 4,607 HERV and MaLR loci that were modulated as a result of
stimulation with LPS. The HERV-H group showed the highest number of differentially expressed most intact proviruses. We characterized the HERV and MaLR loci as differentially expressed, checking their genomic context of insertion and observing a general colocalization with genes that are involved and modulated in the immune response, as a consequence of LPS stimulation. The analyses of HERV and MaLR expression and modulation show that these LTR retrotransposons are expressed in PBMCs and regulated in inflammatory settings. The similar regulation of HERVs/MaLRs and genes after LPS stimulation suggests possible interactions of LTR retrotransposons and the immune host response.
The complexity of sepsis pathophysiology hinders patient management and therapeutic decisions. In this proof-of-concept study we characterised the underlying host immune response alterations using a ...standardised immune functional assay (IFA) in order to stratify a sepsis population. In septic shock patients, ex vivo LPS and SEB stimulations modulated, respectively, 5.3% (1/19) and 57.1% (12/21) of the pathways modulated in healthy volunteers (HV), highlighting deeper alterations induced by LPS than by SEB. SEB-based clustering, identified 3 severity-based groups of septic patients significantly different regarding mHLA-DR expression and TNFα level post-LPS, as well as 28-day mortality, and nosocomial infections. Combining the results from two independent cohorts gathering 20 HV and 60 patients, 1 cluster grouped all HV with 12% of patients. The second cluster grouped 42% of patients and contained all non-survivors. The third cluster grouped 46% of patients, including 78% of those with nosocomial infections. The molecular features of these clusters indicated a distinctive contribution of previously described genes defining a "healthy-immune response" and a "sepsis-related host response". The third cluster was characterised by potential immune recovery that underlines the possible added value of SEB-based IFA to capture the sepsis immune response and contribute to personalised management.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
PDF
