Parametric Instabilities of Interacting Bosons in Periodically Driven 1D Optical Lattices

Periodically-driven quantum systems are currently explored in view of realizing novel many-body phases of matter. This approach is particularly promising in gases of ultracold atoms, where sophisticated shaking protocols can be realized and inter-particle interactions are well controlled. The combination of interactions and time-periodic driving, however, often leads to uncontrollable heating and instabilities, potentially preventing practical applications of Floquet-engineering in large many-body quantum systems. In this work, we experimentally identify the existence of parametric instabilities in weakly-interacting Bose-Einstein condensates in strongly-driven optical lattices through momentum-resolved measurements. Parametric instabilities can trigger the destruction of weakly-interacting Bose-Einstein condensates through the rapid growth of collective excitations, in particular in systems with weak harmonic confinement transverse to the lattice axis

Cytomegalovirus-Specific T Cells Persist at Very High Levels during Long-Term Antiretroviral Treatment of HIV Disease

Background: In healthy, HIV seronegative, CMV seropositive adults, a large proportion of T cells are CMV-specific. High-level CMV-specific T cell responses are associated with accelerated immunologic aging (‘‘immunosenesence’’) in the elderly population. The impact of untreated and treated HIV infection on the frequency of these cells remains undefined. Methodology/Principal Findings: We measured the proportion of CD4+ and CD8+ T cells responding to CMV pp65 and IE proteins was measured using flow cytometry in 685 unique HIV seronegative and seropositive individuals. The proportion of CMV-specific CD8+ T cells was consistently higher in the HIV-seropositive subjects compared to the HIV-seronegative subjects. This HIV effect was observed even in patients who lacked measurable immunodeficiency. Among the HIV-seropositive subjects, CMV-specific CD8+ T cell responses were proportionately lower during recent infection, higher during chronic untreated infection and higher still during long-term antiretroviral treated infection. The CD8+ T cell response to just two CMV proteins (pp65 and IE) was approximately 6% during long-term therapy, which was over twice that seen in HIV-seronegative persons. CMV-specific CD4+ T cell responses followed the same trends, but the magnitude of the effect was smaller. Conclusions/Significance: Long-term successfully treated HIV infected patients have remarkably high levels of CMV-specific effector cells. These levels are similar to that observed in the elderly, but occur at much younger ages. Future studies should focus on defining the potential role of the CMV-specific inflammatory response in non-AIDS morbidity and mortality, including immunosenescence

The “Connection” Between HIV Drug Resistance and RNase H

Currently, nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) are two classes of antiretroviral agents that are approved for treatment of HIV-1 infection. Since both NRTIs and NNRTIs target the polymerase (pol) domain of reverse transcriptase (RT), most genotypic analysis for drug resistance is limited to the first ∼300 amino acids of RT. However, recent studies have demonstrated that mutations in the C-terminal domain of RT, specifically the connection subdomain and RNase H domain, can also increase resistance to both NRTIs and NNRTIs. In this review we will present the potential mechanisms by which mutations in the C-terminal domain of RT influence NRTI and NNRTI susceptibility, summarize the prevalence of the mutations in these regions of RT identified to date, and discuss their importance to clinical drug resistance

Left Atrial Transverse Diameter on Computed Tomography Angiography Can Accurately Diagnose Left Atrial Enlargement in Patients With Atrial Fibrillation

PurposeLeft atrial (LA) enlargement is associated with increased risk for adverse cardiovascular events. We assessed the accuracy of LA transverse and antero-posterior (AP) diameters obtained from chest computed tomography (CT) angiography in patients with atrial fibrillation.Materials and methodsNongated contrast-enhanced 64-slice multidetector CT angiography (slice thickness of 0.625 to 1.25 mm) was used to measure the volume and transverse and AP diameters of the LA in 222 subjects. The internal contours of the LA and LA appendage were outlined in 1 of every 5 axial images, and the LA area was multiplied by 5 times the slice thickness. Maximum transverse and AP diameters of the LA were measured, excluding the appendage. Receiver operating characteristic curves were fitted to assess the accuracy of the diameters. A Wald test was used to compare the area under the curves.ResultsThe mean age of patients was 60.0±10.6 years, and 71% were male. Median LA volume was 55.9±24.4 mL/m. LA enlargement was present in 83% of the patients. Transverse and AP LA diameters were accurate estimators of the LA enlargement. The transverse diameter demonstrated higher accuracy than the AP diameter, with area under the curves of 0.89 (0.84 to 0.94) and 0.81 (0.73 to 0.89), respectively (P<0.05). A transverse LA diameter of 7.3 cm had a sensitivity and specificity of 85% for detection of LA enlargement. At the same sensitivity level, an AP diameter of 4.3 cm had a specificity of 60.5%.ConclusionsTransverse LA diameter can accurately detect LA enlargement in patients with atrial fibrillation. This parameter can be used for detection of patients with possible LA enlargement on chest CT angiography

Impact of HIV on CD8+ T Cell CD57 Expression Is Distinct from That of CMV and Aging

Background: Chronic antigenic stimulation by cytomegalovirus (CMV) is thought to increase ‘‘immunosenesence’’ of aging, characterized by accumulation of terminally differentiated CD28- CD8+ T cells and increased CD57, a marker of proliferative history. Whether chronic HIV infection causes similar effects is currently unclear. Methods: We compared markers of CD8+ T cell differentiation (e.g., CD28, CD27, CCR7, CD45RA) and CD57 expression on CD28- CD8+ T cells in healthy HIV-uninfected adults with and without CMV infection and in both untreated and antiretroviral therapy (ART)-suppressed HIV-infected adults with asymptomatic CMV infection. Results: Compared to HIV-uninfected adults without CMV (n = 12), those with asymptomatic CMV infection (n = 31) had a higher proportion of CD28-CD8+ T cells expressing CD57 (P = 0.005). Older age was also associated with greater proportions of CD28-CD8+ T cells expressing CD57 (rho: 0.47, P = 0.007). In contrast, untreated HIV-infected CMV+ participants (n = 55) had much lower proportions of CD28- CD8+ cells expressing CD57 than HIV-uninfected CMV+ participants (P,0.0001) and were enriched for less well-differentiated CD28- transitional memory (TTR) CD8+ T cells (P,0.0001). Chronically HIV-infected adults maintaining ART-mediated viral suppression (n = 96) had higher proportions of CD28-CD8+ T cells expressing CD57 than untreated patients (P,0.0001), but continued to have significantly lower levels than HIV-uninfected controls (P = 0.001). Among 45 HIV-infected individuals initiating their first ART regimen, the proportion of CD28-CD8+ T cells expressing CD57 declined (P,0.0001), which correlated with a decline in percent of transitional memory CD8+ T cells, and appeared to be largely explained by a decline in CD28-CD57- CD8+ T cell counts rather than an expansion of CD28-CD57+ CD8+ T cell counts. Conclusions: Unlike CMV and aging, which are associated with terminal differentiation and proliferation of effector memory CD8+ T cells, HIV inhibits this process, expanding less well-differentiated CD28- CD8+ T cells and decreasing the proportion of CD28- CD8+ T cells that express CD57

Parvovirus Minute Virus of Mice Induces a DNA Damage Response That Facilitates Viral Replication

Infection by DNA viruses can elicit DNA damage responses (DDRs) in host cells. In some cases the DDR presents a block to viral replication that must be overcome, and in other cases the infecting agent exploits the DDR to facilitate replication. We find that low multiplicity infection with the autonomous parvovirus minute virus of mice (MVM) results in the activation of a DDR, characterized by the phosphorylation of H2AX, Nbs1, RPA32, Chk2 and p53. These proteins are recruited to MVM replication centers, where they co-localize with the main viral replication protein, NS1. The response is seen in both human and murine cell lines following infection with either the MVMp or MVMi strains. Replication of the virus is required for DNA damage signaling. Damage response proteins, including the ATM kinase, accumulate in viral-induced replication centers. Using mutant cell lines and specific kinase inhibitors, we show that ATM is the main transducer of the signaling events in the normal murine host. ATM inhibitors restrict MVM replication and ameliorate virus-induced cell cycle arrest, suggesting that DNA damage signaling facilitates virus replication, perhaps in part by promoting cell cycle arrest. Thus it appears that MVM exploits the cellular DNA damage response machinery early in infection to enhance its replication in host cells

CD56negCD16+NK cells are activated mature NK cells with impaired effector function during HIV-1 infection

BACKGROUND: A subset of CD3(neg)CD56(neg)CD16(+) Natural Killer (NK) cells is highly expanded during chronic HIV-1 infection. The role of this subset in HIV-1 pathogenesis remains unclear. The lack of NK cell lineage-specific markers has complicated the study of minor NK cell subpopulations. RESULTS: Using CD7 as an additional NK cell marker, we found that CD3(neg)CD56(neg)CD16(+) cells are a heterogeneous population comprised of CD7(+) NK cells and CD7(neg) non-classical myeloid cells. CD7(+)CD56(neg)CD16(+) NK cells are significantly expanded in HIV-1 infection. CD7(+)CD56(neg)CD16(+) NK cells are mature and express KIRs, the C-type lectin-like receptors NKG2A and NKG2C, and natural cytotoxicity receptors similar to CD7(+)CD56(+)CD16(+) NK cells. CD7(+)CD56(neg) NK cells in healthy donors produced minimal IFNγ following K562 target cell or IL-12 plus IL-18 stimulation; however, they degranulated in response to K562 stimulation similar to CD7(+)CD56(+) NK cells. HIV-1 infection resulted in reduced IFNγ secretion following K562 or cytokine stimulation by both NK cell subsets compared to healthy donors. Decreased granzyme B and perforin expression and increased expression of CD107a in the absence of stimulation, particularly in HIV-1-infected subjects, suggest that CD7(+)CD56(neg)CD16(+) NK cells may have recently engaged target cells. Furthermore, CD7(+)CD56(neg)CD16(+) NK cells have significantly increased expression of CD95, a marker of NK cell activation. CONCLUSIONS: Taken together, CD7(+)CD56(neg)CD16(+) NK cells are activated, mature NK cells that may have recently engaged target cells

NS2 is required for efficient translation of viral mRNA in minute virus of mice-infected murine cells

Detailed analysis of five NS2 mutants of the autonomous parvovirus minute virus of mice (MVMp) has revealed the following. At low multiplicities of infection, NS2 mutants killed NB324K cells as well as wild-type (wt) MVM did and grew to high titers, while in contrast they grew poorly and did not readily kill murine A9 cells. Following CaPO4 transfection of murine fibroblasts, NS2 mutant infectious clones generated approximately 10-fold less monomer replicative-form DNA than wt and no detectable progeny single-stranded DNA. On nonmurine semipermissive NB324K cells, however, these mutant plasmid clones generated near wt levels of all replicative DNA forms. After infection of highly synchronized murine fibroblasts by NS2 mutant virus at inputs equivalent to those of the wt, mutant monomer replicative-form DNA was decreased 5- to 10-fold compared with that of the wt, and progeny single-stranded DNA accumulation was decreased to an even greater extent. Both total and cytoplasmic NS2 mutant RNA was decreased, but the amount of total viral mRNA generated, relative to accumulated viral DNA in the same experiments, was similar to that seen in wt infection. The accumulation of virus-generated proteins was also decreased in NS2 mutant infection; however, the magnitude of this decrease, compared with that of wt infections, was significantly greater than the concomitant decrease in mutant-generated levels of accumulated cytoplasmic RNA, and this effect was most dramatic for VP2. There was no such disparity between the relative accumulation of mutant-generated RNA and protein in cells permissive for the growth of these mutants. These results suggest that translation of MVM viral RNA is specifically reduced in NS2 mutant infection of restrictive cells. Because the affected viral proteins are required for the efficient production of viral replicative DNA forms, these results reveal a fundamental, although perhaps not the only, role for NS2 in parvovirus infection.</jats:p