Patients Infected with CRF07_BC Have Significantly Lower Viral Loads than Patients with HIV-1 Subtype B: Mechanism and Impact on Disease Progression

The circulating recombinant form (CRF) 07_BC is the most prevalent HIV-1 strain among injection drug users (IDUs) in Taiwan. It contains a 7 amino-acid deletion in its p6gag. We conducted a cohort study to compare viral loads and CD4 cell count changes between patients infected with subtype B and CRF07_BC and to elucidate its mechanism. Twenty-one patients infected with CRF07_BC and 59 patients with subtype B were selected from a cohort of 667 HIV-1/AIDS patients whom have been followed up for 3 years. Generalized estimated equation was used to analyze their clinical data and the results showed that patients infected with CRF07_BC had significantly lower viral loads (about 58,000 copies per ml less) than patients with subtype B infection (p = 0.002). The replicative capacity of nine CRF07_BC and four subtype B isolates were compared and the results showed that the former had significantly lower replicative capacity than the latter although all of them were CCR5- tropic and non-syncytium inducing viruses. An HIV-1-NL4-3 mutant virus which contains a 7 amino-acid deletion in p6gag (designated as 7d virus) was generated and its live cycle was investigated. The results showed that 7d virus had significantly lower replication capacity, poorer protease-mediated processing and viral proteins production. Electron microscopic examination of cells infected with wild-type or 7d virus demonstrated that the 7d virus had poorer and slower viral maturation processes: more viruses attached to the cell membrane and higher proportion of immature virions outside the cells. The interaction between p6gag and Alix protein was less efficient in cells infected with 7d virus. In conclusion, patients infected with CRF07_BC had significantly lower viral loads than patients infected with subtype B and it may due to the deletion of 7 amino acids which overlaps with Alix protein-binding domain of the p6gag

Conformal anomaly c-coefficients of superconformal 6d theories

We propose general relations between the conformal anomaly and the chiral (R-symmetry and gravitational) anomaly coefficients in 6d (1,0) superconformal theories. The suggested expressions for the three type B conformal anomaly c-coefficients complement the expression for the type A anomaly a-coefficient found in arXiv:1506.03807. We check them on several examples -- the standard (1,0) hyper and tensor multiplets as well as some higher derivative short multiplets containing vector fields that generalize the superconformal 6d vector multiplet discussed in arXiv:1506.08727. We also consider a family of higher derivative superconformal (2,0) 6d multiplets associated to 7d multiplets in the KK spectrum of 11d supergravity compactified on S^4. In particular, we prove that (2,0) 6d conformal supergravity coupled to 26 tensor multiplets is free of all chiral and conformal anomalies. We discuss some interacting (1,0) superconformal theories, predicting the c-coefficients for the "E-string" theory on multiple M5-branes at E_8 9-brane and for the theory describing M5-branes at an orbifold singularity. Finally, we elaborate on holographic computation of subleading corrections to conformal anomaly coefficients coming from R^2+R^3 terms in 7d effective action, revisiting, in particular, the (2,0) theory case.Comment: 32 pages, v4: Added footnotes 8, 25, 26 clarifying that the available data leads to a 1-parameter family of the conformal anomaly coefficients c_1, c_2 as functions of chiral anomaly coefficients; the results for c_i in recent arXiv:1702.03518 also belong to this famil

Homeologous proteins synthesis controlled by homeologous chromosomes in wheat

Two homeologous proteins have been isolated from the endosperm of common wheat (genomes ABD). Synthesis of these two proteins is controlled by the homeologous chromosomes 7B and 7D respectively. However, Aegilops speltoides, the more generally accepted B genome donor, does not synthesize the 7B protein

Conformal anomaly c-coefficients of superconformal 6d theories

We propose general relations between the conformal anomaly and the chiral (R-symmetry and gravitational) anomaly coefficients in 6d (1, 0) superconformal theories. The suggested expressions for the three type B conformal anomaly ci-coefficients complement the expression for the type A anomaly a-coefficient found in arXiv:1506.03807. We check them on several examples — the standard (1, 0) hyper and tensor multiplets as well as some higher derivative short multiplets containing vector fields that generalize the super-conformal 6d vector multiplet discussed in arXiv:1506.08727. We also consider a family of higher derivative superconformal (2, 0) 6d multiplets associated to 7d multiplets in the KK spectrum of 11d supergravity compactified on S4. In particular, we prove that (2,0) 6d conformal supergravity coupled to 26 tensor multiplets is free of all chiral and conformal anomalies. We discuss some interacting (1, 0) superconformal theories, predicting the ci-coefficients for the “E-string” theory on multiple M5-branes at E8 9-brane and for the theory describing M5-branes at an orbifold singularity C2/ΓC2/Γ . Finally, we elaborate on holographic computation of subleading corrections to conformal anomaly coefficients coming from R2 + R3 terms in 7d effective action, revisiting, in particular, the (2,0) theory case

On Heterotic Orbifolds, M Theory and Type I' Brane Engineering

Horava--Witten M theory -- heterotic string duality poses special problems for the twisted sectors of heterotic orbifolds. In [1] we explained how in M theory the twisted states couple to gauge fields apparently living on M9 branes at both ends of the eleventh dimension at the same time. The resolution involves 7D gauge fields which live on fixed planes of the (T^4/Z_N) x (S^1/Z_2) x R^{5,1} orbifold and lock onto the 10D gauge fields along the intersection planes. The physics of such intersection planes does not follow directly from the M theory but there are stringent kinematic constraints due to duality and local consistency, which allowed us to deduce the local fields and the boundary conditions at each intersection. In this paper we explain various phenomena at the intersection planes in terms of duality between HW and type I' superstring theories. The orbifold fixed planes are dual to stacks of D6 branes, the M9 planes are dual to O8 orientifold planes accompanied by D8 branes, and the intersections are dual to brane junctions. We engineer several junction types which lead to distinct patterns of 7D/10D gauge field locking, 7D symmetry breaking and/or local 6D fields. Another aspect of brane engineering is putting the junctions together; sometimes, the combined effect is rather spectacular from the HW point of view and the quantum numbers of some twisted states have to `bounce' off both ends of the eleventh dimension before their heterotic identity becomes clear. Some models involve D6/O8 junctions where the string coupling diverges towards the orientifold plane. We use the heterotic-HW-I' duality to predict what should happen at such junctions.Comment: 118 pages, uses phyzzx, color printer advice

Skin TLR7 triggering promotes accumulation of respiratory dendritic cells and natural killer cells.

The TLR7 agonist imiquimod has been used successfully as adjuvant for skin treatment of virus-associated warts and basal cell carcinoma. The effects of skin TLR7 triggering on respiratory leukocyte populations are unknown. In a placebo-controlled experimental animal study we have used multicolour flow cytometry to systematically analyze the modulation of respiratory leukocyte subsets after skin administration of imiquimod. Compared to placebo, skin administration of imiquimod significantly increased respiratory dendritic cells (DC) and natural killer cells, whereas total respiratory leukocyte, alveolar macrophages, classical CD4+ T helper and CD8+ T killer cell numbers were not or only moderately affected. DC subpopulation analyses revealed that elevation of respiratory DC was caused by an increase of respiratory monocytic DC and CD11b(hi) DC subsets. Lymphocyte subpopulation analyses indicated a marked elevation of respiratory natural killer cells and a significant reduction of B lymphocytes. Analysis of cytokine responses of respiratory leukocytes after stimulation with Klebsiella pneumonia indicated reduced IFN-γ and TNF-α expression and increased IL-10 and IL-12p70 production after 7 day low dose skin TLR7 triggering. Additionally, respiratory NK cytotoxic activity was increased after 7d skin TLR7 triggering. In contrast, lung histology and bronchoalveolar cell counts were not affected suggesting that skin TLR7 stimulation modulated respiratory leukocyte composition without inducing overt pulmonary inflammation. These data suggest the possibility to modulate respiratory leukocyte composition and respiratory cytokine responses against pathogens like Klebsiella pneumonia through skin administration of a clinically approved TLR7 ligand. Skin administration of synthetic TLR7 ligands may represent a novel, noninvasive means to modulate respiratory immunity

A shared neural ensemble links distinct contextual memories encoded close in time.

Recent studies suggest that a shared neural ensemble may link distinct memories encoded close in time. According to the memory allocation hypothesis, learning triggers a temporary increase in neuronal excitability that biases the representation of a subsequent memory to the neuronal ensemble encoding the first memory, such that recall of one memory increases the likelihood of recalling the other memory. Here we show in mice that the overlap between the hippocampal CA1 ensembles activated by two distinct contexts acquired within a day is higher than when they are separated by a week. Several findings indicate that this overlap of neuronal ensembles links two contextual memories. First, fear paired with one context is transferred to a neutral context when the two contexts are acquired within a day but not across a week. Second, the first memory strengthens the second memory within a day but not across a week. Older mice, known to have lower CA1 excitability, do not show the overlap between ensembles, the transfer of fear between contexts, or the strengthening of the second memory. Finally, in aged mice, increasing cellular excitability and activating a common ensemble of CA1 neurons during two distinct context exposures rescued the deficit in linking memories. Taken together, these findings demonstrate that contextual memories encoded close in time are linked by directing storage into overlapping ensembles. Alteration of these processes by ageing could affect the temporal structure of memories, thus impairing efficient recall of related information