The HIV-1 Gp120/CXCR4 Axis Promotes CCR7 Ligand-Dependent CD4 T Cell Migration: CCR7 Homo- and CCR7/CXCR4 Hetero-Oligomer Formation as a Possible Mechanism for Up-Regulation of Functional CCR7

During human immunodeficiency virus (HIV) infection, enhanced migration of infected cells to lymph nodes leads to efficient propagation of HIV-1. The selective chemokine receptors, including CXCR4 and CCR7, may play a role in this process, yet the viral factors regulating chemokine-dependent T cell migration remain relatively unclear. The functional cooperation between the CXCR4 ligand chemokine CXCL12 and the CCR7 ligand chemokines CCL19 and CCL21 enhances CCR7-dependent T cell motility in vitro as well as cell trafficking into the lymph nodes in vivo. In this study, we report that a recombinant form of a viral CXCR4 ligand, X4-tropic HIV-1 gp120, enhanced the CD4 T cell response to CCR7 ligands in a manner dependent on CXCR4 and CD4, and that this effect was recapitulated by HIV-1 virions. HIV-1 gp120 significantly enhanced CCR7-dependent CD4 T cell migration from the footpad of mice to the draining lymph nodes in in vivo transfer experiments. We also demonstrated that CXCR4 expression is required for stable CCR7 expression on the CD4 T cell surface, whereas CXCR4 signaling facilitated CCR7 ligand binding to the cell surface and increased the level of CCR7 homo- as well as CXCR4/CCR7 hetero-oligomers without affecting CCR7 expression levels. Our findings indicate that HIV-evoked CXCR4 signaling promotes CCR7-dependent CD4 T cell migration by up-regulating CCR7 function, which is likely to be induced by increased formation of CCR7 homo- and CXCR4/CCR7 hetero-oligomers on the surface of CD4 T cells.     

Effectiveness of Trivalent Inactivated Influenza Vaccine in Children Estimated by a Test-Negative Case-Control Design Study Based on Influenza Rapid Diagnostic Test Results

We assessed vaccine effectiveness (VE) against medically attended, laboratory-confirmed influenza in children 6 months to 15 years of age in 22 hospitals in Japan during the 2013–14 season. Our study was conducted according to a test-negative case-control design based on influenza rapid diagnostic test (IRDT) results. Outpatients who came to our clinics with a fever of 38°C or over and had undergone an IRDT were enrolled in this study. Patients with positive IRDT results were recorded as cases, and patients with negative results were recorded as controls. Between November 2013 and March 2014, a total of 4727 pediatric patients (6 months to 15 years of age) were enrolled: 876 were positive for influenza A, 66 for A(H1N1)pdm09 and in the other 810 the subtype was unknown; 1405 were positive for influenza B; and 2445 were negative for influenza. Overall VE was 46% (95% confidence interval [CI], 39–52). Adjusted VE against influenza A, influenza A(H1N1)pdm09, and influenza B was 63% (95% CI, 56–69), 77% (95% CI, 59–87), and 26% (95% CI, 14–36), respectively. Influenza vaccine was not effective against either influenza A or influenza B in infants 6 to 11 months of age. Two doses of influenza vaccine provided better protection against influenza A infection than a single dose did. VE against hospitalization influenza A infection was 76%. Influenza vaccine was effective against influenza A, especially against influenza A(H1N1)pdm09, but was much less effective against influenza B.     

Foraminifera and their associations of a possibly Rhaetian section of the Nayband Formation in central Iran,northeast of Esfahan

The following paper describes the foraminiferal fauna and associated faunal assemblages of the bedded and reef carbonates of the Upper Triassic (most probably Rhaetian) Nayband Formation, which are exposed in a section south of the small town of Bagher-Abad, northeast of Esfahan. Foraminifers are extremely rare in sponge- or coral-dominated bioconstructions and in the bedded carbonates of the Nayband Formation in central Iran. Some carbonate beds are composed of bioclastic wackstone/packstone. These are exposed in the solenoporacean horizon at the uppermost part of the section. Here, the aulotortid- and trocholinid-type foraminifers are relatively abundant. The following foraminiferal taxa with different abundances were found within the carbonates of the investigated section: Trocholina umbo Frentzen, T. turris Frentzen, T. gracilis Blau, Aulotortus tumidus (Kristan-Tollmann), Aulotortus tenuis (Kristan), Aulotortus friedli (Kristan-Tollmann), Coronipora etrusca (Pirini), Semiinvoluta clari Kristan, Turrispirillina? licia variabilis Blau, Galeanella? laticarinata Al-Shaibani, Carter and Zaninetti, Ophthalmidium sp., Agathammina sp., “Sigmoilina” schaeferae Zaninetti, Planiinvoluta carinata Leischner, Planiinvoluta sp., Nubecularia sp., Endothyra sp., Paeolituonella sp. and some sessile agglutinated and nodosariid types. All mentioned taxa are very rare, except the involutinid and trocholinid types. The following species are described as new: Trocholina blaui nov. sp., Spirilina? iranica nov. sp., and Coronipora serraforma nov. sp. Trocholina blaui is usually attached to solenoporacean thalli. Four foraminiferal associations, which are named after the occurrence of the abundant species, were distinguished as Aulotortus tumidus association, Aulotortus friedli association, Trocholina umbo association, and Trocholina blaui association. Aulotortid types and Trocholina umbo were found within the bioclastic wackstone/packstone carbonates. Trocholina blaui is abundant in solenoporacean framestones. The foraminiferal association of investigated carbonates contains a mixed fauna, known from Upper Triassic–Liassic in the Tethyan realm. Carbonates of the whole investigated section are dated—due to occurrence of the genus Aulotortus, with species A. tumidus (Kristan-Tollmann), A. tenuis (Kristan), and A. friedli (Kristan-Tollmann)—as Upper Triassic (most probably Rhaetian). The “typical” foraminifers occurring in the reef biotopes in the northwestern Tethys are either missing or extremely rare in the Iranian bioconstructions.     

Dasycladales from the Permian Jamal Formation of the Shotori Mountains,northeast Iran

Calcareous algae of the Permian Jamal Formation were studied in three sections of the Shotori Mountains, located in northeastern Iran. In this paper, four genera including Imperiella Elliott and Süssli, Nanjinoporella Mu and Elliott, Tabasoporella nov. gen., and Pseudotabasoporella nov. gen. are described from the Howz-e Dorah locality, which is exposed about 2 km northeast of the type section of Jamal Formation in Mount Jamal. Tabasoporella nov. gen. is characterized by metaspondyl arrangement of phloiophore and wine-glass-shaped laterals with a stalk grouped to tufts. The individual tufts are separated by a ring-like cavity appearing as triangular, oval, or trapezoid in longitudinally dissected section. The arrangement and shape of the laterals in Pseudotabasoporella nov. gen. is similar to Tabasoporella nov. gen., but there are no cavities between the tufts. All four genera are highly developed and limited to the Permian period. They disappear at the end of Permian and are not found in the Triassic sediments. Until today, two species of Imperiella are found in Iran and Afghanistan. I. iranica Elliott and Süssli was described only from the Ruteh Formation of Alborz Mountains in north Iran and I. afghanica was described from the Permian of Afghanistan. The Jamal Formation of the Shotori Mountains is the second locality where both species are discovered. Moreover, species I. crassiparietalis and I. gracilis are the two new species described here. The genus Nanjinoporella—with type species N. pagoda Mu and Elliott—was known from the Permian (Artinskian) Chishia Formation of Nanjing, China. We describe the new species Nanjinoporella iranica from the Permian Jamal Formation of the Shotori Mountains, northeast Iran.     

Stiffness of γ subunit of F1-ATPase

F₁-ATPase is a molecular motor in which the γ subunit rotates inside the α₃β₃ ring upon adenosine triphosphate (ATP) hydrolysis. Recent works on single-molecule manipulation of F₁-ATPase have shown that kinetic parameters such as the on-rate of ATP and the off-rate of adenosine diphosphate (ADP) strongly depend on the rotary angle of the γ subunit (Hirono-Hara et al. 2005; Iko et al. 2009). These findings provide important insight into how individual reaction steps release energy to power F₁ and also have implications regarding ATP synthesis and how reaction steps are reversed upon reverse rotation. An important issue regarding the angular dependence of kinetic parameters is that the angular position of a magnetic bead rotation probe could be larger than the actual position of the γ subunit due to the torsional elasticity of the system. In the present study, we assessed the stiffness of two different portions of F₁ from thermophilic Bacillus PS3: the internal part of the γ subunit embedded in the α₃β₃ ring, and the complex of the external part of the γ subunit and the α₃β₃ ring (and streptavidin and magnetic bead), by comparing rotational fluctuations before and after crosslinkage between the rotor and stator. The torsional stiffnesses of the internal and remaining parts were determined to be around 223 and 73 pNnm/radian, respectively. Based on these values, it was estimated that the actual angular position of the internal part of the γ subunit is one-fourth of the magnetic bead position upon stalling using an external magnetic field. The estimated elasticity also partially explains the accommodation of the intrinsic step size mismatch between F_o and F₁-ATPase.     

Near-full-length REV3L appears to be a scarce maternal factor in Xenopus laevis eggs that changes qualitatively in early embryonic development

REV3 is the catalytic subunit of DNA polymerase ζ (pol ζ), which is responsible for the damage-induced mutagenesis that arises during error-prone translesion synthesis in eukaryotes. The related REV3L genes in human and mouse encode proteins of approximately 350 kDa, twice as large as yeast REV3, but full-length REV3L has not been identified in any vertebrate cell. We report that Xenopus laevis REV3L encodes a 352-kDa protein that has high overall amino acid sequence similarity to its mammalian counterparts, and, for the first time in a vertebrate species, we have detected putative REV3L polypeptides of 300 and 340 kDa in X. laevis oocytes. Only the 300-kDa form is stored in eggs, where its concentration of about 65 pM is much lower than those of other replication and repair proteins including the accessory pol ζ subunit REV7. In fertilized eggs, the levels of this polypeptide did not change until neurula; the larger 340-kDa form first appeared at stages after gastrula, suggesting a pattern of regulation during development. These observations indicate the existence of REV3L as a scarce protein, of approximately the full predicted size, whose level may impose severe constraints on the assembly of pol ζ in X. laevis.     

Protein disulfide isomerase-P5, down-regulated in the final stage of boar epididymal sperm maturation,catalyzes disulfide formation to inhibit protein function in oxidative refolding of reduced denatured lysozyme

In mammalian spermiogenesis, sperm mature during epididymal transit to get fertility. The pig sharing many physiological similarities with humans is considered a promising animal model in medicine. We examined the expression profiles of proteins from boar epididymal caput, corpus, and cauda sperm by two-dimensional gel electrophoresis and peptide mass fingerprinting. Our results indicated that protein disulfide isomerase-P5 (PDI-P5) human homolog was down-regulated from the epididymal corpus to cauda sperm, in contrast to the constant expression of protein disulfide isomerase A3 (PDIA3) human homolog. To examine the functions of PDIA3 and PDI-P5, we cloned and sequenced cDNAs of pig PDIA3 and PDI-P5 protein precursors. Each recombinant pig mature PDIA3 and PDI-P5 expressed in Escherichia coli showed thiol-dependent disulfide reductase activities in insulin turbidity assay. Although PDIA3 showed chaperone activity to promote oxidative refolding of reduced denatured lysozyme, PDI-P5 exhibited anti-chaperone activity to inhibit oxidative refolding of lysozyme at an equimolar ratio. SDS-PAGE and Western blotting analysis suggested that disulfide cross-linked and non-productively folded lysozyme was responsible for the anti-chaperone activity of PDI-P5. These results provide a molecular basis and insights into the physiological roles of PDIA3 and PDI-P5 in sperm maturation and fertilization.     

Ca signaling and STIM1

An increase in the intracellular calcium ion concentration ([Ca²⁺]) impacts a diverse range of cell functions, including adhesion, motility, gene expression and proliferation. Elevation of intracellular calcium ion (Ca²⁺) regulates various cellular events after the stimulation of cells. Initial increase in Ca²⁺ comes from the endoplasmic reticulum (ER), intracellular storage space. However, the continuous influx of extracellular Ca²⁺ is required to maintain the increased level of Ca²⁺ inside cells. Store-operated Ca²⁺ entry (SOCE) manages this process, and STIM1, a newly discovered molecule, has a unique and essential role in SOCE. STIM1 can sense the exhaustion of Ca²⁺ in the ER, and activate the SOC channel in the plasma membrane, leading to the continuous influx of extracellular Ca²⁺. STIM1 senses the status of the intracellular Ca²⁺ stores via a luminal N-terminal Ca²⁺-binding EF-hand domain. Dissociation of Ca²⁺ from this domain induces the clustering of STIM1 to regions of the ER that lie close to the plasma membrane, where it regulates the activity of the store-operated Ca²⁺ channels/entry (calcium-release-activated calcium channels/entry). In this review, we summarize the mechanism by which STIM1 regulates SOCE, and also its role in the control of mast cell functions and allergic responses.     

Breaking the apple embryo dormancy by nitric oxide involves the stimulation of ethylene production

Mature seeds of apple (Mallus domestica Borb. cv. Antonówka) are dormant and do not germinate unless their dormancy is removed by several weeks of moist-cold treatment. We investigated the effect of short-term (3 h) nitric oxide (NO) pretreatment on breaking of apple embryonic dormancy expressed as inhibition of germination and morphological abnormalities of young seedlings. Imbibition of embryos isolated from dormant apple seeds with sodium nitroprusside (SNP) or S-nitroso,N-acetyl penicillamine (SNAP) as NO donors resulted in enhanced germination. Moreover, NO treatment removed morphological abnormalities of seedlings developing from dormant embryo. The NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-teramethylimidazoline-1-oxyl-3 oxide (cPTIO) removed the above effects. NO-mediated breaking of embryonic dormancy correlated well with enhanced ethylene production. Inhibitor of ethylene synthesis (AOA) reversed the stimulatory effect of NO donors on embryo germination. Additionally SNP reduced embryo sensitivity to exogenously applied ABA ensuing dormancy breakage. We can conclude that NO acts as a regulatory factor included in the control of apple embryonic dormancy breakage by stimulation of ethylene biosynthesis.