Observation of the Exotic 0_{2}

We report here the first observation of the 0_{2}^{+} state of ^{8}He, which has been predicted to feature the condensatelike α+^{2}n+^{2}n cluster structure. We show that this state is characterized by a spin parity of 0^{+}, a large isoscalar monopole transition strength, and the emission of a strongly correlated neutron pair, in line with theoretical predictions. Our finding is further supported by the state-of-the-art microscopic α+4n model calculations. The present results may lead to new insights into clustering in neutron-rich nuclear systems and the pair correlation and condensation in quantum many-body systems under strong interactions.

[Characteristics of genotype of monogenic nephrolithiasis in Chinese pediatric patients with nephrolithiasis].

Objective: To analyze the genotype characteristics of children with monogenic nephrolithiasis. Methods: The clinical data and genetic test results of 56 children with monogenic nephrolithiasis diagnosed and treated in Beijing Friendship Hospital, Capital Medical University from January 2016 to December 2020 were analyzed retrospectively. All pediatric patients were diagnosed by whole exome sequencing, and the genotype characteristics of the children were analyzed. Results: Among 56 children with monogenic nephrolithiasis, there were 39 males and 17 females, with an average age of 4 years (range, 5 months to 14 years). A total of 11 genes were found to have mutations, including 7 autosomal recessive genes, 1 X-linked recessive gene, and 3 genes with both recessive and dominant, of which HOGA1 gene mutation was the most common (16 cases, 28.6%), followed by AGXT gene (15 cases, 26.8%), SLC3A1 gene (6 cases, 10.7%), SLC7A9 gene (5 cases, 8.9%) and GRHPR gene (5 cases, 8.9%). The mutation types included nonsense mutations, frameshift mutations and splicing mutations, with 14 novel mutations. Genes such as AGXT, GRHPR and HOGA1 have hotspot mutations or hotspot mutation regions, which are c. 815-816 insGA and c. 33dupC mutation, c.864-865delTG mutation and c. 834-834+1 mutation region; SLC3A1 and SLC7A9 genes had 9 novel mutations, but no hotspot mutation or hotspot regions were found. Conclusion: Monogenic nephrolithiasis is rare and mostly autosomal recessive in Chinese children, with mutations in the causative genes HOGA1, AGXT, SLC3A1,SLC7A9 and GRHPR. AGXT, GRHPR and HOGA1 genes have hotspot mutations or hotspot mutation regions, and mutations may have ethnic differences.

Positive-Parity Linear-Chain Molecular Band in

An inelastic excitation and cluster-decay experiment ^{2}H(^{16}C,^{4}He+^{12}Be or ^{6}He+^{10}Be)^{2}H was carried out to investigate the linear-chain clustering structure in neutron-rich ^{16}C. For the first time, decay paths from the ^{16}C resonances to various states of the final nuclei were determined, thanks to the well-resolved Q-value spectra obtained from the threefold coincident measurement. The close-threshold resonance at 16.5 MeV is assigned as the J^{π}=0^{+} band head of the predicted positive-parity linear-chain molecular band with (3/2_{π}^{-})^{2}(1/2_{σ}^{-})^{2} configuration, according to the associated angular correlation and decay analysis. Other members of this band were found at 17.3, 19.4, and 21.6 MeV based on their selective decay properties, being consistent with the theoretical predictions. Another intriguing high-lying state was observed at 27.2 MeV which decays almost exclusively to ^{6}He+^{10}Be(∼6 MeV) final channel, corresponding well to another predicted linear-chain structure with the pure σ-bond configuration.

Observation of enhanced monopole strength and clustering in (12)Be.

In a recent breakup-reaction experiment using a Be12 beam at 29 MeV/nucleon, the 0+ band head of the expected He4+He8 molecular rotation was clearly identified at about 10.3 MeV, from which a large monopole matrix element of 7.0±1.0 fm2 and a large cluster-decay width were determined for the first time. These findings support the picture of strong clustering in Be12, which has been a subject of intense investigations over the past decade. The results were obtained thanks to a specially arranged detection system around zero degrees, which is essential in determining the newly emphasized monopole strengths to signal the cluster formation in a nucleus.

Cross talk between cAMP and p38 MAPK pathways in the induction of leptin by hCG in human placental syncytiotrophoblasts.

Leptin produced by the placental syncytiotrophoblasts participates in a number of processes in pregnancy including implantation, proliferation of the cytotrophoblasts, and nutrient transfer across the placenta. Despite the functional significance of leptin in pregnancy, the regulation of leptin synthesis is poorly understood in human placental syncytiotrophoblasts. In this study, we investigated the role of endogenous human chorionic gonadotropin (hCG) in the regulation of leptin production as well as the underlying mechanism involving the cross talk between cAMP and p38 mitogen-activated protein kinase (MAPK) pathways. We found that neutralization of endogenous hCG with its antibody dose dependently decreased leptin mRNA level and secretion, whereas exogenous hCG increased leptin mRNA level and secretion. Activation of the cAMP pathway with dibutyryl cAMP (db cAMP) or forskolin recapitulated the stimulatory effect of hCG on leptin expression. Inhibition of protein kinase A with H89 not only reduced the basal leptin expression but also attenuated the induced leptin expression by hCG. Treatment of the syncytiotrophoblasts with db cAMP and hCG phosphorylated p38 MAPK. Inhibition of p38 MAPK with SB203580 not only reduced the basal leptin production but also attenuated the leptin-induced production by both hCG and db cAMP. These data suggest that endogenous hCG plays a significant role in maintaining leptin production in human placental syncytiotrophoblasts, and this effect involves a cross talk between cAMP and p38 MAPK pathways.

Changing epidemiology of HIV type 1 infections in India: evidence of subtype B introduction in Bombay from a common source.

India has experienced multiple introductions of diverse HIV-1 subtypes A, B, C, and E, along with subtype B of HIV-2 between the 1980s and early 1990s. In this study, we have carried out a molecular investigation of 21 heterosexually and vertically acquired HIV-infected individuals from the New Bombay area, who tested positive for HIV-1 by commercial enzyme-linked immunosorbent assay (ELISA) and Western blot assay. We have sequenced the proviral DNA segments from the uncultured PBMCs in the hypervariable env V(3) region (286 bp) and a full-length vpr gene (291 bp). Overall, phylogenetic clustering of all Indian strains and also their clustering with subtype B strains were evident from both V(3)- and vpr gene-based trees, strongly supporting their recent introduction from a common source. This is the first report on subtype B introduction in Bombay, a region where subtype C predominates. Overall, these subtype B strains from Bombay shared genetic closeness with subtype B strains from Europe, the United States, and Asia.

Unique HIV type 1 V3 region sequences derived from six different regions of brain: region-specific evolution within host-determined quasispecies.

HIV type 1 viral quasispecies were amplified by polymerase chain reaction (PCR) in the hypervariable V3 region of gp120 from six different regions of the brain (right and left frontal; right and left parietal; and right and left occipital) and from the peripheral blood mononuclear cells (PBMCs) of a patient who died of AIDS dementia complex (ADC). Cloning and sequencing of the entire V3 region suggested the presence of genetically unique sequences in different regions of the brain. In contrast, the blood-derived viral quasispecies carried homogeneous sequences that were characterized by a single octapeptide crest motif (HLGPGSAF), a motif important in viral fusion. The brain-derived viral strains showed extensive sequence heterogeneity and the presence of seven different octapeptide and four different tetrapeptide crest motifs (HIGPGRAF, RIGPGRAF, HIGPGSAI, HLGPGSAF, HIGPESAI, HLGPESAI, and YLRPGSAF). In addition, the brain-derived strains were also characterized by variable net V3 loop charge and hydrophilicity, along with distinct amino acid changes specific to different brain regions. Together, the sequence and phylogenetic analyses are unique in identifying the complexity of a viral quasispecies and its independent regional evolution within the brain compartment. Uniquely divergent viral strains were identified in the frontal regions and their presence was further supported by the presence of multinucleated giant cells (characteristic of HIV encephalopathy) predominantly in the left and right frontal regions. In summary, these analyses suggest that genetically different populations of HIV-1 may be present in different brain compartments and confirm that specific neurotropic variants may exist.

Simian T cell leukemia virus type I from naturally infected feral monkeys from central and west Africa encodes a 91-amino acid p12 (ORF-I) protein as opposed to a 99-amino acid protein encoded by HTLV type I from humans.

A single protein of 12 kDa, p12 is encoded by the HTLV-I genome from both the singly spliced mRNA pX-ORF-I and doubly spliced mRNA pX-rex-ORF-I. While many full-length sequences of HTLV-1 are known, data on the p12 regions of African STLV-I are unavailable. We have undertaken to sequence the p12 gene in STLV-I from Central and West Africa naturally infected primates, and have compared them to known p12 sequences of HTLV-I. Our data on sequence and in vitro transcription-translation analyses indicate that p12 is a 91-amino acid (aa) protein among STLV-I strains from Central and West Africa, in contrast to the 99-aa protein found among HTLV-I strains around the globe. The p12 sequences of STLV-I exhibit a marked genetic variability at the level of both nucleotide and peptide sequences. Hydropathic and helical wheel analyses reveal that 60% of residues in HTLV-I p12 are hydrophobic, in contrast to 55% in STLV-I from Africa. Although HTLV-I and STLV-I show a similar putative antigenic site, a second potential site was located exclusively in STLV-I from Africa. There are differences in the predicted transmembrane domains in p12 between STLV-I and HTLV-I. Furthermore, the secondary structure data according to the Chou and Fasman algorithm predict an alpha-helical domain at the carboxy terminus in HTLV-I, and this domain may be truncated in STLV-I p12. The amino acid sequence of p12 shows two leucine zipper motifs (LZMs) at the amino terminus and in the middle region, respectively. This is the first report describing the size differences in p12 protein between HTLV-I and STLV-I, which may provide insights into pathogenic mechanisms used by HTLV-I and STLV-I.

Simulation of epileptiform activity in the hippocampus using transputers.

Transputer technology is exploited to provide fast and interactive simulations of the electrical behaviour in large networks of neurones derived from experimental data of individual neurones and their connections. A synchronous numerical integration routine and an efficient communication scheme have been developed to run on toroidally configured transputer arrays of any sizes. A population of neurones up to 6400 from the hippocampus has been simulated on 19 Inmos T800 transputers. The activity of individual cells has been modelled using a similar approach to that of Traub; but the non-linear dynamics of the Na(+)-K+ channels is emphasised to explain intrinsic bursting. This model includes a description of the cellular channel currents INa, IK(DR), IK(C), ICa and IAHP. Preliminary studies indicate that this anatomically based model can be used to study the dynamic properties of neurones in the hippocampus, including monitoring the behaviour of subpopulation of cells that contribute to epileptiform activity.

Coinfection and genetic recombination between HIV-1 strains: possible biological implications in Australia and South East Asia.

It has been recognised that human immunodeficiency virus (HIV) mutates rapidly and that nucleotide substitutions, deletions, insertions, and rearrangements resulting from recombination events are the main factors that result in variation of the HIV-1 genome. Together, these processes are actively contributing to the diversity and virulence of viral forms comprising the acquired immune deficiency syndrome (AIDS) pandemic. There are 9 HIV-1 subtypes recognised (A-H and O), based on the envelope region segments. Inter-subtype recombination has been already described, whereas intra-subtype recombination has been difficult to detect. In this study, we have identified in vivo genetic recombination between HIV-1 strains belonging to subtype B in a patient who presented both intravenous drug use (IVDU) and homosexual sex as risk factors. Genetic analysis of viral strains in the hypervariable V3 region of the envelope gene indicated the presence of three distinct sequence groups categorized according to their respective tetrapeptide motifs-GPGR, GLGR and GPGK. Detailed genetic and phylogenetic analyses suggested the recombination occurring only between sequence groups with GPGR and GPGK tetrapeptide motifs. These data suggest that coinfection with closely related strains can occur in vivo, and the generation of hybrid HIV-1 genomes via genetic recombination between subtype B strains can result in further antigenic diversity which may thwart diagnosis and future vaccine efforts. Since HIV-1 subtype B is still the most commonly found subtype around the globe, the hybrid genomes between different subtype B strains may result in epidemiologic shifts and altered pathogenesis.

Subtype B isolates of human immunodeficiency virus type 1 detected in Australia.

The human immunodeficiency virus type 1 (HIV-1) can be subtyped on the basis of nucleotide sequence variability. Knowledge of circulating HIV-1 genotypes or subtypes allows understanding of the origin and spread of HIV-1 in different geographical regions, and is required for rational vaccine development. A study was undertaken to determine the predominant HIV-1 subtype in Australia. Part of the HIV-1 envelope gene (including the variable domain, V3) was sequenced directly from DNA extracted from peripheral blood mononuclear cells of 17 HIV-1 seropositive people in Sydney, Australia. Phylogenetic analysis based on nucleotide sequence suggested that all patients (including individual cases acquired in New Zealand, Papua New Guinea and Thailand) were infected with HIV-1 subtype B. Octapeptides from the HIV-1 envelope V3 loop tip indicated variation but included a predominance of the most common subtype B octapeptides HIGPGRAF (4 cases), NIGPGRAF (3 cases) and PIGPGRAF (1 case). These data suggest that subtype B is the major HIV-1 strain in Australia (and probably in New Zealand and Papua New Guinea), although the importation of HIV-1 acquired overseas is likely to lead to the detection and dissemination of other subtypes in Australia.

An HIV-1 infected long-term non-progressor (LTNP): molecular analysis of HIV-1 strains in the vpr and nef genes.

We describe a long-term non-progressive injecting drug user (IDU) who was infected with human immunodeficiency virus type-1 (HIV-1) in 1984, and has survived with stable CD4+ T-cell counts (> 800/microliters blood) without any acquired immune deficiency syndrome (AIDS) related illness. With a goal to investigate the molecular nature of HIV-1 strains infecting this patient, we amplified the nef and vpr genes directly from the fresh uncultured peripheral blood mononuclear cells (PBMCs), and carried out co-culture studies. Sequence analysis of the nef gene (from 1994 samples) showed no deletions (as has been previously reported) expected for a 7 base pair duplication at the C-terminus which prematurely terminated the nef reading frame, whereas even after repeated attempts the nef gene could not be amplified from the 1992 PBMC samples. In contrast, the vpr gene (from 1992 and 1994 samples) revealed two distinct quasispecies with no apparent defects. We observed five amino acid substitutions, between residues 83-90, at the C-terminus which has been recently implicated in G2 cell cycle arrest as an early step to HIV-1 infection. In the light of recent evidence on the role of nef gene defects/attenuations in long-term survival of HIV-1 infected patients, it may be that the nef gene defect created by gene duplication, which eliminated the cysteine-206 crucial in disulfide bond formation, may play a role in chronic HIV-1 infection in this patient. These data further suggest that deletions in the nef gene may not be the only reason for long-term non-progression of HIV-1 infection in some individuals, but the gene defects like duplication and subtle mutations in the functional motifs of both nef and vpr genes may confer similar protection in HIV-1 infected patients surviving for longer periods of time with stable CD4 counts.

[Studies on the chemical constituents of Rhodiola fastigita].

The root and rhizoma of Rhodiola fastigita S. H. Fu. is a traditional Tibetan medicine used for promoting blood circulation and relieving cough. In recent years, it was generally used as a tonic. So, its chemical constituents were studied. A new flavonoid and six known compounds were obtained. The known compounds were: 4'-methoxyl herbacetin (I), rhodiolin (II), dihydrokaempferol (III), daucosterol (IV), tyrosyl (V) and salidroside (VI). The structure of the new flavonoid was elucidated as herbacetin-8-O-alpha-D-lyxopyranoside (VII), by means of UV, IR, MS, 1H and 13C-NMR spectral data and chemical methods.

[Chemical constituents of Rhodiola kirilowii (Regel) Regel].

Five compounds were isolated from the rhizome of Rhodiola kirilowii. Based on spectral studies and chemical analysis the structures were established as tyrosol, daucosterol, lotaustralin, salidroside and sucrose.

The Sp1 transcription factor is crucial for the expression of 11beta-hydroxysteroid dehydrogenase type 2 in human placental trophoblasts.

CONTEXT: Overexposure of the fetus to glucocorticoids early in gestation is detrimental to fetal development. Glucocorticoid concentrations in the fetal circulation are kept low by 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD2, encoded by HSD11B2) in the placental syncytiotrophoblasts. However, cytotrophoblasts, the progenitors of syncytiotrophoblasts, express low levels of 11ß-HSD2. Here we studied the molecular mechanisms underlying 11ß-HSD2 induction upon syncytialization. METHODS: Freshly isolated human term placental cytotrophoblasts and in vitro differentiated syncytiotrophoblasts were examined to determine the methylation status of HSD11B2 promoter. The transcription factor responsible for 11ß-HSD2 induction was identified by observing its expression upon syncytialization, the effect of its attenuation, and its binding to the HSD11B2 promoter. RESULTS: 11ß-HSD2 expression was markedly increased upon syncytialization in vitro. No methylation differences of HSD11B2 promoter were found between cytotrophoblasts and syncytiotrophoblasts. Expression of the transcription factor Sp1 was markedly induced during syncytialization and further increased by activation of the cAMP pathway, which correlated with 11ß-HSD2 expression. Importantly, small interfering RNA-mediated knockdown of Sp1 expression or inhibition of Sp1 activity with mithramycin A markedly attenuated not only basal but also cAMP pathway-stimulated expression of 11ß-HSD2 in the syncytiotrophoblasts. Stimulation of the cAMP pathway also increased the binding of Sp1 and RNA polymerase II to HSD11B promoter in syncytiotrophoblasts. Concomitantly, acetylation at histone H3K9 was increased whereas methylation at histone H3K9 was decreased. CONCLUSIONS: 11ß-HSD2 induction upon syncytialization is at least in part due to the increased expression of Sp1 upon activation of the cAMP pathway rather than the differential methylation of the HSD11B2 promoter.