Application of hepatitis B virus (HBV) DNA sequence polymorphisms to the study of HBV transmission

Short sequences in hypervariable regions of the hepatitis B virus (HBV) genome can be used to identify different strains, providing a novel approach to the study of HBV transmission. The nucleotide sequence in positions 2551-2650 (1: EcoRI site) was determined for serum HBV DNA from 96 Chinese children living in Hong Kong and from 38 of their parents. HBV DNA was extracted and sequenced after amplification with the polymerase chain reaction, using as primers oligonucleotides corresponding to two conserved sequences. Among 82 unrelated children, 32 HBV DNA variants were present. One sequence was present in 33 children and 31 variants were found among the other 49. Siblings within each of nine families had the same variant; in three families siblings had different variants. Six of the eight fathers and 28 of the 30 mothers had HBV DNA sequences identical to those of their offspring. A total of 34 variants were found among the 134 individuals. The hypothesis of random assortment of sequences in parents and children was rejected (P < .00005). Thus, this new approach proves the occurrence of intrafamilial transmission of HBV among Chinese.published_or_final_versio

The connection between superconducting phase correlations and spin excitations in YBa2_2Cu3_3O6.6_{6.6}: A magnetic field study

One of the most striking universal properties of the high-transition-temperature (high-$T_c$) superconductors is that they are all derived from the hole-doping of their insulating antiferromagnetic (AF) parent compounds. From the outset, the intimate relationship between magnetism and superconductivity in these copper-oxides has intrigued researchers. Evidence for this link comes from neutron scattering experiments that show the unambiguous presence of short-range AF correlations (excitations) in cuprate superconductors. Even so, the role of such excitations in the pairing mechanism and superconductivity is still a subject of controversy. For YBa$_2$Cu$_3$O$_{6+x}$, where $x$ controls the hole-doping level, the most prominent feature in the magnetic excitations spectra is the ``resonance''. Here we show that for underdoped YBa$_2$Cu$_3$O$_{6.6}$, where $x$ and $T_c$ are below the optimal values, modest magnetic fields suppress the resonance significantly, much more so for fields approximately perpendicular rather than parallel to the CuO$_2$ planes. Our results indicate that the resonance measures pairing and phase coherence, suggesting that magnetism plays an important role in the superconductivity of cuprates. The persistence of a field effect above $T_c$ favors mechanisms with preformed pairs in the normal state of underdoped cuprates.Comment: 12 pages, 4 figures, Nature (in press

How older people enact care involvement during transition from hospital to home: A systematic review and model

Background Current models of patient‐enacted involvement do not capture the nuanced dynamic and interactional nature of involvement in care. This is important for the development of flexible interventions that can support patients to ‘reach‐in’ to complex health‐care systems. Objective To develop a dynamic and interactional model of patient‐enacted involvement in care. Search strategy Electronic search strategy run in five databases and adapted to run in an Internet search engine supplemented with searching of reference lists and forward citations. Inclusion criteria Qualitative empirical published reports of older people's experiences of care transitions from hospital to home. Data extraction and synthesis Reported findings meeting our definition of involvement in care initially coded into an existing framework. Progression from deductive to inductive coding leads to the development of a new framework and thereafter a model representing changing states of involvement. Main results Patients and caregivers occupy and move through multiple states of involvement in response to perceived interactions with health‐care professionals as they attempt to resolve health‐ and well‐being‐related goals. ‘Non‐involvement’, ‘information‐acting’, ‘challenging and chasing’ and ‘autonomous‐acting’ were the main states of involvement. Feeling uninvolved as a consequence of perceived exclusion leads patients to act autonomously, creating the potential to cause harm. Discussion and conclusion The model suggests that involvement is highly challenging for older people during care transitions. Going forward, interventions which seek to support patient involvement should attempt to address the dynamic states of involvement and their mediating factors

Signatures of arithmetic simplicity in metabolic network architecture

Metabolic networks perform some of the most fundamental functions in living cells, including energy transduction and building block biosynthesis. While these are the best characterized networks in living systems, understanding their evolutionary history and complex wiring constitutes one of the most fascinating open questions in biology, intimately related to the enigma of life's origin itself. Is the evolution of metabolism subject to general principles, beyond the unpredictable accumulation of multiple historical accidents? Here we search for such principles by applying to an artificial chemical universe some of the methodologies developed for the study of genome scale models of cellular metabolism. In particular, we use metabolic flux constraint-based models to exhaustively search for artificial chemistry pathways that can optimally perform an array of elementary metabolic functions. Despite the simplicity of the model employed, we find that the ensuing pathways display a surprisingly rich set of properties, including the existence of autocatalytic cycles and hierarchical modules, the appearance of universally preferable metabolites and reactions, and a logarithmic trend of pathway length as a function of input/output molecule size. Some of these properties can be derived analytically, borrowing methods previously used in cryptography. In addition, by mapping biochemical networks onto a simplified carbon atom reaction backbone, we find that several of the properties predicted by the artificial chemistry model hold for real metabolic networks. These findings suggest that optimality principles and arithmetic simplicity might lie beneath some aspects of biochemical complexity

Analogue peptides for the immunotherapy of human acute myeloid leukemia

Accepted manuscript. The final publication is available at: http://link.springer.com/article/10.1007%2Fs00262-015-1762-9The use of peptide vaccines, enhanced by adjuvants, has shown some efficacy in clinical trials. However, responses are often short-lived and rarely induce notable memory responses. The reason is that self-antigens have already been presented to the immune system as the tumor develops, leading to tolerance or some degree of host tumor cell destruction. To try to break tolerance against self-antigens, one of the methods employed has been to modify peptides at the anchor residues to enhance their ability to bind major histocompatibility complex molecules, extending their exposure to the T-cell receptor. These modified or analogue peptides have been investigated as stimulators of the immune system in patients with different cancers with variable but sometimes notable success. In this review we describe the background and recent developments in the use of analogue peptides for the immunotherapy of acute myeloid leukemia describing knowledge useful for the application of analogue peptide treatments for other malignancies

Contribution to the understanding of tribological properties of graphite intercalation compounds with metal chloride

Intrinsic tribological properties of lamellar compounds are usually attributed to the presence of van der Waals gaps in their structure through which interlayer interactions are weak. The controlled variation of the distances and interactions between graphene layers by intercalation of electrophilic species in graphite is used in order to explore more deeply the friction reduction properties of low-dimensional compounds. Three graphite intercalation compounds with antimony pentachloride, iron trichloride and aluminium trichloride are studied. Their tribological properties are correlated to their structural parameters, and the interlayer interactions are deduced from ab initio bands structure calculations

Resonance in the electron-doped high-Tc superconductor Pr0.88LaCe0.12CuO(4-delta)

In conventional superconductors, the interaction that pairs the electrons to form the superconducting state is mediated by lattice vibrations (phonons). In high-transition temperature (high-Tc) copper oxides, it is generally believed that magnetic excitations play a fundamental role in the superconducting mechanism because superconductivity occurs when mobile 'electrons' or 'holes' are doped into the antiferromagnetic parent compounds. Indeed, a sharp magnetic excitation termed "resonance" has been observed by neutron scattering in a number of hole-doped materials. The resonance is intimately related to superconductivity, and its interaction with charged quasi-particles observed by photoemission, optical conductivity, and tunneling suggests that it plays a similar role as phonons in conventional superconductors. However, the relevance of the resonance to high-Tc superconductivity has been in doubt because so far it has been found only in hole-doped materials. Here we report the discovery of the resonance in electron-doped superconducting Pr0.88LaCe0.12CuO(4-delta) (Tc = 24 K). We find that the resonance energy (Er) is proportional to Tc via Er = 5.8kBTc (kB is the Boltzmann's constant) for all high-Tc superconductors irrespective of electron- or hole-doping (Fig. 1e). Our results demonstrate that the resonance is a fundamental property of the superconducting copper oxides and therefore must play an essential role in the mechanism of superconductivity.Comment: PDF file with 4 Figure

Problem and Pathological Gambling in a Sample of Casino Patrons

Relatively few studies have examined gambling problems among individuals in a casino setting. The current study sought to examine the prevalence of gambling problems among a sample of casino patrons and examine alcohol and tobacco use, health status, and quality of life by gambling problem status. To these ends, 176 casino patrons were recruited by going to a Southern California casino and requesting that they complete an anonymous survey. Results indicated the following lifetime rates for at-risk, problem, and pathological gambling: 29.2, 10.7, and 29.8%. Differences were found with regards to gambling behavior, and results indicated higher rates of smoking among individuals with gambling problems, but not higher rates of alcohol use. Self-rated quality of life was lower among pathological gamblers relative to non-problem gamblers, but did not differ from at-risk or problem gamblers. Although subject to some limitations, our data support the notion of higher frequency of gambling problems among casino patrons and may suggest the need for increased interventions for gambling problems on-site at casinos

One-dimensional nature of the magnetic fluctuations in YBa2_2Cu3_3O6.6_{6.6}

There is increasing evidence that inhomogeneous distributions of charge and spin--so-called "striped phases"--play an important role in determining the properties of the high-temperature superconductors. For example, recent neutron-scattering measurements on the YBa$_2$Cu$_3$O$_{7-x}$ family of materials show both spin and charge fluctuations that are consistent with the striped-phase picture. But the fluctuations associated with a striped phase are expected to be one-dimensional, whereas the magnetic fluctuations observed to date appear to display two-dimensional symmetry. We show here that this apparent two-dimensionality results from measurements on twinned crystals, and that similar measurements on substantially detwinned crystals of YBa$_2$Cu$_3$O$_{6.6}$ reveal the one-dimensional character of the magnetic fluctuations, thus greatly strengthening the striped-phase interpretation. Moreover, our results also suggest that superconductivity originates in charge stripes that extend along the b crystal axis, where the superfluid density is found to be substantially larger than for the a direction.Comment: 3 pages, PDF onl

Functional Diversity and Structural Disorder in the Human Ubiquitination Pathway

The ubiquitin-proteasome system plays a central role in cellular regulation and protein quality control (PQC). The system is built as a pyramid of increasing complexity, with two E1 (ubiquitin activating), few dozen E2 (ubiquitin conjugating) and several hundred E3 (ubiquitin ligase) enzymes. By collecting and analyzing E3 sequences from the KEGG BRITE database and literature, we assembled a coherent dataset of 563 human E3s and analyzed their various physical features. We found an increase in structural disorder of the system with multiple disorder predictors (IUPred - E1: 5.97%, E2: 17.74%, E3: 20.03%). E3s that can bind E2 and substrate simultaneously (single subunit E3, ssE3) have significantly higher disorder (22.98%) than E3s in which E2 binding (multi RING-finger, mRF, 0.62%), scaffolding (6.01%) and substrate binding (adaptor/substrate recognition subunits, 17.33%) functions are separated. In ssE3s, the disorder was localized in the substrate/adaptor binding domains, whereas the E2-binding RING/HECT-domains were structured. To demonstrate the involvement of disorder in E3 function, we applied normal modes and molecular dynamics analyses to show how a disordered and highly flexible linker in human CBL (an E3 that acts as a regulator of several tyrosine kinase-mediated signalling pathways) facilitates long-range conformational changes bringing substrate and E2-binding domains towards each other and thus assisting in ubiquitin transfer. E3s with multiple interaction partners (as evidenced by data in STRING) also possess elevated levels of disorder (hubs, 22.90% vs. non-hubs, 18.36%). Furthermore, a search in PDB uncovered 21 distinct human E3 interactions, in 7 of which the disordered region of E3s undergoes induced folding (or mutual induced folding) in the presence of the partner. In conclusion, our data highlights the primary role of structural disorder in the functions of E3 ligases that manifests itself in the substrate/adaptor binding functions as well as the mechanism of ubiquitin transfer by long-range conformational transitions. © 2013 Bhowmick et al