Enzootic Transmission of Yellow Fever Virus in Peru

The prevailing paradigm of yellow fever virus (YFV) ecology in South America is that of wandering epizootics. The virus is believed to move from place to place in epizootic waves involving monkeys and mosquitoes, rather than persistently circulating within particular locales. After a large outbreak of YFV illness in Peru in 1995, we used phylogenetic analyses of virus isolates to reexamine the hypothesis of virus movement. We sequenced a 670-nucleotide fragment of the prM/E gene region of from 25 Peruvian YFV samples collected from 1977 to 1999, and delineated six clades representing the states (Departments) of Puno, Pasco, Junin, Ayacucho, San Martin/Huanuco, and Cusco. The concurrent appearance of at least four variants during the 1995 epidemic and the genetic stability of separate virus lineages over time, indicate that Peruvian YFV is locally maintained and circulates continuously in discrete foci of enzootic transmission

Theory of anyon excitons: Relation to excitons of nu=1/3 and nu=2/3 incompressible liquids

Elementary excitations of incompressible quantum liquids (IQL's) are anyons, i.e., quasiparticles carrying fractional charges and obeying fractional statistics. To find out how the properties of these quasiparticles manifest themselves in the optical spectra, we have developed the anyon exciton model (AEM) and compared the results with the finite-size data for excitons of nu=1/3 and nu=2/3 IQL's. The model considers an exciton as a neutral composite consisting of three quasielectrons and a single hole. The AEM works well when the separation between electron and hole confinement planes, h, is larger than the magnetic length l. In the framework of the AEM an exciton possesses momentum k and two internal quantum numbers, one of which can be chosen as the angular momentum, L, of the k=0 state. Existence of the internal degrees of freedom results in the multiple branch energy spectrum, crater-like electron density shape and 120 degrees density correlations for k=0 excitons, and the splitting of the electron shell into bunches for non-zero k excitons. For h larger than 2l the bottom states obey the superselection rule L=3m (m are integers starting from 2), all of them are hard core states. For h nearly 2l there is one-to-one correspondence between the low-energy spectra found for the AEM and the many- electron exciton spectra of the nu=2/3 IQL, whereas some states are absent from the many-electron spectra of the nu=1/3 IQL. We argue that this striking difference in the spectra originates from the different populational statistics of the quasielectrons of charge conjugate IQL's and show that the proper account of the statistical requirements eliminates excessive states from the spectrum. Apparently, this phenomenon is the first manifestation of the exclusion statistics in the anyon bound states.Comment: 26 pages with 9 figures, typos correcte

Interpersonal interactions in instrumental lessons: teacher/students verbal and non-verbal behaviours

This study examined verbal and non-verbal teacher/student interpersonal interactions in higher education instrumental music lessons. Twenty-four lessons were videotaped and teacher/ student behaviours were analysed using a researcher-designed instrument. The findings indicate predominance of student and teacher joke among the verbal behaviours with no substantial gender differences between males and females. Deceit cues were the most frequent among the non-verbal behaviours, with the males displaying more gestures of deceit than the females. Other gender differences include the female students using courting signals towards both teacher groups and the female teachers showing interest towards the male students. The presence of positive verbal and negative non-verbal behaviours highlights the mixed messages present in teaching. Implications for instrumental teaching practice include greater focus on gender differences in interpersonal interactions and visual cues to improve communication and teacher/student relationship in the instrumental studio

Simultaneous expression of different transgenes in neurons and glia by combining in utero electroporation with the Tol2 transposon-mediated gene transfer system

In utero electroporation is widely used to study neuronal development and function by introducing plasmid DNA into neural progenitors during embryogenesis. This is an effective and convenient method of introducing plasmid DNA into neural precursors and is suitable for manipulating gene expression in cells of the CNS. However, the applicability of this technique is comparatively limited to neuronal research, as the plasmid DNA introduced into neural progenitors during embryogenesis is diluted by cell proliferation and is not stably maintained in glial cells generated around and after birth. To overcome this limitation, we applied the Tol2 transposon system, which integrates a transgene into the genome of the host cell, to in utero electroporation. With this system, we confirmed that the transgene was effectively maintained in the progeny of embryonic neural precursors, astrocytes and oligodendrocytes. Using the glial promoters GFAP and S100β, targeted and stable expressions of transgenes in glia were obtained, which enabled the expression of different transgenes simultaneously in neurons and glia. Glia-targeted expression of the transgene that causes neuronal migration defect was achieved without the defect. Thus, use of the Tol2 transposon system in combination with in utero electroporation is a powerful method for studying glia-neuron interactions in vivo

Integrated genomics and proteomics define huntingtin CAG length-dependent networks in mice.

To gain insight into how mutant huntingtin (mHtt) CAG repeat length modifies Huntington's disease (HD) pathogenesis, we profiled mRNA in over 600 brain and peripheral tissue samples from HD knock-in mice with increasing CAG repeat lengths. We found repeat length-dependent transcriptional signatures to be prominent in the striatum, less so in cortex, and minimal in the liver. Coexpression network analyses revealed 13 striatal and 5 cortical modules that correlated highly with CAG length and age, and that were preserved in HD models and sometimes in patients. Top striatal modules implicated mHtt CAG length and age in graded impairment in the expression of identity genes for striatal medium spiny neurons and in dysregulation of cyclic AMP signaling, cell death and protocadherin genes. We used proteomics to confirm 790 genes and 5 striatal modules with CAG length-dependent dysregulation at the protein level, and validated 22 striatal module genes as modifiers of mHtt toxicities in vivo

Building the foundation for a community-generated national research blueprint for inherited bleeding disorders: research priorities for mucocutaneous bleeding disorders

BACKGROUND: Excessive or abnormal mucocutaneous bleeding (MCB) may impact all aspects of the physical and psychosocial wellbeing of those who live with it (PWMCB). The evidence base for the optimal diagnosis and management of disorders such as inherited platelet disorders, hereditary hemorrhagic telangiectasia (HHT), hypermobility spectrum disorders (HSD), Ehlers-Danlos syndromes (EDS), and von Willebrand disease (VWD) remains thin with enormous potential for targeted research. RESEARCH DESIGN AND METHODS: National Hemophilia Foundation and American Thrombosis and Hemostasis Network initiated the development of a National Research Blueprint for Inherited Bleeding Disorders with extensive all-stakeholder consultations to identify the priorities of people with inherited bleeding disorders and those who care for them. They recruited multidisciplinary expert working groups (WG) to distill community-identified priorities into concrete research questions and score their feasibility, impact, and risk. RESULTS: WG2 detailed 38 high priority research questions concerning the biology of MCB, VWD, inherited qualitative platelet function defects, HDS/EDS, HHT, bleeding disorder of unknown cause, novel therapeutics, and aging. CONCLUSIONS: Improving our understanding of the basic biology of MCB, large cohort longitudinal natural history studies, collaboration, and creative approaches to novel therapeutics will be important in maximizing the benefit of future research for the entire MCB community

Energy spectra of fractional quantum Hall systems in the presence of a valence hole

The energy spectrum of a two-dimensional electron gas (2DEG) in the fractional quantum Hall regime interacting with an optically injected valence band hole is studied as a function of the filling factor $\nu$ and the separation $d$ between the electron and hole layers. The response of the 2DEG to the hole changes abruptly at $d$ of the order of the magnetic length $\lambda$. At $d<\lambda$, the hole binds electrons to form neutral ($X$) or charged ($X^-$) excitons, and the photoluminescence (PL) spectrum probes the lifetimes and binding energies of these states rather than the original correlations of the 2DEG. The ``dressed exciton'' picture (in which the interaction between an exciton and the 2DEG was proposed to merely enhance the exciton mass) is questioned. Instead, the low energy states are explained in terms of Laughlin correlations between the constituent fermions (electrons and $X^-$'s) and the formation of two-component incompressible fluid states in the electron--hole plasma. At $d>2\lambda$, the hole binds up to two Laughlin quasielectrons (QE) of the 2DEG to form fractionally charged excitons $h$QE$_n$. The previously found ``anyon exciton'' $h$QE$_3$ is shown to be unstable at any value of $d$. The critical dependence of the stability of different $h$QE$_n$ complexes on the presence of QE's in the 2DEG leads to the observed discontinuity of the PL spectrum at $\nu={1\over3}$ or ${2\over3}$.Comment: 16 pages, 14 figures, submitted to PR

Glucocorticoids—All-Rounders Tackling the Versatile Players of the Immune System

Glucocorticoids regulate fundamental processes of the human body and control cellular functions such as cell metabolism, growth, differentiation, and apoptosis. Moreover, endogenous glucocorticoids link the endocrine and immune system and ensure the correct function of inflammatory events during tissue repair, regeneration, and pathogen elimination via genomic and rapid non-genomic pathways. Due to their strong immunosuppressive, anti-inflammatory and anti-allergic effects on immune cells, tissues and organs, glucocorticoids significantly improve the quality of life of many patients suffering from diseases caused by a dysregulated immune system. Despite the multitude and seriousness of glucocorticoid-related adverse events including diabetes mellitus, osteoporosis and infections, these agents remain indispensable, representing the most powerful, and cost-effective drugs in the treatment of a wide range of rheumatic diseases. These include rheumatoid arthritis, vasculitis, and connective tissue diseases, as well as many other pathological conditions of the immune system. Depending on the therapeutically affected cell type, glucocorticoid actions strongly vary among different diseases. While immune responses always represent complex reactions involving different cells and cellular processes, specific immune cell populations with key responsibilities driving the pathological mechanisms can be identified for certain autoimmune diseases. In this review, we will focus on the mechanisms of action of glucocorticoids on various leukocyte populations, exemplarily portraying different autoimmune diseases as heterogeneous targets of glucocorticoid actions: (i) Abnormalities in the innate immune response play a crucial role in the initiation and perpetuation of giant cell arteritis (GCA). (ii) Specific types of CD4+ T helper (Th) lymphocytes, namely Th1 and Th17 cells, represent important players in the establishment and course of rheumatoid arthritis (RA), whereas (iii) B cells have emerged as central players in systemic lupus erythematosus (SLE). (iv) Allergic reactions are mainly triggered by several different cytokines released by activated Th2 lymphocytes. Using these examples, we aim to illustrate the versatile modulating effects of glucocorticoids on the immune system. In contrast, in the treatment of lymphoproliferative disorders the pro-apoptotic action of glucocorticoids prevails, but their mechanisms differ depending on the type of cancer. Therefore, we will also give a brief insight into the current knowledge of the mode of glucocorticoid action in oncological treatment focusing on leukemia

Transmission pathways for sporadic Shiga-toxin producing E. coli infections: A systematic review and meta-analysis

Background: Shiga-toxin E. coli infections remain a public health concern because of the severity of the gastrointestinal illness and associated complications. Transmission pathways are typically elucidated from outbreaks, with foodborne transmission the primary source. However, most STEC cases are sporadic. This systematic review aimed to identify the most common pathways for sporadic STEC transmission and quantify their importance. Methods: We systematically reviewed epidemiological studies of sporadic (non-outbreak) STEC cases that investigated potential risk factors. Searches were run in Medline, EMBASE, and Scopus. Included studies needed to confirm STEC infection and investigate ≥20 cases. Results: 31 studies were included, of which 25 were case-control or case-case studies. 62.5% found consumption of undercooked/raw meat associated with STEC infection while 70.4% found contact with animals or their environment a risk factor. Random-effects meta-analysis provided pooled odds ratios and population attributable fraction (PAF). The PAF was 19% for undercooked/raw meat, followed by person to person transmission at 15%. Contact with animals and visiting farm environments had PAFs of 14% and 12% respectively. Conclusions: Out of potential sources for STEC exposure, undercooked meat and contact with animals and their environment were the most frequently found transmission routes. Decreasing the chances of acquiring the bacteria by these methods would additionally cut down on the other major transmission route, person-to-person spread

IGF-1 and Bone: New Discoveries From Mouse Models

Insulin-like growth factor-1 (IGF-1) plays a central role in cellular growth, differentiation, survival, and cell cycle progression. It is expressed early during development and its effects are mediated through binding to a tyrosine kinase receptor, the insulin-like growth factor-1 receptor (IGF-1R). In the circulation, the IGFs bind to IGF-binding proteins (IGFBPs), which determine their bioavailability and regulate the interaction between the IGFs and IGF-1R. Studies in animal models and in humans have established critical roles for IGFs in skeletal growth and development. In this review we present new and old findings from mouse models of the IGF system and discuss their clinical relevance to normal and pathological skeletal physiology. © 2010 American Society for Bone and Mineral Research