Distinct functions of POT1 at telomeres.

The mammalian protein POT1 binds to telomeric single-stranded DNA (ssDNA), protecting chromosome ends from being detected as sites of DNA damage. POT1 is composed of an N-terminal ssDNA-binding domain and a C-terminal protein interaction domain. With regard to the latter, POT1 heterodimerizes with the protein TPP1 to foster binding to telomeric ssDNA in vitro and binds the telomeric double-stranded-DNA-binding protein TRF2. We sought to determine which of these functions-ssDNA, TPP1, or TRF2 binding-was required to protect chromosome ends from being detected as DNA damage. Using separation-of-function POT1 mutants deficient in one of these three activities, we found that binding to TRF2 is dispensable for protecting telomeres but fosters robust loading of POT1 onto telomeric chromatin. Furthermore, we found that the telomeric ssDNA-binding activity and binding to TPP1 are required in cis for POT1 to protect telomeres. Mechanistically, binding of POT1 to telomeric ssDNA and association with TPP1 inhibit the localization of RPA, which can function as a DNA damage sensor, to telomeres.

B-lymphocyte effector functions in health and disease.

B-lymphocytes have traditionally been thought to contribute to immunity and autoimmune disease through terminal differentiation into plasma cells that secrete antibody. However, studies in mice and recent clinical studies have demonstrated that genetically altered B-cell function and B-cell-targeted therapies can significantly affect autoimmune diseases that were predominantly thought to be T-cell-mediated. B-cell depletion in mouse models of disease has also led to the identification of alternative B-cell effector functions that regulate normal immune responses and autoimmune disease. This review highlights multiple B-cell effector mechanisms, including the promotion of cellular immunity, the negative regulation of immune responses, and the production of pathogenic antibodies.

Scale-wise evolution of rainfall probability density functions fingerprints the rainfall generation mechanism

© 2010 by the American Geophysical Union.The cross-scale probabilistic structure of rainfall intensity records collected over time scales ranging from hours to decades at sites dominated by both convective and frontal systems is investigated. Across these sites, intermittency build-up from slow to fast time-scales is analyzed in terms of heavy tailed and asymmetric signatures in the scale-wise evolution of rainfall probability density functions (pdfs). The analysis demonstrates that rainfall records dominated by convective storms develop heavier-Tailed power law pdfs toward finer scales when compared with their frontal systems counterpart. Also, a concomitant marked asymmetry build-up emerges at such finer time scales. A scale-dependent probabilistic description of such fat tails and asymmetry appearance is proposed based on a modified q-Gaussian model, able to describe the cross-scale rainfall pdfs in terms of the nonextensivity parameter q, a lacunarity (intermittency) correction and a tail asymmetry coefficient, linked to the rainfall generation mechanism.

Desensitization, internalization, and signaling functions of beta-arrestins demonstrated by RNA interference.

Beta-arrestins bind to activated G protein-coupled receptor kinase-phosphorylated receptors, which leads to their desensitization with respect to G proteins, internalization via clathrin-coated pits, and signaling via a growing list of "scaffolded" pathways. To facilitate the discovery of novel adaptor and signaling roles of beta-arrestins, we have developed and validated a generally applicable interfering RNA approach for selectively suppressing beta-arrestins 1 or 2 expression by up to 95%. Beta-arrestin depletion in HEK293 cells leads to enhanced cAMP generation in response to beta(2)-adrenergic receptor stimulation, markedly reduced beta(2)-adrenergic receptor and angiotensin II receptor internalization and impaired activation of the MAP kinases ERK 1 and 2 by angiotensin II. This approach should allow discovery of novel signaling and regulatory roles for the beta-arrestins in many seven-membrane-spanning receptor systems.

A tale of three functions: The self-reported uses of autobiographical memory

Theories hold that autobiographical memory serves several broad functions (directive, self, and social). In the current study, items were derived from the theoretical literature to create the Thinking About Life Experiences (TALE) questionnaire to empirically assess these three functions. Participants (N = 167) completed the TALE. To examine convergent validity, they also rated their overall tendency to think about and to talk about the past and completed the Reminiscence Functions Scale (Webster, 1997). The results lend support to the existence of these theoretical functions, but also offer room for refinements in future thinking about both the breadth and specificity of the functions that autobiographical memory serves.

Mix it and fix it: functions of composite olfactory signals in ring-tailed lemurs.

Animals communicating via scent often deposit composite signals that incorporate odorants from multiple sources; however, the function of mixing chemical signals remains understudied. We tested both a 'multiple-messages' and a 'fixative' hypothesis of composite olfactory signalling, which, respectively, posit that mixing scents functions to increase information content or prolong signal longevity. Our subjects-adult, male ring-tailed lemurs (Lemur catta)-have a complex scent-marking repertoire, involving volatile antebrachial (A) secretions, deposited pure or after being mixed with a squalene-rich paste exuded from brachial (B) glands. Using behavioural bioassays, we examined recipient responses to odorants collected from conspecific strangers. We concurrently presented pure A, pure B and mixed A + B secretions, in fresh or decayed conditions. Lemurs preferentially responded to mixed over pure secretions, their interest increasing and shifting over time, from sniffing and countermarking fresh mixtures, to licking and countermarking decayed mixtures. Substituting synthetic squalene (S)-a well-known fixative-for B secretions did not replicate prior results: B secretions, which contain additional chemicals that probably encode salient information, were preferred over pure S. Whereas support for the 'multiple-messages' hypothesis underscores the unique contribution from each of an animal's various secretions, support for the 'fixative' hypothesis highlights the synergistic benefits of composite signals.

Effector functions of heparin-binding hemagglutinin-specific CD8+ T lymphocytes in latent human tuberculosis.

BACKGROUND: Most individuals infected with Mycobacterium tuberculosis do not develop tuberculosis (TB) and can be regarded as being protected by an appropriate immune response to the infection. The characterization of the immune responses of individuals with latent TB may thus be helpful in the definition of correlates of protection and the development of new vaccine strategies. The highly protective antigen heparin-binding hemagglutinin (HBHA) induces strong interferon (IFN)- gamma responses during latent, but not active, TB. Because of the recently recognized importance of CD8(+) T lymphocytes in anti-TB immunity, we characterized the CD8(+) T lymphocyte responses to HBHA in subjects with latent TB. RESULTS: HBHA-specific CD8(+) T lymphocytes expressed memory cell markers and synthesized HBHA-specific IFN- gamma .They also restricted mycobacterial growth and expressed cytotoxicity by a granule-dependent mechanism. This activity was associated with the intracellular expression of HBHA-induced perforin. Surprisingly, the perforin-producing CD8(+) T lymphocytes were distinct from the IFN- gamma -producing CD8(+) T lymphocytes. CONCLUSION: During latent TB, the HBHA-specific CD8(+) T lymphocyte population expresses all 3 effector functions associated with CD8(+) T lymphocyte-mediated protective immune mechanisms, which supports the notion that HBHA may be protective in humans and suggests that markers of HBHA-specific CD8(+) T lymphocyte responses may be useful in the monitoring of protection.

Stochastic comparability and dual q-functions

In this paper we discuss the relationship and characterization of stochastic comparability, duality, and Feller–Reuter–Riley transition functions which are closely linked with each other for continuous time Markov chains. A necessary and sufficient condition for two Feller minimal transition functions to be stochastically comparable is given in terms of their density q-matrices only. Moreover, a necessary and sufficient condition under which a transition function is a dual for some stochastically monotone q-function is given in terms of, again, its density q-matrix. Finally, for a class of q-matrices, the necessary and sufficient condition for a transition function to be a Feller–Reuter–Riley transition function is also given.

Maximum curves and isolated points of entire functions

Given M(r; f) =maxjzj=r (jf(z)j) , curves belonging to the set of points M = fz : jf(z)j = M(jzj; f)g were de�ned by Hardy to be maximum curves. Clunie asked the question as to whether the set M could also contain isolated points. This paper shows that maximum curves consist of analytic arcs and determines a necessary condition for such curves to intersect. Given two entire functions f1(z) and f2(z), if the maximum curve of f1(z) is the real axis, conditions are found so that the real axis is also a maximum curve for the product function f1(z)f2(z). By means of these results an entire function of in�nite order is constructed for which the set M has an in�nite number of isolated points. A polynomial is also constructed with an isolated point.

Applications of Feller-Reuter-Riley transition functions

A Feller–Reuter–Riley function is a Markov transition function whose corresponding semigroup maps the set of the real-valued continuous functions vanishing at infinity into itself. The aim of this paper is to investigate applications of such functions in the dual problem, Markov branching processes, and the Williams-matrix. The remarkable property of a Feller–Reuter–Riley function is that it is a Feller minimal transition function with a stable q-matrix. By using this property we are able to prove that, in the theory of branching processes, the branching property is equivalent to the requirement that the corresponding transition function satisfies the Kolmogorov forward equations associated with a stable q-matrix. It follows that the probabilistic definition and the analytic definition for Markov branching processes are actually equivalent. Also, by using this property, together with the Resolvent Decomposition Theorem, a simple analytical proof of the Williams' existence theorem with respect to the Williams-matrix is obtained. The close link between the dual problem and the Feller–Reuter–Riley transition functions is revealed. It enables us to prove that a dual transition function must satisfy the Kolmogorov forward equations. A necessary and sufficient condition for a dual transition function satisfying the Kolmogorov backward equations is also provided.

Strong ergodicity of monotone transition functions

By revealing close links among strong ergodicity, monotone, and the Feller–Reuter–Riley (FRR) transition functions, we prove that a monotone ergodic transition function is strongly ergodic if and only if it is not FRR. An easy to check criterion for a Feller minimal monotone chain to be strongly ergodic is then obtained. We further prove that a non-minimal ergodic monotone chain is always strongly ergodic. The applications of our results are illustrated using birth-and-death processes and branching processes.

Feller transition functions, Resolvent Decomposition Theorems, and their application in unstable denumerable Markov processes

This paper surveys the recent progresses made in the field of unstable denumerable Markov processes. Emphases are laid upon methodology and applications. The important tools of Feller transition functions and Resolvent Decomposition Theorems are highlighted. Their applications particularly in unstable denumerable Markov processes with a single instantaneous state and Markov branching processes are illustrated.

Hemolymph Functions In Mytilus-Californianus - Cytochemistry Of Hemocytes And Their Responses To Foreign Implants And Hemolymph Factors In Phagocytosis

The hemocytes of Mytilus californianus are of three types: small and large basophils and large granular acidophils. The basophils contain lysosomal enzymes and phagocytose colloidal carbon. Agglutinins for yeast and human A Rh+ve erythrocytes are present in plasma, but are not needed for effective phagocytosis; in vitro both acidophilic and basophilic hemocytes rapidly phagocytose these particles. Plasma proteins, analyzed electrophoretically, are under strong homeostatic control. When Mya arenaria mantle is placed orthotopically on M. californianus mantle, the implant is invaded by host hemocytes in a manner consistent with that described in other published reports on molluscan graft rejection. Steady state is achieved by 26 days postimplant. Second- and third-set implants are rejected more rapidly than are first-set implants, but this is not a specific response. Third-set implants elicit a host cellular response that is more localized than the response to first-set implants. These data do not permit conclusions with respect to memory in these molluscan immune responses, but do imply a qualitative “improvement” in this quasi-immune response of M. californianus.