Ca2+ Influx Regulates BDNF Transcription by a CREB Family Transcription Factor-Dependent Mechanism

AbstractCREB is a transcription factor implicated in the control of adaptive neuronal responses. Although one function of CREB in neurons is believed to be the regulation of genes whose products control synaptic function, the targets of CREB that mediate synaptic function have not yet been identified. This report describes experiments demonstrating that CREB or a closely related protein mediates Ca2+-dependent regulation of BDNF, a neurotrophin that modulates synaptic activity. In cortical neurons, Ca2+ influx triggers phosphorylation of CREB, which by binding to a critical Ca2+ response element (CRE) within the BDNF gene activates BDNF transcription. Mutation of the BDNF CRE or an adjacent novel regulatory element as well as a blockade of CREB function resulted in a dramatic loss of BDNF transcription. These findings suggest that a CREB family member acts cooperatively with an additional transcription factor(s) to regulate BDNF transcription. We conclude that the BDNF gene is a CREB family target whose protein product functions at synapses to control adaptive neuronal responses

Non-Pauli Effects from Noncommutative Spacetimes

Noncommutative spacetimes lead to nonlocal quantum field theories (qft's) where spin-statistics theorems cannot be proved. For this reason, and also backed by detailed arguments, it has been suggested that they get corrected on such spacetimes leading to small violations of the Pauli principle. In a recent paper \cite{Pauli}, Pauli-forbidden transitions from spacetime noncommutativity were calculated and confronted with experiments. Here we give details of the computation missing from this paper. The latter was based on a spacetime $\mathcal{B}_{\chi\vec{n}}$ different from the Moyal plane. We argue that it quantizes time in units of $\chi$. Energy is then conserved only mod $\frac{2\pi}{\chi}$. Issues related to superselection rules raised by non-Pauli effects are also discussed in a preliminary manner.Comment: 15 Pages, 1 Table, Full details and further developments of arXiv:1003.2250. This version is close to the one accepted by JHE

Denominators of Eisenstein cohomology classes for GL_2 over imaginary quadratic fields

We study the arithmetic of Eisenstein cohomology classes (in the sense of G. Harder) for symmetric spaces associated to GL_2 over imaginary quadratic fields. We prove in many cases a lower bound on their denominator in terms of a special L-value of a Hecke character providing evidence for a conjecture of Harder that the denominator is given by this L-value. We also prove under some additional assumptions that the restriction of the classes to the boundary of the Borel-Serre compactification of the spaces is integral. Such classes are interesting for their use in congruences with cuspidal classes to prove connections between the special L-value and the size of the Selmer group of the Hecke character.Comment: 37 pages; strengthened integrality result (Proposition 16), corrected statement of Theorem 3, and revised introductio

Self-Organization, Layered Structure, and Aggregation Enhance Persistence of a Synthetic Biofilm Consortium

Microbial consortia constitute a majority of the earth’s biomass, but little is known about how these cooperating communities persist despite competition among community members. Theory suggests that non-random spatial structures contribute to the persistence of mixed communities; when particular structures form, they may provide associated community members with a growth advantage over unassociated members. If true, this has implications for the rise and persistence of multi-cellular organisms. However, this theory is difficult to study because we rarely observe initial instances of non-random physical structure in natural populations. Using two engineered strains of Escherichia coli that constitute a synthetic symbiotic microbial consortium, we fortuitously observed such spatial self-organization. This consortium forms a biofilm and, after several days, adopts a defined layered structure that is associated with two unexpected, measurable growth advantages. First, the consortium cannot successfully colonize a new, downstream environment until it selforganizes in the initial environment; in other words, the structure enhances the ability of the consortium to survive environmental disruptions. Second, when the layered structure forms in downstream environments the consortium accumulates significantly more biomass than it did in the initial environment; in other words, the structure enhances the global productivity of the consortium. We also observed that the layered structure only assembles in downstream environments that are colonized by aggregates from a previous, structured community. These results demonstrate roles for self-organization and aggregation in persistence of multi-cellular communities, and also illustrate a role for the techniques of synthetic biology in elucidating fundamental biological principles

Twisted convolution and Moyal star product of generalized functions

We consider nuclear function spaces on which the Weyl-Heisenberg group acts continuously and study the basic properties of the twisted convolution product of the functions with the dual space elements. The final theorem characterizes the corresponding algebra of convolution multipliers and shows that it contains all sufficiently rapidly decreasing functionals in the dual space. Consequently, we obtain a general description of the Moyal multiplier algebra of the Fourier-transformed space. The results extend the Weyl symbol calculus beyond the traditional framework of tempered distributions.Comment: LaTeX, 16 pages, no figure

The First Magnetic Fields

We review current ideas on the origin of galactic and extragalactic magnetic fields. We begin by summarizing observations of magnetic fields at cosmological redshifts and on cosmological scales. These observations translate into constraints on the strength and scale magnetic fields must have during the early stages of galaxy formation in order to seed the galactic dynamo. We examine mechanisms for the generation of magnetic fields that operate prior during inflation and during subsequent phase transitions such as electroweak symmetry breaking and the quark-hadron phase transition. The implications of strong primordial magnetic fields for the reionization epoch as well as the first generation of stars is discussed in detail. The exotic, early-Universe mechanisms are contrasted with astrophysical processes that generate fields after recombination. For example, a Biermann-type battery can operate in a proto-galaxy during the early stages of structure formation. Moreover, magnetic fields in either an early generation of stars or active galactic nuclei can be dispersed into the intergalactic medium.Comment: Accepted for publication in Space Science Reviews. Pdf can be also downloaded from http://canopus.cnu.ac.kr/ryu/cosmic-mag1.pd

Improved outcomes of pediatric dilated cardiomyopathy with utilization of heart transplantation

AbstractObjectivesWe studied the outcomes of pediatric patients diagnosed with dilated cardiomyopathy (DCM) and their relation to epidemiologic and echocardiographic variables at the time of presentation.BackgroundThe outcome of pediatric DCM patients ranges from recovery to a 50% to 60% chance of death within five years of diagnosis. The impact of heart transplantation and other emerging therapies on the outcomes of pediatric DCM patients is uncertain.MethodsWe performed a retrospective study of the outcomes in 91 pediatric patients diagnosed with DCM from 1990 to 1999. Routine therapy included use of digoxin, diuretics, angiotensin-converting enzyme inhibitors, and heart transplantation.ResultsAt the time of last follow-up, 11 patients (12%) had died without transplantation; 20 (22%) underwent transplantation; 27 (30%) had persistent cardiomyopathy; and 33 (36%) had recovery of left ventricular systolic function. Overall actuarial one-year survival was 90%, and five-year survival was 83%. However, actuarial freedom from “heart death” (death or transplantation) was only 70% at one year and 58% at five years. Multivariate analysis found age <1 year (hazard ratio 7.1), age >12 years (hazard ratio 4.5), and female gender (hazard ratio 3.0) to be significantly associated with a greater risk of death or transplantation and a higher left ventricular shortening fraction at presentation (hazard ratio 0.92), with a slightly decreased risk of death or transplantation.ConclusionsPediatric DCM patients continue to have multiple outcomes, with recovery of left ventricular systolic function occurring most frequently. Utilization of heart transplantation has led to improved survival after the diagnosis of pediatric DCM

Widespread Occurrence of Dosage Compensation in Candida albicans

The important human pathogen Candida albicans possesses an unusual form of gene regulation, in which the copy number of an entire specific chromosome or a large portion of a specific chromosome changes in response to a specific adverse environment, thus, insuring survival. In the absence of the adverse environment, the altered portion of the genome can be restored to its normal condition. One major question is how C. albicans copes with gene imbalance arising by transitory aneuploid states. Here, we compared transcriptomes from cells with either two copies or one copy of chromosome 5 (Ch5) in, respectively, a diploid strain 3153A and its representative derivative Sor55. Statistical analyses revealed that at least 40% of transcripts from the monosomic Ch5 are fully compensated to a disomic level, thus, indicating the existence of a genome-wide mechanism maintaining cellular homeostasis. Only approximately 15% of transcripts were diminished twofold in accordance with what would be expected for Ch5 monosomy. Another minor portion of approximately 6% of transcripts, unexpectedly, increased up to twofold and higher than the disomic level, demonstrating indirect control by monosomy. Array comparative genome hybridization revealed that only few out of approximately 500 genes on the monosomic Ch5b were duplicated, thus, not causing a global up regulation. Dosage compensation was confirmed with several representative genes from another monosomic Ch5a in the mutant Sor60. We suggest that C. albicans's unusual regulation of gene expression by the loss and gain of entire chromosomes is coupled with widespread compensation of gene dosage at the transcriptional level

The influence of the accessory genome on bacterial pathogen evolution

Bacterial pathogens exhibit significant variation in their genomic content of virulence factors. This reflects the abundance of strategies pathogens evolved to infect host organisms by suppressing host immunity. Molecular arms-races have been a strong driving force for the evolution of pathogenicity, with pathogens often encoding overlapping or redundant functions, such as type III protein secretion effectors and hosts encoding ever more sophisticated immune systems. The pathogens’ frequent exposure to other microbes, either in their host or in the environment, provides opportunities for the acquisition or interchange of mobile genetic elements. These DNA elements accessorise the core genome and can play major roles in shaping genome structure and altering the complement of virulence factors. Here, we review the different mobile genetic elements focusing on the more recent discoveries and highlighting their role in shaping bacterial pathogen evolution