Gap Junction Gene Expression In The Developing Nervous System

Gap junctions provide for the transfer of low molecular weight molecules and ions between cytoplasms of adjacent cells. Connexins exist as a multigene family with one or more members found in almost all adult tissues. In the central nervous system, gap junctions have been detected in a variety of cell types including neurons, astrocytes and oligodendrocytes. Gap junctions have been detected in the developing brain in a spacial and temporal pattern. This study examines gap junction expression and cellular specificity during development of the rodent central nervous system. To investigate the role of gap junctions during development, a model of neural development is examined with respect to its connexin expression.;In the developing rodent brain, connexin32 and connexin43 were detected by Northern blot analysis. Connexin43 mRNA was detected pre- and postnatally, whereas connexin32 mRNA was differentially expressed, being first detectable at postnatal day 10 in hindbrain and day 15 in forebrain. Western blot analysis demonstrated the presence of connexin protein during postnatal development of the rodent brain. To examine connexin expression in greater detail, in situ hybridization studies were performed. Connexin43 mRNA was found in the leptomeninges and astrocytes. Oligodendrocytes and select populations of neurons were shown to express connexin32 mRNA. Cultured astrocytes express cx43 confirming the in vivo findings. Initially, in culture, neurons express connexin26 protein which becomes less abundant with time. Neurons cultured for extended periods of time express cx32.;The embryonal carcinoma cell line, P19, differentiates into neurons and astrocytes following treatment with retinoic acid. Undifferentiated P19 cells express connexin26 and 43. The mRNA level of these two connexins do not change when P19 cells were exposed to retinoic acid. Connexin43 protein, however, is significantly reduced after exposure to retinoic acid. During differentiation, the neurons expressed connexin26 and astroctyes expressed connexin43.;These investigations have determined that gap junctions are differentially expressed during development of the central nervous system. Astrocytes express connexin43 whereas neurons and oligodendrocytes express connexin32. Connexin26 is present in immature neurons in culture. The studies on P19 cells further support the presence of connexin26 in neurons and represents a model of neural differentiation that modulates connexin expression

Fundamental limits on the rate of bacterial growth

Recent years have seen an experimental deluge interrogating the relationship between bacterial growth rate, cell size, and protein content, quantifying the abundance of proteins across growth conditions with unprecedented resolution. However, we still lack a rigorous understanding of what sets the scale of these quantities and when protein abundances should (or should not) depend on growth rate. Here, we seek to quantitatively understand this relationship across a collection of Escherichia coli proteomic data covering ≈ 4000 proteins and 36 growth rates. We estimate the basic requirements for steady-state growth by considering key processes in nutrient transport, cell envelope biogenesis, energy generation, and the central dogma. From these estimates, ribosome biogenesis emerges as a primary determinant of growth rate. We expand on this assessment by exploring a model of proteomic regulation as a function of the nutrient supply, revealing a mechanism that ties cell size and growth rate to ribosomal content

Sensory Island Task (SIT): A New Behavioral Paradigm to Study Sensory Perception and Neural Processing in Freely Moving Animals

A central function of sensory systems is the gathering of information about dynamic interactions with the environment during self-motion. To determine whether modulation of a sensory cue was externally caused or a result of self-motion is fundamental to perceptual invariance and requires the continuous update of sensory processing about recent movements. This process is highly context-dependent and crucial for perceptual performances such as decision-making and sensory object formation. Yet despite its fundamental ecological role, voluntary self-motion is rarely incorporated in perceptual or neurophysiological investigations of sensory processing in animals. Here, we present the Sensory Island Task (SIT), a new freely moving search paradigm to study sensory processing and perception. In SIT, animals explore an open-field arena to find a sensory target relying solely on changes in the presented stimulus, which is controlled by closed-loop position tracking in real-time. Within a few sessions, animals are trained via positive reinforcement to search for a particular area in the arena (“target island”), which triggers the presentation of the target stimulus. The location of the target island is randomized across trials, making the modulated stimulus feature the only informative cue for task completion. Animals report detection of the target stimulus by remaining within the island for a defined time (“sit-time”). Multiple “non-target” islands can be incorporated to test psychometric discrimination and identification performance. We exemplify the suitability of SIT for rodents (Mongolian gerbil, Meriones unguiculatus) and small primates (mouse lemur, Microcebus murinus) and for studying various sensory perceptual performances (auditory frequency discrimination, sound source localization, visual orientation discrimination). Furthermore, we show that pairing SIT with chronic electrophysiological recordings allows revealing neuronal signatures of sensory processing under ecologically relevant conditions during goal-oriented behavior. In conclusion, SIT represents a flexible and easily implementable behavioral paradigm for mammals that combines self-motion and natural exploratory behavior to study sensory sensitivity and decision-making and their underlying neuronal processing

Fundamental limits on the rate of bacterial growth

Recent years have seen an experimental deluge interrogating the relationship between bacterial growth rate, cell size, and protein content, quantifying the abundance of proteins across growth conditions with unprecedented resolution. However, we still lack a rigorous understanding of what sets the scale of these quantities and when protein abundances should (or should not) depend on growth rate. Here, we seek to quantitatively understand this relationship across a collection of Escherichia coli proteomic data covering ≈ 4000 proteins and 36 growth rates. We estimate the basic requirements for steady-state growth by considering key processes in nutrient transport, cell envelope biogenesis, energy generation, and the central dogma. From these estimates, ribosome biogenesis emerges as a primary determinant of growth rate. We expand on this assessment by exploring a model of proteomic regulation as a function of the nutrient supply, revealing a mechanism that ties cell size and growth rate to ribosomal content

The p75 Neurotrophin Receptor Mediates Neuronal Apoptosis and Is Essential for Naturally Occurring Sympathetic Neuron Death

Abstract. To determine whether the p75 neurotrophin receptor (p75NTR) plays a role in naturally occurring neuronal death, we examined neonatal sympathetic neurons that express both the TrkA tyrosine kinase receptor and p75NTR. When sympathetic neuron survival is maintained with low quantities of NGF or KCl, the neurotrophin brain-derived neurotrophic factor (BDNF), which does not activate Trk receptors on sympathetic neurons, causes neuronal apoptosis and increased phosphorylation of c-jun. Function-blocking antibody studies indicate that this apoptosis is due to BDNF-mediated activation of p75NTR. To determine the physiological relevance of these culture findings, we examined sympathetic neurons in BDNF−/− and p75NTR−/− mice. In BDNF−/− mice, sympathetic neuron number is increased relative to BDNF+/+ littermates, and in p75NTR−/− mice, the normal period of sympathetic neuron death does not occur, with neuronal attrition occurring later in life. This deficit in apoptosis is intrinsic to sympathetic neurons, since cultured p75NTR−/− neurons die more slowly than do their wild-type counterparts. Together, these data indicate that p75NTR can signal to mediate apoptosis, and that this mechanism is essential for naturally occurring sympathetic neuron death

Upwelling on the continental slope of the Alaskan Beaufort Sea : storms, ice, and oceanographic response

Author Posting. © American Geophysical Union, 2009. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 114 (2009): C00A13, doi:10.1029/2008JC005009.The characteristics of Pacific-born storms that cause upwelling along the Beaufort Sea continental slope, the oceanographic response, and the modulation of the response due to sea ice are investigated. In fall 2002 a mooring array located near 152°W measured 11 significant upwelling events that brought warm and salty Atlantic water to shallow depths. When comparing the storms that caused these events to other Aleutian lows that did not induce upwelling, interesting trends emerged. Upwelling occurred most frequently when storms were located in a region near the eastern end of the Aleutian Island Arc and Alaskan Peninsula. Not only were these storms deep but they generally had northward-tending trajectories. While the steering flow aloft aided this northward progression, the occurrence of lee cyclogenesis due to the orography of Alaska seems to play a role as well in expanding the meridional influence of the storms. In late fall and early winter both the intensity and frequency of the upwelling diminished significantly at the array site. It is argued that the reduction in amplitude was due to the onset of heavy pack ice, while the decreased frequency was due to two different upper-level atmospheric blocking patterns inhibiting the far field influence of the storms.The following grants provided support for this study: National Science Foundation grants OPP-0731928 (R.S.P.) and OPP-0713250 (R.S.P. and P.S.F.), Office of Naval Research grant N00014-07-1-1040 (D.J.T. and R.A.G.), Natural Sciences and Engineering Research Council of Canada (G.W.K.M.), Woods Hole Oceanographic Institution Arctic Initiative (J.Y.)

Identification of common genetic risk variants for autism spectrum disorder

Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD