Homophilic Protocadherin Cell-Cell Interactions Promote Dendrite Complexity

SummaryGrowth of a properly complex dendrite arbor is a key step in neuronal differentiation and a prerequisite for neural circuit formation. Diverse cell surface molecules, such as the clustered protocadherins (Pcdhs), have long been proposed to regulate circuit formation through specific cell-cell interactions. Here, using transgenic and conditional knockout mice to manipulate γ-Pcdh repertoire in the cerebral cortex, we show that the complexity of a neuron’s dendritic arbor is determined by homophilic interactions with other cells. Neurons expressing only one of the 22 γ-Pcdhs can exhibit either exuberant or minimal dendrite complexity, depending only on whether surrounding cells express the same isoform. Furthermore, loss of astrocytic γ-Pcdhs, or disruption of astrocyte-neuron homophilic matching, reduces dendrite complexity cell non-autonomously. Our data indicate that γ-Pcdhs act locally to promote dendrite arborization via homophilic matching, and they confirm that connectivity in vivo depends on molecular interactions between neurons and between neurons and astrocytes

Absorption of Energy at a Metallic Surface due to a Normal Electric Field

The effect of an oscillating electric field normal to a metallic surface may be described by an effective potential. This induced potential is calculated using semiclassical variants of the random phase approximation (RPA). Results are obtained for both ballistic and diffusive electron motion, and for two and three dimensional systems. The potential induced within the surface causes absorption of energy. The results are applied to the absorption of radiation by small metal spheres and discs. They improve upon an earlier treatment which used the Thomas-Fermi approximation for the effective potential.Comment: 19 pages (Plain TeX), 2 figures, 1 table (Postscript

The Experiences of Lesbian, Gay, Bisexual, Transgender and Queer Students in Social Work Programs. A Study Report from the CSWE Council on Sexual Orientation and Gender Identity and Expression

This online North American study of lesbian, gay, bisexual, transgender, and queer (LGBTQ) social work students (n=1,018) in bachelor of social work (BSW; 24%) or master’s of social work (MSW; 76%) programs explored educational experiences in 126 programs in 44 U. S. states and 7 Canadian provinces. Forty-four percent of students reported limited inclusion of LGBTQ content in classes, yet 64% indicated some degree of support for their LGBTQ identities in their programs. One-third reported homophobic experiences in programs, yet many (63%) were aware of “out” LGBTQ faculty. Overall, students reported fairly low levels of self-assessed practice readiness with specific subpopulations (i.e., gay, lesbian, bisexual, transgender), with participants reporting the highest (somewhat prepared) self-assessed readiness with gay populations and the lowest (not well-prepared) self-assessed readiness with transgender populations. Participants suggested lower readiness for their non-LGBTQ colleagues. Implications for social work education are discussed

Dysflective cones: Visual function and cone reflectivity in long-term follow-up of acute bilateral foveolitis.

PURPOSE:Confocal adaptive optics scanning laser ophthalmoscope (AOSLO) images provide a sensitive measure of cone structure. However, the relationship between structural findings of diminished cone reflectivity and visual function is unclear. We used fundus-referenced testing to evaluate visual function in regions of apparent cone loss identified using confocal AOSLO images. METHODS:A patient diagnosed with acute bilateral foveolitis had spectral-domain optical coherence tomography (SD-OCT) (Spectralis HRA + OCT system [Heidelberg Engineering, Vista, CA, USA]) images indicating focal loss of the inner segment-outer segment junction band with an intact, but hyper-reflective, external limiting membrane. Five years after symptom onset, visual acuity had improved from 20/80 to 20/25, but the retinal appearance remained unchanged compared to 3 months after symptoms began. We performed structural assessments using SD-OCT, directional OCT (non-standard use of a prototype on loan from Carl Zeiss Meditec) and AOSLO (custom-built system). We also administered fundus-referenced functional tests in the region of apparent cone loss, including analysis of preferred retinal locus (PRL), AOSLO acuity, and microperimetry with tracking SLO (TSLO) (prototype system). To determine AOSLO-corrected visual acuity, the scanning laser was modulated with a tumbling E consistent with 20/30 visual acuity. Visual sensitivity was assessed in and around the lesion using TSLO microperimetry. Complete eye examination, including standard measures of best-corrected visual acuity, visual field tests, color fundus photos, and fundus auto-fluorescence were also performed. RESULTS:Despite a lack of visible cone profiles in the foveal lesion, fundus-referenced vision testing demonstrated visual function within the lesion consistent with cone function. The PRL was within the lesion of apparent cone loss at the fovea. AOSLO visual acuity tests were abnormal, but measurable: for trials in which the stimulus remained completely within the lesion, the subject got 48% correct, compared to 78% correct when the stimulus was outside the lesion. TSLO microperimetry revealed reduced, but detectible, sensitivity thresholds within the lesion. CONCLUSIONS AND IMPORTANCE:Fundus-referenced visual testing proved useful to identify functional cones despite apparent photoreceptor loss identified using AOSLO and SD-OCT. While AOSLO and SD-OCT appear to be sensitive for the detection of abnormal or absent photoreceptors, changes in photoreceptors that are identified with these imaging tools do not correlate completely with visual function in every patient. Fundus-referenced vision testing is a useful tool to indicate the presence of cones that may be amenable to recovery or response to experimental therapies despite not being visible on confocal AOSLO or SD-OCT images

Magnetic Dipole Absorption of Radiation in Small Conducting Particles

We give a theoretical treatment of magnetic dipole absorption of electromagnetic radiation in small conducting particles, at photon energies which are large compared to the single particle level spacing, and small compared to the plasma frequency. We discuss both diffusive and ballistic electron dynamics for particles of arbitrary shape. The conductivity becomes non-local when the frequency is smaller than the frequency \omega_c characterising the transit of electrons from one side of the particle to the other, but in the diffusive case \omega_c plays no role in determining the absorption coefficient. In the ballistic case, the absorption coefficient is proportional to \omega^2 for \omega << \omega_c, but is a decreasing function of \omega for \omega >> \omega_c.Comment: 25 pages of plain TeX, 2 postscipt figure

Enhancing the Infrared Photoresponse of Silicon by Controlling the Fermi Level Location within an Impurity Band

Strong absorption of sub-band gap radiation by an impurity band has recently been demonstrated in silicon supersaturated with chalcogen impurities. However, despite the enhanced absorption in this material, the transformation of infrared radiation into an electrical signal via extrinsic photoconductivity—the critical performance requirement for many optoelectronic applications—has only been reported at low temperature because thermal impurity ionization overwhelms photoionization at room temperature. Here, dopant compensation is used to manipulate the optical and electronic properties and thereby improve the room-temperature infrared photoresponse. Silicon co-doped with boron and sulfur is fabricated using ion implantation and nanosecond pulsed laser melting to achieve supersaturated sulfur concentrations and a matched boron distribution. The location of the Fermi level within the sulfur-induced impurity band is controlled by tuning the acceptor-to-donor ratio, and through this dopant compensation, three orders of magnitude improvement in infrared detection at 1550 nm is demonstrated.Engineering and Applied Science

Social Jetlag Inhibits Exercise-Induced Adaptations in the Heart and Alters Markers of Mitochondrial Dynamics

Social jetlag (SJL), or the shifting of behavior and sleep times between weekdays and weekends, is a pervasive form of circadian rhythm disruption that affects nearly 70% of the population to some extent. The magnitude of SJL can be determined by the difference in the mid-sleep phase between weekends and weekdays. Higher levels of SJL have been associated with lower levels of cardiorespiratory fitness, and increased incidence of cardiometabolic disease, which may be due, in part, to mitochondrial dysfunction. However, no studies to date have evaluated the effects of long term SJL on cardiac mitochondrial dynamics. PURPOSE: To determine the effect of SJL on mitochondrial fission and fusion signaling in the heart, and if exercise protects the heart against SJL. METHODS: Male C57BL/6 mice (n = 40) were allocated to four groups (n = 10/group): 1) Control Light:Dark cycle, Sedentary (CON-SED), 2) Control Light:Dark cycle, Exercise (CON-EX), 3) SJL, sedentary (SJL-SED), or SJL, exercise (SJL-EX). SJL was implemented by delaying the LD cycle 4 hours on ‘Fridays,’ and advancing the LD cycle on Mondays. Exercise was provided ad libitum with a disc. Conditions persisted for 6 weeks at which point hearts were harvested for gravimetric analysis and western blotting of markers of mitochondrial dynamics. RESULTS: Exercise caused myocardial hypertrophy in both control and SJL LD conditions (Main Effect – EX, p \u3c 0.05), with no difference between CON and SJL conditions. We did not observe any significant differences in mitochondrial content (OXPHOS antibody cocktail, p \u3e 0.05), SJL decreased expression of mitochondrial fusion proteins MFN1 and OPA1 (Main Effect – SJL, p \u3c 0.05). Importantly, SJL inhibited exercise-induced increases in MFN2 (p \u3c 0.05), suggesting that SJL specifically ameliorates some exercise-induced adaptations in mitochondrial dynamics in the heart. CONCLUSION: These findings suggest that exercise induces adaptations in mitochondrial dynamics, potentially increasing mitochondrial function, and SJL may disrupt mitochondrial dynamics both in the sedentary and exercise trained states

γH2AX Foci Form Preferentially in Euchromatin after Ionising-Radiation

BACKGROUND: The histone variant histone H2A.X comprises up to 25% of the H2A complement in mammalian cells. It is rapidly phosphorylated following exposure of cells to double-strand break (DSB) inducing agents such as ionising radiation. Within minutes of DSB generation, H2AX molecules are phosphorylated in large chromatin domains flanking DNA double-strand breaks (DSBs); these domains can be observed by immunofluorescence microscopy and are termed gammaH2AX foci. H2AX phosphorylation is believed to have a role mounting an efficient cellular response to DNA damage. Theoretical considerations suggest an essentially random chromosomal distribution of X-ray induced DSBs, and experimental evidence does not consistently indicate otherwise. However, we observed an apparently uneven distribution of gammaH2AX foci following X-irradiation with regions of the nucleus devoid of foci. METHODOLOGY/PRINCIPLE FINDINGS: Using immunofluorescence microscopy, we show that focal phosphorylation of histone H2AX occurs preferentially in euchromatic regions of the genome following X-irradiation. H2AX phosphorylation has also been demonstrated previously to occur at stalled replication forks induced by UV radiation or exposure to agents such as hydroxyurea. In this study, treatment of S-phase cells with hydroxyurea lead to efficient H2AX phosphorylation in both euchromatin and heterochromatin at times when these chromatin compartments were undergoing replication. This suggests a block to H2AX phosphorylation in heterochromatin that is at least partially relieved by ongoing DNA replication. CONCLUSIONS/SIGNIFICANCE: We discuss a number of possible mechanisms that could account for the observed pattern of H2AX phosphorylation. Since gammaH2AX is regarded as forming a platform for the recruitment or retention of other DNA repair and signaling molecules, these findings imply that the processing of DSBs in heterochromatin differs from that in euchromatic regions. The differential responses of heterochromatic and euchromatic compartments of the genome to DSBs will have implications for understanding the processes of DNA repair in relation to nuclear and chromatin organization