Regionally Distinct N -Methyl-D-Aspartate Receptors Distinguished by Quantitative Autoradiography of [ 3 H]MK-801 Binding in Rat Brain

Quantitative autoradiography of [ 3 H]MK-801 binding was used to characterize regional differences in N -methyl-d-aspartate (NMDA) receptor pharmacology in rat CNS. Regionally distinct populations of NMDA receptors were distinguished on the basis of regulation of [ 3 H]MK-801 binding by the NMDA antagonist 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP). CPP inhibited [ 3 H]MK-801 binding in outer cortex (OC) and medial cortex (MC) with apparent K i values of 0.32-0.48 Μ M , whereas in the medial striatum (MS), lateral striatum (LS), CA1, and dentate gyrus (DG) of hippocampus, apparent K i values were 1.1-1.6 Μ M . In medial thalamus (MT) and lateral thalamus (LT) the apparent K i values were 0.78 Μ M . In the presence of added glutamate (3 Μ M ), the relative differences in apparent K i values between regions maintained a similar relationship with the exception of the OC. Inhibition of [ 3 H]MK-801 binding by the glycine site antagonist 7-chlorokynurenic acid (7-ClKyn) distinguished at least two populations of NMDA receptors that differed from populations defined by CPP displacement. 7-ClKyn inhibited [ 3 H]MK-801 binding in OC, MC, MS, and LS with apparent K i values of 6.3-8.6 Μ M , whereas in CA1, DG, LT, and MT, K i values were 11.4-13.6 Μ M . In the presence of added glycine (1 Μ M ), the relative differences in apparent K i values were maintained. Under conditions of differential receptor activation, regional differences in NMDA receptor pharmacology can be detected using [ 3 H]MK-801 binding.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65616/1/j.1471-4159.1993.tb03295.x.pd

A microchip optomechanical accelerometer

The monitoring of accelerations is essential for a variety of applications ranging from inertial navigation to consumer electronics. The basic operation principle of an accelerometer is to measure the displacement of a flexibly mounted test mass; sensitive displacement measurement can be realized using capacitive, piezo-electric, tunnel-current, or optical methods. While optical readout provides superior displacement resolution and resilience to electromagnetic interference, current optical accelerometers either do not allow for chip-scale integration or require bulky test masses. Here we demonstrate an optomechanical accelerometer that employs ultra-sensitive all-optical displacement read-out using a planar photonic crystal cavity monolithically integrated with a nano-tethered test mass of high mechanical Q-factor. This device architecture allows for full on-chip integration and achieves a broadband acceleration resolution of 10 \mu g/rt-Hz, a bandwidth greater than 20 kHz, and a dynamic range of 50 dB with sub-milliwatt optical power requirements. Moreover, the nano-gram test masses used here allow for optomechanical back-action in the form of cooling or the optical spring effect, setting the stage for a new class of motional sensors.Comment: 16 pages, 9 figure

Biochemical analysis of the N-terminal domain of human RAD54B

The human RAD54B protein is a paralog of the RAD54 protein, which plays important roles in homologous recombination. RAD54B contains an N-terminal region outside the SWI2/SNF2 domain that shares less conservation with the corresponding region in RAD54. The biochemical roles of this region of RAD54B are not known, although the corresponding region in RAD54 is known to physically interact with RAD51. In the present study, we have biochemically characterized an N-terminal fragment of RAD54B, consisting of amino acid residues 26–225 (RAD54B26–225). This fragment formed a stable dimer in solution and bound to branched DNA structures. RAD54B26–225 also interacted with DMC1 in both the presence and absence of DNA. Ten DMC1 segments spanning the entire region of the DMC1 sequence were prepared, and two segments, containing amino acid residues 153–214 and 296–340, were found to directly bind to the N-terminal domain of RAD54B. A structural alignment of DMC1 with the Methanococcus voltae RadA protein, a homolog of DMC1 in the helical filament form, indicated that these RAD54B-binding sites are located near the ATP-binding site at the monomer–monomer interface in the DMC1 helical filament. Thus, RAD54B binding may affect the quaternary structure of DMC1. These observations suggest that the N-terminal domain of RAD54B plays multiple roles of in homologous recombination

Physical Links: Defining and detecting inter-chain entanglement

Fluctuating filaments, from densely-packed biopolymers to defect lines in structured fluids, are prone to become interlaced and form intricate architectures. Understanding the ensuing mechanical and relaxation properties depends critically on being able to capture such entanglement in quantitative terms. So far, this has been an elusive challenge. Here we introduce the first general characterization of non-ephemeral forms of entanglement in linear curves by introducing novel descriptors that extend topological measures of linking from close to open curves. We thus establish the concept of physical links. This general method is applied to diverse contexts: equilibrated ring polymers, mechanically-stretched links and concentrated solutions of linear chains. The abundance, complexity and space distribution of their physical links gives access to a whole new layer of understanding of such systems and open new perspectives for others, such as reconnection events and topological simplification in dissipative fields and defect lines

Orexin Neurons Receive Glycinergic Innervations

Glycine, a nonessential amino-acid that acts as an inhibitory neurotransmitter in the central nervous system, is currently used as a dietary supplement to improve the quality of sleep, but its mechanism of action is poorly understood. We confirmed the effects of glycine on sleep/wakefulness behavior in mice when administered peripherally. Glycine administration increased non-rapid eye movement (NREM) sleep time and decreased the amount and mean episode duration of wakefulness when administered in the dark period. Since peripheral administration of glycine induced fragmentation of sleep/wakefulness states, which is a characteristic of orexin deficiency, we examined the effects of glycine on orexin neurons. The number of Fos-positive orexin neurons markedly decreased after intraperitoneal administration of glycine to mice. To examine whether glycine acts directly on orexin neurons, we examined the effects of glycine on orexin neurons by patch-clamp electrophysiology. Glycine directly induced hyperpolarization and cessation of firing of orexin neurons. These responses were inhibited by a specific glycine receptor antagonist, strychnine. Triple-labeling immunofluorescent analysis showed close apposition of glycine transporter 2 (GlyT2)-immunoreactive glycinergic fibers onto orexin-immunoreactive neurons. Immunoelectron microscopic analysis revealed that GlyT2-immunoreactive terminals made symmetrical synaptic contacts with somata and dendrites of orexin neurons. Double-labeling immunoelectron microscopy demonstrated that glycine receptor alpha subunits were localized in the postsynaptic membrane of symmetrical inhibitory synapses on orexin neurons. Considering the importance of glycinergic regulation during REM sleep, our observations suggest that glycine injection might affect the activity of orexin neurons, and that glycinergic inhibition of orexin neurons might play a role in physiological sleep regulation

Quality of Life of Caregivers of Older Patients with Advanced Cancer

OBJECTIVES: To evaluate the relationships between aging-related domains captured by geriatric assessment (GA) for older patients with advanced cancer and caregivers’ emotional health and quality of life (QOL). DESIGN: In this cross sectional study of baseline data from a nationwide investigation of older patients and their caregivers, patients completed a GA that included validated tests to evaluate eight domains of health (eg, function, cognition). SETTING: Thirty-one community oncology practices throughout the United States. PARTICIPANTS: Enrolled patients were aged 70 and older, had one or more GA domain impaired, and had an incurable solid tumor malignancy or lymphoma. Each could choose one caregiver to enroll. MEASUREMENTS: Caregivers completed the Generalized Anxiety Disorder-7, Distress Thermometer, Patient Health Questionnaire-2 (depression), and Short Form Health Survey-12 (SF-12 for QOL). Separate multivariate linear or logistic regression models were used to examine the association of the number and type of patient GA impairments with caregiver outcomes, controlling for patient and caregiver covariates. RESULTS: A total of 541 patients were enrolled, 414 with a caregiver. Almost half (43.5%) of the caregivers screened positive for distress, 24.4% for anxiety, and 18.9% for depression. Higher numbers of patient GA domain impairments were associated with caregiver depression (adjusted odds ratio [aOR] = 1.29; P <.001], caregiver physical health on SF-12 (regression coefficient [β] = −1.24; P <.001), and overall caregiver QOL (β = −1.14; P <.01). Impaired patient function was associated with lower caregiver QOL (β = −4.11; P <.001). Impaired patient nutrition was associated with caregiver depression (aOR = 2.08; P <.01). Lower caregiver age, caregiver comorbidity, and patient distress were also associated with worse caregiver outcomes. CONCLUSION: Patient GA impairments were associated with poorer emotional health and lower QOL of caregivers

Genome-Wide Crossover Distribution in Arabidopsis thaliana Meiosis Reveals Sex-Specific Patterns along Chromosomes

In most species, crossovers (COs) are essential for the accurate segregation of homologous chromosomes at the first meiotic division. Their number and location are tightly regulated. Here, we report a detailed, genome-wide characterization of the rate and localization of COs in Arabidopsis thaliana, in male and female meiosis. We observed dramatic differences between male and female meiosis which included: (i) genetic map length; 575 cM versus 332 cM respectively; (ii) CO distribution patterns: male CO rates were very high at both ends of each chromosome, whereas female CO rates were very low; (iii) correlations between CO rates and various chromosome features: female CO rates correlated strongly and negatively with GC content and gene density but positively with transposable elements (TEs) density, whereas male CO rates correlated positively with the CpG ratio. However, except for CpG, the correlations could be explained by the unequal repartition of these sequences along the Arabidopsis chromosome. For both male and female meiosis, the number of COs per chromosome correlates with chromosome size expressed either in base pairs or as synaptonemal complex length. Finally, we show that interference modulates the CO distribution both in male and female meiosis

A bacterial genome in transition - an exceptional enrichment of IS elements but lack of evidence for recent transposition in the symbiont Amoebophilus asiaticus

<p>Abstract</p> <p>Background</p> <p>Insertion sequence (IS) elements are important mediators of genome plasticity and are widespread among bacterial and archaeal genomes. The 1.88 Mbp genome of the obligate intracellular amoeba symbiont <it>Amoebophilus asiaticus </it>contains an unusually large number of transposase genes (n = 354; 23% of all genes).</p> <p>Results</p> <p>The transposase genes in the <it>A. asiaticus </it>genome can be assigned to 16 different IS elements termed ISCaa1 to ISCaa16, which are represented by 2 to 24 full-length copies, respectively. Despite this high IS element load, the <it>A. asiaticus </it>genome displays a GC skew pattern typical for most bacterial genomes, indicating that no major rearrangements have occurred recently. Additionally, the high sequence divergence of some IS elements, the high number of truncated IS element copies (n = 143), as well as the absence of direct repeats in most IS elements suggest that the IS elements of <it>A. asiaticus </it>are transpositionally inactive. Although we could show transcription of 13 IS elements, we did not find experimental evidence for transpositional activity, corroborating our results from sequence analyses. However, we detected contiguous transcripts between IS elements and their downstream genes at nine loci in the <it>A. asiaticus </it>genome, indicating that some IS elements influence the transcription of downstream genes, some of which might be important for host cell interaction.</p> <p>Conclusions</p> <p>Taken together, the IS elements in the <it>A. asiaticus </it>genome are currently in the process of degradation and largely represent reflections of the evolutionary past of <it>A. asiaticus </it>in which its genome was shaped by their activity.</p

Nonlinearity and Topology

The interplay of nonlinearity and topology results in many novel and emergent properties across a number of physical systems such as chiral magnets, nematic liquid crystals, Bose-Einstein condensates, photonics, high energy physics, etc. It also results in a wide variety of topological defects such as solitons, vortices, skyrmions, merons, hopfions, monopoles to name just a few. Interaction among and collision of these nontrivial defects itself is a topic of great interest. Curvature and underlying geometry also affect the shape, interaction and behavior of these defects. Such properties can be studied using techniques such as, e.g. the Bogomolnyi decomposition. Some applications of this interplay, e.g. in nonreciprocal photonics as well as topological materials such as Dirac and Weyl semimetals, are also elucidated