Temporal morphological changes in the Imhotep region of comet 67P/Churyumov-Gerasimenko

Aims. We report on the first major temporal morphological changes observed on the surface of the nucleus of comet 67P/Churyumov-Gerasimenko in the smooth terrains of the Imhotep region. Methods. We used images of the OSIRIS cameras onboard Rosetta to follow the temporal changes from 24 May 2015 to 11 July 2015. Results. The morphological changes observed on the surface are visible in the form of roundish features that are growing in size from a given location in a preferential direction at a rate of 5.6-8.1 x 10(-5) m s(-1) during the observational period. The location where the changes started and the contours of the expanding features are bluer than the surroundings, which suggests that ices (H2O and/or CO2) are exposed on the surface. However, sublimation of ices alone is not sufficient to explain the observed expanding features. No significant variations in the dust activity pattern are observed during the period of changes.

Large-scale dust jets in the coma of 67P/Churyumov-Gerasimenko as seen by the OSIRIS instrument onboard Rosetta

Context. During the most recent perihelion passage in 2009 of comet 67P/Churyumov-Gerasimenko (67P), ground-based observations showed an anisotropic dust coma where jet-like features were detected at similar to 1.3 AU from the Sun. The current perihelion passage is exceptional as the Rosetta spacecraft is monitoring the nucleus activity since March 2014, when a clear dust coma was already surrounding the nucleus at 4.3 AU from the Sun. Subsequently, the OSIRIS camera also witnessed an outburst in activity between April 27 and 30, and since mid-July, the dust coma at rh similar to 3.7-3.6 AU preperihelion is clearly non-isotropic, pointing to the existence of dust jet-like features. Aims. We aim to ascertain on the nucleus surface the origin of the dust jet-like features detected as early as in mid-July 2014. This will help to establish how the localized comet nucleus activity compares with that seen in previous apparitions and will also help following its evolution as the comet approaches its perihelion, at which phase most of the jets were detected from ground-based observations. Determining these areas also allows locating them in regions on the nucleus with spectroscopic or geomorphological distinct characteristics. Methods. Three series of dust images of comet 67P obtained with the Wide Angle Camera (WAC) of the OSIRIS instrument onboard the Rosetta spacecraft were processed with different enhancement techniques. This was made to clearly show the existence of jet-like features in the dust coma, whose appearance toward the observer changed as a result of the rotation of the comet nucleus and of the changing observing geometry from the spacecraft. The position angles of these features in the coma together with information on the observing geometry, nucleus shape, and rotation, allowed us to determine the most likely locations on the nucleus surface where the jets originate from. Results. Geometrical tracing of jet sources indicates that the activity of the nucleus of 67P gave rise during July and August 2014 to large-scale jet-like features from the Hapi, Hathor, Anuket, and Aten regions, confirming that active regions may be present on the nucleus localized at 60. northern latitude as deduced from previous comet apparitions. There are also hints that large-scale jets observed from the ground are possibly composed, at their place of origin on the nucleus surface, of numerous small-scale features.

Scientific assessment of the quality of OSIRIS images

Context. OSIRIS, the scientific imaging system onboard the ESA Rosetta spacecraft, has been imaging the nucleus of comet 67P/Churyumov-Gerasimenko and its dust and gas environment since March 2014. The images serve different scientific goals, from morphology and composition studies of the nucleus surface, to the motion and trajectories of dust grains, the general structure of the dust coma, the morphology and intensity of jets, gas distribution, mass loss, and dust and gas production rates. Aims. We present the calibration of the raw images taken by OSIRIS and address the accuracy that we can expect in our scientific results based on the accuracy of the calibration steps that we have performed. Methods. We describe the pipeline that has been developed to automatically calibrate the OSIRIS images. Through a series of steps, radiometrically calibrated and distortion corrected images are produced and can be used for scientific studies. Calibration campaigns were run on the ground before launch and throughout the years in flight to determine the parameters that are used to calibrate the images and to verify their evolution with time. We describe how these parameters were determined and we address their accuracy. Results. We provide a guideline to the level of trust that can be put into the various studies performed with OSIRIS images, based on the accuracy of the image calibration.

CHOLINERGIC MODULATION OF THALAMIC INPUT INTO THE CINGULATE CORTEX

This research demonstrates cholinergic modulation of thalamic input into the limbic cortex. A projection from the mediodorsal thalamus (MD) to the anterior cingulate cortex was defined anatomically and physiologically. Injections of horse-radish peroxidase into the anterior cingulate cortex labels neurons in the lateral, parvocellular, region of MD. Electrical Stimulation of this area produces a complex field potential in the anterior cingulate cortex which was further characterized by current density analysis and single cell recordings.^ The monsynaptic component of the response was identified as a large negative field which is maximal in layer IV of the anterior cingulate cortex. This response shows remarkable tetanic potentiation of frequencies near 7 Hz. During a train of 50 or more stimuli, the response would grow quickly and remain at a fairly stable potentiated level throughout the train.^ Cholinergic modulation of this thalamic response was demonstrated by iontophoretic application of the cholinergic agonist carbachol decreased the effectiveness of the thalamic imput by rapidly attenuation the response during a train of stimuli. The effect was apparently mediated by muscarinic receptors since the effect of carbachol was blocked by atropine but not by hexamethonium.^ To determine the source of the cingulate cortex cholinergic innervation, lesions were made in the anterior and medial thalamus and in the nucleus of the diagonal band of Broca. The effects of these lesions on choline acetyltranferase activity in the cingulate cortex were determined by a micro-radio-enzymatical assay. Only the lesions of the nucleus of the diagonal band significantly decreased the choline acetyltransferase activity in the cingulate cortex regions. Therefore, the diagonal band appears to be a major source of sensory cholinergic innervation and may be involved in gating of sensory information from the thalamus into the limbic cortex. Attempts to modulate the cingulate response to MD stimulation with electrical stimulation of the diagonal band, however were not successful.^

LOCALIZATION OF DNA REPAIR FUNCTIONS TO THE NUCLEAR MATRIX

The nucleus of a eukaryotic cell contains both structural and functional elements that contribute to the controlled operation of the cell. In this context, functional components refers to those nuclear constituents that perform metabolic activities such as DNA replication and RNA transcription. Structural nuclear components, designated nuclear matrix, organize the DNA into loops or domains and appear to provide a framework for nuclear DNA organization. However, the boundary between structural and functional components is not clear cut as evinced by reports of associations between metabolic functions and the nuclear matrix. The studies reported here attempt to determine the relationship of another nuclear function, DNA repair, to the nuclear matrix.^ One objective of these studies was to study the initiation of DNA repair by directly measuring the UV-incision activities in human cells and determine the influence of various extractable nuclear components on these activities. The assay for incision activities required the development of a nuclear isolation protocol that produced nuclei with intact DNA; the conformation of the nuclear DNA and its physical characteristics in response to denaturing conditions were determined.^ The nuclei produced with this protocol were then used as substrates for endogenous UV-specific nuclease activities. The isolated nuclei were shown to contain activities that cause breaks in nuclear DNA in response to UV-irradiation. These UV-responsive activities were tightly associated with nuclear components, being unextractable with salt concentration of up to 0.6 M.^ The tight association of the incision activities with salt-extracted nuclei suggested that other repair function might also be associated with salt-stable components of the nucleus. The site of unscheduled DNA synthesis (UDS) was determined in salt-extracted nuclei (nucleoids) using autoradiography and fluorescent microscopy. UDS was found to occur in association with the nuclear matrix following low-doses (2.55 J/M('2)) of ultraviolet light, but the association became looser after higher doses of ultraviolet light (10-30 J/m('2)). ^

Importance of sperm transition proteins demonstrated in mice carrying Tnp1- and Tnp2-null alleles

Chromatin condensation within the nucleus of developing spermatids involves replacement of histones by transition proteins, which are in turn replaced by protamines. The importance of transition proteins in the complex process of spermiogenesis has, to date, been only speculative. This study sought to investigate the extent to which transition proteins are essential or have redundant functions by characterizing sperm produced in mice expressing all combinations of Tnp-null alleles. Results from breeding trials of 8 weeks duration revealed that, on average, wildtype males produced about 14 offspring whereas TP2 and TP1 single-knockout males produced about 8 and 1 offspring, respectively, demonstrating their subfertility. Genotypes with less than two Tnp wildtype alleles, as well as double-knockout mutants, were completely infertile. Sperm from males with impaired fertility had poor progressive motility, heterogeneous chromatin condensation, incompletely processed protamine 2 and head and tail abnormalities. Generally, as the number of Tnp-null alleles increased so did the severity of abnormalities. However, specific morphological abnormalities were associated with the absence of an individual TP. Studies which sought to identify possible root causes for abnormalities in thiol-rich sperm structures revealed no differences in thiol content or sulfhydryl oxidation status within the nucleus but nuclei and tails from single-knockout mutants were severely disrupted following thiol reduction. Binding of fluorescent dyes to DNA was normal in sperm recovered from caput but abnormal in cauda epididymal sperm from TP1 knockouts and infertile double mutants. Injection of cauda epididymal sperm from double knockouts into oocytes produced very few offspring; however, after injection with testicular sperm, the efficiency was no different from wildtype. These results suggest DNA structural alterations or degradation during epididymal transport of sperm resulting in a diminished capacity of the paternal DNA of these sperm to produce offspring. The overall importance of transition proteins for normal chromatin condensation and production of fertile sperm has been demonstrated. Furthermore, identification of specific morphological abnormalities associated with the absence of an individual transition protein provides new evidence that the proteins are not completely redundant and each fulfills some unique function. ^

ROLE OF SOX9 IN UTERINE GLAND DEVELOPMENT AND DISEASE INITIATION

The female reproductive tract (FRT) develops midway through embryogenesis, and consists of oviducts, uterine horns, cervix and upper part of the vagina. The uterine horns are composed of an epithelial layer, luminal (LE) and glandular epithelium (GE), surrounded by a mesenchymal layer, the stroma and myometrium. Interestingly, in most mammals the GE forms after birth and it only becomes fully differentiated as the female reaches sexual maturity. Uterine glands (UG) are made up of GE and are present in all mammals. They secrete nutrients, cytokines and several other proteins, termed histotroph, that are necessary for embryo implantation and development. Experiments in ewes and mice have revealed that females who lack UGs are infertile mainly due to impaired implantation and early pregnancy loss, suggesting that UGs are essential for fertility. Fortunately for us, UGs develop after birth allowing us to peer into the genetic mechanism of tubulogenesis and branching morphogenesis; two processes that are disrupted in various adenocarcinomas (cancer derived from glands). We created 3D replicas of the epithelium lining the FRT using optical projection tomography and characterized UG development in mice using lineagetracing experiments. Our findings indicate that mouse UGs develop as simple tubular structures and later grow multiple secretory units that stem from the main duct. The main aim of this project was to study the role of SOX9 in the UGs. Preliminary studies revealed that Sox9 is mostly found in the nucleus of the GE. vii This observation led to the hypothesis that Sox9 plays a role in the formation and/or differentiation of the GE. To study the role of Sox9 in UGs differentiation, we conditionally knocked out and overexpressed Sox9 in both the LE and GE using the progesterone receptor (Pgr) promoter. Overexpressing Sox9 in the uterine epithelium, parts of the stroma, and myometrium led to formation of multiple cystic structures inside the endometrium. Histological analysis revealed that these structures appeared morphologically similar to structures present in histological tissue sections obtained from patients with endometrial polyps. We have accounted for the presence of simple and complex hyperplasia with atypia, metaplasia, thick-walled blood vessels, and stromal fibrosis; all “hallmarks” that indicate overexpressing Sox9 leads to development of a polyp-like morphology. Therefore, we can propose the use of Sox9-cOE mice to study development of endometrial cystic lesions and disease progression into hyperplastic lesions.

Geochemistry and age determination of zircons in Cretaceous to Quaternary sediments

In central Antarctica, drainage today and earlier back to the Paleozoic radiates from the Gamburtsev Subglacial Mountains (GSM). Proximal to the GSM past the Permian-Triassic fluvial sandstones in the Prince Charles Mountains (PCM) are Cretaceous, Eocene, and Pleistocene sediment in Prydz Bay (ODP741, 1166, and 1167) and pre-Holocene sediment in AM04 beneath the Amery Ice Shelf. We analysed detrital zircons for U-Pb ages, Hf-isotope compositions, and trace elements to determine the age, rock type, source of the host magma, and "crustal" model age (T(C)DM). These samples, together with others downslope from the GSM and the Vostok Subglacial Highlands (VSH), define major clusters of detrital zircons interpreted as coming from (1) 700 to 460 Ma mafic granitoids and alkaline rock, epsilon-Hf 9 to -28, signifying derivation 2.5 to 1.3 Ga from fertile and recycled crust, and (2) 1200-900 Ma mafic granitoids and alkaline rock, epsilon-Hf 11 to -28, signifying derivation 1.8 to 1.3 Ga from fertile and recycled crust. Minor clusters extend to 3350 Ma. Similar detrital zircons in Permian-Triassic, Ordovician, Cambrian, and Neoproterozoic sandstones located along the PaleoPacific margin of East Antarctica and southeast Australia further downslope from central Antarctica reflect the upslope GSM-VSH nucleus of the central Antarctic provenance as a complex of 1200-900 Ma (Grenville) mafic granitoids and alkaline rocks and older rocks embedded in 700-460 Ma (Pan-Gondwanaland) fold belts. The wider central Antarctic provenance (CAP) is tentatively divided into a central sector with negative ?Hf in its 1200-900 Ma rocks bounded on either side by positive epsilon-Hf. The high ground of the GSM-VSH in the Permian and later to the present day is attributed to crustal shortening by far-field stress during the 320 Ma mid-Carboniferous collision of Gondwanaland and Laurussia. Earlier uplifts in the ~500 Ma Cambrian possibly followed the 700-500 Ma assembly of Gondwanaland, and in the Neoproterozoic the 1000-900 Ma collisional events in the Eastern Ghats-Rayner Province at the end of the 1300-1000 Ma assembly of Rodinia.

OSIRIS observations of meter-sized exposures of H2O ice at the surface of 67P/Churyumov-Gerasimenko and interpretation using laboratory experiments

Since OSIRIS started acquiring high-resolution observations of the surface of the nucleus of comet 67P/Churyumov-Gerasimenko, over one hundred meter-sized bright spots have been identified in numerous types of geomorphologic regions, but mostly located in areas receiving low insolation. The bright spots are either clustered, in debris fields close to decameter-high cliffs, or isolated without structural relation to the surrounding terrain. They can be up to ten times brighter than the average surface of the comet at visible wavelengths and display a significantly bluer spectrum. They do not exhibit significant changes over a period of a few weeks. All these observations are consistent with exposure of water ice at the surface of boulders produced by dislocation of the weakly consolidated layers that cover large areas of the nucleus. Laboratory experiments show that under simulated comet surface conditions, analog samples acquire a vertical stratification with an uppermost porous mantle of refractory dust overlaying a layer of hard ice formed by recondensation or sintering under the insulating dust mantle. The evolution of the visible spectrophotometric properties of samples during sublimation is consistent with the contrasts of brightness and color seen at the surface of the nucleus. Clustered bright spots are formed by the collapse of overhangs that is triggered by mass wasting of deeper layers. Isolated spots might be the result of the emission of boulders at low velocity that are redepositioned in other regions.

Characterization of the Abydos region through OSIRIS high-resolution images in support of CIVA measurements

Context. On 12 November 2014, the European mission Rosetta delivered the Philae lander on the nucleus of comet 67P /Churyumov-Gerasimenko (67P). After the first touchdown, the lander bounced three times before finally landing at a site named Abydos. Aims. We provide a morphologically detailed analysis of the Abydos landing site to support Philae's measurements and to give context for the interpretation of the images coming from the Comet Infrared and Visible Analyser (CIVA) camera system onboard the lander. Methods. We used images acquired by the OSIRIS Narrow Angle Camera (NAC) on 6 December 2014 to perform the analysis of the Abydos landing site, which provided the geomorphological map, the gravitational slope map, the size-frequency distribution of the boulders. We also computed the albedo and spectral reddening maps. Results. The morphological analysis of the region could suggest that Philae is located on a primordial terrain. The Abydos site is surrounded by two layered and fractured outcrops and presents a 0.02 km(2) talus deposit rich in boulders. The boulder size frequency distribution gives a cumulative power-law index of 4.0 + 0.3/0.4, which is correlated with gravitational events triggered by sublimation and /or thermal fracturing causing regressive erosion. The average value of the albedo is 5.8% at lambda(1) = 480.7 nm and 7.4% at lambda(2) = 649.2 nm, which is similar to the global albedos derived by OSIRIS and CIVA, respectively.

Contribution to the Analysis, Design and Assessment of Compact Antenna Test Ranges At Millimeter Wavelengths - Contribución al Análisis, Diseño y Caracterización de Sistemas de Medida de Antenas en Rango Compacto para Frecuencias Milimétricas

This Doctoral Thesis entitled Contribution to the analysis, design and assessment of compact antenna test ranges at millimeter wavelengths aims to deepen the knowledge of a particular antenna measurement system: the compact range, operating in the frequency bands of millimeter wavelengths. The thesis has been developed at Radiation Group (GR), an antenna laboratory which belongs to the Signals, Systems and Radiocommunications department (SSR), from Technical University of Madrid (UPM). The Radiation Group owns an extensive experience on antenna measurements, running at present four facilities which operate in different configurations: Gregorian compact antenna test range, spherical near field, planar near field and semianechoic arch system. The research work performed in line with this thesis contributes the knowledge of the first measurement configuration at higher frequencies, beyond the microwaves region where Radiation Group features customer-level performance. To reach this high level purpose, a set of scientific tasks were sequentially carried out. Those are succinctly described in the subsequent paragraphs. A first step dealed with the State of Art review. The study of scientific literature dealed with the analysis of measurement practices in compact antenna test ranges in addition with the particularities of millimeter wavelength technologies. Joint study of both fields of knowledge converged, when this measurement facilities are of interest, in a series of technological challenges which become serious bottlenecks at different stages: analysis, design and assessment. Thirdly after the overview study, focus was set on Electromagnetic analysis algorithms. These formulations allow to approach certain electromagnetic features of interest, such as field distribution phase or stray signal analysis of particular structures when they interact with electromagnetic waves sources. Properly operated, a CATR facility features electromagnetic waves collimation optics which are large, in terms of wavelengths. Accordingly, the electromagnetic analysis tasks introduce an extense number of mathematic unknowns which grow with frequency, following different polynomic order laws depending on the used algorithmia. In particular, the optics configuration which was of our interest consisted on the reflection type serrated edge collimator. The analysis of these devices requires a flexible handling of almost arbitrary scattering geometries, becoming this flexibility the nucleus of the algorithmia’s ability to perform the subsequent design tasks. This thesis’ contribution to this field of knowledge consisted on reaching a formulation which was powerful at the same time when dealing with various analysis geometries and computationally speaking. Two algorithmia were developed. While based on the same principle of hybridization, they reached different order Physics performance at the cost of the computational efficiency. Inter-comparison of their CATR design capabilities was performed, reaching both qualitative as well as quantitative conclusions on their scope. In third place, interest was shifted from analysis - design tasks towards range assessment. Millimetre wavelengths imply strict mechanical tolerances and fine setup adjustment. In addition, the large number of unknowns issue already faced in the analysis stage appears as well in the on chamber field probing stage. Natural decrease of dynamic range available by semiconductor millimeter waves sources requires in addition larger integration times at each probing point. These peculiarities increase exponentially the difficulty of performing assessment processes in CATR facilities beyond microwaves. The bottleneck becomes so tight that it compromises the range characterization beyond a certain limit frequency which typically lies on the lowest segment of millimeter wavelength frequencies. However the value of range assessment moves, on the contrary, towards the highest segment. This thesis contributes this technological scenario developing quiet zone probing techniques which achieves substantial data reduction ratii. Collaterally, it increases the robustness of the results to noise, which is a virtual rise of the setup’s available dynamic range. In fourth place, the environmental sensitivity of millimeter wavelengths issue was approached. It is well known the drifts of electromagnetic experiments due to the dependance of the re sults with respect to the surrounding environment. This feature relegates many industrial practices of microwave frequencies to the experimental stage, at millimeter wavelengths. In particular, evolution of the atmosphere within acceptable conditioning bounds redounds in drift phenomena which completely mask the experimental results. The contribution of this thesis on this aspect consists on modeling electrically the indoor atmosphere existing in a CATR, as a function of environmental variables which affect the range’s performance. A simple model was developed, being able to handle high level phenomena, such as feed - probe phase drift as a function of low level magnitudes easy to be sampled: relative humidity and temperature. With this model, environmental compensation can be performed and chamber conditioning is automatically extended towards higher frequencies. Therefore, the purpose of this thesis is to go further into the knowledge of millimetre wavelengths involving compact antenna test ranges. This knowledge is dosified through the sequential stages of a CATR conception, form early low level electromagnetic analysis towards the assessment of an operative facility, stages for each one of which nowadays bottleneck phenomena exist and seriously compromise the antenna measurement practices at millimeter wavelengths.

Identification of a homolog of Arabidopsis DSP4 (SEX4) in chestnut: its induction and accumulation in stem amyloplasts during winter or in response to the cold_

Oligosaccharide synthesis is an important cryoprotection strategy used by woody plants during winter dormancy. At the onset of autumn, starch stored in the stem and buds is broken down in response to the shorter days and lower temperatures resulting in the buildup of oligosaccharides. Given that the enzyme DSP4 is necessary for diurnal starch degradation in Arabidopsis leaves, this study was designed to address the role of DSP4 in this seasonal process in Castanea sativa Mill. The expression pattern of the CsDSP4 gene in cells of the chestnut stem was found to parallel starch catabolism. In this organ, DSP4 protein levels started to rise at the start of autumn and elevated levels persisted until the onset of spring. In addition, exposure of chestnut plantlets to 4 °C induced the expression of the CsDSP4 gene. In dormant trees or cold-stressed plantlets, the CsDSP4 protein was immunolocalized both in the amyloplast stroma and nucleus of stem cells, whereas in the conditions of vegetative growth, immunofluorescence was only detected in the nucleus. The studies indicate a potential role for DSP4 in starch degradation and cold acclimation following low temperature exposure during activity–dormancy transition.

Observations of Comet 9P/Tempel 1 around the Deep Impact event by the OSIRIS cameras onboard Rosetta

The OSIRIS cameras on the Rosetta spacecraft observed Comet 9P/Tempel 1 from 5 days before to 10 days after it was hit by the Deep Impact projectile. The Narrow Angle Camera (NAC) monitored the cometary dust in 5 different filters. The Wide Angle Camera (WAC) observed through filters sensitive to emissions from OH, CN, Na, and OI together with the associated continuum. Before and after the impact the comet showed regular variations in intensity. The period of the brightness changes is consistent with the rotation period of Tempel 1. The overall brightness of Tempel 1 decreased by about 10% during the OSIRIS observations. The analysis of the impact ejecta shows that no new permanent coma structures were created by the impact. Most of the material moved with View the MathML source∼200ms−1. Much of it left the comet in the form of icy grains which sublimated and fragmented within the first hour after the impact. The light curve of the comet after the impact and the amount of material leaving the comet (View the MathML source4.5–9×106kg of water ice and a presumably larger amount of dust) suggest that the impact ejecta were quickly accelerated by collisions with gas molecules. Therefore, the motion of the bulk of the ejecta cannot be described by ballistic trajectories, and the validity of determinations of the density and tensile strength of the nucleus of Tempel 1 with models using ballistic ejection of particles is uncertain.

Region-dependent dynamics of cAMP response element-binding protein phosphorylation in the basal ganglia

The cAMP response element-binding protein (CREB) is an activity-dependent transcription factor that is involved in neural plasticity. The kinetics of CREB phosphorylation have been suggested to be important for gene activation, with sustained phosphorylation being associated with downstream gene expression. If so, the duration of CREB phosphorylation might serve as an indicator for time-sensitive plastic changes in neurons. To screen for regions potentially involved in dopamine-mediated plasticity in the basal ganglia, we used organotypic slice cultures to study the patterns of dopamine- and calcium-mediated CREB phosphorylation in the major subdivisions of the striatum. Different durations of CREB phosphorylation were evoked in the dorsal and ventral striatum by activation of dopamine D1-class receptors. The same D1 stimulus elicited (i) transient phosphorylation (≤15 min) in the matrix of the dorsal striatum; (ii) sustained phosphorylation (≤2 hr) in limbic-related structures including striosomes, the nucleus accumbens, the fundus striati, and the bed nucleus of the stria terminalis; and (iii) prolonged phosphorylation (up to 4 hr or more) in cellular islands in the olfactory tubercle. Elevation of Ca2+ influx by stimulation of L-type Ca2+ channels, NMDA, or KCl induced strong CREB phosphorylation in the dorsal striatum but not in the olfactory tubercle. These findings differentiate the response of CREB to dopamine and calcium signals in different striatal regions and suggest that dopamine-mediated CREB phosphorylation is persistent in limbic-related regions of the neonatal basal ganglia. The downstream effects activated by persistent CREB phosphorylation may include time-sensitive neuroplasticity modulated by dopamine.

Aberrant intracellular localization of Varicella-Zoster virus regulatory proteins during latency

Varicella-Zoster virus (VZV) is a herpesvirus that becomes latent in sensory neurons after primary infection (chickenpox) and subsequently may reactivate to cause zoster. The mechanism by which this virus maintains latency, and the factors involved, are poorly understood. Here we demonstrate, by immunohistochemical analysis of ganglia obtained at autopsy from seropositive patients without clinical symptoms of VZV infection that viral regulatory proteins are present in latently infected neurons. These proteins, which localize to the nucleus of cells during lytic infection, predominantly are detected in the cytoplasm of latently infected neurons. The restriction of regulatory proteins from the nucleus of latently infected neurons might interrupt the cascade of virus gene expression that leads to a productive infection. Our findings raise the possibility that VZV has developed a novel mechanism for maintenance of latency that contrasts with the transcriptional repression that is associated with latency of herpes simplex virus, the prototypic alpha herpesvirus.