Timing of the martian dynamo: New constraints for a core field 4.5 and 3.7 Ga ago.

The absence of crustal magnetic fields above the martian basins Hellas, Argyre, and Isidis is often interpreted as proof of an early, before 4.1 billion years (Ga) ago, or late, after 3.9 Ga ago, dynamo. We revisit these interpretations using new MAVEN magnetic field data. Weak fields are present over the 4.5-Ga old Borealis basin, with the transition to strong fields correlated with the basin edge. Magnetic fields, confined to a near-surface layer, are also detected above the 3.7-Ga old Lucus Planum. We conclude that a dynamo was present both before and after the formation of the basins Hellas, Utopia, Argyre, and Isidis. A long-lived, Earth-like dynamo is consistent with the absence of magnetization within large basins if the impacts excavated large portions of strongly magnetic crust and exposed deeper material with lower concentrations of magnetic minerals.

Vagus nerve stimulation promotes gastric emptying by increasing pyloric opening measured with magnetic resonance imaging.

BACKGROUND: Vagus nerve stimulation (VNS) is an emerging electroceutical therapy for remedying gastric disorders that are poorly managed by pharmacological treatments and/or dietary changes. Such therapy seems promising as the vagovagal neurocircuitry modulates the enteric nervous system to influence gastric functions. METHODS: Here, the modulatory effects of left cervical VNS on gastric emptying in rats were quantified using a (i) feeding protocol in which the animal voluntarily consumed a postfast, gadolinium-labeled meal and (ii) a non-invasive imaging method to measure antral motility, pyloric activity and gastric emptying based on contrast-enhanced magnetic resonance imaging (MRI) and computer-assisted image processing pipelines. KEY RESULTS: Vagus nerve stimulation significantly accelerated gastric emptying (sham vs VNS: 29.1% ± 1.5% vs 40.7% ± 3.9% of meal emptied per 4 hours), caused a greater relaxation of the pyloric sphincter (sham vs VNS: 1.5 ± 0.1 vs 2.6 ± 0.4 mm2 cross-sectional area of lumen), and increased antral contraction amplitude (sham vs VNS: 23.3% ± 3.0% vs 32.5% ± 3.0% occlusion), peristaltic velocity (sham vs VNS: 0.50 ± 0.02 vs 0.67 ± 0.03 mm s-1 ), but not its contraction frequency (sham vs VNS: 6.1 ± 0.2 vs 6.4 ± 0.2 contractions per minute, P = .22). The degree to which VNS relaxed the pylorus was positively correlated with gastric emptying rate (r = .5887, P < .001). CONCLUSIONS & INFERENCES: The MRI protocol employed in this study is expected to enable advanced preclinical studies to understand stomach pathophysiology and its therapeutics. Results from this study suggest an electroceutical treatment approach for gastric emptying disorders using cervical VNS to control the degree of pyloric sphincter relaxation.

Orogen-scale uplift in the central Italian Apennines drives episodic behaviour of earthquake faults.

Many areas of the Earth's crust deform by distributed extensional faulting and complex fault interactions are often observed. Geodetic data generally indicate a simpler picture of continuum deformation over decades but relating this behaviour to earthquake occurrence over centuries, given numerous potentially active faults, remains a global problem in hazard assessment. We address this challenge for an array of seismogenic faults in the central Italian Apennines, where crustal extension and devastating earthquakes occur in response to regional surface uplift. We constrain fault slip-rates since ~18 ka using variations in cosmogenic 36Cl measured on bedrock scarps, mapped using LiDAR and ground penetrating radar, and compare these rates to those inferred from geodesy. The 36Cl data reveal that individual faults typically accumulate meters of displacement relatively rapidly over several thousand years, separated by similar length time intervals when slip-rates are much lower, and activity shifts between faults across strike. Our rates agree with continuum deformation rates when averaged over long spatial or temporal scales (104 yr; 102 km) but over shorter timescales most of the deformation may be accommodated by <30% of the across-strike fault array. We attribute the shifts in activity to temporal variations in the mechanical work of faulting.

Alpha-synuclein expression patterns in the colonic submucosal plexus of the aging Fischer 344 rat: implications for biopsies in aging and neurodegenerative disorders?

BACKGROUND: This experiment assessed normative expression patterns of alpha-synuclein (SYNC), including ganglionic remodeling and development of SYNC pathologies, in the submucosal plexus (SMP) of the colon during healthy aging. The observations address age-associated changes in bowel function and are relevant to evaluations of SMP-containing colonic biopsies for SYNC or synucleinopathies associated with aging and peripheral neurodegenerative diseases. METHODS: Colonic submucosal whole mounts from groups of virgin male Fischer 344 rats (n ≥ 8 per group) at 4, 8, 16, and 24 months of age were processed immunohistochemically for SYNC and the pan-neuronal marker HuC/D. In addition, macrophages immunoreactive for MHCII were examined. Stereological protocols were used to generate unbiased estimates of neuron density, neurons per ganglion, neurons per ganglionic area, and neuron size. KEY RESULTS: The protein SYNC was expressed in a subpopulation of SMP neurons, in both nucleus and cytoplasm. The general age-associated pattern across different cell counts was an increase in the number of SYNC+ neurons between 4 and 8 months of age, with progressively decreasing numbers of both SYNC+ and SYNC- neurons over the remaining lifespan. The soma size of SYNC+ neurons increased progressively with age. Aggregated SYNC occurred in the aging SMP, and macrophages with alternatively activated profiles were located adjacent to pathological SYNC deposits, consistent with ongoing phagocytosis. CONCLUSIONS & INFERENCES: Changes in SYNC expression with age, including a baseline of accumulating synucleinopathies in the healthy aging SMP, need to be considered when interpreting either functional disturbances or biopsies of the aging colon.

Vagal sensory innervation of the gastric sling muscle and antral wall: implications for gastro-esophageal reflux disease?

BACKGROUND: The gastric sling muscle has not been investigated for possible sensory innervation, in spite of the key roles the structure plays in lower esophageal sphincter (LES) function and gastric physiology. Thus, the present experiment used tracing techniques to label vagal afferents and survey their projections in the lesser curvature. METHODS: Sprague-Dawley rats received injections of dextran biotin into the nodose ganglia. Fourteen days postinjection, animals were euthanized and their stomachs were processed to visualize the vagal afferent innervation. In different cases, neurons, muscle cells, or interstitial cells of Cajal (ICC) were counterstained. KEY RESULTS: The sling muscle is innervated throughout its length by vagal afferent intramuscular arrays (IMAs) associated with ICC. In addition, the distal antral attachment site of the sling muscle is innervated by a novel vagal afferent terminal specialization, an antral web ending. The muscle wall of the distal antrum is also innervated by conventional IMAs and intraganglionic laminar endings, the two types of mechanoreceptors found throughout stomach smooth muscle. CONCLUSIONS & INFERENCES: The innervation of sling muscle by IMAs, putative stretch receptors, suggests that sling sensory feedback may generate vago-vagal or other reflexes with vagal afferent limbs. The restricted distribution of afferent web endings near the antral attachments of sling fibers suggests the possibility of specialized mechanoreceptor functions linking antral and pyloric activity to the operation of the LES. Dysfunctional sling afferents could generate LES motor disturbances, or normative compensatory sensory feedback from the muscle could compromise therapies targeting only effectors.

Vagal intramuscular array afferents form complexes with interstitial cells of Cajal in gastrointestinal smooth muscle: analogues of muscle spindle organs?

Intramuscular arrays (IMAs), vagal mechanoreceptors that innervate gastrointestinal smooth muscle, have not been completely described structurally or functionally. To delineate more fully the architecture of IMAs and to consider the structure-function implications of the observations, the present experiment examined the organization of the IMA terminal arbors and the accessory tissue elements of those arbors. IMA terminal fields, labeled by injection of biotinylated dextran into the nodose ganglia, were examined in whole mounts of rat gastric smooth muscle double-labeled with immunohistochemistry for interstitial cells of Cajal (ICCs; c-Kit) and/or inputs of different neuronal efferent transmitter (markers: tyrosine hydroxylase (TH), vesicular acetylcholine transporter (VAChT), and nitric oxide synthase (NOS)) or afferent neuropeptidergic (calcitonin gene-related peptide (CGRP)) phenotypes. IMAs make extensive varicose and lamellar contacts with ICCs. In addition, axons of the multiple efferent and afferent phenotypes examined converge and articulate with IMA terminal arbors innervating ICCs. This architecture is consistent with the hypothesis that IMAs, or the multiply innervated IMA-ICC complexes they form, can function as stretch receptors. The tissue organization is also consonant with the proposal that those units can operate as functional analogues of muscle spindle organs. For electrophysiological assessments of IMA functions, experiments will need protocols that preserve both the complex architecture and the dynamic operations of IMA-ICC complexes.

Genes for prostaglandin synthesis, transport and inactivation are differentially expressed in human uterine tissues, and the prostaglandin F synthase AKR1B1 is induced in myometrial cells by inflammatory cytokines.

Prostaglandins (PGs) are important factors in the physiology of human parturition and the control of uterine contractility. We have characterized the expression of 15 genes from all stages of the PG pathway in human pregnant and non-pregnant (NP) myometrium and in other uterine tissues at delivery, and the results show patterns indicative of different capacities for PG synthesis and catabolism in each tissue. In placenta, the PG synthase expression profile favours production of PGD2, PGE2 and PGF2, with high levels of PG transporters and catabolic PG dehydrogenase suggesting rapid PG turnover. Choriodecidua is primed for PGE2, PGF2 and PGD2 production and high PG turnover, whereas amnion expresses genes for PGE2 synthesis with low levels of PG transporters and dehydrogenase. In umbilical cord, PGI2 synthase is highly expressed. In pregnant myometrium, PGI2, PGD2 and PGF2 synthases are highly expressed, whereas PG dehydrogenase is underexpressed. Myometrium from women with spontaneous or induced labour had higher expression of the PGH2 synthase PTGS2 than tissue from women not-in-labour. Myometrium from NP women had lower levels of PG synthases and higher levels of PG dehydrogenase than pregnant myometrium. Discriminant function analysis showed that expression of selected genes in myometrium could distinguish groups of women with different modes of labour from each other and from NP women. In cultured myometrial cells, there was a dose-dependent stimulatory effect of interleukin 1ß and tumour necrosis factor α on PTGS2, PTGES and AKR1B1 (PGF synthase) expression.

The construction of Chasma Boreale on Mars.

The polar layered deposits of Mars contain the planet's largest known reservoir of water ice and the prospect of revealing a detailed Martian palaeoclimate record, but the mechanisms responsible for the formation of the dominant features of the north polar layered deposits (NPLD) are unclear, despite decades of debate. Stratigraphic analyses of the exposed portions of Chasma Boreale-a large canyon 500 km long, up to 100 km wide, and nearly 2 km deep-have led most researchers to favour an erosional process for its formation following initial NPLD accumulation. Candidate mechanisms include the catastrophic outburst of water, protracted basal melting, erosional undercutting, aeolian downcutting and a combination of these processes. Here we use new data from the Mars Reconnaissance Orbiter to show that Chasma Boreale is instead a long-lived, complex feature resulting primarily from non-uniform accumulation of the NPLD. The initial valley that later became Chasma Boreale was matched by a second, equally large valley that was completely filled in by subsequent deposition, leaving no evidence on the surface to indicate its former presence. We further demonstrate that topography existing before the NPLD began accumulating influenced successive episodes of deposition and erosion, resulting in most of the present-day topography. Long-term and large-scale patterns of mass balance achieved through sedimentary processes, rather than catastrophic events, ice flow or highly focused erosion, have produced the largest geomorphic anomaly in the north polar ice of Mars.

Altered mechanosensitive properties of vagal afferent fibers innervating the stomach following gastric surgery in rats.

BACKGROUND AND AIMS: Several types of gastric surgeries have been associated with early satiety, dyspepsia and food intolerances. We aimed to examine alterations in gastric vagal afferents following gastric surgery-fundus ligation. METHODS: Six week old, male Sprague-Dawley rats underwent chronic ligation (CL) of the fundus. Sham rats underwent abdominal surgery, but without ligation. Another group of rats underwent acute ligation (AL) of the fundus immediately prior to experiments. CL and sham rats were allowed to grow to age 3-4 months. Food intake and weights were recorded post-operatively. Gastric compliance and gastric wall thickness was measured at baseline and during gastric distension (GD). Extracellular recordings were made to examine response characteristics of vagal afferent fibers to GD and to map the stomach receptive field (RF). The morphological structures of afferent terminals in the stomach were examined with retrograde tracings from the nodose ganglion. RESULTS: The CL group consumed significantly less food and weighed less than sham control. The mean compliance of the CL group was significantly less than control, but higher than the AL group. The spontaneous firing and responses to GD of afferent fibers from the CL rats were significantly higher than AL rats. There was a marked expansion of the gastric RF in the CL rats with significant reorganization and regeneration of intramuscular array (IMA) terminals. There was no difference in total wall or muscle thickness among the groups. CONCLUSION: CL results in aberrant remodeling of IMAs with expansion of the gastric RF and alters the mechanotransduction properties of vagal afferent fibers. These changes could contribute to altered sensitivity following gastric surgery.

Treatment of acne with oral isotretinoin in patients with cystic fibrosis.

BACKGROUND: Theoretical concerns about liver disease and vitamin A deficiency have limited the use of oral isotretinoin for troublesome acne in adolescents with cystic fibrosis. METHODS: Oral isotretinoin was administered to nine patients with cystic fibrosis who had troublesome acne unresponsive to antibiotics. All patients were followed for 1-4 years after cessation of treatment. RESULTS: Isotretinoin treatment cleared active acne lesions in all patients. It was well tolerated, and no patient had significant side effects. All nine patients were pleased or delighted with the improvement in their skin. CONCLUSIONS: Adolescents with cystic fibrosis and acne can be treated with oral isotretinoin. Oral isotretinoin should be considered for adolescents with cystic fibrosis who have acne associated with scarring, acne not clearing with topical and antibiotic treatment, acne associated with depression or severe cystic acne.

Alpha-synuclein-immunopositive myenteric neurons and vagal preganglionic terminals: autonomic pathway implicated in Parkinson's disease?

The protein alpha-synuclein is implicated in the development of Parkinson's disease. The molecule forms Lewy body aggregates that are hallmarks of the disease, has been associated with the spread of neuropathology from the peripheral to the CNS, and appears to be involved with the autonomic disorders responsible for the gastrointestinal (GI) symptoms of individuals afflicted with Parkinson's. To characterize the normative expression of alpha-synuclein in the innervation of the GI tract, we examined both the postganglionic neurons and the preganglionic projections by which the disease is postulated to retrogradely invade the CNS. Specifically, in Fischer 344 and Sprague-Dawley rats, immunohistochemistry in conjunction with injections of the tracer Dextran-Texas Red was used to determine, respectively, the expression of alpha-synuclein in the myenteric plexus and in the vagal terminals. Alpha-synuclein is expressed in a subpopulation of myenteric neurons, with the proportion of positive somata increasing from the stomach (approximately 3%) through duodenum (proximal, approximately 6%; distal, approximately 13%) to jejunum (approximately 22%). Alpha-synuclein is co-expressed with the nitrergic enzyme nitric oxide synthase (NOS) or the cholinergic markers calbindin and calretinin in regionally specific patterns: approximately 90% of forestomach neurons positive for alpha-synuclein express NOS, whereas approximately 92% of corpus-antrum neurons positive for alpha-synuclein express cholinergic markers. Vagal afferent endings in the myenteric plexus and the GI smooth muscle do not express alpha-synuclein, whereas, virtually all vagal preganglionic projections to the gut express alpha-synuclein, both in axons and in terminal varicosities in apposition with myenteric neurons. Vagotomy eliminates most, but not all, alpha-synuclein-positive neurites in the plexus. Some vagal preganglionic efferents expressing alpha-synuclein form varicose terminal rings around myenteric plexus neurons that are also positive for the protein, thus providing a candidate alpha-synuclein-expressing pathway for the retrograde transport of putative Parkinson's pathogens or toxins from the ENS to the CNS.

Ultrastructural evidence for communication between intramuscular vagal mechanoreceptors and interstitial cells of Cajal in the rat fundus.

To assess whether afferent vagal intramuscular arrays (IMAs), putative gastrointestinal mechanoreceptors, form contacts with interstitial cells of Cajal of the intramuscular type (ICC-IM) and to describe any such contacts, electron microscopic analyses were performed on the external muscle layers of the fundus containing dextran-labelled diaminobenzidin (DAB)-stained IMAs. Special staining and embedding techniques were developed to preserve ultrastructural features. Within the muscle layers, IMA varicosities were observed in nerve bundles traversing major septa without contact with ICC-IM, contacting unlabelled neurites and glial cells. IMA varicosities were encountered in minor septa in contact with ICC-IM which were not necessarily in close contact with muscle cells. In addition, IMA varicosities were observed within muscle bundles in close contact with ICC-IM which were in gap junction contact with muscle cells. IMAs formed varicosities containing predominantly small agranular vesicles, occasionally large granular vesicles and prejunctional thickenings in apposition to ICC-IM processes, indicating communication between ICC and IMA via synapse-like contacts. Taken together, these different morphological features are consistent with a hypothesized mechanoreceptor role for IMA-ICC complexes. Intraganglionic laminar ending varicosities contacted neuronal somata and dendrites in the myenteric plexus of the fundus, but no contacts with ICC associated with Auerbach's plexus were encountered.

Inhibitory effects on intake of cholecystokinin-8 and cholecystokinin-33 in rats with hepatic proper or common hepatic branch vagal innervation.

The relative potencies of cholecystokinin (CCK)-8 and CCK-33 for decreasing meal size depend on the route of administration. Inhibitory potencies are equal after intraperitoneal administration, but CCK-33 is significantly more potent after intraportal administration. This suggests that CCK-33 is a more effective stimulant of hepatic afferent vagal nerves than is CCK-8. To investigate this possibility, we administered both peptides intraperitoneally in rats with abdominal vagotomies that spared only the hepatic proper vagal nerves (H) and in rats with abdominal vagotomies that spared the common hepatic branch that contains the fibers of the hepatic proper and gastroduodenal nerves (HGD). The vagal afferent innervation in H and HGD rats was verified with a wheat germ agglutinin-horseradish tracer strategy. Intraperitoneal administration of CCK-33 decreased 30-min intake of 10% sucrose in H rats as much as in sham rats, but CCK-8 decreased intake significantly less in H rats than in sham rats. The larger inhibitory effect of CCK-33 than of CCK-8 in H rats is consistent with the hypothesis that CCK-33 is a more effective stimulant of the hepatic proper vagal afferent nerves than CCK-8. In contrast to the results in H rats, the inhibitory potencies of both peptides were significantly and equivalently reduced in HGD rats compared with sham rats. This suggests that there is an inhibitory interaction between the stimulation of the gastroduodenal and hepatic proper afferent fibers by CCK-33.

Neurotrophin-4 deficient mice have a loss of vagal intraganglionic mechanoreceptors from the small intestine and a disruption of short-term satiety.

Intraganglionic laminar endings (IGLEs) and intramuscular arrays (IMAs) are the two putative mechanoreceptors that the vagus nerve supplies to gastrointestinal smooth muscle. To examine whether neurotrophin-4 (NT-4)-deficient mice, which have only 45% of the normal number of nodose ganglion neurons, exhibit selective losses of these endings and potentially provide a model for assessing their functional roles, we inventoried IGLEs and IMAs in the gut wall. Vagal afferents were labeled by nodose ganglion injections of wheat germ agglutinin-horseradish peroxidase, and a standardized sampling protocol was used to map the terminals in the stomach, duodenum, and ileum. NT-4 mutants had a substantial organ-specific reduction of IGLEs; whereas the morphologies and densities of both IGLEs and IMAs in the stomach were similar to wild-type patterns, IGLEs were largely absent in the small intestine (90 and 81% losses in duodenum and ileum, respectively). Meal pattern analyses revealed that NT-4 mutants had increased meal durations with solid food and increased meal sizes with liquid food. However, daily total food intake and body weight remained normal because of compensatory changes in other meal parameters. These findings indicate that NT-4 knock-out mice have a selective vagal afferent loss and suggest that intestinal IGLEs (1) may participate in short-term satiety, probably by conveying feedback about intestinal distension or transit to the brain, (2) are not essential for long-term control of feeding and body weight, and (3) play different roles in regulation of solid and liquid diet intake.

C-Kit mutant mice have a selective loss of vagal intramuscular mechanoreceptors in the forestomach.

Intramuscular arrays are one of two major classes of vagal afferent mechanoreceptors that innervate the smooth muscle wall of the proximal gastrointestinal tract. They consist of rectilinear telodendria that distribute in the muscle sheets, parallel to the long axes of muscle fibers. Intramuscular arrays appear to make direct contact with the muscle fibers, but they also course on, and form appositions with, intramuscular interstitial cells of Cajal. These complexes formed by intramuscular arrays and intramuscular interstitial cells of Cajal suggest that intramuscular arrays might require either structural or trophic support of the interstitial cells of Cajal for normal differentiation and/or maintenance. To evaluate this hypothesis, we have examined the morphology and distribution of vagal afferent endings in the c-Kit mutant mouse that lacks intramuscular interstitial cells of Cajal. Vagal afferents were labeled by nodose ganglion injection of either wheat germ agglutinin-horseradish peroxidase conjugate or a tagged dextran, and the labeled afferent terminals in the stomach were mapped using a standardized quantitative sampling scheme. Intramuscular arrays were dramatically reduced (in circular muscle by 63%; in longitudinal muscle by 78%) in the c-Kit mutant mice relative to their wild-type littermates. Additionally, a substantial number of the surviving axons and terminals in the mutant stomachs were morphologically aberrant. Moreover, the loss of intramuscular arrays in mutants appeared to be selective: the structure, distribution and density of intraganglionic laminar endings, i.e., the other vagal mechanoreceptors in smooth muscle, were not significantly altered. Finally, the conspicuous decrease in intramuscular array density in mutants was associated with a non-significant trend toward loss of nodose ganglion neurons. Collectively these findings suggest that interstitial cells are required for the normal development or maintenance of vagal intramuscular arrays. Therefore, the c-Kit mutant mouse will be valuable for determining the role(s) of interstitial cells in intramuscular array development as well as for providing an animal model with the intramuscular array class of vagal afferents selectively ablated.

Gastrointestinal projection maps of the vagus nerve are specified permanently in the perinatal period.

The vagal innervation of the proximal gastrointestinal (GI) tract is lateralized. To determine whether this pattern is specified as early as the perinatal period, neonatal rat pups were given unilateral cervical vagotomies. Separate groups received (1) transections below the left nodose ganglion, (2) left cervical resections that included removal of the nodose ganglion, or (3) sham surgeries. At 4 months of age, each animal's vagal afferent projections from the unoperated side were mapped by injecting the nodose with WGA-HRP, preparing the stomach as wholemounts, and processing the tissue with tetramethyl benzidine. The two types of vagal afferent endings in GI smooth muscle, namely intraganglionic laminar endings and intramuscular arrays, were surveyed separately, and their regional distributions were mapped. Changes in the nucleus of the solitary tract (NST) and dorsal motor nucleus of the vagus (DMNX) were assessed with cell counts and area measurements. Neonatal loss of the vagus innervating one side of the GI tract, with or without ganglionectomy, did not cause the unoperated vagus to sprout to the denervated side. In addition, removal of the projections to the one side of the target organ did not produce a reorganization of the projection maps of the unoperated vagus within its normal or ipsilateral wall of the GI tract. Although the regional patterns of the unoperated ipsilateral vagus were not affected, the packing densities of both types of afferents supplied by this trunk were moderately reduced. The DMNX of the vagotomized side displayed extensive (approximately 83%) neuronal loss; the DMNX on the unoperated side as well as the NST on both sides exhibited limited (approximately 20--25%) losses. The lack of a peripheral projection field reorganization -- except for a moderate down-regulation -- after complete unilateral denervation suggests that both the laterality and the afferent terminal phenotypes (or target tissues) of the vagus in the proximal GI tract are specified by postnatal day one in the rat. The present results, taken together with other observations, also suggest that three different combinations of signals orchestrate the commitments of vagal afferents respectively to (1) the side of the organ, (2) the region within the organ wall, and (3) the accessory and innervated tissues that complex with the fully differentiated ending.

Mars' volatile and climate history.

There is substantial evidence that the martian volatile inventory and climate have changed markedly throughout the planet's history. Clues come from areas as disparate as the history and properties of the deep interior, the composition of the crust and regolith, the morphology of the surface, composition of the present-day atmosphere, and the nature of the interactions between the upper atmosphere and the solar wind. We piece together the relevant observations into a coherent view of the evolution of the martian climate, focusing in particular on the observations that provide the strongest constraints.

As the gut ages: timetables for aging of innervation vary by organ in the Fischer 344 rat.

To explore the effects of aging on the vagal innervation of the gastrointestinal (GI) tract, male Fischer 344 rats at 3 and 24 months of age were injected in the left nodose ganglion with 3 microl of either 4% wheat germ agglutinin-horseradish peroxidase (to label sensory endings) or 1% cholera toxin subunit B-horseradish peroxidase (to label motor endings). The stomach and duodenum were prepared as wholemounts and processed with tetramethyl benzidine. In addition, to study age-related changes in the myenteric plexus, the stomachs, small intestines, and large intestines from 3-, 12-, 21-, 24- and 27-month-old rats were prepared as wholemounts and processed with Cuprolinic Blue (to stain the neurons). Vagal afferent endings, motor terminal profiles, and myenteric neurons were counted and mapped with a sampling grid. In the stomach, both the vagal and myenteric innervation were stable between the ages of 3 and 24 months; however, a decrease in the number of myenteric neurons in the forestomach was noted at 27 months. In the small and large intestines, myenteric cell loss occurred by 12 months of age, progressed with age, and appeared to be governed by several general principles: (1) the rate of cell loss was organ-specific, with a gradient of increasing severity from proximal to distal in the gut; (2) within organs of the GI tract, the rate of cell loss differed between regions; and (3) for given regions, cell losses progressed linearly with increasing age. The findings suggest that a positive relationship exists between the density of vagal extrinsic innervation and myenteric neuron survival; however, whether this results from the vagal innervation and/or other factor(s) protecting or rescuing myenteric neurons from age-related attrition remains to be determined.

Ancient geodynamics and global-scale hydrology on Mars.

Loading of the lithosphere of Mars by the Tharsis rise explains much of the global shape and long-wavelength gravity field of the planet, including a ring of negative gravity anomalies and a topographic trough around Tharsis, as well as gravity anomaly and topographic highs centered in Arabia Terra and extending northward toward Utopia. The Tharsis-induced trough and antipodal high were largely in place by the end of the Noachian Epoch and exerted control on the location and orientation of valley networks. The release of carbon dioxide and water accompanying the emplacement of approximately 3 x 10(8) cubic kilometers of Tharsis magmas may have sustained a warmer climate than at present, enabling the formation of ancient valley networks and fluvial landscape denudation in and adjacent to the large-scale trough.

NF-kappa B activation by the pre-T cell receptor serves as a selective survival signal in T lymphocyte development.

Activation of the transcription factor NF-kappa B and pre-T cell receptor (pre-TCR) expression is tightly correlated during thymocyte development. Inhibition of NF-kappa B in isolated thymocytes in vitro results in spontaneous apoptosis of cells expressing the pre-TCR, whereas inhibition of NF-kappa B in transgenic mice through expression of a mutated, superrepressor form of I kappa B alpha leads to a loss of beta-selected thymocytes. In contrast, the forced activation of NF-kappa B through expression of a dominant-active I kappa B kinase allows differentiation to proceed to the CD4(+)CD8(+) stage in a Rag1(-/-) mouse that cannot assemble the pre-TCR. Therefore, signals emanating from the pre-TCR are mediated at least in part by NF-kappa B, which provides a selective survival signal for developing thymocytes with productive beta chain rearrangements.