Inferring within-host bottleneck size: A Bayesian approach.

Recent technical developments in microbiology have led to new discoveries on the within-host dynamics of bacterial infections in laboratory animals. In particular, they have highlighted the importance of stochastic bottlenecks at the onset of invasive disease. A number of approaches exist for bottleneck-size estimation with respect to within-host bacterial infections; however, some are more appropriate than others under certain circumstances. A Bayesian comparison of several approaches is made in terms of the availability of isogenic multitype bacteria (e.g., WITS), knowledge of post-bottleneck dynamics, and the suitability of dilution with monotype bacteria. A sampling approach to bottleneck-size estimation is also introduced. The results are summarised by a guiding flowchart, which we hope will promote the use of quantitative models in microbiology to refine the analysis of animal experiment data.

A model for malaria treatment evaluation in the presence of multiple species.

Plasmodium falciparum and P. vivax are the two most common causes of malaria. While the majority of deaths and severe morbidity are due to P. falciparum, P. vivax poses a greater challenge to eliminating malaria outside of Africa due to its ability to form latent liver stage parasites (hypnozoites), which can cause relapsing episodes within an individual patient. In areas where P. falciparum and P. vivax are co-endemic, individuals can carry parasites of both species simultaneously. These mixed infections complicate dynamics in several ways: treatment of mixed infections will simultaneously affect both species, P. falciparum can mask the detection of P. vivax, and it has been hypothesised that clearing P. falciparum may trigger a relapse of dormant P. vivax. When mixed infections are treated for only blood-stage parasites, patients are at risk of relapse infections due to P. vivax hypnozoites. We present a stochastic mathematical model that captures interactions between P. falciparum and P. vivax, and incorporates both standard schizonticidal treatment (which targets blood-stage parasites) and radical cure treatment (which additionally targets liver-stage parasites). We apply this model via a hypothetical simulation study to assess the implications of different treatment coverages of radical cure for mixed and P. vivax infections and a "unified radical cure" treatment strategy where P. falciparum, P. vivax, and mixed infections all receive radical cure after screening glucose-6-phosphate dehydrogenase (G6PD) normal. In addition, we investigated the impact of mass drug administration (MDA) of blood-stage treatment. We find that a unified radical cure strategy leads to a substantially lower incidence of malaria cases and deaths overall. MDA with schizonticidal treatment was found to decrease P. falciparum with little effect on P. vivax. We perform a univariate sensitivity analysis to highlight important model parameters.

Clindamycin adjunctive therapy for severe Staphylococcus aureus treatment evaluation (CASSETTE)-an open-labelled pilot randomized controlled trial.

BACKGROUND: Combination antibiotic therapy with an antitoxin agent, such as clindamycin, is included in some guidelines for severe, toxin-mediated Staphylococcus aureus infections. The evidence to support this practice is currently limited to in vitro, animal and observational human case-series data, with no previous randomized controlled trials (RCTs). OBJECTIVES: This pilot RCT aimed to determine the feasibility of conducting a clinical trial to examine if adjunctive clindamycin with standard therapy has greater efficacy than standard therapy alone for S. aureus infections. METHODS: We performed an investigator-initiated, open-label, multicentre, pilot RCT (ACTRN12617001416381p) in adults and children with severe S. aureus infections, randomized to standard antibiotic therapy with or without clindamycin for 7 days. RESULTS: Over 28 months, across nine sites, 127 individuals were screened and 34 randomized, including 11 children (32%). The primary outcome-number of days alive and free of systemic inflammatory response syndrome ≤14 days-was similar between groups: clindamycin (3 days [IQR 1-6]) versus standard therapy (4 days [IQR 0-8]). The 90 day mortality was 0% (0/17) in the clindamycin group versus 24% (4/17) in the standard therapy group. Secondary outcomes-microbiological relapse, treatment failure or diarrhoea-were similar between groups. CONCLUSIONS: As the first clinical trial assessing adjunctive clindamycin for S. aureus infections, this study indicates feasibility and that adults and children can be incorporated into one trial using harmonized endpoints, and there were no safety concerns. The CASSETTE trial will inform the definitive S. aureus Network Adaptive Platform (SNAP) trial, which includes an adjunctive clindamycin domain and participants with non-severe disease.

Domain-wall spin dynamics in kagome antiferromagnets.

We report magnetization and neutron scattering measurements down to 60 mK on a new family of Fe based kagome antiferromagnets, in which a strong local spin anisotropy combined with a low exchange path network connectivity lead to domain walls intersecting the kagome planes through strings of free spins. These produce unfamiliar slow spin dynamics in the ordered phase, evolving from exchange-released spin flips towards a cooperative behavior on decreasing the temperature, probably due to the onset of long-range dipolar interaction. A domain structure of independent magnetic grains is obtained that could be generic to other frustrated magnets.

Patient-initiated mandatory boluses for ambulatory continuous interscalene analgesia: an effective strategy for optimizing analgesia and minimizing side-effects.

BACKGROUND: This prospective, randomized study tested the hypothesis that a reduced dose continuous interscalene regimen incorporating a low background infusion with mandatory boluses would provide similar shoulder surgery analgesia compared with a dose regimen incorporating a conventional higher background infusion. METHODS: After rotator cuff surgery, patients received via an interscalene catheter, one of two elastomeric pumps, each having a 5 ml per 60 min bolus function and a 2 ml h⁻¹ (n=38) or 5 ml h⁻¹ (n=43) ropivacaine 2 mg ml⁻¹ infusion. Boluses commenced from the onset of pain and continued for >48 h as required (pro re nata, PRN) up to every hour for a numerical rating pain score (NRPS, 0-10) >2. Group 2 ml h⁻¹ received mandatory 6 hourly boluses irrespective of the NRPS. Rescue tramadol was available. Patients were questioned on postoperative days 1 and 2 for treatment effectiveness and side-effects. RESULTS: Postoperative pain was similar between the groups [Group 2 ml h⁻¹ day 2 median (IQR) (95% confidence interval of the mean) worst movement pain=4 (1-5) (2.8-4.7) vs 4 (2-5) (3.1-4.6), P=0.99], as were night awakenings and tramadol consumption. Numerically rated numbness and weakness were similar between the groups; however, nine patients (21%) in the 5 ml h⁻¹ group vs one (3%) in the 2 ml h⁻¹ group required a temporary infusion cessation due to side-effects (predominantly hand numbness) (P=0.02). CONCLUSIONS: Continuous interscalene ropivacaine 0.2% 2 ml h⁻¹ with mandatory 6 hourly (and PRN) boluses provides similar analgesia after rotator cuff repair but with reduced side-effects compared with 5 ml h⁻¹ with PRN only boluses.

Recombinant fragment of protein kinase inhibitor blocks cyclic AMP-dependent gene transcription.

Transcriptional regulation by cyclic adenosine monophosphate (cAMP) in mammalian cells could be mediated by a phosphoprotein substrate of the cAMP-dependent protein kinase or, as in prokaryotes, by a cAMP-binding protein. Two synthetic genes that code for an active fragment of the protein inhibitor of this kinase and a mutant inactive fragment were constructed and used to distinguish these alternatives. Transient expression of the active peptide product specifically inhibited the cAMP-stimulated expression of a cotransfected reporter gene by more than 90 percent, whereas the expression of the inactive peptide did not alter cAMP-stimulated gene expression. The results indicate that an active kinase catalytic subunit is a necessary intermediate in the cAMP stimulation of gene transcription.

Rapamycin-induced inhibition of the 70-kilodalton S6 protein kinase.

The immunosuppressant rapamycin inhibited proliferation of the H4IIEC hepatoma cell line. Rapamycin, but not its structural analog FK506, also inhibited the basal and insulin-stimulated activity of the p70 ribosomal protein S6 kinase. By contrast, insulin stimulation of the p85 Rsk S6 kinase and mitogen-activated protein (MAP) kinase activity were unaffected by drug. Rapamycin treatment of COS cells transfected with recombinant p70 S6 kinase completely inhibited the appearance of the hyperphosphorylated form of p70 S6 kinase concomitant with the inhibition of enzyme activity toward 40S subunits. Thus, rapamycin inhibits a signal transduction element that is necessary for the activation of p70 S6 kinase and mitogenesis but unnecessary for activation of p85 Rsk S6 kinase or MAP kinase.

Analgesic effectiveness of ropivacaine 0.2% vs 0.4% via an ultrasound-guided C5-6 root/superior trunk perineural ambulatory catheter.

BACKGROUND: In this prospective, randomized, triple-blinded study, we tested the hypothesis that a 48 h continuous C5-6 root/superior trunk patient-controlled infusion of ropivacaine 0.4% would provide superior analgesia after shoulder surgery compared with the same infusion of ropivacaine 0.2%. METHODS: Patients presenting for painful shoulder surgery were recruited. A perineural catheter was placed under ultrasound guidance immediately adjacent to the C5-6 roots/superior trunk. Ropivacaine 5 mg ml(-1) (30 ml) was administered via this catheter before surgery under general anaesthesia. At the end of surgery, patients were randomized to receive ropivacaine 2 mg ml(-1) (0.2%) (n=32) or 4 mg ml(-1) (0.4%) (n=33) via an elastomeric pump delivering 2 ml h(-1) with on-demand patient-controlled boluses of 5 ml as required. Acetaminophen and diclofenac were administered if any postoperative pain occurred, ropivacaine boluses for a numerical rating pain score (NRPS, 0-10) of >2, and rescue tramadol for an NRPS >3. All patients were phoned on postoperative days 1 and 2 and questioned for indices of treatment effectiveness and adverse effects. RESULTS: NRPS, patient ropivacaine demands, and supplemental tramadol consumption were similar in each group [median 'average daily pain' days 1/2 (0.2%=1/3, 0.4%=2/3)]. Episodes of an insensate/densely blocked arm occurred only with ropivacaine 0.4% (5 vs 0 episodes, P=0.05). Satisfaction (numerical rating scale, 0-10) was higher for ropivacaine 0.2% [mean difference (95% confidence interval)=1.3 (0.3-2.4), P=0.01)]. CONCLUSIONS: After major shoulder surgery, ropivacaine 0.2% at 2 ml h(-1) with on-demand 5 ml boluses administered via an ultrasound-guided C5-6 root/superior trunk perineural catheter produces similar analgesia, but higher patient satisfaction compared with ropivacaine 0.4%. TRIAL REGISTRATION: ANZCTR: ACTRN12608000591358. URL: www.anzctr.org.au/registry/trial_review.aspx?ID=83028.

Histopathological frequency of feline hepatobiliary disease in the UK.

OBJECTIVES: To determine the histopathological frequency of feline hepatobiliary diseases in the UK and to identify breed, age and gender predispositions to developing individual diseases. METHODS: Histopathology results from 1452 feline liver biopsies were assessed. A control population of microchipped cats was used for breed comparison. Data were retrospectively categorised into hepatobiliary diseases according to World Small Animal Veterinary Association standards. Odds ratios and 95% confidence intervals were calculated to determine breed predispositions to the 10 most frequent diseases. Gender and age distributions were also evaluated. RESULTS: The most frequent diseases based on histopathology were neutrophilic cholangitis (20·5%), reactive hepatitis (20·4%), reversible hepatocellular injury (8·4%), lymphocytic cholangitis (6·8%), biliary cysts (5·7%), acute hepatitis (5·6%), haematopoietic neoplasia (5·6%), hepatocellular neoplasia (4·9%), congenital portosystemic shunt (3·8%) and cholangiocellular neoplasia (3·1%). Some previously unreported breed and age predispositions were identified. CLINICAL SIGNIFICANCE: This is the first study to document the histopathological frequency of hepatobiliary diseases in a large cohort of cats in the UK, as well as novel breed and age predispositions. These data may help increase the index of suspicion of a particular disease in the absence of a biopsy-confirmed diagnosis.

Cloning and expression of two human p70 S6 kinase polypeptides differing only at their amino termini.

Two classes of human cDNA encoding the insulin/mitogen-activated p70 S6 kinase have been isolated; the two classes differ only in the 5' region, such that the longer polypeptide (p70 S6 kinase alpha I; calculated Mr 58,946) consists of 525 amino acids, of which the last 502 residues are identical in sequence to the entire polypeptides encoded by the second cDNA (p70 S6 kinase alpha II; calculated Mr 56,153). Both p70 S6 kinase polypeptides predicted by these cDNAs are present in p70 S6 kinase purified from rat liver, and each is thus expressed in vivo. Moreover, both polypeptides are expressed from a single mRNA transcribed from the (longer) p70 S6 kinase alpha I cDNA through the utilization of different translational start sites. Although the two p70 S6 kinase polypeptides differ by only 23 amino acid residues, the slightly longer alpha I polypeptide exhibits anomalously slow mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), migrating at an apparent Mr of 90,000 probably because of the presence of six consecutive Arg residues immediately following the initiator methionine. Transient expression of p70 alpha I and alpha II S6 kinase cDNA in COS cells results in a 2.5- to 4-fold increase in overall S6 kinase activity. Upon immunoblotting, the recombinant p70 polypeptides appear as a closely spaced ladder of four to five bands between 65 and 70 kDa (alpha II) and 85 and 90 kDa (alpha I). Transfection with the alpha II cDNA yields only the smaller set of bands, while transfection with the alpha I cDNA generates both sets of bands. Mutation of Met-24 in the alpha I cDNA to Leu or Thr suppresses synthesis of the alpha II polypeptides. Only the p70 alpha I and alpha II polypeptides of slowest mobility on SDS-PAGE comigrate with the 70- and 90-kDa proteins observed in purified rat liver S6 kinase. Moreover, it is the recombinant p70 polypeptides of slowest mobility that coelute with S6 kinase activity on anion-exchange chromatography. The slower mobility and higher enzymatic activity of these p70 proteins is due to Ser/Thr phosphorylation, inasmuch as treatment with phosphatase 2A inactivates kinase activity and increases the mobility of the bands on SDS-PAGE in an okadaic acid-sensitive manner. Thus, the recombinant p70 S6 kinase undergoes multiple phosphorylation and partial activation in COS cells. Acquisition of S6 protein kinase catalytic function, however, is apparently restricted to the most extensively phosphorylated recombinant polypeptides.

Target-derived neurotrophic factors regulate the death of developing forebrain neurons after a change in their trophic requirements.

Many neurons die as the normal brain develops. How this is regulated and whether the mechanism involves neurotrophic molecules from target cells are unknown. We found that cultured neurons from a key forebrain structure, the dorsal thalamus, develop a need for survival factors including brain-derived neurotrophic factor (BDNF) from their major target, the cerebral cortex, at the age at which they innervate it. Experiments in vivo have shown that rates of dorsal thalamic cell death are reduced by increasing cortical levels of BDNF and are increased in mutant mice lacking functional BDNF receptors or thalamocortical projections; these experiments have also shown that an increase in the rates of dorsal thalamic cell death can be achieved by blocking BDNF in the cortex. We suggest that the onset of a requirement for cortex-derived neurotrophic factors initiates a competitive mechanism regulating programmed cell death among dorsal thalamic neurons.

Purification of a major tyrosine kinase from RBL-2H3 cells phosphorylating Fc epsilon RI gamma-cytoplasmic domain and identification as the Btk tyrosine kinase.

Immunoglobulin E high affinity receptor-mediated signal transduction in mast cells results in a number of protein tyrosine kinases being activated as very early events in the process leading to degranulation. Some of these, such as the src kinases and the syk kinase, are known to be involved in this receptor-associated activation. In this paper we describe the search for other activation-associated tyrosine kinases by the ability to phosphorylate a cytoplasmic domain peptide of the Fc epsilon RI gamma-subunit. In utilizing a purification step previously used to isolate the 72 kDa syk kinase, we detected another kinase of molecular weight 79 kDa which we designated cd gamma kinase. The kinase was purified to near homogeneity by Heparin-agarose, Mono Q, and CM Sepharose chromatographies. The yield of enzyme was approx. 200 micrograms/10(9) cells. We characterized this kinase by its ability to phosphorylate both the cd gamma peptide (Km = 0.2 mM) and the cytoplasmic fragment of the Band III protein. The cd gamma kinase was distinguished from syk by inability to be precipitated by anti-syk antiserum and by partial peptide mapping. Cd gamma kinase was also distinguished from syk by cd gamma peptide and Band III substrate specificity. We identified the cd gamma kinase by Western blotting and by partial phosphopeptide mapping as Btk, the B-cell tyrosine kinase found to be defective in X-linked agammaglobulinemia.

The transcription factor Pax6 is required for development of the diencephalic dorsal midline secretory radial glia that form the subcommissural organ.

During brain development, Pax6 is expressed in specific regions of the diencephalon including secretory cells of the subcommissural organ (SCO), a circumventricular organ at the forebrain-midbrain boundary that originates from the pretectal dorsal midline neuroepithelial cells beneath the posterior commissure (PC). Homozygous small eye (Sey/Sey) mice lack functional Pax6 protein and fail to develop the SCO, a normal PC and the pineal gland. Small eye heterozygotes (Sey/+) show defective development of the SCO's basal processes which normally penetrate the PC, indicating that normal development of the gland requires normal Pax6 gene-dosage. A correlation between the defects of SCO formation and altered R- and OB-cadherin expression patterns in the SCO is observed in mutants suggesting a role for cadherins in SCO development.

Autoregulation of thyroid iodide transport: evidence for the mediation of protein synthesis in iodide-induced suppression of iodide transport.

The role of protein synthesis in iodide-induced suppression of subsequent iodide transport (iodide autoregulation) was studied in cat thyroid slices. Thyroid slices were pretreated for 60-120 min in the presence or absence of either excess (30 microM) sodium iodide, inhibitors of protein synthesis, or both. Tissue was then washed in the presence of 2 mM methimazole to prevent subsequent iodination reaction and remove excess iodide. Iodide transport activity was finally evaluated by measurement of the ratio of tissue to medium iodide concentrations in 90-min incubations. Addition of 0.1 mM cycloheximide during the preexposure of thyroid tissue to excess iodide had no effect on either control levels of iodide transport or iodide-induced autoregulation. However, if thyroid tissue was treated with cycloheximide alone for 1 h before preexposure to excess iodide, there was a significant reduction in the degree of iodide-induced induced autoregulation. Similar results were obtained with pretreatment of the tissue with 0.5 mM puromycin and 1 microgram/ml emetine. These findings suggest that protein synthesis is involved in the mechanism of thyroid autoregulation of iodide transport. Cycloheximide had no effect on the ability of excess iodide to reduce TSH-stimulated cAMP formation. Two-dimensional gel electrophoresis-isoelectric focusing and Sephadex G-25 column chromatography employing dual-isotope comparison of iodoprotein labeling of control and cycloheximide-treated tissue suggest that the ability of cycloheximide to suppress iodide-induced autoregulation is associated with the reduced iodination of an 8- to 10-kilodalton soluble component of the thyroid gland.

Autoregulation of iodide transport in the rabbit: absence of autoregulation in fetal tissue and comparison of maternal and fetal thyroid iodination products.

Maternal and fetal rabbit thyroid glands were compared as to their ability to respond to excess iodide in vitro with a reduction in subsequent iodide transport activity. Preincubation of maternal thyroid tissue slices for 2 h with excess iodide (30 microM) resulted in a 31% reduction in the subsequently measured thyroid-medium radioiodide concentration ratio. In contrast, similar iodide pretreatment had no significant effect on fetal iodide transport. In all other respects, fetal iodide transport, although it was 10 times higher, did not differ significantly from maternal transport activity. Combined radiolabeled maternal (125I) and fetal (131I) rabbit thyroid tissue was eluted on Sephadex G-25 columns. Fractions were analyzed for both 125I and 131I activity, and the maternal to fetal ratios (125I/131I) were determined for each fraction. The majority of iodoproteins eluted with the void volume, and the 125I/131I ratio was constant in these fractions. Thereafter, two peaks of elevated 125I/131I activity could be observed. Peak A eluted below lysozyme (Mr = 14,300) and above insulin (Mr = 6,000), with an apparent mol wt of 8,000 to 10,000. A second peak, peak B, eluted from the column at a site similar to that of MIT or a protein of Mr of 2,000. Ascending paper chromatography of this latter peak of 125I/131I activity and MIT was carried out in two solvent systems. In both systems, peak B comigrated with MIT. These findings suggest that the failure of fetal thyroid tissue to exhibit autoregulation may be associated with the reduced iodination of a compound with an approximate Mr of 8,000 to 10,000. The role of this substance in iodide transport remains to be identified. The reason for the apparent increase in the labeling of MIT observed in maternal vs. fetal tissue is unknown.

Cloning and sequencing of a leech homolog to the Drosophila engrailed gene.

We have cloned and sequenced a homolog (ht-en) to the Drosophila engrailed (en) gene from the glossiphoniid leech, Helobdella triserialis. Amino acid comparisons of the ht-en homeodomain and C-terminal residues with the corresponding residues encoded by en-class genes of other species reveal 75-79% sequence identity. In addition, the ht-en sequence appears to have a serine-rich region 16 residues C-terminal from the homeodomain, which by analogy to Drosophila may be a target site for phosphorylation. The leech gene encodes some amino acid substitutions for residues that are highly conserved in other species. These are found within the second and third of the three putative helices of the homeodomain, and in both of the intervening turn regions.

Organization of association projections from area 17 to areas 18 and 19 and to suprasylvian areas in the cat's visual cortex.

Cells in area 17 that are labelled by single, discrete injections of retrogradely transported tracers into extrastriate visual areas are discontinuously distributed in dense patches. In this study we made multiple, closely spaced injections of fluorescent dyes into extrastriate areas, to generate large deposits that would reveal whether the distributions of corticocortical cell bodies in area 17 are truly patchy or appear clustered only after small injections. By injecting a different tracer into each extrastriate area, or group of areas, we examined the spatial relationships between the populations of association cells. All deposits of tracers in areas 18, 19, or suprasylvian cortex, irrespective of size, label cells in a series of clusters in topographically related parts of area 17. We conclude that the complete populations of cells in area 17 that project to areas 18, 19, and the lateral suprasylvian cortex are all genuinely distributed in a patchy fashion. There appears to be a complex relationship between the sets of association cells projecting to different extrastriate regions: they do not completely overlap, only partially, and share some cortical zones but not others. In these experiments, only tiny percentages (2-5%) of labelled cells in the overlapping regions were filled with both tracers, suggesting that very few association cells in area 17 project to more than one of the extrastriate areas we studied. By comparing the dimensions of each injection site and of the labelled region in area 17, we estimated the extent of the convergence from area 17 to areas 18, 19, and posteromedial suprasylvian areas in retinotopic terms. The functional convergence was very similar in these pathways.

Fates of the earliest generated cells in the developing murine neocortex.

In mammalian species studied to date, the first-born neocortical cells normally form two layers, one above and one below the cortical plate, called the marginal zone (future layer 1) and the subplate. In primates and carnivores, many of these first-born cells die early in postnatal life. Whether this also occurs in rodents is highly controversial. In this study, we injected pregnant mice with bromodeoxyuridine on embryonic days (E) 11-14 to label the earliest generated neocortical cells, and examined their fates between birth and postnatal day 21. At birth, most cells born on embryonic day 11 were below the cortical plate, and a smaller proportion were above it. Very few of these cells remained by postnatal day 3 and there were none at any depth in the neocortex at older ages. At birth, the largest proportion of cells born on embryonic days 12 and 13 were in the subplate and smaller proportions were in the cortical plate and marginal zone. At older ages, almost all of these cells had disappeared from the marginal zone and from below the cortical plate, although some were retained in the cortical plate. The density of the remaining E12- and E13-born cells decreased more than could be explained by neocortical expansion alone. As a control, we studied cells born on embryonic day 14. These cells were restricted to the cortical plate at birth. By postnatal day 21, their density had decreased by an amount that could be explained by neocortical expansion alone. We conclude that, as in other species, many of the earliest generated cells of the murine neocortex die.

Effects of monoamine oxidase A inhibition on barrel formation in the mouse somatosensory cortex: determination of a sensitive developmental period.

Genetic inactivation of monoamine oxidase A (MAOA) in C3H/HeJ mice causes a complete absence of barrels in the somatosensory cortex, and similar alterations are caused by pharmacological inhibition of MAOA in wild type mice. To determine when and how MAOA inhibition affects the development of the barrel field, the MAOA inhibitor clorgyline was administered to mice of the outbred strain OF1 for various time periods between embryonic day 15 (E15) and postnatal day 7 (P7), and the barrel fields were analyzed with cytochrome oxidase and Nissl stains in P10 and adult mice. High-pressure liquid chromatography measures of brain serotonin (5-HT) showed three- to eightfold increases during the periods of clorgyline administration. Perinatal mortality was increased and weight gain was slowed between P3 and P6. Clorgyline treatments from E15 to P7 or from P0 to P7 disrupted the formation of barrels in the anterior snout representation and in parts of the posteromedial barrel subfield (PMBSF). Treatments from P0 to P4 caused similar although less severe barrel field alterations. Clorgyline treatments only during embryonic life or starting on P4 caused no detectable abnormalities. In cases with barrel field alterations, a rostral-to-caudal gradient of changes was noted: Rostral barrels of the PMBSF were most frequently fused and displayed an increased size tangentially. Thus, MAOA inhibition resulting in increased brain levels of 5-HT affects barrel development during the entire first postnatal week, with a sensitive period between P0 and P4. The rostral-to-caudal gradient of changes in the barrel field parallels known developmental gradients in the sensory periphery and in the maturation thalamocortical afferents. The observed barrel fusions could correspond to a default in the initial segregation of thalamic fibers or to a continued, exuberant growth of these fibers that overrides the tangential domain that is normally devoted to individual whiskers.

Solvothermal Synthesis of the Canted Antiferromagnet {K2 [CoO3 PCH2 N(CH2 CO2 )2 ]}6 ⋠x H2 O.

A rare example of a molecular species prepared by solvothermal synthesis is the macrocyclic cobalt phosphonate/carboxylate 1, whose structure is shown schematically. At low temperatures this compound displays spontaneous magnetization due to canted antiferromagnetic ordering, which is very unusual for a discrete molecular material.