Tonic signaling from O₂ sensors sets neural circuit activity and behavioral state

Tonic receptors convey stimulus duration and intensity and are implicated in homeostatic control. However, how tonic homeostatic signals are generated and how they reconfigure neural circuits and modify animal behavior is poorly understood. Here we show that Caenorhabditis elegans O(2)-sensing neurons are tonic receptors that continuously signal ambient [O(2)] to set the animal's behavioral state. Sustained signaling relied on a Ca(2+) relay involving L-type voltage-gated Ca(2+) channels, the ryanodine and the inositol-1,4,5-trisphosphate receptors. Tonic activity evoked continuous neuropeptide release, which helps elicit the enduring behavioral state associated with high [O(2)]. Sustained O(2) receptor signaling was propagated to downstream neural circuits, including the hub interneuron RMG. O(2) receptors evoked similar locomotory states at particular O(2) concentrations, regardless of previous d[O(2)]/dt. However, a phasic component of the URX receptors' response to high d[O(2)]/dt, as well as tonic-to-phasic transformations in downstream interneurons, enabled transient reorientation movements shaped by d[O(2)]/dt. Our results highlight how tonic homeostatic signals can generate both transient and enduring behavioral change.     

A Variety of Opportunities for Immune Interactions During Trophoblast Development and Invasion

During human implantation and placentation, the direct cell to cell contact of fetal and maternal tissues gives room for a variety of immune interactions. Especially, the invasion of a subset of fetal trophoblast cells, called extravillous trophoblast, generate a very close interplay between the two individuals, enabling the attachment of the placenta to the uterine wall and the transformation of maternal spiral arteries to facilitate adequate nutrition of the fetus. During pregnancy, maternal and fetal factors closely interact to maintain pregnancy and smooth the process of delivery. At each and every stage and site, immunological interactions take place, including attachment of the blastocyst, development and invasion of trophoblast, and flow of maternal plasma and blood through the intervillous space of the placenta. Control mechanisms tightly regulate these interactions helping to evade fetal rejection by the mother. In this review, we highlight the morphological sites of development and feto‐maternal interaction to help immunological interested scientists and clinicians to develop hypotheses on the feto‐maternal immunological network during pregnancy.     

Myeloid- and lymphoid-specific breakpoint cluster regions in chromosome band 13q14 in acute leukemia.

Abnormalities of chromosome band 13q14 occur in hematologic malignancies of all lineages and at all stages of differentiation. Unlike other chromosomal translocations, which are usually specific for a given lineage, the chromosomal translocation t(12;13)(p12;q14) has been observed in both B-cell and T-cell precursor acute lymphoblastic leukemia (BCP-, TCP-ALL), in differentiated and undifferentiated acute myeloblastic leukemia (AML), and in chronic myeloid leukemia (CML) at progression to blast crisis. The nature of these translocations and their pathologic consequences remain unknown. To begin to define the gene(s) involved on chromosome 13, we have performed fluorescence in situ hybridization (FISH) using a panel of YACs from the region, on a series of 10 cases of acute leukemia with t(12;13)(p12;q14) and 1 case each with "variant" translocations including t(12;13)(q21;q14), t(10;13)(q24;q14) and t(9;13)(p21;q14). In 8/13 cases/cell lines, the 13q14 break fell within a single 1.4 Mb CEPH MegaYAC. This YAC fell immediately telomeric of the forkhead (FKHR) gene, which is disrupted in the t(2;13)(q35;q14) seen in pediatric alveolar rhabdomyosarcoma. Seven of the 8 cases with breaks in this YAC were AML. In 4/13 cases, the 13q14 break fell within a 1.7-Mb YAC located about 3 Mb telomeric of the retinoblastoma (RB1) gene: all 4 cases were ALL. One case of myelodysplastic syndrome exhibited a break within 13q12, adjacent to the BRCA2 gene. These data indicate the presence of myeloid- and lymphoid-specific breakpoint cluster regions within chromosome band 13q14 in acute leukemia.     

Functional neuroanatomy of human sleep states after zolpidem and placebo: a H215O-PET study

Changes in the functional organization of the brain during the course of sleep and waking are reflected by different patterns of regional cerebral blood flow (rCBF). To investigate the effect of the hypnotic zolpidem, a benzodiazepine receptor agonist, drug or placebo were administered to eight young, healthy men prior to bedtime. The subjects were sleep-deprived to promote sleep during the 4-h recording period in the positron emission tomography scanner. Intravenous injections of labelled water were administered during pre-drug wakefulness, and during Stage 2, Stage 4 and rapid eye movement (REM) sleep, each injection being followed by an emission scan. Statistical parametric mapping was used to investigate the effects of treatment and sleep states. During sleep (combined Stages 2 and 4, and REM sleep) relative rCBF was lower after zolpidem than after placebo in the basal ganglia and insula, and higher in the parietal cortex. A 'multiple study' analysis of REM sleep revealed that rCBF in the anterior cingulum was lower after zolpidem than after placebo, whereas rCBF in the occipital and parietal cortex, parahippocampal gyrus and cerebellum was higher. When the pooled data (drug and placebo) of Stages 2 and 4 were compared with wakefulness, rCBF was lower in prefrontal cortex and insula, and higher in the occipital and parietal cortex. The results indicate that some differences in rCBF from wakefulness to non-REM sleep are further augmented by zolpidem.     

Infantile colic, prolonged crying and maternal postnatal depression

Aim:  To study if infant crying is associated with maternal postnatal depression.
Methods:  Data from 1015 mothers and their children participating in a prospective European multicentre study were analysed. Infantile colic and prolonged crying were defined as excessive crying as reported by the mothers 2 and 6 months after delivery, and at the same time the mothers completed the Edinburgh Postnatal Depression Scale (EPDS).
Results:  In cross-sectional analyses, infant crying was associated with high EPDS scores both 2 (OR: 4.4; 95% CI: 2.4–8.2) and 6 months postpartum (OR: 10.8; 95% CI: 4.3–26.9). More than one-third of the others of infants with prolonged crying had high EPDS scores 6 months postpartum. Longitudinal analyses showed that mothers of infants with colic had increased odds of having high EPDS scores 6 months after delivery even if crying had resolved (OR: 3.7; 95% CI: 1.4–10.1).
Conclusion: Both infantile colic and prolonged crying were associated with high maternal depression scores. Most noteworthy, infantile colic at 2 months of age was associated with high maternal depression scores
4 months later.     

MALT lymphoma in patients with autoimmune diseases: a comparative analysis of characteristics and clinical course.

MALT lymphoma, especially of extragastric origin, is thought to be associated with an underlying autoimmune disease (AD) in a significant proportion of patients. No systematic assessment of the clinical characteristics of MALT lymphoma arising in AD as opposed to patients without AD has been performed so far. Therefore, all patients diagnosed and treated for MALT lymphoma at our institution have prospectively undergone routine clinical and serological assessment for AD since 1997. In total, 158 patients were available for analysis, and 61 out of 158 patients (39%) were diagnosed with an underlying AD. Patients with AD were predominantly women and significantly younger at lymphoma diagnosis (56 versus 67 years, P=0.004), with a significantly higher rate of extragastric lymphomas (P=0.012). Furthermore, lymphomas in these patients showed a lower frequency of trisomy 3 (P=0.04) and a significantly lower response rate to Helicobacter pylori eradication therapy in the case of gastric lymphomas (P=0.03). All other parameters including estimated median time to relapse were comparable between both groups. Our data suggest that patients with AD develop MALT lymphoma significantly earlier in life. The clinical course, however, does not appear to be adversely influenced by the presence of AD, as neither rate of relapse nor times to relapse or survival are significantly different.     

Treatment of hypercholesterolemia in children and adolescents

In patients with severe genetic hypercholesterolemia, therapeutic reduction of elevated serum total cholesterol and LDL cholesterol should begin in early childhood to lower the risks of cardiovascular disease later in life. We evaluated the effects of outpatient therapy with diet alone and with combined diet and drug therapy in children and adolescents with hypercholesterolemia of apparent dominant inheritance. Serum lipid values before and during dietary treatment were available in 35 patients (mean age at start of treatment 7.9 years, range 2.0-17.6 years) followed for an average duration of 17.5 months (range 4-70 months). A comparison between untreated state and combined therapy with diet and cholestyramine was possible in 14 patients (mean age 8.6 years, range 2.4-17.0 years) followed for 27.9 months (range 4-97 months). Dietary modification achieved by repeated counseling and training lowered serum total cholesterol by mean (+/- SE) 11.7 +/- 1.9% (p < 0.0001) and LDL cholesterol by 17.3 +/- 3.5% (p < 0.0001). However, five of 35 patients did not show an appreciable effect of therapy (cholesterol reduction < 5%), possibly because of non-compliance. Diet combined with cholestyramine in an average dose of 0.36 g/kg body weight/day reduced total cholesterol by 33.0 +/- 2.4% (p < 0.0001) and LDL cholesterol by 37.5 +/- 4.3% (p < 0.0001) and was effective in all patients. Both forms of treatment had no effect on serum triglycerides and HLD cholesterol. No serious side effects were noted, and percentile values for weight and height remained unchanged in all but three obese children.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma Neurotensin: Lack of a Differentiation and Tumor Marker in Children with Neuroblastoma

Neurotensin is a tridecapeptide with changing receptor expression in central and peripheral neural cells during ontogeny suggesting its potential use as a differentiation and tumor marker in neuroectodermal malignancies. We investigated the neurotensin levels in plasma samples of 58 patients with neuroblastoma using a sensitive radioimmunoassay. Elevated levels were found only in one stage III and in one stage IVs patient, while the neurotensin concentrations of 56 patients were in the range of control children. We conclude that plasma neurotensin reflects neither the differentiation nor the tumor status in children with neuroblastoma.