Partial duplication of the long arm of chromosome 5: A case due to balanced paternal translocation and review of the literature

Summary A partial duplication of the distal segment of the long arm of chromosome 5 (q31qter) was observed in an infant with congenital malformations and dysmorphic features. The phenotypically normal father had a balanced translocation between the long arm of chromosome 5 and the short arm of chromosome 9: 46,XY,t(5;9)(q31;p24).The clinical and cytogenetic data obtained from six patients with partial duplications of two different long arm segments of chromosome 5 suggest that partial duplication of the distal long arm of chromosome 5 is associated with microcephaly, hypertelorism, epicanthus, strabismus, large upper lip, low-set, dysplastic ears, in addition to growth and psychomotor retardation. Partial duplication of the proximal part of the long arm of chromosome 5, on the other hand, is associated mainly with musculoskeletal abnormalities including muscle hypotrophy and hypotonia, scoliosis, lordosis, pectus carinatum, cubitus valgus, and genu valgum, in addition to psychomotor retardation. The dysmorphic features in this latter group include a bulging forehead, short nose, thick upper lip, low-set protruding ears and tapering, thin fingers.     

Postpartum,hormonal, and nonhormonal induction of maternal behavior in rats: Effects on T-maze retrieval of pups

It is known that the home-cage maternal behavior of rats which become maternal after daily pup exposure (sensitization) is almost indistinguishable from that of lactating mothers, but that sensitized and lactating rats can be distinguished by their pup-retrieval performance in a T-maze extension of the home cage. The present study explored this difference further. Postpartum mothers which could not suckle due to prior nipple removal (thelectomy) retrieved as well, if not better, than intact controls in the T-maze. Hormonal induction of maternal behavior (in ? 3 days) was carried out by hysterectomy-ovariectomy plus 100 μg/kg estradiol benzoate; the performance of these females was similar to that of the postpartum groups. In contrast, only a small percentage of the sensitized mothers retrieved in the T-maze, whether the latency to onset of their maternal behavior was long (4–10 days) or short (? 3 days). Thus, hormonal factors associated with pregnancy and/or parturition, but not suckling stimulation, may facilitate T-maze retrieval of pups. The possible ethological significance of the T-maze test as a measure of maternal responsiveness is discussed.     

Why does viral RNA sometimes persist after recovery from acute infections?

DNA viruses often persist in the body of their host, becoming latent and recurring many months or years later. By contrast, most RNA viruses cause acute infections that are cleared from the host as they lack the mechanisms to persist. However, it is becoming clear that viral RNA can persist after clinical recovery and elimination of detectable infectious virus. This persistence can either be asymptomatic or associated with late progressive disease or nonspecific lingering symptoms, such as may be the case following infection with Ebola or Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Why does viral RNA sometimes persist after recovery from an acute infection? Where does the RNA come from? And what are the consequences?

Most RNA viruses cause acute infections that are cleared from the host as they lack the mechanisms to persist; however, phenomena such as "long COVID" suggest that viral RNA can persist after clinical recovery and elimination of detectable infectious virus. This Unsolved Mystery article explores the meaning, origins and consequences of such persistent RNA.     

Transactivation of the epidermal growth factor receptor mediates parathyroid hormone and prostaglandin F2 alpha-stimulated mitogen-activated protein kinase activation in cultured transgenic murine osteoblasts

Recent data suggest that G protein-coupled receptors (GPCRs), including those for PTH and prostaglandins (PGs), contribute to the proliferation and differentiation of osteoblasts in vivo. To understand how these signals are transduced, we studied activation of the ERK1/2 MAPK cascade in cultures of differentiating TMOb murine osteoblasts. In TMOb cells, stimulation of endogenous Gs/Gq-coupled PTH receptors, Gq-coupled PGF2 alpha receptors, and Gi/Gq-coupled lysophosphatidic acid receptors, but not Gs-coupled PGE2 receptors, caused a rapid 5- to 10-fold increase in ERK1/2 phosphorylation. GPCR-stimulated ERK1/2 activation coincided with increased tyrosine phosphorylation of epidermal growth factor (EGF) receptors and was blocked by the EGF receptor inhibitor, tyrphostin AG1478, and the metalloprotease inhibitor, batimastat, suggesting that the response involved transactivation of EGF receptors through the proteolytic release of an EGF receptor ligand. To further examine the mechanism of PTH-stimulated EGF receptor transactivation, we employed COS-7 cells expressing the rat PTH receptor. Here, stimulation with PTH(1-34) caused proteolysis of hemagglutinin epitope-tagged heparin binding-EGF, increased tyrosine autophosphorylation of EGF receptors, and AG1478-sensitive ERK1/2 activation. When PTH receptor-expressing COS-7 cells were placed in a mixed culture with cells lacking the PTH receptor but expressing a green fluorescent protein-tagged ERK2, stimulation with PTH(1-34) induced phosphorylation of green fluorescent protein-ERK2 that was abolished by either batimastat or tyrphostin AG1478. These data suggest that autocrine/paracrine cross-talk between EGF receptors and Gi- or Gq/11-coupled GPCRs represents the predominant mechanism of GPCR-mediated activation of ERK1/2 in cultured TMOb osteoblasts.     

Evaluation of selective inhibitors of 11β-HSD1 for the treatment of hypertension

In an effort to understand the origin of blood-pressure lowering effects observed in recent clinical trials with 11β-HSD1 inhibitors, we examined a set of 11β-HSD1 inhibitors in a series of relevant in vitro and in vivo assays. Select 11β-HSD1 inhibitors reduced blood pressure in our preclinical models but most or all of the blood pressure lowering may be mediated by a 11β-HSD1 independent pathway.     

Cyclooxygenase and 5-lipoxygenase inhibitory activity of 2,6 di-t-butylphenols linked by a sulfur atom to 1,3,4-thiadiazoles and 1,3,4-oxadiazoles

The preparation of a series of 1,3,4-thiadiazoles and 1,3,4-oxadizoles linked by a thioether to 2,6-di-t-butylphenol and the inhibition of cyclooxygenase (CO) and 5-lipoxygenase (5-LO) by these compounds is dicussed.     

Simple high-performance liquid chromatography method for the simultaneous determination of serum caffeine and paraxanthine following rapid sample preparation

A simple reversed-phase high-performance liquid chromatography (HPLC) method for the simultaneous determination of caffeine and paraxanthine in human serum is described. Serum proteins are precipitated with perchloric acid and the resulting supernatant neutralized for direct injection onto an HPLC column. The method uses a phosphate–methanol mobile phase (85:15, v/v) at pH 4.9 with a flow-rate of 1.75 ml/min and quantitation is by UV absorbance at 274 nm. Elution times are approximately 18 min for caffeine and 8 min for paraxanthine. Theobromine and theophylline have elution times of 5.4 and 9.4 min and do not interfere in the assay. The intra-assay and between-assay means for precision and accuracy for both drugs are: 4.5% C.V. and 3.3% deviation. The sensitivity of the method is 50 ng/ml for each drug.