A low frequency mosaicism for monosomy 21 in a live born female

Summary Monosomy 21, whether homogeneous or as a mosaicism, is very uncommon. We report here a 3-month-old white female with a low degree of monosomy 21 in the blood karyotype (6.5%, 110 cells counted) but not in the skin fibroblasts, which contained only the normal chromosome complement.The patient's physical features included microcephaly with frontal slanting; prominent occiput; ridge-shaped sutures; agenesis of the corpus callosum; large, prominent ears; high and narrow palate; micrognathia; tetralogy of Fallot; crowded toes; and dry, thick skin with very little subcutaneous tissue. The case is discussed in light of the suggested clinical features of the monosomy 21 syndrome and the possible implications of such a low-grade mosaicism in prenatal diagnosis.     

Localization of the nucleolar organizer by computer-aided analysis of a variant no. 21 in a human isolate

Summary A variant chromosome no. 21 consisting of two stalks and two satellites in tandem was detected during a survey of a human isolate. The variant segregated in three generations of a large kindred. One male had the variant no. 21, a metacentric Y, and a 47, XXY complement; however, no other evidence of chromosomal nondisjunction was found. Computer-aided analysis of sequentially stained variant no. 21 chromosomes indicated that silver-stained material corresponded to the proximal stalk region (as defined defined by Giemsa). These data support the hypothesis that human nucleolar organizers are localized to the stalks of acrocentric chromosomes.     

Central cardiovascular and thermal effects of prostaglandin F2α in rats

Administration of PGF_2α (0.2–6.4 μg) into the lateral cerebral ventricle (i.c.v.) induced dosedependent increases in blood pressure, heart rate and body temperature in urethane-anaesthetised rats, but had no effect on these parameters when the same dose range was administered intravenously. Peripheral pretreatment with sodium meclofenamate (50 mg/kg s.c.) shifted all the dose-response curves for PGF_2α (i.c.v.) to the left, but indomethacin (50 mg/kg s.c.) did not significantly affect those changes. Central pretreatment with sodium meclofenamate or indomethacin (1.25 mg per rat i.c.v.) failed to modify significantly the effects of centrally administered PGF_2α.The results support previous suggestions that PGF_2α may participate in the central control of the cardiovascular and thermoregulatory systems, and also suggest that there may be differences in the sites and/or modes of action between sodium meclofenamate and indomethacin.     

The nascent polypeptide-associated complex (NAC) controls translation initiation in cis by recruiting nucleolin to the encoding mRNA

Protein aggregates and abnormal proteins are toxic and associated with neurodegenerative diseases. There are several mechanisms to help cells get rid of aggregates but little is known on how cells prevent aggregate-prone proteins from being synthesised. The EBNA1 of the Epstein-Barr virus (EBV) evades the immune system by suppressing its own mRNA translation initiation in order to minimize the production of antigenic peptides for the major histocompatibility (MHC) class I pathway. Here we show that the emerging peptide of the disordered glycine–alanine repeat (GAr) within EBNA1 dislodges the nascent polypeptide-associated complex (NAC) from the ribosome. This results in the recruitment of nucleolin to the GAr-encoding mRNA and suppression of mRNA translation initiation in cis. Suppressing NAC alpha (NACA) expression prevents nucleolin from binding to the GAr mRNA and overcomes GAr-mediated translation inhibition. Taken together, these observations suggest that EBNA1 exploits a nascent protein quality control pathway to regulate its own rate of synthesis that is based on sensing the nascent GAr peptide by NAC followed by the recruitment of nucleolin to the GAr-encoding RNA sequence.     

Effects of the availability of floral resources and neighboring plants on nectar robbery in a specialized pollination system

Many plants pollinated by nectar-foraging animals have to maintain a balance between legitimate visitor attraction strategies and mechanisms that minimize illegitimate visits. This study investigated how floral display and neighboring species composition influences nectar robbing by hummingbirds in the tropical ornithophilous herb Heliconia spathocircinata. We tested the role of inflorescence display, flower abundance, and neighboring species in the reduction of nectar robbing in H. spathocircinata. Our results indicate that nectar robbing hummingbird activity was higher in moderately large inflorescence displays and that the frequency of nectar robbing in H. spathocircinata decreases with increased flower abundance and the presence of neighboring plant species. Neighboring non-ornithophilous plants decreased the frequency of nectar robbing in H. spathocircinata flowers to a greater extent than ornithophilous ones. These results suggest that nectar robbing hummingbirds are attracted to similar conditions that attract legitimate visitors and that spatial aggregation and mixed-species displays may represent a mechanism to dilute nectar robbing effects at an individual level.     

Development of a novel spatiotemporal depletion system for cellular cholesterol

Cholesterol is an essential component of mammalian cell membranes whose subcellular concentration and function are tightly regulated by de novo biosynthesis, transport, and storage. Although recent reports have suggested diverse functions of cellular cholesterol in different subcellular membranes, systematic investigation of its site-specific roles has been hampered by the lack of a methodology for spatiotemporal manipulation of cellular cholesterol levels. Here, we report the development of a new cholesterol depletion system that allows for spatiotemporal manipulation of intracellular cholesterol levels. This system utilizes a genetically encoded cholesterol oxidase whose intrinsic membrane binding activity is engineered in such a way that its membrane targeting can be controlled in a spatiotemporally specific manner via chemically induced dimerization. In combination with in situ quantitative imaging of cholesterol and signaling activity measurements, this system allows for unambiguous determination of site-specific functions of cholesterol in different membranes, including the plasma membrane and the lysosomal membrane.     

Regulation of neural progenitor cell state by ephrin-B

Maintaining a balance between self-renewal and differentiation in neural progenitor cells during development is important to ensure that correct numbers of neural cells are generated. We report that the ephrin-B-PDZ-RGS3 signaling pathway functions to regulate this balance in the developing mammalian cerebral cortex. During cortical neurogenesis, expression of ephrin-B1 and PDZ-RGS3 is specifically seen in progenitor cells and is turned off at the onset of neuronal differentiation. Persistent expression of ephrin-B1 and PDZ-RGS3 prevents differentiation of neural progenitor cells. Blocking RGS-mediated ephrin-B1 signaling in progenitor cells through RNA interference or expression of dominant-negative mutants results in differentiation. Genetic knockout of ephrin-B1 causes early cell cycle exit and leads to a concomitant loss of neural progenitor cells. Our results indicate that ephrin-B function is critical for the maintenance of the neural progenitor cell state and that this role of ephrin-B is mediated by PDZ-RGS3, likely via interacting with the noncanonical G protein signaling pathway, which is essential in neural progenitor asymmetrical cell division.     

The characteristics and transparent exopolymer particle (TEP) content of marine snow formed from thecate dinoflagellates

Abundant marine snow containing diatoms and detritus, but dominatedby large, bioluminescent thecate dinoflagellates and their temporaryvegetative cysts, especially several species of the genus Gonyoulax,was observed at six stations in the Santa Barbara Channel, California,in 1989 and 1994. These aggregates were unusually cohesive andmucus rich, and contained 2–4 times more mass, particulateorganic carbon (POC), particulate organic nitrogen (PON) andchlorophyll a per unit aggregate volume than more common typesof marine snow formed from diatoms, fecal matter, larvaceanhouses or miscellaneous detritus. However, the relationshipbetween aggregate size and the concentration of TEP (transparentexopolymer particles which form the mucus matrix of most marinesnow) was similar to that of other types of aggregates, suggestingthat much of the copious gel-like material within dinoflagellateaggregates was not TEP. While this is the first report of abundantthecate dinoflagellates occurring within large, rapidly sinkingmarine aggregates, the data do not support the conclusion thatmass aggregation and subsequent sedimentation of blooms is partof the life history adaptations of thecate dinoflagellates,as it is for some diatoms. The high abundance of free-livingdinoflagellate cells and temporary cysts, and the similar proportionof dinoflagellates relative to other algal and chemical componentsin both aggregates and the surrounding seawater, indicate thatthe dinoflagellates were not differentially aggregating. Evenso, passive accumulation of dinoflagellates in marine snow throughaggregation processes may result in more rapid transport ofdinoflagellate-generated material to the deep ocean, alter thenature of sinking particulate matter following dinoflagellateblooms, and increase the nutritional value of marine snow asa food source for zooplankton and fish.     

Modulation of cell-cycle dynamics is required to regulate the number of cerebellar GABAergic interneurons and their rhythm of maturation

The progenitors of cerebellar GABAergic interneurons proliferate up to postnatal development in the prospective white matter, where they give rise to different neuronal subtypes, in defined quantities and according to precise spatiotemporal sequences. To investigate the mechanisms that regulate the specification of distinct interneuron phenotypes, we examined mice lacking the G1 phase-active cyclin D2. It has been reported that these mice show severe reduction of stellate cells, the last generated interneuron subtype. We found that loss of cyclin D2 actually impairs the whole process of interneuron genesis. In the mutant cerebella, progenitors of the prospective white matter show reduced proliferation rates and enhanced tendency to leave the cycle, whereas young postmitotic interneurons undergo severe delay of their maturation and migration. As a consequence, the progenitor pool is precociously exhausted and the number of interneurons is significantly reduced, although molecular layer interneurons are more affected than those of granular layer or deep nuclei. The characteristic inside-out sequence of interneuron placement in the cortical layers is also reversed, so that later born cells occupy deeper positions than earlier generated ones. Transplantation experiments show that the abnormalities of cyclin D2(-/-) interneurons are largely caused by cell-autonomous mechanisms. Therefore, cyclin D2 is not required for the specification of particular interneuron subtypes. Loss of this protein, however, disrupts regulatory mechanisms of cell cycle dynamics that are required to determine the numbers of interneurons of different types and impairs their rhythm of maturation and integration in the cerebellar circuitry.