Movement of internalized ligand-receptor complexes along a continuous endosomal reticulum

Complexes of cell-surface receptors and their ligands are commonly internalized by endocytosis and enter a prelysosomal endosomal pathway for further processing. Fluorescence microscopy and video recording of living cells to trace the passage of ligand-receptor complexes has identified the endosomal compartment as an extensive network of tubular cisternae. Endocytosed material entering this reticulum enters discrete swellings, identified as multivesicular bodies by electron microscopy, which move along the reticulum towards the pericentriolar area.     

Genetic variation at the alcohol dehydrogenase locus inDrosophila melanogaster: A third ubiquitous allele

Summary A 3rd allele at theAdh locus,Adh ^FCh.D., has been found at polymorphic frequencies in natural populations ofD. melanogaster. The ADH-FChD enzyme has properties distinct from those of the 2 more common forms of ADH. TheAdh polymorphism should now be analyzed as a triallelic system.     

A VIP-containing system concentrated in the lumbosacral region of human spinal cord

Neuropeptides were first localized in the human spinal cord by immunocytochemistry and substance P has been shown, by the same method, to be reduced ipsilaterally in the dorsal horn after limb amputation and bilaterally in the Riley-Day syndrome. Several neuropeptides increasingly fulfil the criteria to establish them as neurotransmitters or neuromodulators, and they may also have trophic actions in the spinal cord. Using radioimmunoassay and immunocytochemistry, we present here for the first time a quantitative regional distribution and localization of vasoactive intestinal polypeptide (VIP), substance P, somatostatin, bombesin and cholecystokinin (CCK-8) in normal postmortem human spinal cord. A comparison of the distribution of these peptides reveals an exceptional pattern for VIP, with relatively much higher levels in the lumbosacral region. Immunocytochemical analysis shows a distinctive distribution of VIP-containing fibres and terminals at the lumbosacral segments. This VIP-containing system may have an important role in the spinal control of urogenital function in man.     

Acquired protein appetite in rats: dependence on a protein-specific need state

Rats are shown to acquire a preference for protein-predictive olfactory cues which depends on a state of mild deficit in protein intake--i.e. a learned protein-specific appetite.     

DNA sequence and expression of the B95-8 Epstein-Barr virus genome

The complete (172,282 base pairs) nucleotide sequence of the B95-8 strain of Epstein-Barr virus has been established using the dideoxynucleotide/M13 sequencing procedure. Many RNA polymerase II promoters have been mapped and the mRNAs from these promoters have been assigned to the latent or early/late productive virus cycles. Likely protein-coding regions have been identified and three of these have been shown to encode a ribonucleotide reductase, a DNA polymerase and two surface glycoproteins.     

fferences in the number of molecules produced by two allelic electrophoretic enzyme variantsD. melanogaster

Résumé Les techniques immunologiques ont démontré que chezDrosophila melanogaster une forme électrophorétique «Fast» d'alcool déshydrogénase produit plus de molécules d'enzyme qu'une forme électrophorétique Slow. On expose les résultats en les comparant à d'autres suggérant des mécanismes autorégulatoire.

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Acknowledgement. I am grateful to Dr.D. Roberts for helpful discussions.     

Subtypes of medulloblastoma have distinct developmental origins

Medulloblastoma encompasses a collection of clinically and molecularly diverse tumour subtypes that together comprise the most common malignant childhood brain tumour. These tumours are thought to arise within the cerebellum, with approximately 25% originating from granule neuron precursor cells (GNPCs) after aberrant activation of the Sonic Hedgehog pathway (hereafter, SHH subtype). The pathological processes that drive heterogeneity among the other medulloblastoma subtypes are not known, hindering the development of much needed new therapies. Here we provide evidence that a discrete subtype of medulloblastoma that contains activating mutations in the WNT pathway effector CTNNB1 (hereafter, WNT subtype) arises outside the cerebellum from cells of the dorsal brainstem. We found that genes marking human WNT-subtype medulloblastomas are more frequently expressed in the lower rhombic lip (LRL) and embryonic dorsal brainstem than in the upper rhombic lip (URL) and developing cerebellum. Magnetic resonance imaging (MRI) and intra-operative reports showed that human WNT-subtype tumours infiltrate the dorsal brainstem, whereas SHH-subtype tumours are located within the cerebellar hemispheres. Activating mutations in Ctnnb1 had little impact on progenitor cell populations in the cerebellum, but caused the abnormal accumulation of cells on the embryonic dorsal brainstem which included aberrantly proliferating Zic1(+) precursor cells. These lesions persisted in all mutant adult mice; moreover, in 15% of cases in which Tp53 was concurrently deleted, they progressed to form medulloblastomas that recapitulated the anatomy and gene expression profiles of human WNT-subtype medulloblastoma. We provide the first evidence, to our knowledge, that subtypes of medulloblastoma have distinct cellular origins. Our data provide an explanation for the marked molecular and clinical differences between SHH- and WNT-subtype medulloblastomas and have profound implications for future research and treatment of this important childhood cancer.