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At least 613 records · Page 34Linked to original sources
PubMed1997

Distribution of vasopressin and vasoactive intestinal polypeptide (VIP) fibers in the human hypothalamus with special emphasis on suprachiasmatic nucleus efferent projections.

The human suprachiasmatic nucleus (SCN) is located in the basal part of the anterior hypothalamus and is considered as the biological clock that generates circadian rhythms and synchronizes the daily activity pattern with the environmental light-dark cycle. However, the mechanisms and pathways by which the SCN transmits its information to the other brain areas are unknown. Therefore, in the present study, we investigated the efferent projections of the SCN by the immunocytochemical staining of two major peptidergic SCN neurotransmitters: vasopressin (VP) and vasoactive intestinal polypeptide (VIP). It confirmed that these peptides are present in different subdivisions of the SCN. The results of this investigation show that VP and VIP fibers arising from the SCN were detected to branch extensively and hence seem to innervate the SCN itself and the central and medial part of the anteroventral hypothalamic area (AVH), the area below the paraventricular nucleus (sub-PVN), the ventral part of the paraventricular nucleus (PVN), and the dorsomedial nucleus of the hypothalamus (DMH). There appeared to be substantial congruity between the presumptive human SCN projections and those as observed by tracing in rat or hamster. Regarding the anatomical organization of the human SCN projections, the main projection areas appeared to be the AVH, the sub-PVN, the ventral part of the PVN, and the DMH. The observation that VIP and in particular VP fibers pass between the SCN and the PVN suggests that the human SCN and the PVN may have a direct anatomical connection. In addition, VP and VIP fibers were detected in several other hypothalamic areas that are not known to have clear direct connections to the SCN. The possible origin of these VP and VIP fibers is discussed.

Dorsomedial Hypothalamic Nucleus↗
PubMed1998

Postmortem tracing reveals the organization of hypothalamic projections of the suprachiasmatic nucleus in the human brain.

The suprachiasmatic nucleus (SCN) is a small structure considered to be the site of the major circadian pacemaker of the mammalian brain. Disturbances in human biological clock function may occur in several diseases, such as Alzheimer's disease, sleep problems, and seasonal depression. Since basic knowledge of the anatomical connections of the human SCN is limited due to the lack of suitable neuroanatomical tracing methods, the understanding of physiological mechanisms of human SCN function has obviously been hampered. In the present study, the hypothalamic connections of the human SCN were revealed for the first time with a newly developed in vitro postmortem anterograde tracing method. The human SCN was found to be connected with nuclei in the hypothalamus that are involved in hormone secretion, cardiovascular regulation, and behavior activity. These human SCN projections appear to follow the same general patterns as those in the rodent brain. This homology may indicate an evolutionary conservation of the SCN projections from rodent to human. Through these connections, the human SCN may transmit its circadian information to regulate hormone secretion, body temperature, and behavioral functions as it does in animal species. In addition, the postmortem tracing technique may be a valuable tool that will contribute to our understanding of anatomical connections in the human brain, and may have other applications in the research on the physiology and pathology of the human brain.

Animals↗
PubMed1985

Mammalian pinealocytes: ultrastructural aspects and innervation.

In the mammalian pineal gland it is notoriously difficult to relate structure to function. The pineal-specific cells, the pinealocytes, contain only inconspicuous numbers of secretory granules, and the variable amounts of smooth and rough endoplasmic reticulum also do not point to a particular function. In addition to these widely known cellular components, pinealocytes contain organelles, the so-called 'synaptic' ribbons, histophysiological studies of which provide important insights into the structural and functional complexity of the organ. As synaptic ribbons may be involved in neuronal functions of pinealocytes it is notable that these organelles are structurally heterogeneous. Ribbons fall into at least two categories: rod-like (RSR) and sphere-like (SS) structures. RSR and SS usually do not lie within the same pinealocyte profile and appear to be regulated by different mechanisms. It is conceivable that they are important components of the biological clock system. These findings are related to our knowledge of the innervation of the mammalian pineal gland and to electrophysiological characteristics of pinealocytes.

Animals↗
PubMed1986

Avian B cell precursors: surface immunoglobulin expression is an early, possibly bursa-independent event.

The avian bursa of Fabricius contains about 1 X 10(4) discrete follicles, each of which is colonized by a small number of lymphoid progenitor cells during embryonic life. We have previously shown (J.R.L. Pink et al., Eur. J. Immunol. 1985. 15:617) that all, or almost all B cell progenitors in the bursae of 4-day-old chicks express cell surface IgM. In this report, we have analyzed the distribution of cell surface (s)IgM-1 allotypes within individual follicles of (M-1a/M-1b) allotype heterozygous birds. Although the majority of follicles contained a mixture of sIgM-1a+ and sIgM-1b+ cells, a significant proportion of isolated follicles contained exclusively sIgM-1a+ or sIgM-1b+ cells. Statistical analysis of the frequency of such "M-1a" and "M-1b" follicles demonstrated that the sIg+ B cells in the bursae of 4-8-week-old birds are derived from 2-4 allotypically committed precursor cells per follicle. Since we have previously shown that each bursal follicle is colonized by 2-5 pre-bursal stem cells, these cells must be committed to the eventual expression of one or other allotypic haplotype before they have undergone extensive proliferation within the bursa. In addition, we show that almost all B progenitor cells from the bursae of chicks which had been allotype suppressed as embryos were committed to synthesis of the nonsuppressed allotype, showing that this commitment was essentially complete at the time of suppression (i.e. before 19 days of incubation). Finally the bone marrow of 16-day embryos was used to reconstitute the bursal lymphocytes of cyclophosphamide-treated host embryos. Reconstitution was inhibited by anti-Ig antiserum indicating that most 16-day embryonic BM-derived bursal cell precursors also express sIgM. These results raise the possibility that expression of sIgM may be controlled by a "biological clock" rather than by any inductive capacity of the bursal microenvironment. Furthermore, these results provide further evidence that in normal birds a self-renewing sIg+ B cell population in the hatched chicken is the sole source of B cells in the adult.

Animals↗
PubMed1975

Gene activation during spermatogenesis.

Cell differentiation during spermatogenesis in the rat has been analyzed in terms of the formation of specific "marker" enzymes. Hyaluronidase and other acrosomal enzymes are formed in spermatids according to a highly predictable time schedule which may be termed a "molecular biological clock". The acrosomal enzymes beta-galactosidase and N-acetyl-beta-glucosaminidase exist as isoenzyme forms distinct from enzymes with similar substrate specificities in the lysosomes of precursor cells. Differentiation of spermatids thus involves the loss of gene expression for lysosomal enzymes and the activation of genes for acrosomal isoenzymes. Spermatogenesis is characterized by the sequential loss of expression of many genes, as evidenced by the loss of beta-glucuronidase in the differentiation of spermatogonia to spermatocytes, and the loss of uridine diphosphatase activity in the differentiation of spermatocytes to spermatids. The apparent absence of ornithine decarboxylase activity from spermatids suggests a dependence of these cells upon Sertoli cells for the provision of putrescine and/or spermidine. Such biochemical cooperativity among germinal cells may be necessary as the genes of spermatids are repressed and late spermatids become metabolically inactive. Spermatogenesis is also characterized by changes in the cellular content and rates of synthesis and phosphorylation of specific acidic chromatin proteins. It is hypothesized that these proteins may participate in the activation or repression of genes during spermatogenesis.

Acetylglucosaminidase↗
PubMed1977

The estrous cycle in golden hamsters: a circadian pacemaker times preovulatory gonadotropin release.

In a population of cycling female hamsters entrained to an LD 6:18 light cycle (lights 1000-1600 hours), preovulatory release of luteinizing hormone and follicle-stimulating hormone occurred in some animals at 1300-1400 hours and in others at 1900 hours. In every case peak release was phase-locked (2-3-hour positive phase angle) to the circadian rhythm of locomotor activity. The pattern of entrainment of gonadotropin release on LD 6:18 is fully explicable in terms of the hamster's phase response curve to light. We conclude that periodic gonadotropin release in cycling females is timed by a circadian oscillator (biological clock) that is probably the same oscillator driving the circadian rhythm of locomotor activity.

Animals↗
PubMed1988

Time-lapse cinematography study of the germinal vesicle behaviour in mouse primary oocytes treated with activators of protein kinases A and C.

A passive erratic movement of the germinal vesicle (GV), already visible in small incompetent oocytes, is followed by an active scalloping of the nuclear membrane soon before GV breakdown (GVBD) in cultured competent oocytes. Maturation can be inhibited by activators of protein kinase A (PK-A) and protein kinase C (PK-C). Our time-lapse cinematography analysis allowed us to describe an unexpected behaviour of the GV when PK-C, but not PK-A, is activated: GV undergoes a displacement toward the cortex according to the same biological clock which triggers the programmed translocation of the spindle in control oocytes. It is concluded that, when oocytes become committed to undergo maturation, the cytoplasm acquires a PK-A-controlled "centrifugal displacement property" which is not restricted to the spindle.

Animals↗
PubMed2004

Serotonin-induced phase advances of SCN neuronal firing in vitro: a possible role for 5-HT5A receptors?

Spontaneous firing rates of neurons in the suprachiasmatic nuclei (SCN) follow a consistent pattern, peaking near the midpoint of the light phase in a 12:12 light/dark schedule, and repeating this brief period of increased activity in subsequent circadian cycles. These carefully timed fluctuations reflect the output signal of the SCN, long recognized as the site of the endogenous biological clock in mammals. In rat hypothalamic slices, bath incubations of 8-OH-DPAT had previously been shown to elicit phase advances when applied at ZT6 (or 6 h following the onset of light), an action that could readily be attributed to 5-HT7 receptor activation. The present studies set out with the simple goal of establishing that the same receptor mechanism was responsible for the phase-shifting actions of 5-HT itself. Surprisingly, the phase advances elicited by 5-HT (0.5 microM, 1 h) at ZT6 were reduced by one 5-HT7 antagonist, ritanserin (10 microM), but not by another, mesulergine (10 microM). Receptor binding studies demonstrated a 25-fold greater affinity of ritanserin for h5-HT5A sites compared to mesulergine (Ki = 71 nM vs. 1,800 nM), an observation suggestive of a 5-HT5A mechanism for 5-HT and consistent with earlier observations of robust labeling of 5-HT5A sites in the SCN. 5-HT generated by the addition of L-tryptophan (10 microM, 1 h) to the slices displayed the same pattern of sensitivity, that is, blockade by ritanserin but not by mesulergine. Rp-cAMPS, a cAMP antagonist, failed to block the phase shifts elicited by 5-HT at a concentration (1 microM) previously shown to be effective against 8-OH-DPAT-induced phase shifts, in keeping with the proposed negative coupling of 5-HT5A receptors to cAMP production. Taken together, these results suggest that activation of both 5-HT5A and 5-HT7 receptors can produce phase advances of the circadian clock in vitro when they occur during mid-subjective day.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2000

The living cell: a complex autodynamic multi-oscillator system?

Life cannot be simply defined in biochemical terms but it is associated with autodynamic behaviour. This fact implies that all aspects of cell biology should be viewed in terms of the resultant temporal features. Theoretical arguments indicate that the dynamic state can be explained only by the existence of periodicity. In accordance with this view, experimental evidence indicates the existence of multiple oscillators and at least some are highly complex, implying that failure to understand aspects of cell biology can stem from inadequate concepts.

Animals↗
PubMed2002

Induction of apoptosis by telomere 3' overhang-specific DNA.

Telomeres are tandem repeats of a specific TTAGGG nucleotide sequence at the ends of chromosomes. Telomere shortening is proposed to act as a biological clock and cancer prevention mechanism by inducing a nonproliferative, senescent phenotype after a limited number of cellular divisions. Recent evidence also suggests that telomere disruption can trigger apoptosis in certain cell types, mimicking a major cellular response to DNA damage. Here, we show that addition of DNA oligonucleotides homologous to the telomere 3' overhang sequence causes lymphocytic (Jurkat) cells to undergo apoptosis, as described for lymphocytes following telomere loop disruption. We further implicate the p53 tumor suppressor and transcription factor, as well as the p53 homolog p73 and the E2F1 transcription factor, in mediating the apoptotic response. We propose that exposure of the telomere 3' overhang due to opening of the normal telomere loop structure is a physiologic signal for these DNA damage-like responses in vivo and that oligonucleotides partially or completely homologous to the telomere overhang mimic this signal in the absence of DNA damage or telomere disruption.

3' Flanking Region↗
PubMed2002

Biotinylated dextran amine as a marker for fetal hypothalamic homografts and their efferents.

We have explored the use of biotinylated dextran amine (BDA) as a marker for labeling fetal brain grafts and their connections with the host. As a model system we used transplantation of the hamster suprachiasmatic nucleus, the site of an endogenous biological clock governing circadian rhythms. Similar transplants into arrhythmic hosts have been shown to restore behavioral function with a period specific to the donor. For locomotor rhythms, efferent connections are not necessary. For other responses, including endocrine rhythms, efferent connections may be necessary. In order to visualize homografts and their efferents, injections of BDA, an anterograde tracer, were made into the anterior hypothalamic (AH) region containing the SCN or into the dorsal cortex (CTX) of fetal hamster brains. The fetal AH or CTX was microdissected out and stereotaxically implanted into the third ventricle of intact, adult hamsters. After 2, 4, 8, or 12 weeks, hosts were sacrificed and their brains were processed for detection of BDA by either histochemistry or immunofluorescence. BDA intensely labeled graft neurons, their dendrites, and axons with minimal or no spread to the adjacent host brain. Labeled graft axons could be followed for long distances (>1 mm) into the host brain and graft-derived varicosities formed close contacts with host neurons. BDA-labeled graft neurons, located at the perimeter of the graft, also extended dendrite-like processes into the host parenchyma. We conclude that BDA is a useful marker for fetal homografts and their efferents for survival times of less than 2 months.

Animals↗
PubMed1999

Functional morphology of the suprachiasmatic nucleus.

In mammals, the biological clock (circadian oscillator) is situated in the suprachiasmatic nucleus (SCN), a small bilaterally paired structure just above the optic chiasm. Circadian rhythms of sleep-wakefulness and hormone release disappear when the SCN is destroyed, and transplantation of fetal or neonatal SCN into an arrhythmic host restores rhythmicity. There are several kinds of peptide-synthesizing neurons in the SCN, with vasoactive intestinal peptide, arginine vasopressin, and somatostatine neurons being most prominent. Those peptides and their mRNA show diurnal rhythmicity and may or may not be affected by light stimuli. Major neuronal inputs from retinal ganglion cells as well as other inputs such as those from the lateral geniculate nucleus and raphe nucleus are very important for entrainment and shift of circadian rhythms. In this review, we describe morphological and functional interactions between neurons and glial elements and their development. We also consider the expression of immediate-early genes in the SCN after light stimulation during subjective night and their role in the mechanism of signal transduction. The reciprocal interaction between the SCN and melatonin, which is synthesized in the pineal body under the influence of polysynaptic inputs from the SCN, is also considered. Finally, morphological and functional characteristics of clock genes, particularly mPers, which are considered to promote circadian rhythm, are reviewed.

Animals↗
PubMed2001

Nucleotide sequence of coliphage HK620 and the evolution of lambdoid phages.

HK620 is a temperate lambdoid bacteriophage that adsorbs to the O-antigen of its host, Escherichia coli H. The genome of a temperature-sensitive clear-plaque mutant consists of 38,297 nucleotides in which we recognize 60 open reading frames (orfs). Eighteen of these lie in a region of the genome that we call the virion structure domain. The other 42 orfs lie in what we call the metabolic domain. Virions of HK620 resemble those of phage P22. The virion structural orfs encode three kinds of putative proteins relative to the virion proteins of P22: (1) those that are nearly (about 90 %) identical; (2) those that are weakly (about 30 %) identical; and (3) those composed of nearly and weakly identical segments. We hypothesize that these composite proteins form bridges between the virion proteins of the other two kinds. Three of the putative virion proteins that are only weakly identical to P22 proteins are 71, 60 and 79 % identical to proteins encoded by the phage APSE-1, whose virions also resemble those of P22. Because the hosts of APSE-1 and HK620 have been separated from each other by an estimated 200 My, we propose using the amino acid differences that have accumulated in these proteins to estimate a biological clock for temperate lambdoid phages. The putative transcriptional regulatory gene circuitry of HK620 seems to resemble that of phage lambda. Integration, on the other hand, resembles that of satellite phage P4 in that the attP sequence lies between the leftward promoter and int rather than downstream of int. Comparing the metabolic domains of several lambdoid phage genomes reveals seven short conserved sequences roughly defining boundaries of functional modules. We propose that these boundary sequences are foci of genetic recombination that serve to assort the modules and make the metabolic domain highly mosaic genetically.

Attachment Sites, Microbiological↗
PubMed1996

The circadian system of c-fos deficient mice.

We examined the role of c-fos in the synchronization of circadian rhythms to environmental light cycles using a line of gene-targeted mice carrying a null mutation at this locus. Circadian locomotor rhythms in mutants had similar periods as wild-type controls but took significantly longer than controls to entrain to 12:12 light-dark cycles. Light-induced phase shifts of rhythms in constant dark were attenuated in mutants although the circadian timing of phase delays and advances was not changed. A functional retinohypothalamic projection was indicated from behavioral results and light-induced jun-B expression in the SCN. The results indicate that while c-fos activation is not an absolute requirement for rhythm generation nor photic responses, it is required for normal entrainment of the mammalian biological clock.

Animals↗
PubMed1994

Nuclear genes encoding chloroplast hemoglobins in the unicellular green alga Chlamydomonas eugametos.

When the green unicellular alga Chlamydomonas eugametos is grown under light/dark regimes, nuclear genes are periodically activated in response to the changes in light conditions. These genetic responses are dependent upon the activation of genes associated with photosynthesis (LI616 and LI637), nonphotosynthetic photoreceptors (LI410 and LI818) and the biological clock (LI818). We report here that the LI410 and LI637 genes are part of a small gene family encoding hemoglobins (Hbs) related to those from two unicellular eukaryotes, the ciliated protozoa Paramecium caudatum and Tetrahymena pyriformis, and from the cyanobacterium Nostoc commune. Investigations of the intracellular localization of C. eugametos Hbs by means of immunogold electron microscopy indicate that these proteins are predominantly located in the chloroplast, particularly in the pyrenoid and the thylakoid region. To our knowledge, this constitutes the first evidence for the presence of Hbs in chloroplasts. Alignment of the LI637 cDNA nucleotide sequence with its corresponding genomic sequence indicates that the LI637 gene contains three introns, the positions of which are compared with those in the Hb genes of plants, animals and the ciliate P. caudatum. Although the LI637 gene possesses a three-intron/four-exon pattern similar to that of plant leghemoglobin genes, introns are inserted at different positions. Similarly the position of the single intron in the P. caudatum gene differs from the intron sites in the LI637 gene. The latter observations argue against the current view that all eukaryotic Hbs have evolved from a common ancestor having a gene structure identical to that of plant or animal Hbs.

Amino Acid Sequence↗
PubMed1996

Lymphoid leukosis viruses, their recognition as 'persistent' viruses and comparisons with certain other retroviruses of veterinary importance.

Diseases caused by lymphoid leukosis virus (LLV), a retrovirus, take a long time after infection to develop and have a wide variety of pathological manifestations. This long latent period is characteristic of 'persistent virus infections'. Disease produced by LLV infection and its underlying mechanisms is compared with 'persistent' infections caused by other retroviruses in birds and mammals of veterinary importance. The diseases considered for comparison are those caused by reticuloendotheliosis, feline leukaemia, bovine leukosis and equine infectious anaemia viruses. There are significant changes in the immunological status in all diseases caused by these viruses. LLV infections follow this trend with, in manifestations of neoplastic disease, a perturbation of the normal switch that occurs from IgM to IgG synthesis. There are also indications of other immunological disturbances. Factors other than immunological disturbances may contribute to the length of time after infection required for the many forms of LLV infection to appear. Such additional factors may include the operation of 'biological clocks', such as the arrival of sexual maturity, and also the very nature of retroviruses. These factors, like the immunological changes, play major roles in the maintenance and progression of persistent retrovirus infections.

Alpharetrovirus↗
PubMed1991

Evidence for two types of calcium currents in frog cardiac sinus venosus cells.

Two types of calcium currents were recorded in single sinus venosus cells of the frog heart, using the whole-cell patch-clamp technique. The threshold potentials were approximately -65 mV for T-type current and -40 mV for L-type current. The amplitude and time course of T-type current were unaffected by exchanging calcium for barium, while the amplitude of L-type current was increased and its decay slowed. T-type current was neither modified by 10(-6) M nifedipine nor by 10(-7) M isoprenaline in contrast with the effects of these agents on L-type current. T-type current began to inactivate at -90 mV and was fully inactivated at -45 mV. Its steady-state inactivation curve was approximately 35 mV negative to that of L-type current. Overlap of activation and inactivation relationships was present for both T- and L-type currents and was maximal at -57 and -30 mV, respectively. It was concluded that T- and L-type currents can easily be separated by their voltage, kinetic and pharmacological differences. The presence of a high density of T-type current may be correlated to its contribution to the pacemaking function of the sinus venosus cells.

Animals↗