Analysis of her1 and her7 mutants reveals a spatio temporal separation of the somite clock module

Somitogenesis is controlled by a genetic network consisting of an oscillator (clock) and a gradient (wavefront). The "hairy and Enhancer of Split"- related (her) genes act downstream of the Delta/Notch (D/N) signaling pathway, and are crucial components of the segmentation clock. Due to genome duplication events, the zebrafish genome, possesses two gene copies of the mouse Hes7 homologue: her1 and her7. To better understand the functional consequences of this gene duplication, and to determine possible independent roles for these two genes during segmentation, two zebrafish mutants her1(hu2124) and her7(hu2526) were analyzed. In the course of embryonic development, her1(hu2124) mutants exhibit disruption of the three anterior-most somite borders, whereas her7(hu2526) mutants display somite border defects restricted to somites 8 (+/-3) to 17 (+/-3) along the anterior-posterior axis. Analysis of the molecular defects in her1(hu2124) mutants reveals a her1 auto regulatory feedback loop during early somitogenesis that is crucial for correct patterning and independent of her7 oscillation. This feedback loop appears to be restricted to early segmentation, as cyclic her1 expression is restored in her1(hu2124) embryos at later stages of development. Moreover, only the anterior deltaC expression pattern is disrupted in the presomitic mesoderm of her1(hu2124) mutants, while the posterior expression pattern of deltaC remains unaltered. Together, this data indicates the existence of an independent and genetically separable anterior and posterior deltaC clock modules in the presomitic mesdorm (PSM).     

Partial trisomy of distal 8q derived from mother with mosaic 8q23.3→24.13 deletion,and relatively mild expression of trichorhinophalangeal syndrome I

Summary A 17-month-old girl with a partial trisomy of distal 8q derived from her mother, who has a mosaic 8q23.3q24.13 deletion, was studied. Both showed a relatively mild phenotype of trichorhinophalangeal syndrome I. The karyotype of the proposita was designated as: 46,XX,-8,+der(8),inv ins(8;8)(p23.1;q24.13q23.3)mat. Her phenotype was considered similar to that of her mother despite the trisomies of distal 8q. She seems to be the first example of a partial trisomy of distal 8q derived from a parent with an interstitial deletion of a distal 8q segment and trichorhinophalangeal syndrome I.     

Combined protocol of cell therapy for chronic spinal cord injury. Report on the electrical and functional recovery of two patients

BACKGROUND: This is a preliminary report on successful results obtained during treatment of two patients with chronic spinal cord injury. The therapeutic approach was based on the generation of controlled inflammatory activity at the injury site that induced a microenvironment for the subsequent administration of autologous, BM-driven transdifferentiated neural stem cells (NSC). METHODS: BM mesenchymal stem cells (MSC) were cocultured with the patient's autoimmune T (AT) cells to be transdifferentiated into NSC. Forty-eight hours prior to NSC implant, patients received an i.v. infusion of 5 x 10(8) to 1 x 10(9) AT cells. NSC were infused via a feeding artery of the lesion site. Safety evaluations were performed everyday, from the day of the first infusion until 96 h after the second infusion. After treatment, patients started a Vojta and Bobath neurorehabilitation program. RESULTS: At present two patients have been treated. Patient 1 was a 19-year-old man who presented paraplegia at the eight thoracic vertebra (T8) with his sensitive level corresponding to his sixth thoracic metamere (T6). He received two AT-NSC treatments and neurorehabilitation for 6 months. At present his motor level corresponds to his first sacral metamere (S1) and his sensitive level to the fourth sacral metamere (S4). Patient 2 was a 21-year-old woman who had a lesion that extended from her third to her fifth cervical vertebrae (C3-C5). Prior to her first therapeutic cycle she had severe quadriplegia and her sensitive level corresponded to her second cervical metamere (C2). After 3 months of treatment her motor and sensitive levels reached her first and second thoracic metameres (T1-T2). No adverse events were detected in either patient. DISCUSSION: The preliminary results lead us to think that this minimally invasive approach, which has minor adverse events, is effective for the repair of chronic spinal cord lesions.     

Inherited deficiency of the seventh component of complement associated with meningococcal meningitis: lack of serum bactericidal activity against Neisseria meningitidis in a girl with C7 deficiency and HLA studies of a C7-deficient Japanese family

An 8-year-old girl with meningococcal meningitis lacked serum complement activity. The seventh component of complement (C7) could not be detected in her serum by either functional or immunochemical analysis. The levels of the other components were within the normal range. Her serum complement activity was restored by the addition of purified C7. Her fresh serum showed a total absence of bactericidal activity against Neisseria meningitidis, group Y, but her serum bactericidal activity was restored by the addition of purified C7. The restoration of her serum bactericidal activity was completely inhibited in the presence of Mg2+ EGTA. These findings suggest that restoration of the bactericidal activity of her serum against N. meningitidis might be mediated by the specific antibody against N. meningitidis and the reconstituted complement system in her serum. Heterozygous deficiency of C7 was found in 10 of her family members. Genetic studies showed that the mode of inheritance might be an autosomal codominant trait. No genetic linkage between deficiency of C7 and the HLA system was found.     

Trisomy 8p due to the 3:1 segregation of the balanced translocation t(8;15)mat

Summary An additional small G-like chromosome was found in a newborn female with multiple abnormalities and hemorrhagic diathesis. G banding showed that the index patient was trisomic for the short arm of chromosome 8 and revealed the anomaly t(8;15)(q12;q11) in her mother. The relationship between chromosome 8 and multiple hemorrhages is discussed.     

A fetus with recombinant of chromosome 8 inherited from her carrier father

Summary A pericentric inversion of chromosome 8, inv(8)(p23q22), in a male carrier resulted in an unbalanced recombinant, rec(8)dup q, inv(8)(p23q22), which was diagnosed prenatally. The features seen in the aborted fetus resembled the features seen in a previously affected child who received the identical recombinant from her carrier mother. In this particular inversion involving chromosome 8, both male and female carriers risk producing an unbalanced progeny. Different familial pericentric inversions are reviewed for the presence or absence of unbalanced recombinants.     

Ontogeny of maternal behavior and brood pheromone in crayfish

Summary Third stage crayfish were maze tested to determine their preference for paired stimulus solutions of females in various breeding stages and of males. Formerly unattractive female crayfish begin to produce a brooding attractant when they deposit eggs (Fig. 1). The attractant become maximally effective when the eggs hatch (Fig. 2). Behavioral changes occur as larvae develop into the fourth stage and result in both a reduced larval attraction to any mother's stimulus (Figs. 3, 4) and a tendency to become solitary. At the same time the mother's attractant becomes less potent (Fig. 5). The mother receives feedback from her developing brood which maintains her behavior and attractive stimulus (Fig. 8). In the absence of this feedback, the mother's behavior changes to include larval predation in some species (Fig. 4, 6, 7) and her stimulus is no longer attractive (Figs. 8, 9).I gratefully acknowledge the help received from my graduate committee: Drs. Albert Carlson, Ronald R. Hoy, Emil W. Menzel and Charles Walcott. I also thank Mr. Kenneth Lantz of the District 6 Office of the Louisiana Department of Fisheries and Wildlife for providing laboratory space and assistance during my study in Louisiana. Funded by U.S. National Science Foundation Grant G.U. 3850.     

Zebrafish Her8a is activated by Su(H)-dependent Notch signaling and is essential for the inhibition of neurogenesis

Understanding how diversity of neural cells is generated is one of the main tasks of developmental biology. The Hairy/E(spl) family members are potential targets of Notch signaling, which has been shown to be fundamental to neural cell maintenance, cell fate decisions, and compartment boundary formation. However, their response to Notch signaling and their roles in neurogenesis are still not fully understood. In the present study, we isolated a zebrafish homologue of hairy/E(spl), her8a, and showed this gene is specifically expressed in the developing nervous system. her8a is positively regulated by Su(H)-dependent Notch signaling as revealed by a Notch-defective mutant and injection of variants of the Notch intracellular regulator, Su(H). Morpholino knockdown of Her8a resulted in upregulation of proneural and post-mitotic neuronal markers, indicating that Her8a is essential for the inhibition of neurogenesis. In addition, markers for glial precursors and mature glial cells were down-regulated in Her8a morphants, suggesting Her8a is required for gliogenesis. The role of Her8a and its response to Notch signaling is thus similar to mammalian HES1, however this is the converse of what is seen for the more closely related mammalian family member, HES6. This study not only provides further understanding of how the fundamental signaling pathway, Notch signaling, and its downstream genes mediate neural development and differentiation, but also reveals evolutionary diversity in the role of H/E(spl) genes.     

A Case Study of Primiparous Maternal and Infant Gorilla (Gorilla gorilla gorilla) Behavior

A primiparous mother and her infant were subjects of a longitudinal behavioral study at Lincoln Park Zoo in Chicago, Illinois. From November 1998 to November 1999, we collected a total of 100 hr of focal nonhuman animal instantaneous point sampling and all occurrence data on the mother and her infant. After 8 months, we introduced the 4-member focal group to an 8-member gorilla group, thus providing an opportunity to study the effect of the introduction on mother-infant behavior. Overall, time the pair spent physically apart was notably high with contact and proximate scores steadily decreasing over time. The infant was largely responsible for maintaining social proximity, rarely leaving the mother and frequently approaching her. In contrast, the mother left the infant frequently and approached the infant minimally. Maternal affiliative and nonaffiliative behaviors fluctuated throughout the study. Over time, both decreased. Despite a precarious maternal relationship, infant developmental trends were typical for captive gorillas. The results of this study suggest that allowing flexibility in judging maternal conduct can be of benefit to successful gorilla husbandry.     

A case study of primiparous maternal and infant gorilla (Gorilla gorilla gorilla) behavior

A primiparous mother and her infant were subjects of a longitudinal behavioral study at Lincoln Park Zoo in Chicago, Illinois. From November 1998 to November 1999, we collected a total of 100 hr of focal nonhuman animal instantaneous point sampling and all occurrence data on the mother and her infant. After 8 months, we introduced the 4-member focal group to an 8-member gorilla group, thus providing an opportunity to study the effect of the introduction on mother-infant behavior. Overall, time the pair spent physically apart was notably high with contact and proximate scores steadily decreasing over time. The infant was largely responsible for maintaining social proximity, rarely leaving the mother and frequently approaching her. In contrast, the mother left the infant frequently and approached the infant minimally. Maternal affiliative and nonaffiliative behaviors fluctuated throughout the study. Over time, both decreased. Despite a precarious maternal relationship, infant developmental trends were typical for captive gorillas. The results of this study suggest that allowing flexibility in judging maternal conduct can be of benefit to successful gorilla husbandry.     

固定化生长酵母连续生产酒精的研究

采用固定化生长细胞方法,以柱式生物反应器连续发酵甜菜糖蜜酒精。酒精能力为39.45g/L凝胶/h,停留时间1.8小时。生物反应器具有良好的稳定性,连续工作50天,发酵醪酒精含量在8.5％(v/v)以上。系统研究了最适固定化条件,用L_(16)(4~5)正交试验确定了最佳发酵条件。     

Prostate cancer: 1. The descriptive epidemiology in Canada

A 70-year-old woman who experienced a long period of depression after her first husband''s death from prostate cancer at the age of 63 has become increasingly anxious about her own health and that of her close family. A few years ago she married a man her own age; he is in good physical condition. Last year the family spent much of the winter in Florida, where the woman noticed several studies in the media suggesting that an epidemic of prostate cancer is occurring in North America and that because early detection can save lives men of retirement age should be checked by their physicians as soon as possible. In addition, 2 close friends recently diagnosed with prostate cancer. On his latest fishing trip her husband learned from a friend that 1 in 8 men get prostate cancer. He has not seen his family physician for several years, but his wife has booked an appointment for them to discuss their concerns.     

Complete paternal isodisomy for chromosome 8 unmasked by lipoprotein lipase deficiency.

Uniparental disomy (UPD)-the inheritance of two homologous chromosomes from a single parent-may be unmasked in humans by the unexpected appearance of developmental abnormalities, genetic disorders resulting from genomic imprinting, or recessive traits. Here we report a female patient with familial chylomicronemia resulting from complete lipoprotein-lipase (LPL) deficiency due to homozygosity for a frameshift mutation in exon 2 of the LPL gene. She was the normal term product of an unremarkable pregnancy and had shown normal development until her current age of 5.5 years. The father (age 33 years) and the mother (age 24 years) were unrelated and healthy, with no family history of stillbirths or malformations. The father was a heterozygous carrier of the mutation, whereas no mutation in the LPL gene was detected in the mother. Southern blotting did not reveal any LPL gene rearrangement in the proband or her parents. The proband was homozygous for 17 informative markers spanning both arms of chromosome 8 and specifically for the haplotype containing the paternally derived LPL gene. This shows that homozygosity for the defective mutation in the LPL gene resulted from a complete paternal isodisomy for chromosome 8. This is the first report of UPD for chromosome 8 unmasked by LPL deficiency and suggests that normal development can occur with two paternally derived copies of human chromosome 8.     

Partial trisomy 8p (8p11.2-->pTER) and deletion of 13q (13q32-->qTER): case report

We report a female infant with partial trisomy 8p (8p11.2-->pter) and deletion of 13q (13q32-->qter). She was born with mild hypotonia, intrauterine growth retardation, microcephaly, micrognathia, large low set ears, pectus excavatum, anteriorly placed anus, and bilateral clinodactyly. Echocardiography showed left ventricular hypertrophy, bicuspid aortic valve, dilatation of the aorta and pulmonary artery, and prolapse of atrio-venticular valve leaflets. Cytogenetic investigation of her sister and her father showed that the altered region resulted from a balanced translocation between the part of the long arm of chromosome 13 and short arm of chromosome 8. In partial trisomy 8p, the clinical picture of the patients comprises hypotonia, structural brain abnormalities, facial anomalies including a large mouth with a thin upper lip, a high arched palate, a broad nasal bridge, an abnormal maxilla or mandible, malformed, low set ears, and orthopedic anomalies. Although patients with proximal deletions of 13q that do not extend into band q32 have mild to moderate mental and growth delays with variable minor anomalies, patients with more distal deletions including at least part of band q32 usually have major malformations such as retinoblastoma, mental-motor growth retardation, malformation of brain and heart, anal atresia, and anomalies of the face and limbs. To our knowledge partial trisomy 8p and partial monosomy of 13q have not been reported previously in the same person.     

Valerie Andersen (1959 2007)

Valérie Andersen formally began her career in oceanographywith a PhD from the Université de Pierre et Marie Curiein 1985. Her thesis (Andersen, 1985a) was centred on the developmentof numerical models of the pelagic food web. However, it wasfirmly based on her experimental studies of salps (Andersen,1985b, 1986, 1989; Andersen and Nival, 1986) and data she gatheredon cruises in the N.W. Mediterranean Sea (Andersen and     

Experimental embryology of mammals at the Jastrzebiec Institute of Genetics and Animal Breeding

Our Department of Experimental Embryology originated from The Laboratory of Embryo Biotechnology, which was organized and directed by Dr. Maria Czlonkowska until her premature death in 1991. Proving successful international transfer of frozen equine embryos and generation of an embryonic sheep-goat chimaera surviving ten years were outstanding achievements of her term. In the 1990s, we produced advanced fetuses of mice after reconstructing enucleated oocytes with embryonic stem (ES) cells, as well as mice originating entirely from ES cells by substitution of the inner cell mass with ES cells. Attempts at obtaining ES cells in sheep resulted in the establishment of embryo-derived epithelioid cell lines from Polish Heatherhead and Polish Merino breeds, producing overt chimaeras upon blastocyst injection. Successful re-cloning was achieved from 8-cell rabbit embryos, and healthy animals were born from the third generation of cloned embryos. Recently mice were born after transfer of 8-cell embryonic nuclei into selectively enucleated zygotes, and mouse blastocysts were produced from selectively enucleated germinal vesicle oocytes surrounded by follicular cells, upon their reconstruction with 2-cell nuclei and subsequent activation. Embryonic-somatic chimaeras were born after transfer of foetal fibroblasts into 8-cell embryos (mouse) and into morulae and blastocysts (sheep). We also regularly perform the following applications: in vitro production of bovine embryos from slaughterhouse oocytes or those recovered by ovum pick up; cryopreservation of oocytes and embryos (freezing: mouse, rabbit, sheep, goat; vitrification: rabbit, cow); and banking of somatic cells from endangered wild mammalian species (mainly Cervidae).     

A familial "balanced" 3;9 translocation with cryptic 8q insertion leading to deletion and duplication of 9p23 loci in siblings.

A child with phenotypic features of the 9p- syndrome, including metopic craniosynostosis, small ears, abdominal wall defect, and mental retardation, as well as hypopigmentation, was found to have a cytogenetically balanced 3;9 translocation, with breakpoints at 3p11 and 9p23, inherited from his phenotypically normal father. Molecular analysis showed heterozygous deletion of the TYRP (tyrosinase-related protein) locus, as well as loci D9S157, D9S274, D9S268, and D9S267, in the child but in neither parent. FISH analysis of the proband''s father indicated that loci deleted in his son, including TYRP, were present on neither the der(3) nor the der(9) translocation products but had been inserted into the long arm of chromosome 8. Therefore, the apparent deletion of these loci in the proband was the result of meiotic segregation of the father''s 3;9 translocation chromosomes together with his normal chromosome 8 (not bearing the insertion from 9p23). Neither the deletion of these 9p23 loci from the translocation chromosomes nor their insertion into 8q was detectable by standard chromosome banding techniques. The proband''s sister exhibited speech delay, mild facial dysmorphism, and renal malformation, and her karyotype was 46,XX. Molecular analysis showed that she had inherited normal chromosomes 3 and 9, as well as the chromosome 8 with the insertion of 9p23 material, from her father.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes of cytokines during the course of graft-versus-host disease following bone marrow transplantation: a case report

Allogeneic bone marrow transplantation was performed in a 24-year-old woman with acute myelogenous leukemia in the first remission (FAB classification: M4). Graft-versus-host disease occurred from around day 150 after bone marrow transplantation. The levels of tumour necrosis factor-alpha, interleukin 12, and intercellular adhesion molecule-1 were elevated in the early stage of graft-versus-host disease, followed by elevation of interleukin 10 and interleukin 8. Her symptoms subsequently improved and all of these parameters became normal. The levels of thrombomodulin and plasminogen activator inhibitor type 1 showed changes that were in parallel with the clinical course. Interleukin 1beta, interleukin 6, interleukin 2, and interferon-gamma showed no changes throughout the course of her graft-versus-host disease. These findings suggested the possibility that release of inflammatory molecules occurred at the onset of graft-versus-host disease and caused vascular endothelial damage, which led to the exacerbation of her disease.     

Polymorphism of restriction fragment length in the detection of the precise status of monosomy 21 in a deformed retarded girl

The authors used genomic single copy DNA fragments cloned from chromosome 21 to study cytogenetic abnormalities in patients not easily defined by conventional cytogenetic means. Ten restriction fragment length polymorphisms (RLFP) detected by 8 independent probes were used to detect homologous sequences from chromosome 21 in genomic digests of DNA from one patient and her parents. The proband is a 3 1/2-year-old girl who was referred to us at 1 month of age because of hypertonia, hirsutism, flattened nasal bridge, antimongoloid slant of palpebral fissures, high arched palate and bilateral hip dysplasia. The karyotype of the proband was: 46, XX, -3, -21, + ? del (3) (3 pter----3q1:) +? (3qter----3q1:: 21q21----21 pter). GTG banding and the karyotype of her parents were normal (in peripheral blood and skin fibroblasts). She was re-examined by us every three months, because she showed physical and psychomotor retardation. We traced the inheritance of RFLPs from her parents, and familial molecular studies showed in contrast to the cytogenetic analysis that the patient is disomic for all regions of 21q tested by our collection of probes. The use of molecular technology has resulted in a more precise definition of 21 chromosome abnormalities and especially the "complete" monosomy 21 which is extremely rare in live born infants.