Evidence that postnatal growth retardation in XO mice is due to haploinsufficiency for a non-PAR X gene

XO Turner women, irrespective of the parental source of the X chromosome, are of short stature, and this is now thought to be largely a consequence of haploinsufficiency for the pseudoautosomal region (PAR) gene SHOX. X(p)O mice (with a paternal X) are developmentally retarded in fetal life, are underweight at birth, and show reduced weight gain in the first few weeks after birth. X(m)O mice, on the other hand, are more developmentally advanced than their XX siblings in fetal life; their postnatal growth has not hitherto been assessed. Here we show that X(m)O mice are not underweight at birth, but they nevertheless show reduced weight gain postnatally. The fact that postnatal growth is affected in X(p)O and X(m)O mice, means that this must be due to X dosage deficiency. In order to see if haploinsufficiency for a PAR gene was responsible for this growth deficit (cf SHOX deficiency in Turner women), X(m)Y*(X) females, in which the Y*(X) chromosome provides a second copy of the PAR, were compared with XX females. These X(m)Y*(X) females were also growth-retarded relative to their XX sibs, suggesting that it may be haploinsufficiency for a non-dosage-compensated X gene or genes outside the PAR that is responsible for the postnatal growth deficit in XO mice. The X genes known to escape X inactivation in the mouse have closely similar Y homologues. X(m)YSRY-negative females were therefore compared with XX females to see if the presence of the SRY-negative Y chromosome corrected the growth deficit; this proved to be the case. The postnatal growth deficit of XO mice is therefore probably due to haploinsufficiency for a non-dosage-compensated X gene that has a Y homologue that provides an equivalent function in the somatic tissues of males.     

Factors that affect transduction in microorganisms]

Data from literature concerning general and specialized transduction in microorganisms are given in the paper. The process of exogenic DNA penetration to the cells of bacteria and participation of protein products of separate phage genes in this process are described. The so-called E-proteins in a set with DNA penetrate through a cell membrane. In phage P22 they are protein products of phage genes 7, 16, 20. In P22 mutants with an altered transducing frequencies (HFT and LFT) the due functions are also coded by the phage genes. It is shown that the process of DNA packing in phages P22, phi 80, lambda and others is genetically determined. The gene transfer frequency depends on UV radiation and the very nature of transducing phages itself. In virulent phages the UV radiation up to inactivation level 95-99% evokes a decrease of their "killer" ability, which is accompanied by an increase of survivability of the formed transductants and, as a result, by enhancement of the transduction transfer frequency. An important role of the transduction analysis for fine mapping of a genome of microorganisms and its significance for practice are shown. A mathematical analysis of the data on cotransduction of linkage markers is presented as such that may be used when determining the value of transduced fragment of a chromosome.     

Factors that affect the folding ability of proteins

The folding ability of a heteropolymer model for proteins subject to Monte Carlo dynamics on a simple cubic lattice is shown to be strongly correlated with the stability of the native state. We consider a number of estimates of the stability that can be determined without simulation, including the energy gap between the native state and the structurally dissimilar part of the spectrum (Z score) and, for sequences with fully compact native states, the gap in energy between the native and first excited fully compact states. These estimates are found to be more robust predictors of folding ability than a parameter sigma that requires simulation for its evaluation: sigma = 1 - Tf/Ttheta, where Tf is the temperature at which the fluctuation of an order parameter is at its maximum and Ttheta is the temperature at which the specific heat is at its maximum. We show that the interpretation of Ttheta as the collapse transition temperature is not correct in general and that the correlation between sigma and the folding ability arises from the fact that sigma is related to the energy gap (Z score).     

Inactivation of tensin3 in mice results in growth retardation and postnatal lethality

Tensin family is a group of focal adhesion proteins that interact with integrins, actin, and phosphotyrosine-containing proteins. To explore the in vivo functions of a new member of the family, tensin3, we have generated mutant mice with a disrupted tensin3 gene. Inactivation of tensin3 resulted in growth retardation and postnatal lethality in one third of the homozygous mutants. Histological analysis of those mutants showed incomplete development of the small intestine, lung, and bone. Villus formation in the small intestine was affected and cells migrated slower in the runt mutants. Their lungs also displayed enlarged air space suggesting defects in alveogenesis. In addition, the resting zone was thicker and fewer proliferating cells were present in the growth plates of tensin3(-/-) tibiae. These observations indicate that tensin3 is essential for normal development and functions of the small intestine, lung, and bone. These phenotypes of the runt tensin3(-/-) mice are similar to some clinical features of Silver-Russell syndrome (SRS) which is a genetically inherited defect. About 10% of SRS cases have been linked to abnormality in chromosome 7p11.2-13, where human tensin3 gene is located, suggesting a potential link between tensin3 and SRS.     

The maternal, fetal and postnatal somatotrophic axes in intrauterine growth retardation

Both the maternal and fetal somatotrophic axes are closely linked to fetal substrate supply. Nutritional insults at critical stages of fetal development may lead to permanent reprogramming of the relationships between these factors. The consequences of reprogramming during fetal life may be harmful to metabolic, endocrine and cardiovascular homoeostatic mechanisms in postnatal life. The exact mechanisms that lead to reprogramming during fetal life need thorough investigation before effective strategies to deal with this problem can be devised.     

Factors that affect the horizontal transfer of transposable elements

Transposable elements are characterized by their ability to spread within a host genome. Many are also capable of crossing species boundaries to enter new genomes, a process known as horizontal transfer. Focusing mostly on animal transposable elements, we review the occurrence of horizontal transfer and examine the methods used to detect such transfers. We then discuss factors that affect the frequency of horizontal transfer, with emphasis on the mechanism and regulation of transposition. An intriguing feature of horizontal transfer is that its frequency differs among transposable element families. Evidence summarized in this review indicates that this pattern is due to fundamental differences between Class I and Class II elements. There appears to be a gradient in the incidence of horizontal transfer that reflects the presence of DNA intermediates during transposition. Furthermore, horizontal transfer seems to predominate among families for which copy number is controlled predominantly by self-regulatory mechanisms that limit transposition. We contend that these differences play a major role in the observed predominance of horizontal transfer among Class II transposable elements.     

Deletion of the MBII-85 snoRNA gene cluster in mice results in postnatal growth retardation

Prader-Willi syndrome (PWS [MIM 176270]) is a neurogenetic disorder characterized by decreased fetal activity, muscular hypotonia, failure to thrive, short stature, obesity, mental retardation, and hypogonadotropic hypogonadism. It is caused by the loss of function of one or more imprinted, paternally expressed genes on the proximal long arm of chromosome 15. Several potential PWS mouse models involving the orthologous region on chromosome 7C exist. Based on the analysis of deletions in the mouse and gene expression in PWS patients with chromosomal translocations, a critical region (PWScr) for neonatal lethality, failure to thrive, and growth retardation was narrowed to the locus containing a cluster of neuronally expressed MBII-85 small nucleolar RNA (snoRNA) genes. Here, we report the deletion of PWScr. Mice carrying the maternally inherited allele (PWScr^m−/p+) are indistinguishable from wild-type littermates. All those with the paternally inherited allele (PWScr^m+/p−) consistently display postnatal growth retardation, with about 15% postnatal lethality in C57BL/6, but not FVB/N crosses. This is the first example in a multicellular organism of genetic deletion of a C/D box snoRNA gene resulting in a pronounced phenotype.     

Factors that affect the efficiency of cell transfection by immunoporation

Immunoporation is a recently discovered method that is able to transfect various human cell lines efficiently by targeting the cell surface antigens with antibody-coated beads. For this particular study, HL60, a cell line difficult to transfect by other methods, was used as a model to define the various parameters of the cell membrane that determine the efficiency of this method. The level of antigen expression on the cell surface was the first parameter to be analyzed and experiments indicated that there is a close correlation between the level of expression of surface antigens and the efficiency of immunoporation. The mixing speed, the bead to cell ratio, and the mixing time were all found to affect the ability of the antigen-coated beads to pull holes in the cells and it was found that for HL60 cells the optimum mixing speed was 40 rpm and the bead to cell ratio was 20:1 using a mixing time of 6 h.     

Genes that affect morphogenesis of the murine mandible. Recombinant-inbred strain analysis

The CXB set of recombinant inbred mouse strains provided an opportunity to observe the effects of reassorted subsets of genes on the shape of the mandible. The distances between 12 landmarks in all paired combinations were calculated to evaluate genetic control in small regions. The genetic relationships between interlandmark distances revealed genes to have most of their effects in localized regions, and the greater heritabilities usually to apply to those distances between adjacent landmarks. Interrelationships between measurements are usually explicable on a developmental basis. It is proposed that genes of this sort bring about the changes seen in organ shape during evolution. A model plan for the organization of gene activation during morphogenesis is described.     

Genes that affect the shape of the murine mandible. Congenic strain analysis

Small specific regions of the adult murine mandible are found to be expanded or contracted by the effects of genes sorted out as passenger genes in a set of congenic strains. The large estimated number of such genes could provide a genetic basis for morphological change during speciation.     

Factors that affect fertility in a feral population of sheep

Feral livestock offer an excellent opportunity lo study factors affecting fertility as the physiology of their husbanded relatives is well known and social and environmental influences can be studied free of man's interference. This is so in the population of about 1250 sheep of the primitive Soay breed on the islands of St Kilda, Scotland. There is a high coincidence of oestrus amongst the ewes in mid November, and the breeding season is constant within a few days, from year to year. The breeding season in other British breeds of sheep demonstrates a strong correlation with latitude. On St Kilda, mortality rates in male sheep are higher than in females so that the ratio of rams to ewes at mating time is about 1:5. Competition amongst rams is intense. The optimal time for mating and the place of ram lambs in the social system are discussed.     

Factors that affect transposition mediated by the Tn21 transposase

The frequencies of one-ended transposition mediated by the Tn21 transposase acting on plasmids containing 38-bp inverted repeat sequences (IRs) of both Tn21 and of Tn501/Tn1721 and Tn2501 were measured. The enzyme acted on all these IRs, but more efficiently on the homologous sequences. These differences were magnified when the enzyme acted on plasmids containing two copies of the IRs, inverted with respect to each other. The Tn21 enzyme did not recognize the IR of Tn3. The Tn501 transposase did not mediate measurable one-ended transposition of any of the plasmids used, including those containing an IR of Tn501.     

Hormonal changes affect the bone and bone marrow cells in a rat model

In this study, we used a rat model to investigate the effects of gonad hormones and replacement therapy on bone structure and the immune system. In the first phase of the study, 3- and 11-month-old F344 rats underwent ovariectomy (OVX) or were sham operated. Three months later, severe osteopenia was histologically observed in OVX rats of both age groups. The changes in the bone marrow structure of OVX rats included deterioration of cancellous bone that was associated with a remarkable increase of adipocyte cells. Furthermore, differential analyses for the expression of cell surface antigens by lymph-myeloid cells was studied using flow cytometry (FACS). The number of myeloid cells expressing ED-9(+) or CD-44(+) was similar in both age groups, and unaffected by OVX. However, an augmentation of T-lymphoid cells expressing CD4(+), CD5(+), or both, were observed with age, as well as after OVX. In the second phase of the study, 11-month-old rats were divided into five experimental groups: sham-operated, OVX, and OVX treated with sustained-release pellets of 17beta-estradiol (OVX-E), progesterone (OVX-P), or both (OVX-E/P). Hormone replacement therapy maintained low physiological levels, and rats were tested 12 weeks after treatment initiation. Administration of 17beta-E, with or without the addition of progesterone, prevented the rise of T lymphoid cells observed in OVX rats, whereas progesterone alone had no effect. In agreement with findings from the first phase, neither OVX nor replacement therapy affected the myeloid cells expression of ED-9 or CD-44. In summary, the cellular changes in the bone marrow of OVX rats were associated with an increase in adipocytes that was correlated with bone atrophy. An augmentation of T-lymphopoiesis was noted with increase in age or after OVX. This increase was reversed to baseline levels by 17beta-E treatment.     

Factors that affect the type of cell death induced by chemicals

Surveying about 1000 compounds, we found that several low molecular weight alpha, beta-unsaturated ketones induced non-apoptotic cell death characterized by the formation of autophagosomes, occasionally accompanied by mitochondrial shrinkage. The cytotoxic activity of these compounds was significantly reduced by the addition of N-acetyl-L-cysteine, suggesting their interaction with SH groups of intracellular targeted molecules (the so-called "non-sterically hindered Michael acceptor"). This suggests that the nature of the chemical structure as well as the type of target cells is another factor that determines the type of cell death induced by chemicals.     

真菌毒素形成的影响因素

真菌毒素是真菌产生的次级代谢产物,可污染粮食、水果、食品、饲料、中草药等多种农产品。严重威胁食品安全、危害人畜健康,真菌毒素的形成除了受到产毒菌自身遗传因素的调控外,还受到宿主、环境因素的调控。此外,上述的多种因素的交互作用为真菌毒素的产生和调节增加了另一个层次上的多样性和复杂性。为了探究调控真菌毒素形成的因素,本文综述了真菌毒素合成及调控基因、温度、水分活度、光照、渗透压、基质、酸碱度、植物损伤、宿主抗性等因素对真菌毒素形成的影响,同时探讨了真菌毒素的防控,以期为探究真菌毒素形成的调控机制奠定基础,为真菌毒素防控策略的开发提供理论依据。