A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia.

Cell cycle checkpoints can enhance cell survival and limit mutagenic events following DNA damage. Primary murine fibroblasts became deficient in a G1 checkpoint activated by ionizing radiation (IR) when both wild-type p53 alleles were disrupted. In addition, cells from patients with the radiosensitive, cancer-prone disease ataxia-telangiectasia (AT) lacked the IR-induced increase in p53 protein levels seen in normal cells. Finally, IR induction of the human GADD45 gene, an induction that is also defective in AT cells, was dependent on wild-type p53 function. Wild-type but not mutant p53 bound strongly to a conserved element in the GADD45 gene, and a p53-containing nuclear factor, which bound this element, was detected in extracts from irradiated cells. Thus, we identified three participants (AT gene(s), p53, and GADD45) in a signal transduction pathway that controls cell cycle arrest following DNA damage; abnormalities in this pathway probably contribute to tumor development.     

Impact of Monochorionicity and Twin to Twin Transfusion Syndrome on Prenatal Attachment,Post Traumatic Stress Disorder,Anxiety and Depressive Symptoms

Monochronioric (MC) twin pregnancies are considered as high-risk pregnancies with potential complications requiring in-utero interventions. We aimed to assess prenatal attachment, anxiety, post-traumatic stress disorder (PTSD) and depressive symptoms in MC pregnancies complicated with Twin-To-Twin-transfusion syndrome (TTTS) in comparison to uncomplicated monochorionic (UMC) and dichorionic pregnancies (DC). Auto-questionnaires were filled out at diagnosis of TTTS and at successive milestones. Prenatal attachment, PTSD, anxiety and perinatal depression were evaluated respectively by the Prenatal Attachment Inventory (PAI) completed for each twin, the Post-traumatic Checklist Scale (PCLS), the State-Trait Anxiety Inventory (STAI) and the Edinburgh Perinatal Depression Scale (EPDS). There was no significant difference in the PAI scores between the two twins. In the DC and UMC groups, PAI scores increased throughout pregnancy, whilst it didn’t for TTTS group. TTTS and DC had a similar prenatal attachment while MC mothers expressed a significantly higher attachment to their fetuses and expressed it earlier. At the announcement of TTTS, 72% of the patients present a score over the threshold at the EPDS Scale, with a higher score for TTTS than for DC (p = 0.005), and UMC (p = 0.007) at the same GA. 30% of mothers in TTTS group have PTSD during pregnancy. 50% of TTTS- patients present an anxiety score over the threshold (STAI-Scale), with a score significantly higher in TTTS than in UMC (p<0.001) or DC (p<0.001). The proportion of subject with a STAI–State over the threshold is also significantly higher in TTTS than in DC at 20 GW (p = 0.01) and at 26 GW (p<0.05). The STAI-state scores in UMC and DC increase progressively during pregnancy while they decrease significantly in TTTS. TTTS announcement constitutes a traumatic event during a pregnancy with an important risk of PTSD, high level of anxiety and an alteration of the prenatal attachment. These results should guide the psychological support provided to these patients.     

Dynamics and orientation of glycolipid headgroups by 2H-NMR: gentiobiose

Deuterium nuclear magnetic resonance has been used to investigate the dynamics and determine the orientation of the headgroup of the glycolipid 1,2-di-O-tetradecyl-3-O-(6-O-beta-D-glucopyranosyl-beta-D-glucopyranosyl )-sn- glycerol (beta-DTDGL), in aqueous multilamellar dispersions. In addition, its anomeric analog, having an alpha glucose-glycerol linkage, was prepared and examined. The lipids were labelled with deuterium at specific positions in the disaccharide moiety. Analysis of the deuterium quadrupolar splittings for the first glucose ring (glycerol-linked) gave segmental order parameters of 0.43 and 0.35 for the beta and alpha isomers, respectively. Both isomers had similar orientations of the sugar ring relative to the bilayer surface, as determined for lipid in the liquid-crystalline phase. 2H-NMR results for the lipid labelled at C-6' are consistent with a single conformation about the C-5'-C-6' bond of the first glucose residue, with a dihedral angle (O-5'-C-5'-C-6'-O-6') of -17 degrees. The results obtained for the second sugar ring suggest that two conformers may be present, which are in slow exchange on the 2H-NMR timescale. Measurements of longitudinal relaxation times, T1z, gave similar values for both sugar moieties in the headgroup, suggesting that the disaccharide does not exhibit the flexibility expected about the 1----6 linkage. Since T1z for 2H in these compounds decreases with increasing temperature and increases with magnetic field strength, the motion(s) dominating relaxation is in the long-correlation-time regime [omega 0 tau c)2 greater than 1). Thus, the gentiobiosyl headgroup undergoes the slowest motion of the glycolipid headgroups studied to date.     

The relationship between megakaryocyte nuclear DNA content and gene expression

Megakaryocytes are a distinct population of bone marrow cells that have the unique feature of increasing their DNA content without undergoing division. The biological effect of ploidy distribution on gene expression, receptor expression and protein synthesis is still unknown. Using molecular hybridization techniques, we have started a systematic analysis of mRNA expression in megakaryocytes for a number of proteins involved in clot formation. These data will be related to ploidy. Platelets are the unnucleated product of megakaryocytes, having their protein content derived from the precursor cell. Therefore, the understanding of the molecular mechanisms regulating megakaryocyte biology and the consequent type and reactivity of platelets produced is of fundamental importance in both physiological and pathological conditions.     

CONCHOCELIS GROWTH AND PHOTOPERIODIC CONTROL OF CONCHOSPORE RELEASE IN PORPHYRA TORTA (RHODOPHYTA) 1

We have determined the conditions which give optimal growth and conchospore release in laboratory cultures of free conchocelis of the red alga Porphyra torta Krishnamurthy. With cool white fluorescent light on a 16L.8D photoregime, the fastest sustained growth (5% volume increase d^?1) was observed from 10–15°C and 25–100 μE-m ^?2.s^?1; slightly faster growth was observed at 15°C and 300 μE.m^?2.s^?1, but such conditions are close to lethal. Conchoporangin will form under a wide range of conditions in conchocelis of this species. However, conchospores will mature and release only when the cultures are exposed to a short day photoperiod. The critical pholoperiod is just shorter than 12 h, The minimum number of photoinductive cycles for complete conchospore release is four for a range of conditions but can be just one depending on pretreatment.     

Evidence for Excision of Ultraviolet-Induced Pyrimidine Dimers from the DNA of Human Cells In Vitro

Within 12-24 hr after human cells were irradiated with ultraviolet light, approximately 50% of the ultraviolet-induced pyrimidine dimers were lost from the DNA. Pyrimidine dimers were found in the TCA-soluble fraction of ultraviolet-irradiated cells at 24 hr. Excess thymidine, caffeine, or hydroxyurea had no effect on the loss of pyrimidine dimers from the DNA of ultraviolet-irradiated cells.     

Oxygen exchange during growth of photomixotrophic cell suspensions of Euphorbia characias L.

Growth of photomixotrophic cell culture of Euphorbia characias L. is described; oxygen exchange rates were measured along this growth cycle using a mass-spectrometric technique. During the exponential and mid-stationary phases, photosynthesis was strongly increasing, the major part of oxygen uptake in the light was due to mitochondrial respiration. In the late stationary phase, gross photosynthesis was decreasing; this could not be explained by an alteration of Rubisco because photorespiratory process could be observed; in addition the Mehler reaction must be called upon to explain whole oxygen uptake in the light.     

Skeletal growth and function in the California gull (Larus californicus)

Although the bones of rapidly growing animals are composed of weak tissue, they often must function in locomotor activity. We address the conflict between development and skeletal function by analysing the ontogeny of skeletal strength in the California gull, Larus californicus. Changes in shape and mechanical properties of the femur, tibia, tarsometatarsus, humerus, ulna and carpometacarpus were analysed in a complete post-hatching growth series. During post-hatching growth, strength and stiffness of the skeletal tissue increases six- to ten-fold. At hatching, long bones of the wing are relatively weak and they remain so throughout the major portion of the growth period. However, in the hind limb, relatively thick bones in juveniles compensate for the weak tissue such that the force required to break the bones remains constant relative to body mass. This difference between hind limb and wing parallels the development of locomotor function; young gulls begin to walk within a day or two of hatching, but they do not fly until they are fully grown. Thus, in the bones of the hind limb, the conflict between rapid growth and skeletal function is solved by negative allometry of bone thickness.
After young gulls reach adult size, the breaking strength of the wing bones increases three- to four-fold, the mass of the pectoralis muscle triples and the surface area of the wing doubles. The one aspect of wing development that is not delayed until shortly before fledging is linear growth of the bones. Bones of the wing increase in length at a rapid and relatively constant rate from the time of hatching to the attainment of adult size. Relatively early initiation of linear growth of the wing bones suggests that the rate at which bones grow in length may be the rate limiting factor in wing development.     

Real‐time telemetric monitoring in whole‐body 60Co gamma‐photon irradiated rhesus macaques (Macaca mulatta)

Background Animals undergoing experimental manipulations, such as exposure to radiation, may exhibit physiologic and behavioral signs of pain and distress. Telemetry permits close monitoring of these parameters for early and effective management during procedures. Methods Radiotelemetric units were surgically implanted into 24 Macaca mulatta before 6.5‐Gy cobalt‐60 γ‐photon irradiation. Each unit transmitted electrocardiogram, intrathoracic pressure, and body temperature leads. Primate irradiation‐restraint boxes and housing cages were modified to collect telemetric signals before, during, and after irradiation. Results Differences in respiratory rate, heart rate, or body temperature in telemetric‐collected recordings, which were observed during non‐irradiation and irradiation sessions, were statistically insignificant. Conclusions Insignificant changes in the physiological parameters during monitoring suggest that the animals experienced no detectable pain or distress during irradiation.