Search PubMed⌕ Search

Biomedical subjects

A Grigoriev

Publications and source records attributed to A Grigoriev.

27 records · Page 2Linked to original sources

An algorithm to detect chimeric clones and random noise in genomic mapping.

Experimental noise and noncontiguous clone inserts can pose serious problems in reconstructing genomic maps from hybridization data. We describe an algorithm that easily identifies false positive signals and clones containing chimeric inserts/internal deletions. The algorithm "dechimerizes" clones, splitting them into independent contiguous components and cleaning the initial library into a more consistent data set for further ordering. The effectiveness of the algorithm is demonstrated on both simulated data and the real YAC map of the whole genome of the fission yeast Schizosaccharomyces pombe.

Algorithms↗

An integrated YAC-overlap and 'cosmid-pocket' map of the human chromosome 21.

We describe here the construction of an ordered clone map of human chromosome 21, based on the identification of ordered sets of YAC clones covering > 90% of the chromosome, and their use to identify groups of cosmid clones (cosmid pockets) localised to subregions defined by the YAC clone map. This is to our knowledge the highest resolution map of one human chromosome to date, localising 530 YAC clones covering both arms of the chromosome, spanning > 36 Mbp, and localising more than 6300 cosmids to 145 intervals on both arms of the chromosome. The YAC contigs have been formed by hybridising a 6.1 equivalents chromosome 21 enriched YAC collection displayed on arrayed nylon membranes to a series of 115 DNA markers and Alu-PCR products from YACs. Forty eight mega-YACs from the previously published CEPH-Genethon map of sequence tagged sites (STS) have also been included in the contig building experiments. A YAC tiling path was then size-measured and confirmed by gel-fingerprinting. A minimal tiling path of 70 YACs were then used as probes against the 7.5 genome equivalents flow sorted chromosome 21 cosmid library in order to identify the lists of cosmids mapping to alternating shared--non-shared intervals between overlapping YACs ('cosmid pockets'). For approximately 1/5 of the minimal tiling path of YACs, locations and non-chimaerism have been confirmed by fluorescence in situ hybridisation (FISH), and approximately 1/5 of all cosmid pocket assignments have independent, confirmatory marker hybridizations in the ICRF cosmid reference library system. We also demonstrate that 'pockets' contain overlapping sets of cosmids (cosmid contigs). In addition to being an important logical intermediate step between the YAC maps published so far and a future map of completely ordered cosmids, this map provides immediately available low-complexity cosmid material for high resolution FISH mapping of chromosomal aberrations on interphase nuclei, and for rapid positional isolation of transcripts in the highly resolved regions of genetic interest.

Chromosome Mapping↗

Algorithms and software tools for ordering clone libraries: application to the mapping of the genome of Schizosaccharomyces pombe.

A complete set of software tools to aid the physical mapping of a genome has been developed and successfully applied to the genomic mapping of the fission yeast Schizosaccharomyces pombe. Two approaches were used for ordering single-copy hybridisation probes: one was based on the simulated annealing algorithm to order all probes, and another on inferring the minimum-spanning subset of the probes using a heuristic filtering procedure. Both algorithms produced almost identical maps, with minor differences in the order of repetitive probes and those having identical hybridisation patterns. A separate algorithm fitted the clones to the established probe order. Approaches for handling experimental noise and repetitive elements are discussed. In addition to these programs and the database management software, tools for visualizing and editing the data are described. The issues of combining the information from different libraries are addressed. Also, ways of handling multiple-copy probes and non-hybridisation data are discussed.

Algorithms↗

Changes of hormones regulating electrolyte metabolism after space flight and hypokinesia.

The changes of hormones in plasma involved in the body fluid regulation were studied in human subjects during and after space flights in relation to redistribution of body fluids in the state of weightlessness. Since hypokinesia was used as a model for simulation of some effects of the stay in microgravity the plasma hormone levels in rats exposed to hypokinesia were also investigated. Plasma aldosterone values showed great individual variations during the first inflight days, the increased levels were observed with prolongation of space flights. The important elevation was found in the recovery period, however it was interesting to note, that in some cosmonauts with repeated exposure to space flight, the postflight plasma aldosterone levels were not elevated. The urine excretion of aldosterone was increased inflight, however in postflight period the decrease or increase were found in the first 1-5 days. The increase of plasma renin activity was observed in flight and postflight period. The rats were exposed to hypokinesia (forced restriction of motor activity) for 1, 7 and 60 days and urine was collected during last 24 hours. The animals were sacrificed and the concentration of electrolytes and of levels of corticosterone, aldosterone (A), ANF and plasma-renin activity (PRA) were determined in plasma. In urine excretion of sodium and potassium were estimated. An important increase of plasma renin activity and aldosterone concentration was found after short-term hypokinesia (1 day). These hormonal values appear to decrease with time (7 days) and are not significantly different from controls after long-term hypokinesia (60 days). A decrease of values ANF in plasma was observed after 1 and 7 days hypokinesia. After prolonged hypokinesia a decrease of sodium plasma concentration was observed. The excretion of sodium in urine was higher in long-term hypokinetic animals. There were no significant changes of plasma potassium levels in rats exposed to hypokinesia, however the urinary excretion of potassium was elevated. In rats exposed to hypokinesia for 7 and 60 days an increase of urine osmolality was observed. The results of hormone and electrolyte determination in plasma of cosmonauts after space flight and in experimental animals after hypokinesia suggested that in evaluation of relations between the changes of hormone levels and electrolyte in plasma and urine other factors like emotional stress working load; altered diurnal cycles should be considered in interpretation of homeostatic response of fluid and electrolyte metabolism to space flight conditions.

Aldosterone↗

Bone and body mass changes during space flight.

Body mass, calcium and skeletal changes occur in humans who have worked in microgravity. Physiologic changes are seen as early as one week and are still occurring 312 days into space flight. The physiologic changes in bone and mineral metabolism may be among those which limits long duration space flight if an adequate countermeasure is not developed. The purpose of this paper is to summarize what is known about calcium dynamics and bone mineral changes as well as associated changes of body mass induced by space flight. The data reported is from a variety of studies conducted in both actual and simulated space flight.

Aerospace Medicine↗

Biomedical program of the ALTAIR french russian flight onboard the MIR station.

One year after the achievement of the 2 weeks ANTARES french-russian mission in the MIR station in July 1992, a 22 days ALTAIR mission with a french cosmonaut has been performed in July 1993, making use of the scientific payload remaining on board. Taking benefit of the analysis of the previous mission, the experimental protocols were adapted to refine scientific objectives and gave to the scientists the opportunity to enhance quantitatively and qualitatively their results. The french biomedical program, conducted in close scientific cooperation with IMBP and associated laboratories, was composed of 8 experiments out of which 2 were new with regards to the ANTARES program. In the field of cardio-vascular physiology and fluid regulation, the experiments: ORTHOSTATISME, DIURESE have been renewed and complemented by the TISSU experiment (proposed by a german scientist) and a real-time tele-assistance program using US echography technic and ground support from the french CADMOS support control center located in Toulouse. With respect to neurosciences objectives, to the experiments VIMINAL (cognitive processes) and ILLUSIONS (study of proprioceptives cues), was added the SYNERGIES experiment to analyse the postural adjustments during movement. The IMMUNOLOGIE experiment carried on and the radiobiological experiment BIODOSE ended. Adding the results of the 2 missions ANTARES and ALTAIR, and the data obtained in between onboard with russian cosmonauts, the scientists have received a wealth of physiological data and gained reproducibility and confidence in their results.

Adaptation, Physiological↗

Blood volume regulating hormones, fluid and electrolyte modifications during 21 and 198-day space flights (Altair-MIR 1993).

During the Altair MIR '93 mission we studied several parameters involved in blood volume regulation. The experiment was done on two cosmonauts before (B-60, B-30), during (D6, D12, D18 for French and D7, D12, D17 for Russian) and after the flight (R+1, R+3 and R+7). Space flight durations were different for two cosmonauts: for the Russian the flight duration was 198 days and for the French 21 days. On board the MIR station only urinary (volume and electrolytes, atrial natriuretic peptide (ANP), cyclic guanosine monophosphate (cGMP) and catecholamines) and salivary (cGMP and cortisol) samples were collected, centrifuged and stored in freezer. Lithium was used as a tracer to know exactly the 24 h urine output (CNES urine collection Kit). Before and after flight, blood was drawn with an epicite needle and vacutainer system for hormonal assays (renin, antidiuretic hormone, cGMP, ANP and aldosterone) in two positions: after 30 min rest in upright seated position and after 90 min of supine position. Salivary samples were collected simultaneously. During flight a decrease of diuresis and ANP and an increase of osmolality were found. No modifications of hematocrit, but an increase of salivary cGMP and cortisol were also observed. The decrease of urinary ANP is in favor of hypovolemia as described in previous flights. The postflight examinations revealed changes in fluid-electrolyte metabolism which indicate a hypohydration status and a stimulation of hormonal system responsible for water and electrolyte retention in order to readapt to the normal gravity.

Aldosterone↗