The robot and the satellite for tele-operating echographic examination in Earth isolated sites, or onboard ISS

The objective was to design and validate a method for tele-operating (from an expert site) an echographic examination in an isolated site. METHOD: The isolated places, defined as areas with reduced medical facilities, could be secondary hospitals 20 to 50 km from the university hospital, or dispensaries in Africa or Amazonia, or a moving structure like a rescue vehicle or the International Space Station (ISS). At the expert center, the ultrasound medical expert moves a fictive probe, connected to a computer (n degrees 1) which sends, the coordinate changes of this probe via an ISDN or satellite line to a second computer (n degrees 2), located at the isolated site, which applies them to the robotic arm holding the real echographic probe. RESULTS: The system was tested at Tours Hospital on 105 patients. A complete investigation (visualization) of all the organs requested for different clinical cases was obtained in 76% of the cases with the robot, and 87% at the reference echography: In 11% of the cases, at least one of the organ visualized at reference echo could not be investigated by the robot, thus the diagnostic was not done. The number of repositioning was higher for the robot (6.5 +/- 2) than for the reference echo (5.1 +/- 2 = or > 24% more with robot). The duration of the examination was higher with the robot (16 +/- 10 min) than for the reference echography (11 +/- 4 min = or > +43% with the robot compare to reference echography. The system was also tested successfully using satellite links in a limited number of cases (approx 30).     

hnRNP A1 controls HIV-1 mRNA splicing through cooperative binding to intron and exon splicing silencers in the context of a conserved secondary structure

The removal of the second intron in the HIV-1 rev/tat pre-mRNAs, which involves the joining of splice site SD4 to SA7, is inhibited by hnRNP A1 by a mechanism that requires the intronic splicing silencer (ISS) and the exon splicing silencer (ESS3). In this study, we have determined the RNA secondary structure and the hnRNP A1 binding sites within the 3' splice site region by phylogenetic comparison and chemical/enzymatic probing. A biochemical characterization of the RNA/protein complexes demonstrates that hnRNP A1 binds specifically to primarily three sites, the ISS, a novel UAG motif in the exon splicing enhancer (ESE) and the ESS3 element, which are all situated in experimentally supported stem loop structures. A mutational analysis of the ISS region revealed that the core hnRNP A1 binding site directly overlaps with a major branchpoint used in splicing to SA7, thereby providing a direct explanation for the inhibition of U2 snRNP association with the pre-mRNA by hnRNP A1. Binding of hnRNP A1 to the ISS core site is inhibited by RNA structure but strongly stimulated by the exonic silencer, ESS3. Moreover, the ISS also stimulate binding of hnRNP A1 to the exonic splicing regulators ESS3 and the ESE. Our results suggest a model where a network is formed between hnRNP A1 molecules situated at discrete sites in the intron and exon and that these interactions preclude the recognition of essential splicing signals including the branch point.     

An european pupil project linked to the scientific aims of the experiment AQUARIUS-XENOPUS on the taxi Soyuz flight Andromede to ISS

The German-French biological experiment AQUARIUS-XENOPUS which flew on the Soyuz flight Andromede to the International Space Station ISS (launched October 21, 2001 in Baikonour/Kazakhstan) was extended by an outreach project. Pupils of class 10 to 12 from Ulm/D and Nancy-Tomblaine/F studied swimming behavior of Xenopus tadpoles on ground. They were instructed to perform all experimental steps following the protocol of similar video recordings on ISS. After the flight, they evaluated the kinetics of swimming of both ground controls and space animals. The pupil project included theoretical components to introduce them to the field of gravitational biology. One feature of the project was the exchange of ideas between pupils by meetings which took place in Ulm (June 2001), Nancy (February 2002) and Paris (May 2002). We consider our approach as a successful way to include young people in space experiments on a cheap cost level and to bring ideas of gravitational biology into the curricula of European schools.     

Relevance to prenatal diagnosis of the identification of a human Y/autosome translocation by Y-chromosome-specific in situ hybridisation

Routine cytogenetic analysis of an amniotic fluid sample revealed a large brightly fluorescent region in the short arm of chromosome 14 in an otherwise normal male karyotype (46,XY,14p+ + +). This site was also present in the paternal karyotype. In situ hybridisation to a Y-chromosome-specific DNA probe confirmed that the father had a Y/14 translocation. The incidence of two hybridisation bodies (large hybridisation sites), detecting both the translocated Y chromatin and the normal Y chromosome, was lower in interphase nuclei (44.3%) than in metaphase spreads (95.2%). The relevance of these observations to the potential use of in situ hybridisation to interphase nuclei for prenatal diagnosis is discussed.     

Microbe-I: fungal biota analyses of the Japanese experimental module KIBO of the International Space Station before launch and after being in orbit for about 460 days

In addition to the crew, microbes also find their way aboard the International Space Station (ISS). Therefore, microbial monitoring is necessary for the health and safety of the crew and for general maintenance of the facilities of this station. Samples were collected from three sites in the Japanese experimental module KIBO on the ISS (air diffuser, handrail, and surfaces) for analysis of fungal biota approximately 1 year after this module had docked with the ISS. Samples taken from KIBO before launch and from our laboratory were used as controls. In the case of KIBO, both microbe detection sheet (MDS) and swab culture tests of orbital samples were negative. The MDS were also examined by field emission-scanning electron microscopy; no microbial structures were detected. However, fungal DNAs were detected by real-time PCR and analyzed by the clone library method; Alternaria sp. and Malassezia spp. were the dominant species before launch and in space, respectively. The dominant species found in specimens from the air conditioner diffuser, lab bench, door push panel, and facility surfaces on our laboratory (ground controls) were Inonotus sp., Cladosporium sp., Malassezia spp., and Pezicula sp., respectively. The fungi in the KIBO were probably derived from contamination due to humans, while those in our laboratory came from the environment (e.g., the soil). In conclusion, the cleanliness in KIBO was equivalent to that in a clean room environment on the ground.     

Porte sonde motorisé pour une télé-échographie abdominale en temps différé : étude de faisabilité

PurposeDesign a system of delayed telesonography between expert center and isolated site where there is no sonographer.Materials and methodsA motorized probe holder printing a movement of TILT (± 40°) to any 2D echograph probe available in an isolated site, allows a non-sonographer to capture the patients’ whole organ images. This volume of images is sent to the expert center via internet. The video sequence is decomposed into images in the JPEG format by the software VirtualDub. A post-processing software (ECHO-CNES) allows the expert to find the incidences necessary for the diagnosis. This system has been tested on 50 patients at the CHU Trousseau (Tours, France).ResultsOrgans investigated were liver, portal vein, gall-bladder, kidneys (right and left) and spleen. The acquisition time of the volumes of images was 4 min maximum and allowed to reconstruct images necessary for the diagnosis in 80% of the cases. Scanning duration lasted 4 s on average; processing duration of the volume of images lasted approximately 15 min.ConclusionThis system is in validation in real situation in Togo with the aim of its generalization for medical care according to the obtained results.     

Karyotyping of Brassica oleracea L. based on rDNA and Cot-1 DNA fluorescence in situ hybridization

To explore an effective and reliable karyotyping method in Brassica crop plants,Cot-1 DNA was isolated from Brassica oleracea genome,labeled as probe with Biotin-Nick Translation Mix kit,in situ hybridized to mitotic spreads,and where specific fluorescent bands showed on each chromosome pair.25S and 5S rDNA were labeled as probes with DIG-Nick Translation Mix kit and Biotin-Nick Translation Mix kit,respectively,in situ hybridized to mitotic preparations,where 25S rDNA could be detected on two chromosome pairs and 5S rDNA on only one.Cot-1 DNA contains rDNA and chromosome sites identity between Cot-1 DNA and 25S rDNA was determined by dual-colour fluorescence in situ hybridization.All these showed that the karyotyping technique based on a combination of rDNA and Cot-1 DNA chromosome landmarks is superior to all but one.A more exact karyotype ofB.oleracea has been analyzed based on a combination of rDNA sites,Cot-1 DNA fluorescent bands,chromosome lengths and arm ratios.     

Novel method for the study of receptor Ca2+ signalling exemplified by the NK1 receptor

We have used a novel technology (NovoStar from BMG Labtechnologies) for the study of the Ca2+ signalling of the human tackykinin NK1 (hNK-I receptor). The NovoStar is a microplate reader based on fluorescence and luminescence. The instrument implements a robotic pipettor arm and two microplate carriers, typically one for samples and one for cells. The robotic pipettor arm can transfer sample (agonist or antagonist) from the sample plate or other liquid containers to the cell plate, facilitating the study of Ca2+ signalling to such a degree that the instrument can be used for Medium Throughput Screening (MTS). Using the NovoStar we have found the molecular pharmacology of the NK1 receptor to be comparable to that observed in classical signal transduction assays. Thus, we have observed an EC50 value of 3 nM for substance P induced Ca2+ response. This value corresponds well with previously published values for substance P induced IP and cAMP turnover. [1] Using the NovoStar technology we have studied the pharmacological profile of the well known non-peptide NKI receptor antagonists CP96,345 and SR140,333 [2,3] in respect of inhibition of the Ca2+ response induced by substance P. Interestingly, the antagonistic potency of the antagonists depended greatly on the experimental design, e.g., a dependency of timing in the addition of antagonists vs. agonist was noted. Also, metal-ion site engineered NK1 receptors [2] were tested for the ability of metal-ions to inhibit signalling. It is concluded that the NovoStar is a reliable tool for the study of receptor Ca2+ signalling, both as a research tool and as a MTS system.     

Scanning probe microscopy for Bio & Nanotechnology onboard the ISS

Since February 2002 Kayser-Threde GmbH, Munich (Germany) leads a study under ESA contract in order to study the technical feasibility and the applications of "Scanning Probe Microscopy for Bio & Nanotechnology onboard the ISS (SONOS)". The objective of this effort is to demonstrate the feasibility of an SPM instrument on the ISS. An appropriate breadboard model will be manufactured and tested within the present study. Its development will be based upon the developed pocket size SPM instrument by Professor W. Hecki of the Center for Crystallography and NanoScience (CeNS) at the Ludwig-Maximilians University (LMU) in Munich. Scanning probe microscopy (SPM) investigates surface structures at very high resolution and can perform nanoengineering. These techniques can be applied to non organic as well as to organic or biological materials.     

Sequence-specific and non-specific binding of the Rci protein to the asymmetric recombination sites of the R64 shufflon

Specific cleavages within the shufflon-specific recombination site of plasmid R64 were detected by primer extension when a DNA fragment carrying the recombination site was incubated with the shufflon-specific Rci recombinase. Rci-dependent cleavages occurred in the form of a 5' protruding 7 bp staggered cut, suggesting that DNA cleavage and rejoining in the shufflon system take place at these positions. As a result, shufflon crossover sites were designated as sfx sequences consisting of a central 7 bp spacer sequence, and left and right 12 bp arms. R64 sfx sequences are unique among various site-specific recombination sites, since only the spacer sequence and the right arm sequence are conserved among various R64 sfxs, whereas the left arm sequence is not conserved and is not related to the right arm sequence. From nuclease protection analyses, Rci protein was shown to bind to entire R64 and artificial sfx sequences, suggesting that one Rci molecule binds to the conserved sfx right arm in a sequence-specific manner and the second to the sfx left arm in a non-specific manner. The sfx left arm sequences as well as the right arm sequences were shown to determine affinity to Rci and subsequently inversion frequency. Asymmetry of the sfx sequence may be the reason why Rci protein acts only on the inverted sfx sequences.     

Histological and Transcriptomic Analysis of Adult Japanese Medaka Sampled Onboard the International Space Station

To understand how humans adapt to the space environment, many experiments can be conducted on astronauts as they work aboard the Space Shuttle or the International Space Station (ISS). We also need animal experiments that can apply to human models and help prevent or solve the health issues we face in space travel. The Japanese medaka (Oryzias latipes) is a suitable model fish for studying space adaptation as evidenced by adults of the species having mated successfully in space during 15 days of flight during the second International Microgravity Laboratory mission in 1994. The eggs laid by the fish developed normally and hatched as juveniles in space. In 2012, another space experiment (“Medaka Osteoclast”) was conducted. Six-week-old male and female Japanese medaka (Cab strain osteoblast transgenic fish) were maintained in the Aquatic Habitat system for two months in the ISS. Fish of the same strain and age were used as the ground controls. Six fish were fixed with paraformaldehyde or kept in RNA stabilization reagent (n = 4) and dissected for tissue sampling after being returned to the ground, so that several principal investigators working on the project could share samples. Histology indicated no significant changes except in the ovary. However, the RNA-seq analysis of 5345 genes from six tissues revealed highly tissue-specific space responsiveness after a two-month stay in the ISS. Similar responsiveness was observed among the brain and eye, ovary and testis, and the liver and intestine. Among these six tissues, the intestine showed the highest space response with 10 genes categorized as oxidation–reduction processes (gene ontogeny term GO:0055114), and the expression levels of choriogenin precursor genes were suppressed in the ovary. Eleven genes including klf9, klf13, odc1, hsp70 and hif3a were upregulated in more than four of the tissues examined, thus suggesting common immunoregulatory and stress responses during space adaptation.     

Electrically Stimulated Antagonist Muscle Contraction Increased Muscle Mass and Bone Mineral Density of One Astronaut - Initial Verification on the International Space Station

BackgroundMusculoskeletal atrophy is one of the major problems of extended periods of exposure to weightlessness such as on the International Space Station (ISS). We developed the Hybrid Training System (HTS) to maintain an astronaut’s musculoskeletal system using an electrically stimulated antagonist to resist the volitional contraction of the agonist instead of gravity. The present study assessed the system’s orbital operation capability and utility, as well as its preventative effect on an astronaut’s musculoskeletal atrophy.MethodsHTS was attached to the non-dominant arm of an astronaut staying on the ISS, and his dominant arm without HTS was established as the control (CTR). 10 sets of 10 reciprocal elbow curls were one training session, and 12 total sessions of training (3 times per week for 4 weeks) were performed. Pre and post flight ground based evaluations were performed by Biodex (muscle performance), MRI (muscle volume), and DXA (BMD, lean [muscle] mass, fat mass). Pre and post training inflight evaluations were performed by a hand held dynamometer (muscle force) and a measuring tape (upper arm circumference).ResultsThe experiment was completed on schedule, and HTS functioned well without problems. Isokinetic elbow extension torque (Nm) changed -19.4% in HTS, and -21.7% in CTR. Isokinetic elbow flexion torque changed -23.7% in HTS, and there was no change in CTR. Total Work (Joule) of elbow extension changed -8.3% in HTS, and +0.3% in CTR. For elbow flexion it changed -23.3% in HTS and -32.6% in CTR. Average Power (Watts) of elbow extension changed +22.1% in HTS and -8.0% in CTR. For elbow flexion it changed -6.5% in HTS and -4.8% in CTR. Triceps muscle volume according to MRI changed +11.7% and that of biceps was +2.1% using HTS, however -0.1% and -0.4% respectively for CTR. BMD changed +4.6% in the HTS arm and -1.2% for CTR. Lean (muscle) mass of the arm changed only +10.6% in HTS. Fat mass changed -12.6% in HTS and -6.4% in CTR.ConclusionsThese results showed the orbital operation capability and utility, and the preventive effect of HTS for an astronaut’s musculoskeletal atrophy. The initial flight data together with the ground data obtained so far will be utilized in the future planning of human space exploration.     

Sample preparation with an automated robotic workstation for organic acid analysis by gas chromatography-mass spectrometry

We attempted to automate sample preparation for analysis of organic acids by gas chromatography-mass spectrometry using a computer-controlled, automated robotic workstation that is integrated and connected to the gas chromatography-mass spectrometry (HP-5890/5971) system. Of the two methods developed, one employed solvent extraction, while the other utilized a silica, solid-phase extraction cartridge. Both automated methods were compared to a manual, solvent extraction procedure used routinely in our laboratory. Normal, spiked urine, and urine from patients with a variety of metabolic abnormalities were analyzed. The robotic workstation did not meet all our requirements for a rapid, reliable, laboratory device. Recoveries with the automated procedure were less than with the manual method, and some organic acids important in the diagnosis of inborn errors of metabolism were not detected. Additionally, the robotic device had mechanical and design problems that made it slower and less reliable than the manual procedure.     

Binding to tubulin of an allocolchicine spin probe: interaction with the essential SH groups and other active sites

EPR titration of tubulin with an allocolchicine spin probe showed more than one binding site: one high-affinity binding site (Kd = 8 microM), consistent with the Ki found for competition with colchicine, and one or more low-affinity site(s) (Kd higher than 50 microM). No disturbance of the EPR signal of the tubulin-bound allocolchicine spin probe could be observed at room temperature in the presence of other paramagnetic probes: Mn(II) for the binding site of Mg(II), Co(II) for the Zn(II) binding site and Cr(III)GTP for the binding site of the exchangeable GTP. Labelling of tubulin with both the allocolchicine and a SH-group spin probe also showed lack of interaction. The colchicine-binding site is thus sterically isolated from the binding sites for GTP, Mg(II), Zn(II) and the two essential SH-groups. In the tubulin-colchicin complex, all SH-groups could still be labelled with an excess of the SH-reagent, N-ethylmaleimide. Furthermore, colchicine binding was only minimally influenced by the blocking of the two essential SH-groups. However, the rate constant of the reaction of two equivalents of the SH-reagent, a maleimide spin probe, with the tubulin-colchicine complex was only 50% of the rate constant found with uncomplexed tubulin. As direct steric interaction of the essential SH-groups with the colchicine-binding site can be excluded, we can now definitively decide that binding of colchicine to tubulin induces a conformational change, which affects the accessibility of the most reactive SH-groups.     

Differential affinity and cooperativity functions of the amino-terminal 70 residues of lambda integrase

The site-specific recombinase (Int) of bacteriophage lambda is a heterobivalent DNA-binding protein that binds two different classes of DNA-binding sites within its recombination target sites. The several functions of Int are apportioned between a large carboxy-terminal domain that cleaves and ligates DNA at each of its four "core-type" DNA-binding sites and a small amino-terminal domain, whose primary function is binding to each of its five "arm-type" DNA sites, which are distant from the core region. Int bridges between the two classes of binding sites are facilitated by accessory DNA-bending proteins that along with Int comprise higher-order recombinogenic complexes. We show here that although the 64 amino-terminal residues of Int bind efficiently to a single arm site, this protein cannot form doubly bound complexes on adjacent arm sites. However, 1-70 Int does show the same cooperative binding to adjacent arm sites as the full length protein. We also found that 1-70 Int specifies cooperative interactions with the accessory protein Xis when the two are bound to their adjacent cognate sites P2 and X1, respectively. To complement the finding that these two amino-terminal domain functions (along with arm DNA binding) are all specified by residues 1-70, we determined that Thr75 is the first residue of the minimal carboxy-terminal domain, thereby identifying a specific interdomain linker region. We have measured the affinity constants for Int binding to each of the five arm sites and the cooperativity factors for Int binding to the two pairs of adjacent arm sites, and we have identified several DNA structural features that contribute to the observed patterns of Int binding to arm sites. Taken together, the results highlight several interesting features of arm DNA binding that invite speculation about additional levels of complexity in the regulation of lambda site-specific recombination.     

Toward a forest biomass reference measurement system for remote sensing applications

Forests contribute to climate change mitigation through carbon storage and uptake, but the extent to which this carbon pool varies in space and time is still poorly known. Several Earth Observation missions have been specifically designed to address this issue, for example, NASA's GEDI, NASA-ISRO's NISAR and ESA's BIOMASS. Yet, all these missions' products require independent and consistent validation. A permanent, global, in situ, site-based forest biomass reference measurement system relying on ground data of the highest possible quality is therefore needed. Here, we have assembled a list of almost 200 high-quality sites through an in-depth review of the literature and expert knowledge. In this study, we explore how representative these sites are in terms of their coverage of environmental conditions, geographical space and biomass-related forest structure, compared to those experienced by forests worldwide. This work also aims at identifying which sites are the most representative, and where to invest to improve the representativeness of the proposed system. We show that the environmental coverage of the system does not seem to improve after at least the 175 most representative sites are included, but geographical and structural coverages continue to improve as more sites are added. We highlight the areas of poor environmental, geographical, or structural coverage, including, but not limited to, Canada, the western half of the USA, Mexico, Patagonia, Angola, Zambia, eastern Russia, and tropical and subtropical highlands (e.g. in Colombia, the Himalayas, Borneo, Papua). For the proposed system to succeed, we stress that (1) data must be collected and processed applying the same standards across all countries and continents; (2) system establishment and management must be inclusive and equitable, with careful consideration of working conditions; and (3) training and site partner involvement in downstream activities should be mandatory.     

Mutational analysis of protein binding sites involved in formation of the bacteriophage lambda attL complex.

Bacteriophage lambda site-specific recombination requires the formation of higher-order protein-DNA complexes to accomplish synapsis of the partner attachment (att) sites as well as for the regulation of the integration and excision reactions. The att sites are composed of a core region, the actual site of strand exchange, and flanking arm regions. The attL site consists of two core sites (C and C'), an integration host factor (IHF) binding site (H'), and three contiguous Int binding arm sites (P'1, P'2, and P'3). In this study, we employed bacteriophage P22 challenge phages to determine which protein binding sites participate in attL complex formation in vivo. The C', H', and P'1 sites were critical, because mutations in these sites severely disrupted formation of the attL complex. Mutations in the C and P'2 sites were less severe, and alteration of the P'3 site had no effect on complex formation. These results support a model in which IHF, bound to the H' site, bends the attL DNA so that the Int molecule bound to P'1 also interacts with the C' core site. This bridged complex, along with a second Int molecule bound to P'2, helps to stabilize the interaction of a third Int with the C core site. The results also indicate that nonspecific DNA binding is a significant component of the Int-core interactions and that the cooperativity of Int binding can overcome the effects of mutations in the individual arm sites and core sites.     

Cleavage of a four-way DNA junction by a restriction enzyme spanning the point of strand exchange.

The four-way DNA junction is believed to fold in the presence of metal ions into an X-shaped structure, in which there is pairwise coaxial stacking of helical arms. A restriction enzyme MboII has been used to probe this structure. A junction was constructed containing a recognition site for MboII in one helical arm, positioned such that stacking of arms would result in cleavage in a neighbouring arm. Strong cleavage was observed, at the sites expected on the basis of coaxial stacking. An additional cleavage was seen corresponding to the formation of an alternative stacking isomer, suggesting that the two isomeric forms are in dynamic equilibrium in solution.     

Genetic analysis of the strong gyrase site (SGS) of bacteriophage Mu: localization of determinants required for promoting Mu replication

The Mu strong gyrase site (SGS), located in the centre of the Mu genome, is required for efficient Mu replication, as it promotes synapsis of the prophage termini. Other gyrase sites tested, even very strong ones, were unable to substitute for the SGS in Mu replication. To determine the features required for its unique properties, a deletion analysis was performed on the SGS. For this analysis, we defined the 20 bp centred on the midpoint of the 4 bp staggered cleavage made by gyrase to be the 'core' and the flanking sequences to be the 'arms'. The deletion analysis showed that (i) approximately 40 bp of the right arm is required, in addition to core sequences, for both efficient Mu replication and gyrase cleavage; and (ii) the left arm was not required for efficient Mu replication, although it was required for efficient gyrase cleavage. These observations implicated the right arm as the unique feature of the SGS. The second observation showed that strong gyrase cleavage and Mu replication could be dissociated and suggested that even weak gyrase sites, if supplied with the right arm of the SGS, could promote Mu replication. Hybrid sites were constructed with gyrase sites that could not support efficient Mu replication. The SGS right arm was used to replace one arm of the strong pSC101 gyrase site or the weaker pBR322 site. The pSC101 hybrid site allowed efficient Mu replication, whereas the pBR322 hybrid site allowed substantial, but reduced, replication. Hence, it appears that optimal Mu replication requires a central strong gyrase site with the properties imparted by the right arm sequences. Possible roles for the SGS right arm in Mu replication are addressed.     

Linkage of the evolutionarily-related serum albumin and alpha-fetoprotein genes within q11-22 of human chromosome 4

Albumin and alpha-fetoprotein are structurally related serum proteins, having a similar gene structure and, conceivably, a common evolutionary origin. To test their relative arrangement in the human genome, the serum albumin and alpha-fetoprotein genes were mapped by in situ hybridization of cloned human albumin or alpha-fetoprotein cDNA to human mitotic chromosome preparations. Analysis of cells hybridized with the serum albumin probe showed that 39% of cells exhibited grains on the proximal portion of the long arm of chromosome 4 (bands q11-22), with these grains comprising 30% of all labeled sites throughout these mitoses. Similarly, in cells hybridized with the alpha-fetoprotein probe, 39% of cells were observed to contain silver grains on 4q11-22, these grains constituting 20% of all labeled sites in these cells. These results demonstrate chromosomal localization and linkage of the serum albumin and alpha-fetoprotein genes within bands q11-22 of the long arm of human chromosome 4.