Morphological features of an endangered Japanese strain of Cyprinus carpio: reconstruction based on seven SNP markers.

Morphological analyses of 183 specimens of Japanese common carp Cyprinus carpio (171 from Lake Biwa and 12 from nursery ponds) using genetic hybrid indices demonstrated that the typical native Japanese strain of C. carpio has a more elongate body, more branched dorsal-fin rays, fewer and shorter gill rakers, more developed pneumatic bulb, more coiled pneumatic duct, longer posterior swimbladder and shorter intestine than the typical introduced C. carpio. These results provide a basis for a better understanding of the ecological characteristics and taxonomic status of the endangered Japanese strain of C. carpio.

Non-radiation risk factors for leukemia: A case-control study among chornobyl cleanup workers in Ukraine.

BACKGROUND: Occupational and environmental exposure to chemicals such as benzene has been linked to increased risk of leukemia. Cigarette smoking and alcohol consumption have also been found to affect leukemia risk. Previous analyses in a large cohort of Chornobyl clean-up workers in Ukraine found significant radiation-related increased risk for all leukemia types. We investigated the potential for additional effects of occupational and lifestyle factors on leukemia risk in this radiation-exposed cohort. METHODS: In a case-control study of chronic lymphocytic and other leukemias among Chornobyl cleanup workers, we collected data on a range of non-radiation exposures. We evaluated these and other potential risk factors in analyses adjusting for estimated bone marrow radiation dose. We calculated Odds Ratios and 95% Confidence Intervals in relation to lifestyle factors and occupational hazards. RESULTS: After adjusting for radiation, we found no clear association of leukemia risk with smoking or alcohol but identified a two-fold elevated risk for non-CLL leukemia with occupational exposure to petroleum (OR=2.28; 95% Confidence Interval 1.13, 6.79). Risks were particularly high for myeloid leukemias. No associations with risk factors other than radiation were found for chronic lymphocytic leukemia. CONCLUSIONS: These data - the first from a working population in Ukraine - add to evidence from several previous reports of excess leukemia morbidity in groups exposed environmentally or occupationally to petroleum or its products.

Iodine-131 dose-dependent gene expression: alterations in both normal and tumour thyroid tissues of post-Chernobyl thyroid cancers.

BACKGROUND: A strong, consistent association between childhood irradiation and subsequent thyroid cancer provides an excellent model for studying radiation carcinogenesis. METHODS: We evaluated gene expression in 63 paired RNA specimens from frozen normal and tumour thyroid tissues with individual iodine-131 (I-131) doses (0.008-8.6 Gy, no unirradiated controls) received from Chernobyl fallout during childhood (Ukrainian-American cohort). Approximately half of these randomly selected samples (32 tumour/normal tissue RNA specimens) were hybridised on 64 whole-genome microarrays (Agilent, 4 × 44 K). Associations between I-131 dose and gene expression were assessed separately in normal and tumour tissues using Kruskal-Wallis and linear trend tests. Of 155 genes significantly associated with I-131 after Bonferroni correction and with ≥2-fold increase per dose category, we selected 95 genes. On the remaining 31 RNA samples these genes were used for validation purposes using qRT-PCR. RESULTS: Expression of eight genes (ABCC3, C1orf9, C6orf62, FGFR1OP2, HEY2, NDOR1, STAT3, and UCP3) in normal tissue and six genes (ANKRD46, CD47, HNRNPH1, NDOR1, SCEL, and SERPINA1) in tumour tissue was significantly associated with I-131. PANTHER/DAVID pathway analyses demonstrated significant over-representation of genes coding for nucleic acid binding in normal and tumour tissues, and for p53, EGF, and FGF signalling pathways in tumour tissue. CONCLUSION: The multistep process of radiation carcinogenesis begins in histologically normal thyroid tissue and may involve dose-dependent gene expression changes.

Comparison of All Solid Cancer Mortality and Incidence Dose-Response in the Life Span Study of Atomic Bomb Survivors, 1958-2009.

Recent analysis of all solid cancer incidence (1958-2009) in the Life Span Study (LSS) revealed evidence of upward curvature in the radiation dose response among males but not females. Upward curvature in sex-averaged excess relative risk (ERR) for all solid cancer mortality (1950-2003) was also observed in the 0-2 Gy dose range. As reasons for non-linearity in the LSS are not completely understood, we conducted dose-response analyses for all solid cancer mortality and incidence applying similar methods [1958-2009 follow-up, DS02R1 doses, including subjects not-in-city (NIC) at the time of the bombing] and statistical models. Incident cancers were ascertained from Hiroshima and Nagasaki cancer registries, while cause of death was ascertained from death certificates throughout Japan. The study included 105,444 LSS subjects who were alive and not known to have cancer before January 1, 1958 (80,205 with dose estimates and 25,239 NIC subjects). Between 1958 and 2009, there were 3.1 million person-years (PY) and 22,538 solid cancers for incidence analysis and 3.8 million PY and 15,419 solid cancer deaths for mortality analysis. We fitted sex-specific ERR models adjusted for smoking to both types of data. Over the entire range of doses, solid cancer mortality dose-response exhibited a borderline significant upward curvature among males (P = 0.062) and significant upward curvature among females (P = 0.010); for solid cancer incidence, as before, we found a significant upward curvature among males (P = 0.001) but not among females (P = 0.624). The sex difference in magnitude of dose-response curvature was statistically significant for cancer incidence (P = 0.017) but not for cancer mortality (P = 0.781). The results of analyses in the 0-2 Gy range and restricted lower dose ranges generally supported inferences made about the sex-specific dose-response shape over the entire range of doses for each outcome. Patterns of sex-specific curvature by calendar period (1958-1987 vs. 1988-2009) and age at exposure (0-19 vs. 20-83) varied between mortality and incidence data, particularly among females, although for each outcome there was an indication of curvature among 0-19-year-old male survivors in both calendar periods and among 0-19-year-old female survivors in the recent period. Collectively, our findings indicate that the upward curvature in all solid cancer dose response in the LSS is neither specific to males nor to incidence data; its evidence appears to depend on the composition of sites comprising all solid cancer group and age at exposure or time. Further follow up and site-specific analyses of cancer mortality and incidence will be important to confirm the emerging trend in dose-response curvature among young survivors and unveil the contributing factors and sites.

THYROID SCREENING AND RELIABILITY OF RADIATION THYROID DOSES FOR THE BELARUSIAN IN UTERO COHORT.

OBJECTIVE: To describe the status and results of thyroid disease screening and assessment of reliability of radiationthyroid doses in the Belarusian in utero cohort of 2,965 individuals exposed to Chernobyl (Chornobyl) fallout. MATERIALS AND METHODS: Thyroid screening examinations are currently underway including thyroid palpation by anendocrinologist, ultrasonographic examination by an ultrasonographer and analysis of blood samples for diagnosisof hypo- and hyperthyroidism, autoimmune thyroiditis, thyroid function tests (thyroid-stimulating hormone [TSH],thyroxine [T4], thyroid peroxidase antibody [anti-TPO], and thyroglobulin antibodies [anti-TG]). Reliability of (i)information from 780 pairs of questionnaires obtained during the first and second interviews of the mothers and (ii)thyroid doses, which were calculated for the cohort members using this information, is evaluated. RESULTS: As of 15 August 2021, 1,267 in utero exposed study subjects had been screened. A single thyroid nodule wasdiagnosed in 167 persons (13.2 % of the total) and multiple thyroid nodules in 101 persons (8.0 %): 189 (14.9 %)persons had nodules detected for the first time at the screening while 79 (6.2 %) persons had nodules detected pre-viously (pre-screening nodules). Fifty-nine out of 268 subjects (22.0 %) with a suspicious thyroid nodule werereferred to fine needle aspiration biopsy, and among them 33 (55.9 %) were biopsied. Reasonable agreement wasobserved for modelqbased doses calculated for the Belarusian in utero cohort members using data from the two inter-views (Spearman's rank-correlation coefficient rs = 0.74, p < 0.001), while measurementqbased doses yielded almost per-fect agreement (rs = 0.99, p < 0.001). CONCLUSIONS: During the thyroid screening, at least one thyroid nodule was identified in 268 of 1,267 (21.2 %) inutero exposed cohort members. Seven thyroid cancer cases were identified in the cohort, including 5 pre-screeningcases and 2 cases detected during the screening. Ongoing research on this unique cohort will provide importantinformation on adverse health effects following prenatal and postnatal exposure to radioiodine and radiocesium iso-topes, for which available epidemiological data are scant.

Use of type-specific antimyosins to demonstrate the transformation of individual fibers in chronically stimulated rabbit fast muscles.

Continuous stimulation of a rabbit fast muscle at 10 Hz changes its physiological and biochemical parameters to those of a slow muscle. These transformations include the replacement of myosin of one type by myosin of another type. Two hypotheses could explain the cellular basis of these changes. First, if fibers were permanently programmed to be fast or slow, but not both, a change from one muscle type to another would involve atrophy of one fiber type accompanied by de novo appearance of the other type. Alternatively, preexisting muscle fibers could be changing from the expression of one set of genes to the expression of another. Fluorescein-labeled antibodies against fast (AF) and slow (AS) muscle myosins of rabbits have been prepared by procedures originally applied to chicken muscle. In the unstimulated fast peroneus longus muscle, most fibers stained only with AF; a small percentage stained only with AS; and no fibers stained with both antibodies. In stimulated muscles, most fibers stained with both AF and AS; with increasing time of stimulation, there was a progressive decrease in staining intensity with AF and a progressive increase in staining intensity with AS within the same fibers. These results are consistent with a theory that individual preexisting muscle fibers can actually switch from the synthesis of fast myosin to the synthesis of slow myosin.

Intracellular aggregation of polypeptides with expanded polyglutamine domain is stimulated by stress-activated kinase MEKK1.

Abnormal proteins, which escape chaperone-mediated refolding or proteasome-dependent degradation, aggregate and form inclusion bodies (IBs). In several neurodegenerative diseases, such IBs can be formed by proteins with expanded polyglutamine (polyQ) domains (e.g., huntingtin). This work studies the regulation of intracellular IB formation using an NH(2)-terminal fragment of huntingtin with expanded polyQ domain. We demonstrate that the active form of MEKK1, a protein kinase that regulates several stress-activated signaling cascades, stimulates formation of the IBs. This function of MEKK1 requires kinase activity, as the kinase-dead mutant of MEKK1 cannot stimulate this process. Exposure of cells to UV irradiation or cisplatin, both of which activate MEKK1, also augmented the formation of IBs. The polyQ-containing huntingtin fragment exists in cells in two distinct forms: (a) in a discrete soluble complex, and (b) in association with insoluble fraction. MEKK1 strongly stimulated recruitment of polyQ polypeptides into the particulate fraction. Notably, a large portion of the active form of MEKK1 was associated with the insoluble fraction, concentrating in discrete sites, and polyQ-containing IBs always colocalized with them. We suggest that MEKK1 is involved in a process of IB nucleation. MEKK1 also stimulated formation of IBs with two abnormal polypeptides lacking the polyQ domain, indicating that this kinase has a general effect on protein aggregation.

Behavioural and morphological differences between feral and domesticated strains of common carp Cyprinus carpio.

Morphological and behavioural traits of a feral strain of the common carp Cyprinus carpio from Lake Biwa in Japan were compared with those of two domesticated strains reared in Japan (one commercial strain and one ornamental koi). To compare genetically inherited traits, all fish were reared from eggs under similar environmental conditions. Using these fish, the following five traits were compared among the three strains: body shape, consumption rate of two types of free-swimming shrimp, medaka Oryzias latipes and bottom-dwelling chironomid larvae prey items, preference for a bottom habitat, feeding skills in detecting prey and escape response to predator attack. The feral strain of fish had more streamlined bodies, higher consumption rates for free-swimming prey, a greater preference for a bottom habitat, possessed greater skill in detecting prey and were more cautious of predator attacks, compared with the fish of the two domesticated strains. These characteristics shown by the feral fish are probably adaptive to the natural environment. A genetic analysis based on five nuclear single nucleotide polymorphism markers, however, suggested that the feral strain was relatively recently derived from domesticated stocks. Considering this, the present results appear to indicate the possibility that domesticated C. carpio could re-adapt to the wild environment during a short evolutionary period, although further research using more feral strains is required.

Mitochondrial DNA analysis reveals cryptic large-scale invasion of non-native genotypes of common carp (Cyprinus carpio) in Japan.

Wild common carp (Cyprinus carpio) are probably suffering from biological invasions of conspecific domesticated strains. However, such invasions may be largely camouflaged by morphological similarities between introduced and native strains. We conducted a large survey of mitochondrial DNA sequences (complete D-loop region) from 11 localities in Japan. From a total of 166 individuals, 28 haplotypes were determined to fit into six divergent clades. One of the six clades included 19 closely related haplotypes with moderate nucleotide differences; however, the remaining five clades each included either a single haplotype or two almost identical haplotypes. Phylogenetic analysis together with the previously published Eurasian haplotypes further demonstrated that the 'monotypic' clades were sisters to various Eurasian lineages, whereas the 19 related haplotypes formed a monophyletic group apart from the whole Eurasian clade. Given their monophyly and genetic diversity, the 19 related haplotypes were thought to originate from the Japanese native strain. Conversely, their phylogenetic affinities to Eurasian lineages and unnaturally low genetic diversities caused the haplotypes of the five monotypic clades to be considered as domesticated strains introduced from Eurasia. These hypotheses were supported by further evidences; i.e. the probable non-native haplotypes were frequently found from Japanese domesticated strains, and the probable native population structure was rescued when the probable non-native haplotypes were excluded from the analyses. This study revealed that almost half or more of the haplotypes in all of the locations studied originated from domesticated strains introduced from Eurasia.

Morphologic differences of the distal femur between Caucasian and Japanese women.

PURPOSE: To compare the morphology of the distal femur between Caucasian and Japanese women. METHODS: 30 Caucasian women aged 41 to 84 (mean, 67) years and 70 Japanese women aged 54 to 86 (mean, 70) years who underwent total knee arthroplasty for osteoarthritis were randomly selected. Morphologic measurements of the distal femur were compared using lateral radiographs. Both race and height influenced the morphology. To adjust for the influence of height on morphology, each measurement was divided by the patient's height and the ratios were compared. RESULTS: Caucasian women were generally taller and heavier (p<0.001) and had higher body mass index (p=0.03) than the Japanese women. Each morphologic measurement of the distal femur was significantly longer in the Caucasian women. In both groups, anteroposterior width of the condyle correlated more with height than weight. In women of equal height, the anteroposterior and metaphyseal widths of the femur and the anterior and resected condyles were longer in Caucasian women, but the posterior condyle was longer in Japanese women. CONCLUSION: Both the size of the femur and the anterior and posterior condyles are significantly larger in Caucasian than Japanese women.

Solid cancer incidence in atomic bomb survivors: 1958-1998.

This is the second general report on radiation effects on the incidence of solid cancers (cancers other than malignancies of the blood or blood-forming organs) among members of the Life Span Study (LSS) cohort of Hiroshima and Nagasaki atomic bomb survivors. The analyses were based on 17,448 first primary cancers (including non-melanoma skin cancer) diagnosed from 1958 through 1998 among 105,427 cohort members with individual dose estimates who were alive and not known to have had cancer prior to 1958. Radiation-associated relative risks and excess rates were considered for all solid cancers as a group, for 19 specific cancer sites or groups of sites, and for five histology groups. Poisson regression methods were used to investigate the magnitude of the radiation-associated risks, the shape of the dose response, how these risks vary with gender, age at exposure, and attained age, and the evidence for inter-site variation in the levels and patterns of the excess risk. For all solid cancers as a group, it was estimated that about 850 (about 11%) of the cases among cohort members with colon doses in excess of 0.005 Gy were associated with atomic bomb radiation exposure. The data were consistent with a linear dose response over the 0- to 2-Gy range, while there was some flattening of the dose response at higher doses. Furthermore, there is a statistically significant dose response when analyses were limited to cohort members with doses of 0.15 Gy or less. The excess risks for all solid cancers as a group and many individual sites exhibit significant variation with gender, attained age, and age at exposure. It was estimated that, at age 70 after exposure at age 30, solid cancer rates increase by about 35% per Gy (90% CI 28%; 43%) for men and 58% per Gy (43%; 69%) for women. For all solid cancers as a group, the excess relative risk (ERR per Gy) decreases by about 17% per decade increase in age at exposure (90% CI 7%; 25%) after allowing for attained-age effects, while the ERR decreased in proportion to attained age to the power 1.65 (90% CI 2.1; 1.2) after allowing for age at exposure. Despite the decline in the ERR with attained age, excess absolute rates appeared to increase throughout the study period, providing further evidence that radiation-associated increases in cancer rates persist throughout life regardless of age at exposure. For all solid cancers as a group, women had somewhat higher excess absolute rates than men (F:M ratio 1.4; 90% CI 1.1; 1.8), but this difference disappears when the analysis was restricted to non-gender-specific cancers. Significant radiation-associated increases in risk were seen for most sites, including oral cavity, esophagus, stomach, colon, liver, lung, non-melanoma skin, breast, ovary, bladder, nervous system and thyroid. Although there was no indication of a statistically significant dose response for cancers of the pancreas, prostate and kidney, the excess relative risks for these sites were also consistent with that for all solid cancers as a group. Dose-response estimates for cancers of the rectum, gallbladder and uterus were not statistically significant, and there were suggestions that the risks for these sites may be lower than those for all solid cancers combined. However, there was emerging evidence from the present data that exposure as a child may increase risks of cancer of the body of the uterus. Elevated risks were seen for all of the five broadly classified histological groups considered, including squamous cell carcinoma, adenocarcinoma, other epithelial cancers, sarcomas and other non-epithelial cancers. Although the data were limited, there was a significant radiation-associated increase in the risk of cancer occurring in adolescence and young adulthood. In view of the persisting increase in solid cancer risks, the LSS should continue to provide important new information on radiation exposure and solid cancer risks for at least another 15 to 20 years.

A new multi-electrode array design for chronic neural recording, with independent and automatic hydraulic positioning.

We report on a new microdrive design, which enables the construction of multi-electrode arrays capable of chronically recording the multi-unit neural activity of waking animals. Our principal motivation for inventing this device was to simplify the task of positioning electrodes, which consumes a considerable amount of time and requires a high level of skill. With the new microdrives, each electrode is independently and automatically driven into place. A hydraulic drive system is adopted to reduce the size, weight, and cost of the structure. The hydraulic fluid is also used as a part of the electrical circuit, and facilitates the wiring of the electrodes. A routing system has been attached to reduce the number of tube connections. The microdrive is cylindrical, has a diameter of 23.5 mm, a height of 37 mm, and a weight of 15 g. It allows for up to 22 electrodes, which are arranged on a 0.35 mm grid. Each electrode can be positioned at any depth up to approximately 4mm. The microdrive was evaluated under acute and chronic recording experiments, and is shown to be capable of automatically positioning each electrode and successfully recording the neural signals of waking rats.

Risk factors for male breast cancer.

To investigate risk factors in male breast cancer, a case-control study of 52 histologically diagnosed cases and 52 controls--matched for age, race, marital status, and hospital--was conducted in 5 U.S. metropolitan areas. Cases were significantly more likely to be Jewish than were the controls, supporting earlier suggestions of an increased risk in Jewish males. A significant association of male breast cancer with mumps infections at age 20 years or older, along with the possible association with antecedent testicular injury and the excess frequency of mumps orchitis among cases, suggests that testicular factors may be important in the development of breast cancer among males. An increased frequency of breast cancer among persons who have worked in blast furnaces, steel works, and rolling mills is of interest because of the possible testicular effect of high environmental temperatures. The observed association between breast cancer and a prior history of swollen breast is difficult to interpret because of potential recall bias, and a possible relationship with military service needs further confirmation.

Influence of death certificate errors on cancer mortality trends.

BACKGROUND: Evaluation of mortality data is an important tool in assessing both disease time trends and differences in populations. However, the reasons for changes in cancer mortality rates have been controversial. Questions have been raised concerning whether these increases are real or simply the result of changing diagnoses and death certificate reporting. PURPOSE: Our purpose was to determine on the basis of autopsy data if death certificate reporting varies over age, time, and cancer type and to explore the effect of death certificate error on recent cancer mortality trends. METHODS: Data were analyzed from 5886 autopsies collected by the Radiation Effects Research Foundation in Hiroshima, Japan, between 1961 and 1987. Death certificates were linked to autopsy data for analyses. An adjustment factor was calculated as a ratio of the accuracy of these death certificates in identifying cancer (detection rate) and listing cancer (confirmation rate) as the cause of death. This adjustment factor measures bias in mortality rates due to death certification errors and quantifies underestimation and overestimation of cancer mortality rates. RESULTS: Our analyses focused on lymphoma, breast cancer, neoplasms of the brain, multiple myeloma, and melanoma because of reported mortality increases. For these cancers, the adjustment factor decreased significantly (P = .02) over time, implying that death certificate accuracy has improved. This change appears to account for 60% of the observed increase in these cancers during the time period of study. For total cancer, persons 75 years or older have a high adjustment factor but it decreased over time. This decrease suggests an artifactual increase in total cancer mortality rates of about 1% per year for this older group. CONCLUSIONS: The quality of death certificate reporting has generally remained constant for most groups during the period 1961-1987. In the study population, there was a consistent underestimation of total cancer mortality of about 18%. For the five types of cancer studied, there has been less underestimation of cancer mortality since 1976. For some specific cancers and for persons 75 years or older, improvements in death certificate accuracy have occurred over time. These data imply that the total death certificate error rate varies considerably by cancer type, time period, and age at death. IMPLICATIONS: The changes in death certificate reporting for some sites and the elderly appear to have artifactually created increases in cancer mortality rates. These artifacts need to be considered when using mortality data for prevention research and health care planning.

Expression in insect cells and characterization of the 110 kDa anchoring subunit of myosin light chain phosphatase.

The major myosin light chain phosphatase is composed of three subunits with apparent molecular masses of 130, 38 and 20 kDa, corresponding to the myosin-binding, catalytic and a regulatory subunit of unknown function, respectively. In this work, we have amplified the cDNA coding for each of the three subunits by the polymerase chain reaction, and expressed the 130 kDa subunit in insect cells using the baculovirus expression system. Limited chymotrypsin digestion show that the folding of the expressed protein is similar to that in the native holoenzyme. N-Terminal sequencing reveals that our recombinant protein is authentic. Mass spectrometry shows that the expressed protein is full length. The recombinant protein is capable of binding myosin based on the ELISA assay and myosin affinity chromatography. Finally, rotary shadowing electron microscopy reveals an elongated structure with three globular domains connected by flexible strands. These results pave the way for future biochemical, structural and site-directed mutagenesis studies on the myosin light chain phosphatase. We also found that the cDNA of the 20 kDa subunit may code for a smaller protein with a molecular mass of 18.5 kDa.

Parylene flexible neural probes integrated with microfluidic channels.

The fluidic channel in the flexible probe has three functions: (i) to inject chemicals into the tissues, (ii) to measure the neural activities from the tissues, and (iii) to improve the mechanical stiffness of the probe by filling the channel with a solid material. A 10-microm-thick microfluidic channel was embedded into the probe by using sacrificial photoresist patterns. Polyethylene glycol (PEG), which is solid at room temperature and dissolves when in contact with water, was used to fill the channel and increase the stiffness of the probe before insertion into the tissue. The impedance of the electrode inside the fluidic channel was around 100 kOmega at 1 kHz when the channel was filled with saline solution. We were able to insert the probe into a rat's brain and measure the neural signals with the electrode.

Isoforms of the small non-catalytic subunit of smooth muscle myosin light chain phosphatase.

Chicken gizzard smooth muscle myosin light chain phosphatase is composed of a approximately 37 kDa catalytic subunit, a approximately 110 kDa myosin binding or targeting subunit and a approximately 20 kDa subunit (MPs) whose function is as yet undefined. It was reported previously that a cloned chicken gizzard MPs cDNA encodes a protein of 186 amino acids (aa) [Y.H. Chen, M.X. Chen, D.R. Alessi, D.G. Gampbell, C. Shanahan, P. Cohen, P.T.W. Cohen, FEBS Lett. 356 (1994) 51-55]. More recently, we obtained by PCR amplification another MPs cDNA that encodes a protein of only 161 aa [Y. Zhang, K. Mabuchi, T. Tao, Biochim. Biophys. Acta 1343 (1997) 51-58]. In this work we obtained cDNAs corresponding to both sequences using a different set of PCR primers, indicating that the two sequences correspond to isoforms that most likely arose from alternative splicing of the same gene. Using two polyclonal antibodies, one raised against the recombinant 161 aa isoform of chicken gizzard MPs and the other against a C-terminal polypeptide that is present only in the 186 aa isoform, we found that while the 161 aa isoform is the predominant one in chicken gizzard, in chicken aorta it is the 186 aa one; in chicken stomach both isoforms are present, and in mammalian tissues such as ferret and rat only the 186 aa isoform is detected. Furthermore, we purified the MPs associated with the chicken gizzard myosin light chain phosphatase holoenzyme and determined its molecular weight, amino acid composition and six residues of its C-terminal sequence. The results from these analyses showed conclusively that the predominant isoform in chicken gizzard is the 161 aa one.

Unfolding domains and tryptophan accessibility of a 59 kDa coiled-coil light meromyosin.

Light meromyosin (LMM 77), the C-terminal proteolytic peptide from myosin rod, is a 900 A coiled-coil that contains two pairs of tryptophan residues in d-positions of the heptad repeat (abcdefg)n. Previous studies showed that LMM 77 unfolded in two transitions and suggested that both Trp pairs were located in the least stable unfolding domain. Here, the thermal and denaturant unfolding properties of LMM 59, a recombinant N-terminal truncated LMM, containing only one of the Trp pairs, was compared to LMM 77. LMM 59 unfolded in two transitions with similar midpoints to the two transitions of LMM 77. However, only the second transition of LMM 59 affected the Trp fluorescence, indicating that the two pairs of Trp residues in LMM 77 are in different unfolding domains. Disulfide-crosslinked LMM 59 verified this assignment. Solute-quenching studies showed that the accessibility of the Trp in LMM 59 decreased only by 56% on forming filaments. Electron micrographs indicated that all of LMM 59 is located within the core of a bipolar tactoid with the Trp-containing region the most accessible to negative strain, in agreement with the solute-quenching studies. This suggests that part of the core of the myosin thick filament is appreciably exposed to solvent.

Incidence of haematopoietic malignancies in US radiologic technologists.

BACKGROUND: There are limited data on risks of haematopoietic malignancies associated with protracted low-to-moderate dose radiation. AIMS: To contribute the first incidence risk estimates for haematopoietic malignancies in relation to work history, procedures, practices, and protective measures in a large population of mostly female medical radiation workers. METHODS: The investigators followed up 71,894 (77.9% female) US radiologic technologists, first certified during 1926-80, from completion of a baseline questionnaire (1983-89) to return of a second questionnaire (1994-98), diagnosis of a first cancer, death, or 31 August 1998 (731,306 person-years), whichever occurred first. Cox proportional hazards regression was used to compute risks. RESULTS: Relative risks (RR) for leukaemias other than chronic lymphocytic leukaemia (non-CLL, 41 cases) were increased among technologists working five or more years before 1950 (RR = 6.6, 95% CI 1.0 to 41.9, based on seven cases) or holding patients 50 or more times for x ray examination (RR = 2.6, 95% CI 1.3 to 5.4). Risks of non-CLL leukaemias were not significantly related to the number of years subjects worked in more recent periods, the year or age first worked, the total years worked, specific procedures or equipment used, or personal radiotherapy. Working as a radiologic technologist was not significantly linked with risk of multiple myeloma (28 cases), non-Hodgkin's lymphoma (118 cases), Hodgkin's lymphoma (31 cases), or chronic lymphocytic leukaemia (23 cases). CONCLUSION: Similar to results for single acute dose and fractionated high dose radiation exposures, there was increased risk for non-CLL leukaemias decades after initial protracted radiation exposure that likely cumulated to low-to-moderate doses.

Non-thyroid cancer in Northern Ukraine in the post-Chernobyl period: Short report.

The Chernobyl nuclear power plant accident in Ukraine in 1986 led to widespread radioactive releases into the environment - primarily of radioiodines and cesium - heavily affecting the northern portions of the country, with settlement-averaged thyroid doses estimated to range from 10 mGy to more than 10 Gy. The increased risk of thyroid cancer among exposed children and adolescents is well established but the impact of radioactive contamination on the risk of other types of cancer is much less certain. To provide data on a public health issue of major importance, we have analyzed the incidence of non-thyroid cancers during the post-Chernobyl period in a well-defined cohort of 13,203 individuals who were <18 years of age at the time of the accident. The report is based on standardized incidence ratio (SIR) analysis of 43 non-thyroid cancers identified through linkage with the National Cancer Registry of Ukraine for the period 1998 through 2009. We compared the observed and expected number of cases in three cancer groupings: all solid cancers excluding thyroid, leukemia, and lymphoma. Our analyses found no evidence of a statistically significant elevation in cancer risks in this cohort exposed at radiosensitive ages, although the cancer trends, particularly for leukemia (SIR=1.92, 95% confidence interval: 0.69; 4.13), should continue to be monitored.