[Developmental profile of urine bile acids in preterm infants].
To investigate a developmental profile of urinary 1 beta-hydroxylated cholic acid of preterm infants, a urinary 1 beta-hydroxylated cholic acid/total bile acid ration (%) was measured in 118 preterm infants using Gas Chromatography- Mass Spectrometry (GC-MS). Following results were obtained: (1) The mean value of urinary 1 beta-hydroxylated cholic acid/total bile acid ratio (%) increased rapidly from birth to 0 weeks of corrected postnatal age (Expected date of confinement was denoted as day 0), and decreased thereafter. Thus the mean ratio (%) at week 0 was approximately 50%, and it became less than 10% at week 40. (2) The earlier the gestational weeks of preterm infants at birth were, the smaller the ratio (%) was. (3) The developmental profile of the urinary 1 beta-hydroxylated cholic acid/total bile acid ratio (%) from birth to 110 weeks of corrected postnatal age had almost the same pattern regardless of gestational weeks at birth, weight at birth and whether it was small-for-gestational-age (SGA) or appropriate-for-gestational-age (AGA) in preterm infants. (4) The developmental profile of the urinary 1 beta-hydroxylated cholic acid/total bile acid ratio (%) from birth to 110 weeks of corrected postnatal age had a similar pattern between males and females, although the mean ratios at -13, -10, -5, 0, 20, 60 and 80 weeks of corrected postnatal age of the female group tended to be consistently higher than those of the male group in preterm infants. Based on these results, a possible application of the present analysis in diagnosing hepato-biliary disorders is being investigated.


High-resolution spectroscopy of induced chiral dimers: a study of the dimers of ethanol by Fourier transform microwave spectroscopy.
We present the first recording of the high-resolution spectrum of an induced chiral dimer. Three conformers of the induced chiral dimers of ethanol have been observed using a pulsed molecular-beam Fourier transform microwave spectrometer. The rotational constants of the normal isotopomers of the three species have been determined to be (a) A=5113.826(5), B=1329.7214(4), and C=1257.5151(3) MHz, (b) A=5086.459(5), B=1316.6508(4), and C=1243.6329(4) MHz, and (c) A=4851.608(5), B=1369.7558(6), and C=1243.4184(4) MHz. The observed species have been assigned to calculated structures via Kraitchman double substitution analyses and ab initio calculations. The Kraitchman analyses and the fitted centrifugal distortion parameters suggest that the deuterium bond is significantly stronger than the hydrogen bond in the dimers of ethanol.


Regular participation in leisure time activities and high cardiovascular fitness improve motor sequence learning in older adults.
Older adults show higher interindividual performance variability during the learning of new motor sequences than younger adults. It is largely unknown what factors contribute to this variability. This study aimed to, first, characterize age differences in motor sequence learning and, second, examine influencing factors for interindividual performance differences. 30 young adults (age M = 21.89, SD = 2.08, 20 female) and 29 older adults (age M = 69.55, SD = 3.03, 18 female) participated in the study. Motor sequence learning was assessed with a discrete sequence production (DSP) task, requiring key presses to a sequence of visual stimuli. Three DSP practice phases (á 8 blocks × 16 sequences, two six-element sequences) and two transfer blocks (new untrained sequences) were performed. Older participants conducted the Mini-Mental Status Examination and a visuospatial working-memory task. All participants finished a questionnaire on everyday leisure activities and a cardiovascular fitness test. Performance speed increased with practice in both groups, but young improved more than older adults (significant Group × Time effect for response time, F(1,5) = 4.353, p = 0.004, [Formula: see text] = 0.071). Accuracy did not change in any age group (non-significant Group × Time effect for error rates, F(1,5) = 2.130, p = 0.091, [Formula: see text] = 0.036). Older adults revealed lower transfer costs for performance speed (significant Time × Group effect, e.g., simple sequence, F(1,2) = 10.511, p = 0.002, [Formula: see text] = 0.156). High participation in leisure time activities (β = - 0.58, p = 0.010, R2 = 0.45) and high cardiovascular fitness (β = - 0.49, p = 0.011, R2 = 0.45) predicted successful motor sequence learning in older adults. Results confirmed impaired motor learning in older adults. Younger adults seem to show a better implicit knowledge of the practiced sequences compared to older adults. Regular participation in leisure time activities and cardiovascular fitness seem to prevent age-related decline and to facilitate motor sequence performance and motor sequence learning in older adults.


Innate and adaptive immune response to apoptotic cells.
The immune system is constantly exposed to dying cells, most of which arise during central tolerance and from effete circulating immune cells. Under homeostatic conditions, phagocytes (predominantly macrophages and dendritic cells) belonging to the innate immune system, rapidly ingest cells and their debris. Apoptotic cell removal requires recognition of altered self on the apoptotic membrane, a process which is facilitated by natural antibodies and serum opsonins. Recognition, may be site and context specific. Uptake and ingestion of apoptotic cells promotes an immunosuppressive environment that avoids inflammatory responses to self-antigens. However, it does not preclude a T cell response and it is likely that constant exposure to self-antigen, particularly by immature dendritic cells, leads to T cell tolerance. Tolerance occurs by several different mechanisms including anergy and deletion (for CD8+T cells) and induction of T regulatory cells (for CD4+T cells). Failed apoptotic cell clearance promotes immune responses to self-antigens, especially when the cellular contents are leaked from the cell (necrosis). Inflammatory responses may be induced by nucleic acid stimulation of Toll like receptors and other immune sensors, specific intracellular proteins and non-protein (uric acid) stimulation of inflammasomes.


A complication of myocardial infarction usually requiring surgical intervention.
Rupture of the interventricular septum is uncommon (2%), but a very serious complication of an acute myocardial infarction. The septum receives most of its blood supply from the left anterior descending artery and from the posterior descending branch of the right coronary artery. Perforation of the septum occurs in patients with significant disease of both coronary arteries. The prognosis of this complication with medical therapy is poor. There is an 80% mortality rate in the first few days after septal perforation if surgical repair is not attempted. Early diagnosis of ventricular septal rupture complicating an acute myocardial infarction is possible if physical findings are carefully evaluated at frequent intervals. Acute mitral valve pathology and right ventricular infarction can be ruled out by performing right ventricular catheterization to determine intracardiac pressures and oxygen saturations. The echocardiogram is an additional aid in the differential diagnosis.


CALVARIAL OSTEOSARCOMA WITH CEREBRAL COMPRESSION IN A FREE-RANGING POWERFUL OWL (NINOX STRENUA).
A free-ranging powerful owl (Ninox strenua) presented in a dull state with extensive bruising of the skin overlying the skull, due to suspected trauma. Supportive care was provided, which resulted in the return to a normal state, although intermittent subtle neurologic abnormalities remained. One month from original presentation, intermittent episodes of head turning and a possible seizure were noted, but behavior and appetite were otherwise normal. The owl was referred to Taronga Wildlife Hospital for evaluation. On presentation, the owl exhibited severe neurologic abnormalities, prompting euthanasia. At necropsy the dorsum of the skull exhibited marked osseous proliferation, extending ventrally and compressing the cerebrum. The skull was radiographed and submitted for histopathology. A diagnosis of osteoblastic osteosarcoma was made. This is the first report of a calvarial osteosarcoma in a powerful owl.


The Estonian study of Chernobyl cleanup workers: II. Incidence of cancer and mortality.
A cohort of 4,742 men from Estonia who had participated in the cleanup activities in the Chernobyl area sometime between 1986 and 1991 and were followed through 1993 was analyzed with respect to the incidence of cancer and mortality. Incidence and mortality in the cleanup workers were assessed relative to national rates. No increases were found in all cancers (25 incident cases compared to 26.5 expected) or in leukemia (no cases observed, 1.0 expected). Incidence did not differ statistically significantly from expectation for any individual cancer site or type, though lung cancer and non-Hodgkin's lymphoma both occurred slightly more often than expected. A total of 144 deaths were observed [standardized mortality ratio (SMR) = 0.98; 95% confidence interval (CI) = 0.82-1.14] during an average of 6.5 years of follow-up. Twenty-eight deaths (19.4%) were suicides (SMR = 1.52; 95% CI = 1.01-2.19). Exposure to ionizing radiation while at Chernobyl has not caused a detectable increase in the incidence of cancer among cleanup workers from Estonia. At least for the short follow-up period, diseases directly attributable to radiation appear to be of relatively minor importance when compared with the substantial excess of deaths due to suicide.


Materials with Hierarchical Porosity Enhance the Stability of Infused Ionic Liquid Films.
Defined surface functionalities can control the properties of a material. The layer-by-layer method is an experimentally simple yet very versatile method to coat a surface with nanoscale precision. The method is widely used to either control the chemical properties of the surface via the introduction of functional moieties bound to the polymer or create nanoscale surface topographies if one polymeric species is replaced by a colloidal dispersion. Such roughness can enhance the stability of a liquid film on top of the surface by capillary adhesion. Here, we investigate whether a similar effect allows an increased retention of liquid films within a porous surface and thus potentially increases the stability of ionic liquid films infused within a porous matrix in the supported ionic liquid-phase catalysis. The complex geometry of the porous material, long diffusion pathways, and small sizes of necks connecting individual pores all contribute to difficulties to reliably coat the required porous materials. We optimize the coating process to ensure uniform surface functionalization via two steps. Diffusion limitations are overcome by force-wetting the pores, which transports the functional species convectively into the materials. Electrostatic repulsion, which can limit pore accessibility, is mitigated by the addition of electrolytes to screen charges. We introduce nanoscale topography in microscale porous SiC monoliths to enhance the retention of an ionic liquid film. We use γ-Al2O3 to coat monoliths and test the retention of 1-butyl-2,3-dimethylimidazolium chloride under exposure to a continuous gas stream, a setup commonly used in the water-gas shift reaction. Our study showcases that a hierarchical topography can improve the stability of impregnated ionic liquid films, with a potential advantage of improved supported ionic liquid-phase catalysis.


Effect of mitochondrial DNA transmitted cytoplasmically from nontumorigenic to tumorigenic rat cells on the phenotypic expression of tumorigenicity.
The effect of mitochondrial DNA (mtDNA) on the phenotypic expression of tumorigenicity was examined by its cytoplasmic transmission from nontumorigenic cells to tumorigenic cells. Enucleated cells of the rat embryonic cell line 3Y1CAP, which are nontumorigenic and resistant to chloramphenicol, were fused with whole cells of the rat glioma C6BU-1 line, which are tumorigenic and resistant to 5-bromodeoxyuridine, and the cybrid colonies growing in selective medium with 5-bromodeoxyuridine (30 micrograms/ml) and chloramphenicol (50 micrograms/ml) were isolated clonally. Cytoplasmic transmission of 3Y1CAP mtDNA to C6BU-1 cells was confirmed by quantitative analysis of their mtDNA with restriction endonuclease. Subclones containing various amounts of mtDNA from 3Y1CAP cells were isolated from one cybrid clone, Y22, and their tumorigenicities were examined by inoculating 2 X 10(6) cells s.c. into nude mice. The tumorigenicities of these cybrid cubclones were almost identical to that of the nuclear donor C6BU-1 cells with respect to the tumor incidence (number of animals bearing tumors per number of animals inoculated), latent period, and growth rates of tumors. Moreover, analysis of chromosomes and mtDNAs of the cells recovered from the tumors obtained showed that the tumors were derived from the cells inoculated and that no selective overgrowth of segregants that had lost mtDNA from 3Y1CAP cells occurred in the nude mice. These observations suggest that expression of tumorigenicity of C6BU-1 cells was not suppressed by cytoplasmic transmission of nontumorigenic 3Y1CAP mtDNA.


The Regional Hydrologic Extremes Assessment System: A software framework for hydrologic modeling and data assimilation.
The Regional Hydrologic Extremes Assessment System (RHEAS) is a prototype software framework for hydrologic modeling and data assimilation that automates the deployment of water resources nowcasting and forecasting applications. A spatially-enabled database is a key component of the software that can ingest a suite of satellite and model datasets while facilitating the interfacing with Geographic Information System (GIS) applications. The datasets ingested are obtained from numerous space-borne sensors and represent multiple components of the water cycle. The object-oriented design of the software allows for modularity and extensibility, showcased here with the coupling of the core hydrologic model with a crop growth model. RHEAS can exploit multi-threading to scale with increasing number of processors, while the database allows delivery of data products and associated uncertainty through a variety of GIS platforms. A set of three example implementations of RHEAS in the United States and Kenya are described to demonstrate the different features of the system in real-world applications.


[Chronic fatigue syndrome].
The Chronic Fatigue Syndrome is a disease that originates in the 18th Century of unknown etiology. The chronic fatigue is a common complain with an estimate prevalence of 24%. In 1988 the Chronic Fatigue Syndrome was define by the experts due to an increase in the recognition of the disease. Is a disease that possess similar characteristics to other conditions for which the diagnosis is one of exclusion. Cases has been reported around the world been most common in women between 20-50 years of age. The treatment is mostly supportive.


Dust and biological aerosols from the Sahara and Asia influence precipitation in the western U.S.
Winter storms in California's Sierra Nevada increase seasonal snowpack and provide critical water resources and hydropower for the state. Thus, the mechanisms influencing precipitation in this region have been the subject of research for decades. Previous studies suggest Asian dust enhances cloud ice and precipitation, whereas few studies consider biological aerosols as an important global source of ice nuclei (IN). Here, we show that dust and biological aerosols transported from as far as the Sahara were present in glaciated high-altitude clouds coincident with elevated IN concentrations and ice-induced precipitation. This study presents the first direct cloud and precipitation measurements showing that Saharan and Asian dust and biological aerosols probably serve as IN and play an important role in orographic precipitation processes over the western United States.


Functional phenotype and its correlation with therapeutic response and inflammatory type of bronchoalveolar lavage fluid in feline lower airway disease.
Currently, functional assessment to monitor therapeutic response in feline lower airway disease (FLAD) has limited application. To evaluate if expiratory indices derived from pseudo-tidal breathing flow-volume loop (pTBFVL) representing lower airway obstruction would decrease after clinical improvement and to investigate the correlation between functional phenotype and inflammatory cell type in bronchoalveolar lavage (BAL) fluid. Nineteen client-owned cats with FLAD. Prospective observational study. Functional assessment with pTBFVL indices (eg, peak to mid-expiratory flow; PEF/EF50) and conventional barometric whole body plethysmography (BWBP) parameters (eg, enhanced pause) was carried out before receiving treatment. BAL was performed to analyze inflammatory cell types. Signs were assessed by scoring. The cats were treated with glucocorticoids daily and functional testing was repeated. Loop indices PEF/EF50 and PEF/EF25 were significantly decreased after treatment (P < .001). Conventional BWBP parameters were not significantly different before and after treatment. Cats with PEF/EF50 > 1.51 before treatment had a significantly higher granulocyte (eosinophil plus neutrophil) percentage in BAL fluid (P = .014). Granulocyte percentage in BAL fluid was strongly correlated with PEF/EF25 (P = .001, rs = 0.74) and moderately correlated with PEF/EF50 (P = .022, rs = 0.57), whereas eosinophil or neutrophil percentage alone had no significant correlation with functional parameters. Functional parameters including PEF/EF50 and PEF/EF25 can be used for monitoring therapeutic response. The presence of airflow limitation during mid- to late expiration is affected by the overall extent of granulocyte infiltration.


Cyclosporine blood levels--an evaluation of radioimmunoassay with selective monoclonal or polyclonal antibodies and high-performance liquid chromatography in liver transplant recipients.
Cyclosporine blood levels were measured in 225 blood samples taken 14 days to 3 years after transplantation from 8 adult and 7 pediatric liver graft recipients. Results by high-performance liquid chromatography, radioimmunoassay with a polyclonal antibody (PARIA) or with a selective monoclonal antibody (MARIA) were compared in the context of major clinical events and alterations in serum bilirubin, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, urea, and creatinine. Cyclosporine blood levels by MARIA were significantly higher than HPLC values, but only by mean values of 11 micrograms/L in adult and 20 micrograms/L in pediatric patients. These differences were unaffected by alterations in liver or renal function and seem unlikely to affect clinical management. Minimum PARIA:HPLC ratios of 2-4 were noted in patients with good graft function, with higher ratios (up to 18) associated with hepatic dysfunction. Multiple regression analysis demonstrated that elevations in serum bilirubin and alkaline phosphatase significantly contributed toward the correlation with raised PARIA:HPLC ratios in adults and that gamma-glutamyl transpeptidase and aspartate aminotransferase were additionally important in children. There was no significant contribution from either serum urea or creatinine levels to raised PARIA:HPLC ratios, but in children a positive correlation existed between these indicators of renal function and trough cyclosporine concentrations determined by selective methods (HPLC and MARIA).


Molecular measurement of minimal residual disease in Philadelphia-positive acute lymphoblastic leukaemia.
The Philadelphia chromosome (Ph) is found in approximately 5-25% of acute lymphoblastic leukaemia (ALL) cases and is the harbinger of a poor outcome. Polymerase chain reaction (PCR) assays can detect leukaemia-specific genetic lesions down to a sensitivity approaching one leukaemia cell in a background of a million normal cells. In Ph(+) ALL, the unique BCR-ABL translocation is thus a specific target for the detection of minimal residual disease (MRD). After chemotherapy or transplantation the detection of residual BCR-ABL transcripts is associated with a high risk of subsequent relapse. With the advent of novel therapeutics that target the structure and function of BCR-ABL, the detection of MRD may allow for targeted therapy that could abort a potential relapse.


Characterization of H(+)-ATPase activity in plasma membrane from pea seedlings under altered gravity.
The specific properties and characteristics of the H+-ATPase, lipid and fatty acids content and composition in plasma membrane vesicles isolated from pea seedlings grown under clinorotation (2 rev/min) and stationary conditions were studied.


High mobility group chromosomal proteins isolated from muclei and cytosol of cultured hepatoma cells are similar.
Using sequential chromatography on columns containing immobilized double-stranded DNA and single-stranded DNA, we have purified a protein from the cytosol of an established line of cultured rat hepatoma cells that, by several criteria, is a high mobility group (HMG) protein. Analyses of DNA binding properties, electrophoretic mobilities, amino acid compositions, and immunochemical reactivities reveal that the cytosolic protein is the same protein as HMG-1 isolated from the purified chromatin of the same cell line. Thus, authentic HMG-1 appears to be at least partially responsible for the cytoplasmic fluorescence observed when mammalian cells are stained with fluorescece observed when mammalian cells are stained with fluorescent-labeled, affinity-purified antibodies against HMG-1 [Bustin, M., & Neihart, N.K. (1979) Cell 16, 181-189]. We suggest that HMG-1 cn shuttle between nucleus and cytoplasm, perhaps in response to the nucleus' need for helix destabilizing proteins.


Female sex and burden of depressive symptoms predict insufficient response to telemedical treatment in adult attention-deficit/hyperactivity disorder: results from a naturalistic patient cohort during the COVID-19 pandemic.
Attention-deficit/hyperactivity disorder (ADHD) is a chronic neuropsychiatric disorder, that typically manifests itself during childhood and persists in a majority of the affected individuals into adulthood, negatively affecting physical and mental health. Previous studies have shown detrimental effects of the COVID-19 pandemic on mental health in individuals with ADHD. Thus, telemedicine could be a useful tool for optimizing treatment-outcomes in adult ADHD by improving treatment adherence and persistence. However, data on telemedical treatment outcomes in adult patients with ADHD is scarce. We report here the sub-cohort analysis of a naturalistic cohort of adult patients (N = 254) recruited between April 2020-April 2021, comparing the effects of telemedical treatment on participants either clinically diagnosed with depression (N = 54) or ADHD (N = 67). Participants were asked to fill out the WHO-5 repetitively during >12 weeks of telemedical treatment. Furthermore scores of WHO-5, SCL-90R and BDI-II, psychopathology, psychosocial functioning, sociodemographic data, medical records and a feedback survey were analyzed for both groups and compared. Participants with ADHD were further stratified according to the development of well-being during the study period in order to identify factors associated with a satisfactory treatment outcome. Participants with depression reported a significant improvement of well-being during the course of the study, while no such effect could be seen in participants with ADHD on a group level. Despite the good outcome, participants with depression were more severely affected at baseline, with significantly worse psychopathology and a more precarious labor and financial situation. A detailed analysis of ADHD participants without clinical improvement revealed significantly higher BDI-II scores than for ADHD participants with a satisfactory outcome (p = 0.03, Mann-Whitney-U-Test), suggesting successful treatment was hampered by the combination of ADHD and depressive symptoms. Furthermore, female sex among ADHD patients was correlated with an unfavorable treatment outcome during the course of the study (p = 0.001, Spearman correlation) as well as living with children (p = 0.02, Spearman correlation). Besides screening for depressive symptoms before telemedical treatment, future research should address the specific needs of female ADHD patients as these patients may be at a particularly high risk of being overburdened with family work.


Wegener's granulomatosis and autoantibodies to neutrophil antigens.
We report five cases of Wegener's granulomatosis all of whom had clinical and histological evidence of disease activity at presentation and in whom autoantibodies to neutrophil antigens were detected. This test may prove useful for the diagnosis of this serious condition and help to monitor disease activity during treatment.


COMPARATIVE HYGIENIC ASSESSMENT OF THE POTENTIAL DIQUAT HAZARD TO THE POPULATION WHEN CONSUMING AGRICULTURAL CROPS TREATED WITH THE REGLONE AIR 200 SL FORMULATION USING DIFFERENT APPLICATION TECHNOLOGIES (UAV, AERIAL, HIGH-CLEARANCE ROD SPRAYER TREATMENT).
The aim: Assessment of the hazard to the population when consuming treated crops by using different technologies. Materials and methods: Unmanned aerial vehicle XAG XPlanet 2020 equipped with four rotating rotors, which allows to keep in the air a 20-liter tank was used for spraying field; a manned aircraft AN-2 aggregated with a serial sprayer. High-clearance rod treatment of sunflower and rapeseed crops was carried out by using a PLA MAP II 2010 tractor. Results: When the herbicide was applied by aerial application with UAV, the initial content of diquat dibromide in treated rapeseed and sunflower plants on the day of treatment was significantly higher than in the soil under crops (р≤0.05). The analysis of the diquat content dynamics in sunflower also showed a similar behavior of the a.i. in the plant after processing by another application methods: UAV, aerial and high-clearance rod treatment. The integral index of hazard when using pesticide-contaminated products (IIHPCPC) = ADD+С+ DT50 = 4+1+1 = 6 points. That is why, diquat dibromide can be classified according to this index can be classified as compound of 3rd hazard class. Conclusions: As a result of the conducted researches, it was established that the content of diquat in rapeseed and sunflower samples grown with the Reglone Air 200 SL application (after treatment and before harvesting) was below the maximum residue levels in those crops. There are no statistically significant differences in the behavior of diquat dibromide when applying by different methods of application (UAV, aerial, high-clearance rod treatment) in different agro-climatic zones of Ukraine.


Knockdown of CXCL5 inhibits the invasion, metastasis and stemness of bladder cancer lung metastatic cells by downregulating CD44.
In our previous studies, we found that T24 lung metastatic cancer cells showed high invasion and metastasis abilities and cancer stem cell characteristics compared with T24 primary cancer cells. By screening for the expression of CXC chemokines in both cell lines, we found that CXCL5 is highly expressed in T24-L cells. The aim of this study is to shed light on the relationship of CXCL5 with epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs). RNAi technology was used to decrease CXCL5 expression in the T24-L cell line, and the EMT and CSCs of the shCXCL5 group and the control group were compared. The CXCR2 inhibitor SB225002 was used to inhibit the receptor of CXCL5 to determine the effect of the CXCL5/CXCR2 axis. The knockdown of CXCL5 expression in T24-L cells reduced their EMT and CSC characteristics. RT-PCR and Western blot analyses revealed the downregulation of N-cadherin, Vimentin and CD44. In addition, when CD44 expression was knocked down, the EMT ability of the cells was also inhibited. This phenomenon was most pronounced when both CXCL5 and CD44 were knocked down. CXCL5 and CD44 can affect the EMT and stem cell capacity of T24-L cells through some interaction.


Population dynamics of diploid and hexaploid populations of a perennial herb.
Despite the recent enormous increase in the number of studies on polyploid species, no studies to date have explored the population dynamics of these taxa. It is thus not known whether the commonly reported differences in single life-history traits between taxa of different ploidy levels result in differences in population dynamics. This study explores differences in single life-history traits and in the complete life cycle between populations of different ploidy levels and compares these differences with differences observed between different habitat types and years. Diploid and hexaploid populations of a perennial herb, Aster amellus, are used as the study system. Transition matrix models were used to describe the dynamics of the populations, and population growth rates, elasticity values and life-table response experiments were used to compare the dynamics between populations and years. The results indicate that between-year variation in population dynamics is much larger than variation between different ploidy levels and different habitat conditions. Significant differences exist, however, in the structure of the transition matrices, indicating that the dynamics of the different ploidy levels are different. Strong differences in probability of extinction of local populations were also found, with hexaploid populations having higher probability than diploid populations, indicating strong potential differences in persistence of these populations. This is the first study on complete population dynamics of plants of different ploidy levels. This knowledge will help to understand the ability of new ploidy levels to spread into new areas and persist there, and the interactions of different ploidy levels in secondary contact zones. This knowledge will also contribute to understanding of interactions of different ploidy levels with other plant species or other interacting organisms such as pollinators or herbivores.


Human abdominal aortic aneurysms. Immunophenotypic analysis suggesting an immune-mediated response.
Cellular immunity may play a role in the pathogenesis of atherosclerosis. In this report the potential role of these cells in the formation of abdominal aortic aneurysms by immunohistochemistry was investigated. Aortic tissues from 32 patients were examined: 4 normal aortas, 6 aortas with occlusive atherosclerotic disease, 17 abdominal aortic aneurysms, and 5 inflammatory abdominal aneurysms. Using monoclonal anti-CD3 (T cells), anti-CD19 (B cells), anti-CD11c (macrophages), anti-CD4 (T helper cells), and anti-CD8 (T suppressor cells), several distinctions among these groups were found. The amount of inflammatory cell infiltrate was as follows: inflammatory aneurysms more than abdominal aortic aneurysms more than occlusive aortas more than normal aortas. CD3-positive T lymphocytes rarely were found in the adventitia of normal or occlusive aortas. In contrast, abdominal aortic aneurysms and inflammatory aneurysms exhibited most of the CD3-positive infiltrates in the adventitia. CD19-positive B lymphocytes were present mainly in the adventitia of all pathologic tissues. The CD4-positive:CD8-positive ratio was greater in abdominal aortic aneurysms and inflammatory aneurysms than in the other groups, both in the adventitia and in the media of the aortas. CD11c-positive macrophages were present throughout the diseased tissues, often surrounded by lymphoid aggregates; the greatest numbers of macrophages were found in the inflammatory aneurysm group. Our data suggests that the aneurysmal disease may progress from occlusive disease and is accompanied by an increase in chronic inflammatory cells as well as a redistribution of these cell types. Therefore it is suggested that aneurysmal disease may represent an immune-mediated event.


[Molecular cloning, expression and characterization of the clones encoding soluble TF mutants].
Tissue factor (TF) plays an important role in the pathogenesis of atherosclerotic, sepsis and disseminated intravascular coagulation (DIC). TF pathway is therefore an attractive therapeutic target in a number of disease states. Here two TF mutants were developed and named MCsTF and MFsTF, in which the amino acids of active sites were mutated. Both of them were expressed in E.coli and used to inhibit TF pathway through competitive FVII/VIIa binding with TF. The results indicated that rMCsTF almost lost all activities of FX activation and procoagulation, and rMFsTF lost 90% activity. The specific catalytic constant ( k ( cat )/ K (m)) of FX activation by the complex formed by FVIIa with rMCsTF or rMFsTF were 2.0% and 3.7%, respectively, compared to that of rsTF. The inhibition effects of the mutants were studied in vitro, and it appeared that the prothrombin time were prolonged in a dose-dependent manner. Therefore, these mutants of TF may become new kind of specific inhibitors of TF pathway, as a promising drug for the treatment of patients with over-expression of TF.


Deletion of MBD2 inhibits proliferation of chronic myeloid leukaemia blast phase cells.
Aberrant methylation of tumour suppressor genes is associated with the progression to a blast crisis in chronic myeloid leukaemia (CML). Methyl-CpG-binding domain protein 2 (MBD2) has been studied as a "reader" of DNA methylation in many cancers, but its role in CML is unclear. We constructed cell models of a homozygous deletion mutation of MBD2 using gene-editing technology in K562 cells and BV173 cells. Here, we demonstrated that the deletion of MBD2 inhibited cell proliferation capacity in vitro. MBD2 deletion also significantly inhibited K562 cell proliferation in a xenograft tumour model in vivo. Additionally, the JAK2/STAT3 signalling pathway, which is abnormally active in CML, was inhibited by MBD2 deletion, and MBD2 deletion could up-regulate the expression of SHP1. In conclusion, our findings suggest that MBD2 is a candidate therapeutic strategy for the CML blast phase.


Characterization of singlet oxygen-accumulating mutants isolated in a screen for altered oxidative stress response in Chlamydomonas reinhardtii.
When photosynthetic organisms are exposed to harsh environmental conditions such as high light intensities or cold stress, the production of reactive oxygen species like singlet oxygen is stimulated in the chloroplast. In Chlamydomonas reinhardtii singlet oxygen was shown to act as a specific signal inducing the expression of the nuclear glutathione peroxidase gene GPXH/GPX5 during high light stress, but little is known about the cellular mechanisms involved in this response. To investigate components affecting singlet oxygen signaling in C. reinhardtii, a mutant screen was performed. Mutants with altered GPXH response were isolated from UV-mutagenized cells containing a GPXH-arylsulfatase reporter gene construct. Out of 5500 clones tested, no mutant deficient in GPXH induction was isolated, whereas several clones showed constitutive high GPXH expression under normal light conditions. Many of these GPXH overexpressor (gox) mutants exhibited higher resistance to oxidative stress conditions whereas others were sensitive to high light intensities. Interestingly, most gox mutants produced increased singlet oxygen levels correlating with high GPXH expression. Furthermore, different patterns of altered photoprotective parameters like non-photochemical quenching, carotenoid contents and α-tocopherol levels were detected in the various gox mutants. Screening for mutants with altered GPXH expression resulted in the isolation of many gox mutants with increased singlet oxygen production, showing the relevance of controlling the production of this ROS in photosynthetic organisms. Phenotypic characterization of these gox mutants indicated that the mutations might lead to either stimulated triplet chlorophyll and singlet oxygen formation or reduced detoxification of singlet oxygen in the chloroplast. Furthermore, changes in multiple protection mechanisms might be responsible for high singlet oxygen formation and GPXH expression, which could either result from mutations in multiple loci or in a single gene encoding for a global regulator of cellular photoprotection mechanisms.


Intraocular Foreign Bodies: Clinical Characteristics and Factors Affecting Visual Outcome.
To investigate the clinical characteristics and factors affecting visual outcome in patients with intraocular foreign bodies (IOFBs) and determine the risk factors for the development of endophthalmitis. Study Design. A retrospective case-series study design was adopted. In total, 242 patients (242 eyes) who were hospitalized and underwent surgical treatment for IOFB at the Second Hospital of Hebei Medical University between January 1, 2008, and December 31, 2019, were included. The demographic data, cause of injury, characteristics of IOFBs, postinjury ocular manifestations, and surgical details of the subjects were collected, and the factors affecting visual outcome and endophthalmitis development were analyzed. The most common cause of IOFBs was the propulsion of foreign bodies into the eye due to hammering (149 cases, 61.57%), followed by foreign body penetration (57 cases, 23.55%). Most of the subjects were young adult men who sustained injuries in the work environment. Poorer visual outcomes were found in subjects with initial presenting symptoms visual acuity (PVA) < 0.1, largest IOFB diameter ≥ 3 mm, IOFBs located in the posterior segment, wound length > 5 mm, entrance wound length larger than the largest IOFB diameter, concomitant retinal detachment, concomitant vitreous hemorrhage, concomitant endophthalmitis, and concomitant proliferative vitreoretinopathy (PVR). Factors related to the development of endophthalmitis included lens capsule rupture, time of stage 1 repair surgery ≥ 24 h after trauma, removal of IOFBs ≥ 24 h after trauma, and nonadministration of intravitreal antibiotic injection. Among patients with IOFBs, initial PVA < 0.1, entrance wound length larger than the largest IOFB diameter, concomitant endophthalmitis, and concomitant PVR were risk factors for poor visual outcomes. Lens capsule rupture was a risk factor for endophthalmitis development, and the administration of intravitreal antibiotic injection was a protective factor against endophthalmitis development.


Functional signaling biases in G protein-coupled receptors: Game Theory and receptor dynamics.
Pharmacotherapeutic targeting of G protein-coupled receptors (GPCRs) is perhaps the most important field of drug design, as agents designed to control these receptors constitute more than half of the pharmacopeia. Initially GPCRs were considered to be unitary entities, possessing all of their potential functionality in their characteristic heptahelical core. Early models of the functional activity of GPCRs considered them to possess just a simple 'on' or 'off' status. Recent research however has allowed us to realize that GPCR functionality is dependent upon many other proteins outside of the heptahelical core, on the site of GPCR expression in a tissue or a microdomain in a cell, and, most importantly, on the formation of differential 'active' states preferentially coupled to specific signal transduction structures. The recognition of such signaling diversity has facilitated the ability to appreciate and identify ligands for GPCRs that demonstrate a bias towards one signaling form of a receptor to another. However while potentially increasing our ability for selective signal targeting, our approach to understanding the physiological ramifications of systemic signaling manipulation is underdeveloped. This explosion in the complexity of GPCR signaling is now becoming familiar territory to receptor biologists, yet the application of this knowledge to drug design is relatively limited. This review will attempt to outline potential pitfalls and unseen benefits of using signaling bias in therapeutic design as well as highlighting new applications such as Game Theory for uncovering new therapeutic applications for biased agonists.


Desynchronized wave patterns in synchronized chaotic regions of coupled map lattices.
We analyze the size limits of coupled map lattices with diffusive coupling at the crossover of low-dimensional to high-dimensional chaos. We investigate the existence of standing-wave-type periodic patterns, within the low-dimensional limit, in addition to the stable synchronous chaotic states depending upon the initial conditions. Further, we bring out a controlling mechanism to explain the emergence of standing-wave patterns in the coupled map lattices. Finally, we give an analytic expression in terms of the unstable periodic orbits of the isolated map to represent the standing-wave patterns.


Capsaicin Inhibited Aggressive Phenotypes through Downregulation of Tumor-Associated NADH Oxidase (tNOX) by POU Domain Transcription Factor POU3F2.
Capsaicin has been reported to preferentially inhibit the activity of tumor-associated NADH oxidase (tNOX), which belongs to a family of growth-related plasma membrane hydroquinone oxidases in cancer/transformed cells. The inhibitory effect of capsaicin on tNOX is associated with cell growth attenuation and apoptosis. However, no previous study has examined the transcriptional regulation of tNOX protein expression. Bioinformatic analysis has indicated that the tNOX promoter sequence harbors a binding motif for POU3F2, which is thought to play important roles in neuronal differentiation, melanocytes growth/differentiation and tumorigenesis. In this study, we found that capsaicin-mediated tNOX downregulation and cell migration inhibition were through POU3F2. The protein expression levels of POU3F2 and tNOX are positively correlated, and that overexpression of POU3F2 (and the corresponding upregulation of tNOX) enhanced the proliferation, migration and invasion in AGS (human gastric carcinoma) cells. In contrast, knockdown of POU3F2 downregulates tNOX, and the cancer phenotypes are affected. These findings not only shed light on the molecular mechanism of the anticancer properties of capsaicin, but also the transcription regulation of tNOX expression that may potentially explain how POU3F2 is associated with tumorigenesis.


Collectively Encoded Rydberg Qubit.
We demonstrate a collectively encoded qubit based on a single Rydberg excitation stored in an ensemble of N entangled atoms. Qubit rotations are performed by applying microwave fields that drive excitations between Rydberg states. Coherent readout is performed by mapping the excitation into a single photon. Ramsey interferometry is used to probe the coherence of the qubit, as well as to test the robustness to external perturbations. We show that qubit coherence is preserved even as we lose atoms from the polariton mode, preserving Ramsey fringe visibility. We show that dephasing due to electric field noise scales as the fourth power of field amplitude. These results show that robust quantum information processing can be achieved via collective encoding using Rydberg polaritons, and hence this system could provide an attractive alternative coding strategy for quantum computation and networking.


Requirement of apelin-apelin receptor system for oxidative stress-linked atherosclerosis.
The recently identified endogenous peptide apelin and its specific apelin receptor (APJ) are currently being considered as potential regulators in vascular tissue. Previously, we reported apelin mediates phosphorylation of myosin light chain and elicits vasoconstriction in vascular smooth muscle. In this study, physiological roles of the apelin-APJ system were investigated on atherosclerosis. In APJ and apolipoprotein E double-knockout (APJ(-/-)ApoE(-/-)) mice fed a high-cholesterol diet, atherosclerotic lesions were dramatically reduced when compared with APJ(+/+) ApoE(-/-) mice, in the absence of an effect of cholesterol levels. Immunohistochemical detection of smooth muscle cells, using a smooth muscle alpha-actin antibody, showed greatly reduced staining for these cells in lesions of APJ(-/-)ApoE(-/-) mice fed a high-cholesterol diet. Vascular production of superoxide radicals and the expression of nicotinamide-adenine dinucleotide phosphate oxidase subunits were decreased in APJ(-/-)ApoE(-/-) mice compared with APJ(+/+)ApoE(-/-) mice fed a standard normal diet. In vascular smooth muscle cells, apelin induced nicotinamide-adenine dinucleotide phosphate oxidase subunit expression. Apelin also induced vascular smooth muscle cell proliferation, which was inhibited by superoxide dismutase or diphenylene iodonium. The apelin-APJ system is a mediator of oxidative stress in vascular tissue, and thus we propose it to be a critical factor in atherogenesis under high-cholesterol dietary conditions. APJ deficiency is preventative against oxidative stress-linked atherosclerosis.


The Near Future of Vitrification of Oocytes and Embryos: Looking into Past Experience and Planning into the Future.
Currently vitrification is the method of choice for low-temperature preservation of oocytes and embryos. However, that was not the case until about 10 years ago when freezing methods were used relatively successfully for embryos and investigated (unsuccessfully) for oocyte preservation. In this paper we will review the history of oocyte and embryo cryopreservation and look into ways and methods for overcoming and improving the vitrification method since it suffers from inherent disadvantages since it is a cumbersome, time-consuming and costly procedure.


Respiratory impairment in crustaceans and molluscs due to exposure to heavy metals.
1. We have assessed, using current literature, the respiratory consequences of water-borne heavy metal exposure in crustaceans and molluscs. 2. We suggest that in lethal and sub-lethal concentrations the essential metals Cu and Zn act on the respiratory system primarily by disrupting gill function which results in the development of internal hypoxia, although reparation can be accomplished even at "high" sub-lethal concentrations. 3. The more toxic xenobiotes such as Hg (and perhaps to a lesser extent Cd) may interfere with the respiratory system at every level of organisation including cellular respiration itself.


DDX52 knockdown inhibits the growth of prostate cancer cells by regulating c-Myc signaling.
DDX52 is a type of DEAD/H box RNA helicase that was identified as a novel prostate cancer (PCa) genetic locus and possible causal gene in a European large-scale transcriptome-wide association study. However, the functions of DDX52 in PCa remain undetermined. The c-Myc oncogene plays a crucial role in the development of PCa, but the factors that regulate the activity of c-Myc in PCa are still unknown. We determined DDX52 protein levels in PCa tissues using immunohistochemistry (IHC). DDX52 expression and survival outcomes in other PCa cohorts were examined using bioinformatics analysis. The inhibition of DDX52 via RNA interference with shRNA was used to clarify the effects of DDX52 on PCa cell growth in vitro and in vivo. Gene set enrichment analysis and RNA sequencing were used to explore the signaling regulated by DDX52 in PCa. Western blotting and IHC were used to determine the possible DDX52 signaling mechanism in PCa. DDX52 expression was upregulated in PCa tissues. Bioinformatics analysis showed that the level of DDX52 further increased in advanced PCa, with a high DDX52 level indicating a poor outcome. In vitro and in vivo experiments showed that downregulating DDX52 impeded the growth of PCa cells. High DDX52 levels contributed to activating c-Myc signaling in PCa patients and PCa cells. Furthermore, DDX52 expression was regulated by c-Myc and positively correlated with c-Myc expression in PCa. DDX52 was overexpressed in PCa tissues in contrast to normal prostate tissues. DDX52 knockdown repressed the growth of PCa cells in vitro and in vivo. Deleting c-Myc inhibited DDX52 expression, which affected the activation of c-Myc signaling.


Patient autonomy and disclosure of material information about hospital-acquired infections.
Hospital-acquired infections are nowadays a major health care problem worldwide. The morbidity and mortality associated with them are highest in intensive care units, but their effects are identifiable in virtually any medical department. Information about hospital-acquired infections, especially about their preventive measures, are rarely presented nowadays in a correct fashion to patients. This article aims to present, in a structured manner, the theoretical and practical aspects related to disclosure of hospital-acquired infections-related information to patients and its importance in preventing their spread. We will analyze both the conceptual framework for disclosing medical information related to nosocomial infections (autonomy, veracity, social justice, the principle of double effect, the precautionary principle, and nonmaleficence) and the practicalities regarding the disclosure of proper information to patients.


Flowable glass ionomer cement as a liner: improving marginal adaptation of atraumatic restorative treatment restorations.
The present study aims to evaluate the in vitro microleakage of two layers GIC proximal restorations in primary molars. Forty primary molars received proximal cavity preparations and were randomly divided in two groups. G1 was restored with a regular powder/liquid ratio GIC. G2 firstly received a flowable layer of GIC and secondly a regular GIC layer. After 24h water storage (37 degrees C), the teeth were made impermeable with the exception of the restoration area and 1 mm of their surrounding, immersed in 0.5% methylene blue solution (4h), rinsed and sectioned mesio-distally. One side was polished and analyzed under light microscope. Replicates from the other side were observed under SEM. Microleakage evaluation was carried out by 3 evaluators. The data analysis (Mann-Whitney) showed a significant (P<0.01) better result for G2. Regarding the SEM evaluation, irregularities were observed in the G1 at the tooth/GIC interface. For G2, it was not possible to observe any displacement of the GIC in relation to the tooth structure, which confirmed better adaptation as seen in the microleakage test. the insertion of a flowable GIC layer in proximal cavities before the insertion of a regular GIC layer improves the material adaptation to the tooth.


Nitrate-dependent activation of the Dif signaling pathway of Myxococcus xanthus mediated by a NarX-DifA interspecies chimera.
Myxococcus xanthus fibril exopolysaccharide (EPS), essential for the social gliding motility and development of this bacterium, is regulated by the Dif chemotaxis-like pathway. DifA, an MCP homolog, is proposed to mediate signal input to the Dif pathway. However, DifA lacks a prominent periplasmic domain, which in classical chemoreceptors is responsible for signal perception and for initiating transmembrane signaling. To investigate the signaling properties of DifA, we constructed a NarX-DifA (NafA) chimera from the sensory module of Escherichia coli NarX and the signaling module of M. xanthus DifA. We report here the first functional chimeric signal transducer constructed using genes from organisms in two different phylogenetic subdivisions. When expressed in M. xanthus, NafA restored fruiting body formation, EPS production, and S-motility to difA mutants in the presence of nitrate. Studies with various double mutants indicate that NafA requires the downstream Dif proteins to function. We propose that signal inputs to the Dif pathway and transmembrane signaling by DifA are essential for the regulation of EPS production in M. xanthus. Despite the apparent structural differences, DifA appears to share similar transmembrane signaling mechanisms with enteric sensor kinases and chemoreceptors.


Orbital hypotelorism. An isolated autosomal dominant trait.
Four patients from three consecutive generations of a family with ocular hypotelorism are described. Radiographs document a subnormal distance between the medial orbital walls. To our knowledge, this is the first report of heritable isolated orbital hypotelorism. The pedigree is consistent with an autosomal dominant disorder.


[Examination of the density of the brain parenchyma in different dog breeds using quantitative computed tomography].
In the present study quantitative computed tomography was used to analyze the absorption density in different localisations of the brain parenchyma comparatively in five different dog breeds. The breeds German Shepherd Dog, Dachshund, Boxer, Labrador Retriever and Miniature Poodle were chosen as representatives of different skull shapes and sizes. The mean absorption density for the German Shepherd Dog was 35.8 HU in the cerebellum, 28.5 - 34.8 HU in several locations of the cerebrum, 39.6 HU in the brain stem and 40.8 HU in the hypophyseal region. In the Dachshund, the mean density was 33.8 HU (cerebellum), 34.3 - 44.2 HU (several locations of the cerebrum), 33.3 HU (brain stem) and 38.6 HU (hypophyseal region). The Boxer showed a mean density of 38.7 HU in the cerebellum, 30.2 - 40.8 HU in several locations of the cerebrum, 35.6 HU in the brain stem and 33.1 HU in the hypophyseal region. The mean absorption density in the Labrador Retriever was 37.2 HU in the cerebellum, 29.4 - 32.9 HU (several locations of the cerebrum), 34.7 HU in the brain stem and 47.5 HU in the hypophyseal region. In the Miniature Poodle the mean density was 33.6 HU (cerebellum), 34.9 - 45.5 HU (several locations of the cerebrum), 32.7 HU (brain stem) and 32.4 HU (hypophyseal region). The study showed that the absorption density of the cerebrum, the brain stem and of the hypophyseal region partly were influenced by the different dog breeds. In the cerebellum no difference of density could be seen in the different breeds. The standardised values for the data of absorption densities of the brain parenchyma are the base for further examinations of dogs with clinical CNS diseases.


Pulmonary immune cells in health and disease: mast cells and basophils.
Mast cells and basophils are multifunctional immune cells and have been implicated in the pathogenesis of asthma and other pulmonary diseases. Although they are derived from distinct lineages, they share a number of important features which justifies discussing them collectively. This review covers the cellular characteristics and biological properties of both cell types, including origin, maturation and differentiation, morphological and phenotypical properties, as well as their capacity to secrete preformed and newly generated mediators of inflammation. In addition, the mechanisms of cell activation and priming of mast cells and basophils will be outlined, as well as the putative mechanisms through which both cell types communicate with other inflammatory cells. The final section of the review focuses on the possible pathogenetic role of mast cells and basophils in several pulmonary diseases, such as parasitic infections, allergic diseases, pulmonary fibrosis and malignant disorders.


[Personal exposure to ELF magnetic fields in workers engaged in various occupations].
Using personal dosimeters worn during two complete work-shifts, we measured occupational exposure to Extremely Low Frequency-Magnetic Fields (ELF-MF) in 290 workers employed in 56 jobs, representative of the main occupational activities in the area of Modena and Reggio Emilia (Italy). Environmental nonoccupational exposure was also monitored. In the whole sample, the mean Time-Weighted Average (TWA) exposure during work resulted 0.59 microT (SD 3.2), while the median was 0.13 microT. Exposure was lower than 1 microT in more than 90% of the workers. In one job only exposure was greater than 1 microT (job-related median TWA); in other 8 exposure was between 1 and 0.4 microT, while about 84% of the jobs presented a median TWA lower than 0.4 microT. A high variability among workers engaged in the same job resulted in various occupational tasks. Non-occupational exposure was lower than 0.4 microT in more than 98% of the examined workers. Our results show a low to moderate occupational exposure to ELF-MF in the greatest part of the workers and working activities. Also the non-occupational exposure resulted low in the large majority of the subjects. The high variability observed among workers engaged in some occupations may represent a problem in exposure evaluation. Personal monitoring is particularly useful in such a situations.


Salivaricin A2 and the novel lantibiotic salivaricin B are encoded at adjacent loci on a 190-kilobase transmissible megaplasmid in the oral probiotic strain Streptococcus salivarius K12.
The commercial probiotic Streptococcus salivarius strain K12 is the prototype of those S. salivarius strains that are the most strongly inhibitory in a standardized test of streptococcal bacteriocin production and has been shown to produce the 2,368-Da salivaricin A2 (SalA2) and the 2,740-Da salivaricin B (SboB) lantibiotics. The previously uncharacterized SboB belongs to the type AII class of lantibiotic bacteriocins and is encoded by an eight-gene cluster. The genetic loci encoding SalA2 and SboB in strain K12 have been fully characterized and are localized to nearly adjacent sites on pSsal-K12, a 190-kb megaplasmid. Of 61 strongly inhibitory strains of S. salivarius, 19 (31%) were positive for the sboB structural gene. All but one (strain NR) of these 19 strains were also positive for salA2, and in each of these cases of double positivity, the two loci were separated by fewer than 10 kb. This is the first report of a single streptococcus strain producing two distinct lantibiotics.


Microbially mediated fossil concretions and their characterization by the latest methodologies: a review.
The study of well-preserved organic matter (OM) within mineral concretions has provided key insights into depositional and environmental conditions in deep time. Concretions of varied compositions, including carbonate, phosphate, and iron-based minerals, have been found to host exceptionally preserved fossils. Organic geochemical characterization of concretion-encapsulated OM promises valuable new information of fossil preservation, paleoenvironments, and even direct taxonomic information to further illuminate the evolutionary dynamics of our planet and its biota. Full exploitation of this largely untapped geochemical archive, however, requires a sophisticated understanding of the prevalence, formation controls and OM sequestration properties of mineral concretions. Past research has led to the proposal of different models of concretion formation and OM preservation. Nevertheless, the formation mechanisms and controls on OM preservation in concretions remain poorly understood. Here we provide a detailed review of the main types of concretions and formation pathways with a focus on the role of microbes and their metabolic activities. In addition, we provide a comprehensive account of organic geochemical, and complimentary inorganic geochemical, morphological, microbial and paleontological, analytical methods, including recent advancements, relevant to the characterization of concretions and sequestered OM. The application and outcome of several early organic geochemical studies of concretion-impregnated OM are included to demonstrate how this underexploited geo-biological record can provide new insights into the Earth's evolutionary record. This paper also attempts to shed light on the current status of this research and major challenges that lie ahead in the further application of geo-paleo-microbial and organic geochemical research of concretions and their host fossils. Recent efforts to bridge the knowledge and communication gaps in this multidisciplinary research area are also discussed, with particular emphasis on research with significance for interpreting the molecular record in extraordinarily preserved fossils.


Recovery from post-earthquake psychological morbidity: who suffers and who recovers?
We sought to identify the psychosocial characteristics of high earthquake exposure subjects that were associated with the development of post-disaster morbidity and with recovery. Data reported are from 515 participants in a longitudinal study of the psychosocial effects of the 1989 Newcastle (Australia) earthquake. Subjects were allocated to three subgroups (low morbidity; recovered; and persistent morbidity) on the basis of their Impact of Event Scale scores across the four phases of the study. Differences between these subgroups were examined on a broad range of variables. Several background, dispositional, coping style and exposure-related factors characterised those who developed psychological morbidity, only a small subset of which differentiated between those who recovered and those with persistent morbidity. Post-earthquake morbidity persists longer in those who are older, have a history of emotional problems, have higher neuroticism, use more neurotic defenses, and report higher levels of post-disaster life events.


Clinical diagnosis and detection of genetic mutations of pancreatic metastases: A report of four cases and review of the literature.
The present study aimed to report our clinical experience regarding the diagnosis and detection of genetic mutations of pancreatic metastases, and to review the relevant literature to expand knowledge of this disease. A total of 4 cases involving pancreatic metastases, which were treated at The First Affiliated Hospital of Soochow University between January 2013 and July 2016, were retrospectively analyzed. This retrospective study considered the clinicopathological variables of the 4 patients, and compared this data with those from the literature, which was searched using PubMed, EMBASE and the Cochrane Library. All 4 patients with pancreatic metastases were diagnosed by computed tomography (CT) scan and confirmed by pathological staining and immunohistochemistry. Mutation analysis was performed in 3 patients to obtain precise mutation information for guiding and evaluating the use of molecularly targeted drugs. In summary, pancreatic metastases are rare and the majority of pancreatic metastases develop from renal cell carcinoma. Diagnoses of pancreatic metastases predominantly rely on CT, pathology and immunohistochemistry. Detection of mutations has clinical value in auxiliary diagnosis and therapy of pancreatic metastases. Based on mutation information, molecularly targeted drugs may prolong the survival of patients with unresectable pancreatic metastases.


The insulin gene region and susceptibility to insulin-dependent diabetes mellitus in four races; new insights from Afro-Caribbean race-specific haplotypes.
The IDDM2 component of the genetic susceptibility to insulin-dependent diabetes mellitus (IDDM) has been mapped to chromosome 11p15.5. The exact identity of IDDM2 remains uncertain. It has been suggested that IDDM2 maps within the 5' VNTR (variable number tandem repeat) polymorphism upstream of the insulin gene (INS). This has not been confirmed and a contribution from other INS gene region polymorphisms cannot be excluded. We present INS region genotype data from four racial groups: the Japanese, Hong Kong Chinese, North Indian Asians and Afro-Caribbeans (two groups; one born and resident in the UK, one in Jamaica). These races have not been previously studied with the range of INS region polymorphisms included here. No INS polymorphism was associated with IDDM across all races. These data from this study thus do not identify any INS polymorphism as IDDM2. The Afro-Caribbean race showed a very different distribution of INS genotypes from the other races and novel race-specific INS haplotypes were identified. Analysis of these excluded a contribution to susceptibility to IDDM from the- 23HphI INS polymorphism. An Afro-Caribbean INS haplotype which differed only at the VNTR from the very protective INS haplotype (VPH) identified in white Caucasians was detected. Population analysis of this haplotype will allow direct assessment of the role of the VNTR in susceptibility to IDDM. In conclusion, the diverse Afro-Caribbean TH/INS/IGF2 haplotypes identified in this study will be valuable in mapping IDDM2 more precisely.


Raman and infrared studies of nucleosides at high pressures: II. Cytidine.
Raman and mid-infrared (MIR) spectra have been recorded for crystalline cytidine at pressures up to 10 GPa at room temperature. Broadening and positive wavenumber shifts are observed for most of the Raman and MIR peaks with increasing pressure. However, some of the MIR peaks associated with hydrogen-stretching modes display a negative wavenumber shift as a result of charge transfer effects. Evidence of a phase transition near 4 GPa is presented and attributed to a change in the conformation of the five membered sugar ring.


Limitations of the use of single base changes in the p53 gene to detect minimal residual disease of breast cancer.
Peripheral blood progenitor cell (PBPC) transplantation is frequently used in the treatment of malignant diseases, but contamination of the graft by tumour cells is a real concern and may lead to disease relapse. The feasibility of applying heterogeneous single base genetic changes as tumour specific markers to detect minimal residual disease in PBPC harvests was studied, using the p53 gene and breast cancer as models. Tumour tissues from 51 patients with cellular aliquots from PBPC harvests available were studied. Thirty eight patients had metastatic disease or were at high risk of metastasis, and 13 had high risk stage II/III disease with four or more involved axillary lymph nodes. Tumour DNA was screened for p53 mutations in exons 5 to 9, using denaturing gradient gel electrophoresis, followed by sequencing. Based on sequence information, allele specific primers were designed for each mutation and the non-radioisotopic, amplification refractory mutation system (ARMS) was used to screen DNA from PBPC harvests for minimal residual disease. Attempts were made to optimise each system, based on parameters determined using the T47D breast cancer cell line with a confirmed point mutation in codon 194. Twelve different somatic mutations were found, two of which could not be sequenced. The remainder were point mutations. Only five of the 10 ARMS systems were successfully optimised, and minimal residual disease detection sensitivities ranged from one copy of tumour DNA in 10(2) to 10(3) copies of wild-type DNA. Using ARMS, three of five patients and eight of 12 of their PBPC harvests showed minimal residual disease. These results suggest that the use of single base genetic changes in minimal residual disease detection is relatively insensitive and is limited to a small number of patients and to certain mutations. In addition, it is labourious and therefore unlikely to play an important role in clinical practice.


[Botulinum and ricin toxins].
Due to their acute toxicity, accessibility and history of use, ricin and botulinum toxins are at the present time the most relevant bioterror toxins. We give a brief review of their toxicity and possible uses in bioterror attacks and describe two cases in Denmark in which immunochemical, PCR and mass spectrometric assays developed in-house were used to confirm a foodborne botulinum toxin E case and to identify bovine serum albumin as the powder enclosed in a letter sent to the U.S. Embassy in Copenhagen.


Peptide Receptor Radionuclide Therapy-Induced Gitelman-like Syndrome.
Peptide receptor radionuclide therapy (PRRT) is a molecular-targeted therapy in which a somatostatin analogue (a small peptide) is coupled with a radioligand so that the radiation dose is selectively administered to somatostatin receptor-expressing metastasized neuroendocrine tumors, particularly gastroenteropancreatic. Reported toxicities include myelotoxicity and nephrotoxicity, the latter manifesting as decreased kidney function, often developing months to years after treatment completion. We present a case of PRRT-induced kidney toxicity manifesting as a severe Gitelman-like tubulopathy with preserved kidney function. Because profound hypokalemia and hypocalcemia can lead to life-threatening arrhythmias, we highlight the necessity for careful monitoring of serum and urine electrolytes in patients receiving PRRT.


White matter hyperintensities associated with small vessel disease impair social cognition beside attention and memory.
Age-related white matter hyperintensities (WMH) are a manifestation of white matter damage seen on magnetic resonance imaging (MRI). They are related to vascular risk factors and cognitive impairment. This study investigated the cognitive profile at different stages of WMH in a large community-dwelling sample; 849 subjects aged 21 to 79 years were classified on the 4-stage Fazekas scale according to hyperintense lesions seen on individual T2-weighted fluid-attenuated inversion recovery MRI scans. The evaluation of cognitive functioning included seven domains of cognitive performance and five domains of subjective impairment, as proposed by the DSM-5. For the first time, the impact of age-related WMH on Theory of Mind was investigated. Differences between Fazekas groups were analyzed non-parametrically and effect sizes were computed. Effect sizes revealed a slight overall cognitive decline in Fazekas groups 1 and 2 relative to healthy subjects. Fazekas group 3 presented substantial decline in social cognition, attention and memory, although characterized by a high inter-individual variability. WMH groups reported subjective cognitive decline. We demonstrate that extensive WMH are associated with specific impairment in attention, memory, social cognition, and subjective cognitive performance. The detailed neuropsychological characterization of WMH offers new therapeutic possibilities for those affected by vascular cognitive decline.


Mononuclear complexes of a tridentate redox-active ligand with sulfonamido groups: structure, properties, and reactivity.
The design of molecular complexes of earth-abundant first-row transition metals that can catalyze multi-electron C-H bond activation processes is of interest for achieving efficient, low-cost syntheses of target molecules. To overcome the propensity of these metals to perform single-electron processes, redox-active ligands have been utilized to provide additional electron equivalents. Herein, we report the synthesis of a novel redox active ligand, [ibaps]3-, which binds to transition metals such as FeII and CoII in a meridional fashion through the three anionic nitrogen atoms and provides additional coordination sites for other ligands. In this study, the neutral bidentate ligand 2,2'-bipyridine (bpy) was used to complete the coordination spheres of the metal ions and form NEt4[MII(ibaps)bpy] (M = Fe (1) or Co (1-Co)) salts. The FeII salt exhibited rich electrochemical properties and could be chemically oxidized by 1 and 2 equiv. of ferrocenium to form singly and doubly oxidized species, respectively. The reactivity of 1 towards intramolecular C-H bond amination of aryl azides at benzylic and aliphatic carbon centers was explored, and moderate to good yields of the resulting indoline products were obtained.


Dynamics of economy-wide resource flow and consumption in China, South Korea, and Vietnam-a pan-regional analysis.
The transformation of natural resources across the economy in China, South Korea, and Vietnam has been studied to give a comparative regional perspective based on trends in resource efficiency, bilateral trade dynamics, and progress on regional economic and environmental policy. Consumption of raw materials has been decomposed into economic dynamics and dematerialization, if any, has been tested based on material flow accounting approaches. As per the results, domestic material consumption (DMC) continues to increase in China and Vietnam but has stabilized in South Korea. China and South Korea have become main net importers of raw materials while Vietnam is about to enter this phase. With relatively lower material efficiency in China and Vietnam compared to South Korea, a higher reliance on intensive production and export of raw materials has been identified. As DMC has soared in all three countries, economic affluence is seen as the main driver with marginal contribution from population growth. However, technological improvements have helped reduce material usage with South Korea and China making significant progress. As South Korea has begun to dematerialize, China and Vietnam face the strong challenge of dematerializing economic growth-a reversal that could take several years if resource productivity is not significantly improved. Factors that inhibit better resource efficiency in China and Vietnam include the production and trade of low-end items, energy, and raw materials. However, the increasing economic affluence in China and Vietnam has brought significant environmental improvements from both institutional and technological perspectives-through multiple policy actions. Moreover, as more countries import net resources, regional and global supply chain competition is expected to intensify-making resource efficiency a fundamental economic objective. The results of this study provide important lessons for emerging economies to accelerate resource productivity and reduce the physical intensity of materials for sustainable economic development.


Choline intake influences phosphatidylcholine DHA enrichment in nonpregnant women but not in pregnant women in the third trimester.
Phosphatidylcholine (PC) produced via the S-adenosylmethionine-dependent phosphatidylethanolamine (PE) N-methyltransferase (PEMT) pathway is enriched with docosahexaenoic acid (DHA). DHA plays a critical role in fetal development and is linked to health endpoints in adulthood. It is unknown whether choline, which can serve as a source of S-adenosylmethionine methyl groups, influences PC-DHA or the PC:PE ratio in pregnant and nonpregnant women. This study tested whether choline intake affects indicators of choline-related lipid metabolism, including erythrocyte and plasma PC-DHA and PC:PE ratios, in pregnant women in the third trimester and nonpregnant women. Pregnant (n = 26) and nonpregnant (n = 21) women consumed 480 or 930 mg choline/d and a daily DHA supplement for 12 wk. Blood was collected at baseline and at the midpoint and end of the study. PC-DHA was analyzed as the proportion of total PC fatty acids. Pregnant women had greater (P = 0.002) PC-DHA concentrations than did nonpregnant women at baseline. The proportion of erythrocyte and plasma PC-DHA increased (P ≤ 0.002) in pregnant and nonpregnant women regardless of choline intake. However, in nonpregnant women, consumption of 930 mg choline/d led to greater (P < 0.001) erythrocyte PC-DHA and a more rapid increase (P < 0.001) in plasma PC-DHA. Lower (P = 0.001-0.024) erythrocyte and plasma PC:PE in pregnant women was not modified by choline intake. A higher choline intake may increase PEMT activity, resulting in greater PC-DHA enrichment of the PC molecule in nonpregnant women. Increased production of PC-DHA during pregnancy indicates elevated PEMT activity and a higher demand for methyl donors. This trial was registered at clinicaltrials.gov as NCT01127022.


Mimicry of an HIV broadly neutralizing antibody epitope with a synthetic glycopeptide.
A goal for an HIV-1 vaccine is to overcome virus variability by inducing broadly neutralizing antibodies (bnAbs). One key target of bnAbs is the glycan-polypeptide at the base of the envelope (Env) third variable loop (V3). We have designed and synthesized a homogeneous minimal immunogen with high-mannose glycans reflective of a native Env V3-glycan bnAb epitope (Man9-V3). V3-glycan bnAbs bound to Man9-V3 glycopeptide and native-like gp140 trimers with similar affinities. Fluorophore-labeled Man9-V3 glycopeptides bound to bnAb memory B cells and were able to be used to isolate a V3-glycan bnAb from an HIV-1-infected individual. In rhesus macaques, immunization with Man9-V3 induced V3-glycan-targeted antibodies. Thus, the Man9-V3 glycopeptide closely mimics an HIV-1 V3-glycan bnAb epitope and can be used to isolate V3-glycan bnAbs.


Silver-decorated orthorhombic nanotubes of lithium vanadium oxide: an impeder of bacterial growth and biofilm.
Reoccurrence of infectious diseases and ability of pathogens to resist antibacterial action has raised enormous challenges which may possibly be confronted by nanotechnology routes. In the present study, uniformly embedded silver nanoparticles in orthorhombic nanotubes of lithium vanadium oxide (LiV2O5/Ag) were explored as an impeder of bacterial growth and biofilm. The LiV2O5/Ag nanocomposites have impeded growth of Gram-positive Bacillus subtilis NCIM 2063 and Gram-negative Escherichia coli NCIM 2931 at 60 to 120 μg/mL. It also impeded the biofilm in Pseudomonas aeruginosa NCIM 2948 at 12.5 to 25 μg/mL. Impedance in the growth and biofilm occurs primarily by direct action of the nanocomposites on the cell surfaces of test organisms as revealed by surface perturbation in scanning electron microscopy. As the metabolic growth and biofilm formation phenomena of pathogens play a central role in progression of pathogenesis, LiV2O5/Ag nanocomposite-based approach is likely to curb the menace of reoccurrence of infectious diseases. Thus, LiV2O5/Ag nanocomposites can be viewed as a promising candidate in biofabrication of biomedical materials.


[Dynamic changes of TGF-α and TGF-β1 in rats with liver cirrhosis induced by multiple pathogenic factors].
To explore the dynamic changes of transforming growth factor-α (TGF-α) and transforming growth factor-β1 (TGF-β1) of liver cirrhosis induced by multiple pathogenic factors in rats. Animals in the cirrhosis group were fed a mixture of maize flour, lard, cholesterol and alcohol plus subcutaneously injection with carbon tetrachloride (CCl₄), the CCl₄(0.5 ml/100 g · w) was injected at the first day of experiment and the 40% CCl₄oil solution (0.3 ml /100 g · w) was injected at an interval of three days. The thirty-six male SD rats were randomly divided into liver cirrhosis group of the 4th, 6th and 8 th week, and normal control group of the 4th, 6th and 8th week. The contents of alanine transferase (ALT), endotoxin, tumor necrosis factor-α (TNF-α) and homocysteine (Hcy) in plasma were evaluated. Histopathological changes of the liver were observed under microscope with the staining of HE. The expressions of TGF-α and TGF-β1 were analyzed by the method of immunohistochemistry. Compared with the corresponding normal control group, the levels of ALT, endotoxin, TNF-α and Hcy in plasma were gradually significantly increased in liver cirrhosis group of the 4th, 6th and 8th week (P < 0.05); the expression of TGF-α in the liver tissues was significantly increased at the 4th week (P < 0.05); the expression of TGF-β1 in the liver tissues was gradually significantly increased in every model group (P < 0.05). In the formation process of cirrhosis, the expression of TGF-α was increased in liver of cirrhosis group at the 4th week, and later it was suppressed; the expression of TGF-β1 was continuously increased. The characteristic dynamic changes of TGF-α and TGF-β1 might be related to sustained endotoxemia, the high level of TNF-α and hyperhomocysteinemia.


Trypanosome spliced-leader-associated RNA (SLA1) localization and implications for spliced-leader RNA biogenesis.
Spliced-leader-associated RNA (SLA1) guides the pseudouridylation at position -12 (relative to the 5' splice site) of the spliced-leader (SL) RNA in all trypanosomatid species. Nevertheless, the exact role of this RNA is currently unknown. Here, we demonstrate that the absence of pseudouridine on Leptomonas collosoma SL RNA has only a minor effect on the ability of this RNA to function in trans splicing in vivo. To investigate the possible role of SLA1 during SL RNA biogenesis, the structure of the SL RNA was examined in permeable Trypanosoma brucei cells depleted for CBF5, the H/ACA pseudouridine synthase, lacking SLA1. Our results suggest that in the absence of SLA1, the SL RNA secondary structure is changed, as was detected by differential sensitivity to oligonucleotide-directed RNase H cleavage, suggesting that the association of SLA1 maintains the SL RNA in a structural form which is distinct from the structure of the SL RNA in the steady state. In T. brucei cells depleted for the SL RNA core protein SmD1, SL RNA first accumulates in large amounts in the nucleus and then is expelled to the cytoplasm. Here, we demonstrate by in vivo aminomethyltrimethyl UV cross-linking studies that under SmD1 depletion, SLA1 remains bound to SL RNA and escorts the SL RNA to the cytoplasm. In situ hybridization with SLA1 and SL RNA demonstrates colocalization between SLA1 and the SL RNA transcription factor tSNAP42, as well as with Sm proteins, suggesting that SLA1 associates with SL RNA early in its biogenesis. These results demonstrate that SLA1 is a unique chaperonic RNA that functions during the early biogenesis of SL RNA to maintain a structure that is most probably suitable for cap 4 modification.


Abundant expression of cytokeratin 7 in fibrolamellar carcinoma of the liver.
Two cases of fibrolamellar carcinoma of the liver, one with lymph node metastasis are reported. Using immunohistochemistry as well as one- and two-dimensional gel electrophoresis and Western blotting, tumour cells of both primary lesions and of the metastasis were found to express cytokeratin polypeptides 8 and 18 and, surprisingly, cytokeratin 7. A small number of cells also expressed cytokeratin 19. This is the first detailed analysis of the cytokeratin expression of fibrolamellar carcinoma, and is also the first to present biochemical evidence that, contrary to what has been suggested, hepatocellular carcinomas do not always preserve the pattern of cytokeratin expression of normal hepatocytes.


A New, Short, and Stereocontrolled Synthesis of C2-Symmetric 1,2-Diamines.
The previously unknown 5-spirocyclohexylisoimidazole has been made efficiently and simply by reaction of ammonia, glyoxal hydrate, and cyclohexanone. It is a very useful precursor for the diastereocontrolled synthesis of many C2-symmetric 1,2-diamines, a class which is important for the generation of a variety of C2-symmetric reagents and catalysts for enantioselective synthesis.


Ultrastructural imaging of Candida albicans adhesion to rat genital epithelium through scanning and transmission electron microscopy.
The adhesion of Candida albicans to the genital epithelium has not been fully investigated in vivo. The objective of this study was to evaluate the ultrastructural aspects of C. albicans adhesion in the lower genital system of female Wistar rats through scanning and transmission electron microscopy. The genital infection persisted until the end of the experiment, and all rats showed the same adhesion aspects. Various associated yeast/hyphae were observed in the lumen and adhered both at the vaginal and endocervical levels where the fungal filamentation process occurred. In the vaginal epithelium, closely adhered yeasts were observed as stretched strands bridging between yeasts and the epithelium surface. Different stages of the adhesion, where yeasts internalized into the epithelial cell inside a cytoplasmic vacuole, resembling endocytosis, and a wide fibrillar-floccular, glycocalyx-like layer on the yeasts were observed. On the endocervix, the adhesion occurred between the cilia. In the uterine body, only a yeast-like form was observed with superficial contact. This study reached the initial goal of demonstrating an experimental model for in vivo studies. Continuation of this line of research is important for studies of vulvovaginal candidiasis.


Mechanisms for the anti-obesity actions of bofutsushosan in high-fat diet-fed obese mice.
The Kampo medicine bofutsushosan (BTS; Pulvis ledebouriellae compositae; Fang Feng Tong Sheng San) has been used as an anti-obesity treatment in overweight patients. In this study, we assessed the underlying physiological changes induced by BTS in obese mice maintained on a high-fat diet. Male ICR mice were fed a 60% kcal fat diet for 5 weeks starting at 4 weeks of age and then fed the same diet with administration of water (control) or aqueous BTS extract (1.0-2.0 g/kg) for 25 days. Body weight, wet weight of isolated white adipose tissue, and obesity-related serum parameters (glucose, lipids, leptin, adiponectin) were measured after treatment. The mRNA expression levels of leptin, adiponectin, and UCP1 in the adipose tissues were determined by quantitative real-time polymerase chain reaction after the first 5 days of treatment. Bofutsushosan (1.5-2.0 g/kg) significantly decreased total body weight and total wet weight of white adipose tissue isolated from subcutaneous (retroperitoneal) and visceral regions (epididymal, mesenteric, and perirenal). At 2.0 g/kg, BTS also decreased total fat mass, visceral fat mass, and ratio of fat mass to body weight as measured by computed tomography, and significantly decreased epididymal adipocyte size after 14 and 25 days' treatment. Twenty-five days' treatment lowered serum glucose, insulin, leptin, and triglycerides, and reduced homeostasis model assessment-insulin resistance. Alternatively, 2.0 g/kg BTS significantly increased mRNA levels of adiponectin, leptin, and UCP1 in interscapular brown adipose tissue but not epididymal white adipose tissue after 5 days' administration. In the early administration period, BTS increased mRNA expression levels of leptin, adiponectin, and UCP1 in brown adipose tissues. With longer administration, BTS improved insulin resistance, and subsequently reduced serum levels of leptin and triglyceride in parallel with decreased visceral white adipose tissue volume and adipocyte size.


Religion and Coping with Trauma: Qualitative Examples from Hurricanes Katrina and Rita.
In this article, we consider the intersection of religious coping and the experience of Hurricanes Katrina and Rita in a lifespan sample of adults living in South Louisiana during the 2005 storms. Participants were young, middle-age, older, and oldest-old adults who were interviewed during the post-disaster recovery period. Qualitative analyses confirmed that three dimensions of religion were represented across participants' responses. These dimensions included: 1) faith community, in relation to the significant relief effort and involvement of area churches; 2) religious practices, in the sense of participants' behavioral responses to the storms, such as prayer; and c) spiritual beliefs, referring to faith as a mechanism underlying individual and family-level adjustment, acceptance and personal growth in the post-disaster period. Implications for future disaster preparedness are considered.


(UO2)2[UO4(trz)2](OH)2: a U(VI) coordination intermediate between a tetraoxido core and a uranyl ion with cation-cation interactions.
A uranyl triazole (UO(2))(2)[UO(4)(trz)(2)](OH)(2) (1) (trz = 1,2,4-triazole) was prepared using a mild solvothermal reaction of uranyl acetate with 1,2,4-triazole. Single-crystal X-ray diffraction analysis of 1 revealed it contains sheets of uranium-oxygen polyhedra and that one of the U(VI) cations is in an unusual coordination polyhedron that is intermediate between a tetraoxido core and a uranyl ion. This U(VI) cation also forms cation-cation interactions (CCIs). Infrared, Raman, and XPS spectra are provided, together with a thermogravimetric analysis that demonstrates breakdown of the compound above 300 °C. The UV-vis-NIR spectrum of 1 is compared to those of another compound that has a range of U(VI) coordination enviromments.


Bovine GM-CSF: molecular cloning and biological activity of the recombinant protein.
The lymphokine granulocyte-macrophage colony-stimulating factor (GM-CSF) mediates the growth and differentiation of granulocytes and macrophages from bone marrow progenitors, and regulates biological functions expressed by mature cells of these lineages. In order to isolate a bovine GM-CSF cDNA, a cDNA library, generated from the BT2 bovine T cell line, was screened with a human GM-CSF cDNA probe. A cDNA clone was isolated with an insert of 783 bp, that would encode a protein of 143 amino acids, with a predicted mol. wt of 16,160. Bovine GM-CSF exhibits a high degree of sequence homology with mouse and human GM-CSF at both the nucleotide and amino acid levels. Comparison of GM-CSF amino acid sequences from the three species indicates that the bovine GM-CSF precursor contains a putative 17 amino acid signal sequence, cleavage of which would yield a 14,250 mol. wt protein. The cDNA was inserted into a mammalian expression vector and transfected into COS-7 monkey kidney cells. Biologically active bovine GM-CSF was secreted as judged by a bovine bone marrow proliferation assay. Bovine GM-CSF was weakly active in both human and mouse bone marrow proliferation assays. In contrast, human GM-CSF was weakly active on bovine but not murine mouse bone marrow cells and mouse GM-CSF was only active on murine bone marrow cells.


Central neural connections of the pineal organ and retina in the teleost Gasterosteus aculeatus L.
The relations of the central neural connections of the pineal organ to those of the retinae of the lateral eyes were investigated in the three-spined stickleback, Gasterosteus aculeatus L. (Teleostei), by anterograde and retrograde transport of horseradish peroxidase (HRP). HRP was applied to the crushed pineal stalk and/or injected into the left or the right eye. Both pineal and retinal efferents project to area praetectalis, dorsal and ventral thalamic areas, and dorsal tegmentum. The most notable overlapping occurs in nucleus commissurae posterioris of area praetectalis. Pineal efferents also innervate the habenular nuclei and dorsal hypothalamus, while retinal efferents innervate rostral hypothalamus, ventrolateral thalamus, and tectum opticum. A small number of retinofugal axons recross and innervate the ipsilateral nucleus anterioris periventricularis and area praetectalis. After intraocular HRP injections, labeled perikarya were located both in retinofugal terminal areas and in areas not receiving direct retinal input, such as the telencephalic nucleus olfactoretinalis, deep tectal layers, and an area rostroventral to nucleus dorsolateralis thalami. No neurons afferent to the pineal organ were demonstrated. The close association of pineal efferents with retinofugal and possible retinopetal elements is in accordance with the view that both systems are potential neural mediators of photoperiodic events in the teleostean circadian system.


Vasculitis and the peripheral nervous system.
Peripheral neuropathy is a common feature of systemic vasculitis and can also occur when vessel wall inflammation is confined to the vasa nervorum, as a tissue-specific condition-non-systemic vasculitic neuropathy (NSVN). Typically, the clinical picture in both systemic and non-systemic cases is of a lower limb predominant, distal, asymmetric or multifocal neuropathy, which is painful and subacute in onset. For NSVN, nerve biopsy is required to make the diagnosis, and nerve biopsy also has a role when vasculitic neuropathy is suspected and a systemic process has not yet declared itself. Early recognition of the disorder is important, because it is treatable, and without treatment potentially disabling, or even lethal if part of an undiagnosed systemic process. Treatment is generally with combination therapy (glucocorticoid plus other immunosuppressant), after which motor and sensory recovery are likely to occur, albeit slowly, but the patient may be left with chronic neuropathic pain.


THE SIGNIFICANCE OF OUTCROSSING IN AN INTIMATE PLANT-HERBIVORE RELATIONSHIP. I. DOES OUTCROSSING PROVIDE AN ESCAPE FROM HERBIVORES ADAPTED TO THE PARENT PLANT?
Sexual reproduction may be advantageous for hosts that are preyed on or parasitized by enemies that are highly adapted to them. Sexual reproduction can create rare genotypes that may escape predation by virtue of rarity and can create variable progeny that may escape predation if enemies are specialized to only one genotype of host. Populations of the herbivorous thrips, Apterothrips apteris, have been shown to be adapted to individual Erigeron glaucus clones. Here, we show that thrips adapted to the parental clone could better use plant progeny of the "home" clone produced through selfing than progeny derived from selfing of other clones. Thus, despite recombination, progeny produced by selfing presented a resource that was similar to the parental phenotype with respect to use by adapted thrips. We also show that E. glaucus susceptibility to thrips has a genetic basis and then ask whether outcrossing provides a means for E. glaucus clones to escape attack by adapted thrips. When we compared the success of thrips on progeny produced by selfing or outcrossing of the home clone, we found that the merits or disadvantages associated with outcrossing were dependent on the susceptibility to infestation of the parental clones. Selfing by clones characterized by low infestations of thrips appeared to preserve resistant genotypes; all outcrossed progeny had, on average, higher infestation levels than selfed progeny. In contrast, outcrossed progeny of clones characterized by high infestations of thrips had either the same thrips density as progeny from selfing, when the pollen donor was a highly infested clone, or lower density, when the pollen donor was a low infestation clone. The advantages of outcrossing were caused by the alleles contributed to progeny rather than to progeny variability or rarity.


[5 years' general drug prevention of thromboembolism in general surgery. Comparison of personal experiences with results from the literature].
Despite wide use of physical methods the number of fatal postoperative pulmonary embolisms in surgical patients increased in Kiel until 1976. Because of these results, additional general prophylaxis with 2-3 X 5000 i U of heparin-dihydroergotamine was introduced in 1978. The rate of fatal pulmonary embolism in general surgery proven by autopsy decreased to 0,3% between 1979 and 1983. It should be noted that six of the nine patients who died from pulmonary embolism had also suffered from an infaust disease. This is an excellent result since our study also includes high risk patients after emergency surgery, cases which Kakkar and Gruber did not include in their studies. Due to the extensive analysis of medical records and the pertinent post-mortem reports, the high effectivity of drug induced prophylaxis with 2-3 X 5000 i U of heparin-dihydroergotamine in order to reduce fatal pulmonary embolism in general surgery could be proven.


Rodent epidermal Langerhans cells demonstrate greater histochemical specificity for ADP than for ATP and AMP.
Langerhans cells (LCs) in mammalian epidermis possess the ectoenzyme Ca++/Mg++-dependent adenosine triphosphatase (ATPase), which has served as a useful histochemical marker for these dendritic cells in a variety of tissue preparations. Since ATPase represents only one of several potential cell surface polyphosphatases, we investigated the capacities of 3 related adenine nucleotide substrates to identify rodent epidermal LCs. Cell surface ATPase activity was not inhibited in the presence of ouabain and was observed to be strictly divalent cation-dependent, with complete interchangeability between Ca++ and Mg++. Optimal staining in the presence of either cation occurred at a 20 mM concentration. Substrate concentration dependence was also observed, with optimal staining at 0.33 mM adenosine 5'-triphosphate (ATP). On an equimolar basis, however, adenosine 5'-diphosphate (ADP) was superior to ATP for the identification of LCs both in whole mounts of epidermis and in suspensions of disaggregated epidermal cells. The substrate adenosine 5'-monophosphate (AMP) stained follicular epithelial cells in both rodent species but failed to identify epidermal LCs in the mouse and only weakly stained these dendritic cells in rat epidermis. We conclude from these studies that ADP demonstrates greater specificity for LC surface polyphosphatase activity than ATP and that the inadvertent inclusion of AMP during identification procedures for epidermal cell suspensions will falsely identify cells other than LCs.


The Link between Depression and Chronic Pain: Neural Mechanisms in the Brain.
Chronic pain, as a stress state, is one of the critical factors for determining depression, and their coexistence tends to further aggravate the severity of both disorders. Unfortunately, their association remains unclear, which creates a bottleneck problem for managing chronic pain-induced depression. In recent years, studies have found considerable overlaps between pain- and depression-induced neuroplasticity changes and neurobiological mechanism changes. Such overlaps are vital to facilitating the occurrence and development of chronic pain and chronic pain-induced depression. In this review, we summarized the role of neuroplasticity in the occurrence and development of the two disorders in question and explored individualized application strategies of analgesic drugs and antidepressants that have different pharmacological effects in the treatment of chronic pain-induced depression. Therefore, this review may provide new insights into the understanding of association between chronic pain and depression.