Das Elektrokardiogramm des Sporttreibenden und der Sport-assoziierte plötzliche Herztod.

Regelmässiges körperliches Training induziert strukturelle, elektrische und funktionelle Anpassungen des Herzens. Die grösste Herausforderung für den Arzt liegt darin, Veränderungen hinweisend für eine strukturelle Herzerkrankung von physiologischen, trainingsassoziierten Anpassungen im Sinne eines 'Athlete's heart' zu unterscheiden. Bei zugrundliegender Kardiopathie ist sportliche Aktivität nicht die Ursache, sondern kann ein Trigger für belastungsabhängige Tachyarrhythmien bzw. für den belastungsabhängigen plötzlichen Herztod (SCD) sein. Um Athleten mit einer kardialen Grunderkrankung und erhöhtem Risiko für einen SCD frühzeitig zu identifizieren wird in Europa ein Preparticipation Screening empfohlen, welches von der Schweizerischen Gesellschaft für Sportmedizin (SGSM) übernommen wurde. Dieses Screening umfasst neben der spezifischen Anamnese und der Herzauskultation auch ein Ruhe-Elektrokardiogramm (Ruhe-EKG). Aufgrund der hohen Anzahl falsch-positiver EKG-Befunde wurden in den letzten Jahren die Beurteilungskriterien des Athleten-EKGs wiederholt angepasst, die Sensitivität und insbesondere auch die Spezifität konnte mit den „verfeinerten Seattle Kriterien“ 2014 deutlich verbessert werden. Der frühen Repolarisation galt in den letzten Jahren ein Hauptaugenmerk: neben dem (Ausdauer-) Training besteht eine klare Assoziation zum männlichen Geschlecht, zur Ethnie, zu den Veränderungen des vegetativen Nervensystems und zu erhöhten QRS-Voltage-Kriterien.

Counting is a spatial process: evidence from eye movements

Spatial-numerical associations (small numbers-left/lower space and large numbers-right/upper space) are regularly found in simple number categorization tasks. These associations were taken as evidence for a spatially oriented mental number line. However, the role of spatial-numerical associations during more complex number processing, such as counting or mental arithmetic is less clear. Here, we investigated whether counting is associated with a movement along the mental number line. Participants counted aloud upward or downward in steps of 3 for 45 s while looking at a blank screen. Gaze position during upward counting shifted rightward and upward, while the pattern for downward counting was less clear. Our results, therefore, confirm the hypothesis of a movement along the mental number line for addition. We conclude that space is not only used to represent number magnitudes but also to actively operate on numbers in more complex tasks such as counting, and that the eyes reflect this spatial mental operation.

A TEMPERATURE-SENSITIVE DEFECT IN THE EXPRESSION OF A SARCOMA VIRUS TRANSFORMING GENE

The viral proteins synthesized by a Moloney murine sarcoma virus (Mo-MuSV) with a temperature-sensitive mutation in a function required for the maintenance of the transformed state (ts110) were examined. Normal rat kidney cells (NRK) were infected with the ts110 virus and a non-virus-producing cell clone, termed 6m2, was isolated. This cell clone had a malignant phenotype at 33(DEGREES), the permissive temperature, but changed to a normal phenotype at 39(DEGREES).^ Two viral proteins were detected in 6m2 cells. A 58,000 dalton protein (P58) was detected at both 33(DEGREES) and 39(DEGREES) and contained only core protein (gag) coded sequences. An 85,000 dalton protein (P85) was detected only at 33(DEGREES) and contained sequences of viral core proteins p15, pp12, and part of p30 as well as protein sequences attributed by peptide mapping to P23 and P38, two candidate viral mouse src (v-mos) gene products. These results provide good evidence that P85 is a gag-mos polyprotein. As expected for a functional mos-gene product, P85 synthesis preceded parameters characteristic of the transformed state, including changes in cell morphology, in the cytoplasmic microtubule complex (CMTC) and in the rate of hexose uptake.^ Other studies were conducted to ascertain the defect which prohibited the synthesis of P85 at 39(DEGREES), the non-permissive temperature. When 6m2 cells were treated with actinomycin D at 39(DEGREES) and shifted to 33(DEGREES), the cells were unable to synthesize P85, but P58 continued to be made. P85 mRNA, active at 33(DEGREES), continued to be translated for two to three hours after shifting to 39(DEGREES) as judged by pulse-labeling experiments. Virus harvested at 33(DEGREES) from ts110 MuSV producer cells packaged both P85 and P58 coding RNAs while virus harvested at 39(DEGREES) was deficient in the amount of P85 coding RNA. Agarose gel electrophoresis of 6m2 cellular RNA showed that RNA harvested at 33(DEGREES) contained the 4.0 and 3.5 kb RNAs. Similar experiments on cells maintained at 39(DEGREES) have detected only the 4.0 kb RNA, suggesting that the 3.5 kb RNA codes for P85. The defect appeared to be in the long term stability of the P85 coding RNA at 39(DEGREES), since, in shift-up experiments (33(DEGREES) (--->) 39(DEGREES)), P85 was translated for only three hours at 39(DEGREES), while P58 was synthesized for at least eight hours. However, at 33(DEGREES) in the presence of actinomycin D, the ratio of P85 and P58 synthesis at hourly intervals was similar throughout a 12 hour period. ^

Environmental and Endogenous Factors Influencing Emigration in Juvenile Anadromous Alewives

We analyzed juvenile anadromous alewife migration at Bride Lake, a coastal lake in Connecticut, during summer 2006 and found that migration on 24-hour and seasonal timescales was influenced by conditions of the environment and characteristics of the individual. To identify environmental cues of juvenile migration, we continuously video recorded fish at the lake outflow and employed information-theoretic model selection to identify the best predictors of daily migration rate. More than 80% of the approximately 320,000 juveniles that migrated from mid-June to mid-August departed in three pulses lasting one or two days. Pulses of migration were associated with precipitation events, transient decreases in water temperature and transient increases in stream discharge. Diel timing of migration shifted over the summer. Early in the season most migration occurred around dawn; late in the season migration occurred at night. To identify individual characteristics associated with migratory behavior, we compared migrating juveniles that we collected as they were exiting Bride Lake to non-migrating juveniles that we collected from the center of the lake. Migrants were a non-random subset of the population; they were on average 1 – 12 mm larger, 2 – 14 d older, had grown more rapidly (11% greater length-at-age), and were in better condition (14% greater mass-at-length) than non-migrant fish. We infer that the amount of accumulated energy has a positive effect on the net benefit of migration at any time in the migratory season.

Comparative studies of Hox genes in mammalian limb and vertebral pattern formation

Divergence of anterior-posterior (AP) limb pattern and differences in vertebral column morphology are the two main examples of mammalian evolution. The Hox genes (homeobox containing gene) have been implicated in driving evolution of these structures. However, regarding Hox genes, how they contribute to the generation of mammalian morphological diversities, is still unclear. Implementing comparative gene expression and phenotypic rescue studies for different mammalian Hox genes could aid in unraveling this mystery. In the first part of this thesis, the expression pattern of Hoxd13 gene, a key Hox gene in the establishment of the limb AP pattern, was examined in developing limbs of bats and mice. Bat forelimbs exhibit a pronounced asymmetric AP pattern and offer a good model to study the molecular mechanisms that contribute to the variety of mammalian limbs. The data showed that the expression domain of bat Hoxd13 was shifted prior to the asymmetric limb plate expansion, whereas its domain in mice was much more symmetric. This finding reveals a correlation between the divergence of Hoxd13 expression and the AP patterning difference in limb development. The second part of this thesis details a phenotypic rescue approach by human HOXB1-9 transgenes in mice with Hoxb1-9 deletion, The mouse mutants displayed homeosis in cervical and anterior thoracic vertebrae. The human transgenes entirely rescued the mouse mutants, suggesting that these human HOX genes have similar functions to their mouse orthologues in anterior axial skeletal patterning. The anterior expressing human HOXB transgenes such as HOXB1-3 were expressed in the mouse embryonic trunk in a similar manner as their murine orthologues. However, the anterior boundary of human HOXB9 expression domain was more posterior than that of the mouse Hoxb9 by 2-3 somites. These data provide the molecular support for the hypothesis that Hox genes are responsible for maintaining similar anterior axial skeletal architectures cervical and anterior thoracic regions, but different architectures in lumbar and posterior thoracic regions between humans and mice. ^

Molecular interactions and signal transfer between sensory rhodopsin-I and its cognate transducer

SRI is unique among known photoreceptors in that it produces opposite signals depending on the color of light stimuli. Absorption of orange light (587 nm) triggers an attractant response by the cell, whereas absorption of orange light followed by near-UV light (373 run) triggers a repellent response. Using behavioral mutants that exhibit aberrant color-sensing ability, we tested a two-conformation equilibrium model, using FRET and EPR spectroscopy. The essence of the model applied to SRI-HtrI is that the complex exists in a metastable two-conformer equilibrium which is shifted in one direction by orange light absorption (producing an attractant signal) and in the opposite direction by a second UV-violet photon (producing a repellent signal). First, by FRET we found that the E-F cytoplasmic loop of SRI moves toward the RAMP domain of the HtrI transducer during the formation of the orange-light activated signaling state of the complex. This is the first localization of a change in the physical relationship between the receptor and transducer subunits of the complex and provides a structural property of the two proposed conformers that we can monitor. Second, EPR spectra of a spin label probe at this cytoplasmic position showed shifts in the dark in the mutants toward shorter or longer EF loop-RAMP distances, explaining their behavior in terms of their mutations causing pre-stimulus shifts into one or the other conformer. ^ Next, we applied a novel electrophysiological method for monitoring the directionality of proton movement during photoactivation of SRI, to investigate the process of proton transfer in the photoactive site from the chromophore to proton acceptors on both the wildtype and aberrant color-response mutants. We observed an unexpected and critical difference in the two signaling conformations of the SRI-HtrI complex. The finding is that the vectoriality (i.e. movement away or toward the cytoplasm) of the light-induced proton transfer from the chromophore to the protein is opposite in formation of the two conformations. Retinylidene proton transfer is a common critical process in rhodopsins and these results are the first to show differences in vectoriality in a rhodopsin receptor, and to demonstrate functional importance of the direction of proton transfer. ^

Characterization of cytochrome P450 4F subfamily: Response in traumatic brain injury and gene regulation

CYP4F enzymes metabolize endogenous molecules including arachidonic acid, leukotrienes and prostaglandins. The involvement of these eisosanoids in inflammation has led to the hypothesis that CYP4Fs may modulate inflammatory conditions after traumatic brain injury (TBI). In rat, TBI elicited changes in mRNA expression of CYP4Fs as a function of time in the cerebrum region. These changes in CYP4F mRNA levels inversely correlated with the cerebral leukotriene B4 (LTB4) level following injury at the same time points. TBI also resulted in changes in CYP4F protein expression and localization around the injury site, where CYP4F1 and CYP4F6 immunoreactivity increased in surrounding astrocytes and CYP4F4 immunoreactivity shifted from endothelia of cerebral vessels to astrocytes. The study with rat primary astrocytes indicated that pro-inflammatory cytokines TNFα and IL-1β could affect the transcription of CYP4Fs to a certain degree, whereas the changing pattern in the primary astrocytes appeared to be different from that in the in vivo TBI model.^ In addition, the regulation of CYP4F genes has been an unsolved issue although factors including cytokines and fatty acids appear to affect CYP4Fs expression in multiple models. In this project, HaCaT cells were used as an in vitro cellular model to define signaling pathways involved in the regulation of human CYP4F genes. Retinoic acids inhibited CYP4F11 expression, whereas cytokines TNFα and IL-1β induced transcription of CYP4F11 in HaCaT cells. The induction of CYP4F11 by both cytokines could be blocked by a JNK specific inhibitor, indicating the involvement of the JNK pathway in the up-regulation of CYP4F11. Retinoic acids are known to function in gene regulation through nuclear receptors RARs and RXRs. The RXR agonist LG268 greatly induced transcription of CYP4F11, whereas RAR agonist TTNPB obviously inhibited CYP4F11 transcription, indicating that the down-regulation of CYP4F11 by retinoic acid was mediated by RARs, and that inhibition of CYP4F11 by retinoic acid may also be related to the competition for RXR receptors. Thus, the CYP4F11 gene is regulated by signaling pathways including the RXR pathway and the JNK pathway. In contrast, the regulation mechanism of other CYP4Fs by retinoic acids appears to be different from that of CYP4F11.^

A proposed application of the attributable risk technique in the assessment of unmet need among newly organized populations

In the midst of health care reform, and as health care organizations reorganize to provide more cost-effective healthcare, the population is being shifted into new healthcare delivery systems such as health insurance purchasing alliances, and health maintenance organizations. These new models of delivery are usually organized within resource restricted and data limited environments. Health care planners are faced with the challenge of identifying priorities for preventive and primary care services within these newly organized populations (Medicare HMO, Medicaid HMO, etc.). The author proposes a technique usually employed in epidemiology--attributable risk estimation--as a planning methodology to establish preventive health priorities within newly organized populations. Illustrations of the methodology are provided utilizing the Texas 1992 population. ^

The application of principal component analysis on human development indicators: Temporal approach from 1999 to 2010

Background and Objective. Ever since the human development index was published in 1990 by the United Nations Development Programme (UNDP), many researchers started searching and corporative studying for more effective methods to measure the human development. Published in 1999, Lai’s “Temporal analysis of human development indicators: principal component approach” provided a valuable statistical way on human developmental analysis. This study presented in the thesis is the extension of Lai’s 1999 research. ^ Methods. I used the weighted principal component method on the human development indicators to measure and analyze the progress of human development in about 180 countries around the world from the year 1999 to 2010. The association of the main principal component obtained from the study and the human development index reported by the UNDP was estimated by the Spearman’s rank correlation coefficient. The main principal component was then further applied to quantify the temporal changes of the human development of selected countries by the proposed Z-test. ^ Results. The weighted means of all three human development indicators, health, knowledge, and standard of living, were increased from 1999 to 2010. The weighted standard deviation for GDP per capita was also increased across years indicated the rising inequality of standard of living among countries. The ranking of low development countries by the main principal component (MPC) is very similar to that by the human development index (HDI). Considerable discrepancy between MPC and HDI ranking was found among high development countries with high GDP per capita shifted to higher ranks. The Spearman’s rank correlation coefficient between the main principal component and the human development index were all around 0.99. All the above results were very close to outcomes in Lai’s 1999 report. The Z test result on temporal analysis of main principal components from 1999 to 2010 on Qatar was statistically significant, but not on other selected countries, such as Brazil, Russia, India, China, and U.S.A.^ Conclusion. To synthesize the multi-dimensional measurement of human development into a single index, the weighted principal component method provides a good model by using the statistical tool on a comprehensive ranking and measurement. Since the weighted main principle component index is more objective because of using population of nations as weight, more effective when the analysis is across time and space, and more flexible when the countries reported to the system has been changed year after year. Thus, in conclusion, the index generated by using weighted main principle component has some advantage over the human development index created in UNDP reports.^

A descriptive study of syphilis infection in Houston, Texas, 1999--2008

The rate of syphilis nationally has been on the rise since 2001. Syphilis, if left untreated can facilitate the transmission of HIV infection. An epidemiologic study describing the trends of syphilis is important to the public health community to lay the foundation for the development and implementation of programs to prevent and eliminate syphilis in the United States. ^ The objective of this study was to describe the trends of syphilis among the population in Houston/Harris County, Texas. ^ We reviewed surveillance data that included 11,605 unique cases from the Houston Department of Human and Health Service from 1999 through 2008. The rates were calculated per 100,000 population. ^ We show the prevalence of syphilis at testing (excluding congenital) increased 40% in Houston/Harris County, Texas from 2001 through 2008, and the ratio of syphilis comparing men to women was 2:1. The 18–29 years age group had the highest percentage of cases of syphilis among all age groups in Houston/Harris County. Primary and Secondary (P&S) syphilis, the most infectious stage, had an 85% increase in rate among males from 1999 through 2008. ^ Between 1999 and 2000, 71% of cases were identified through public facilities compared to private facilities. However, after 2001 rates shifted over more to the private facilities. By 2008, private facilities identified 54.7% of cases, compared to 45.3% identified through public facilities. This may be due to an increase among individuals who have a higher socio-economic status with access to health care insurance. ^ In conclusion, syphilis rates from 1999 through 2008 increased among all race ethnicities, age groups, and genders in Houston/Harris County. Blacks still are disproportionally affected by syphilis infections, and for the first time, White males displayed a significant increase in cases among males. It is vital to Houston public health professionals to have improved surveillance techniques to track syphilis trends and engage high risk groups to better understand their risks in hope of treating and preventing syphilis.^

Homology Cloning, Heterologous Expression and Characterization of a New Channelrhodopsin

Channelrhodopsins are phototaxis receptors in the plasma membranes of motile unicellular algae. They function as light-gated cation channels and this channel activity has been exploited to trigger action potentials in neurons with light to control neural circuits (“optogenetics"). Four channelrhodopsins were identified in two algal species, Chlamydomonas reinhardtii and Volvox carteri, with known genome sequences; each species contains 2 channelrhodopsins, one absorbing at longer wavelengths and one at shorter wavelengths, named CrChR1 and CrChR2, respectively. Our goals are to expand knowledge of channelrhodopsin mechanisms and also to identify new channelrhodopsins from various algal species with improved properties for optogenetic use. For these aims we are targeting algae from extreme environments to establish the natural diversity of their properties. We cloned a new channelrhodopsin from the psychrophilic (cold-loving) alga, Chlamydomonas augustae, with degenerate primers based on the 4 known homologs. The new protein is 48% and 52% identical to CrChR1 and CrChR2, respectively. We expressed the channelrhodopsin in HEK293 cells and measured light-induced currents to assess their kinetics and action spectrum. Based on the primary structure, kinetics of light-induced photocurrents in HEK293 cells, and action spectrum maximum of 520 nm near that of the two previously found CrChR1, we named the new channelrhodopsin CaChR1. The properties of robust channel activity at physiological pH, fast on-and-off kinetics, and greatly red-shifted action spectrum maximum from that of CrChR2, make CaChR1 advantageous as an optogenetic tool. To know this new channelrhodopsin better, we expressed His-tagged CaChR1 in Pichia pastoris and the yield is about 6 mg/L. The purified His-tagged CaChR1 exhibited an absorption spectrum identical to the action spectrum of CaChR1-generated photocurrents. The future work will be measurement of the photocycles of CaChR1 by flash photolysis, crystallization of CaChR1 for the structure and mutagenesis of CaChR1 to find the critical amino acids accounting for red-shifted spectra, slow inactivation and rapid on-and-off kinetics. Seven new channelrhodopsins including CaChR1 from different algal species have been cloned in our lab at this time, bringing the total known to 13. The work of cloning of these new channelrhodopsins along with the expression of CaChR1 was published in Photochemistry and Photobiology in January 2012

Family to Family: Child Welfare for the 21st Century

Child welfare services have undergone many revisions and transformations since their initiation. Some scholars trace the beginning of child welfare in the United States to events such as a 1655 Massachusetts conviction for maltreatment leading to the death of a 12-year-old boy (Watkins, 1990). The predominant philosophy of child welfare has shifted over time from an early emphasis on child saving, to child protection, to family preservation. Building on family preservation, one of the current transformations in child welfare that is taking place in isolated pockets to whole states, is family-centered, neighborhood-based services. One force behind implementation of this transformation is the Family to Family Initiative of the Annie E. Casey Foundation. This paper places family-centered, neighborhood-based child welfare services within the historical context of development of child welfare and within the recent move to reinvent human services (Adams & Nelson, 1995). Against this backdrop, a locality-based implementation of the Family to Family Initiative is described.

Changing Tides and Changing Focus: Mapping the Challenges and Successes of One State's Implementation Of the Adoption and Safe Families Act of 1997

In 1997, the Adoption and Safe Families Act shifted from the preservation of families to an emphasis on safety, permanency, and well-being through expediting the termination of parental rights, establishing exceptions to the reasonable efforts clause of preserving the family, and fiscal incentives for finalizing adoptions. The current project assessed the role of a full service array in achieving the outcomes set forth in ASF A. Concept mapping was utilized to elicit information from participants (both urban and rural) regarding the identified research question. Participants recognized family preservation versus safety, community connections, mandates versus reality, and worker recruitment and retention as critical components for meeting ASFA goals. Perceived importance and level of success in implementing these services was also highlighted. Recommendations supported through the data are also provided.

Paleomagnetic of the Cobb Mountin event sections

Detailed paleomagnetic investigations are reported for 283 specimens, sampled from three closely spaced Ocean Drilling Program Leg 135 cores from the Lau Basin. These specimens cover three rather similar records of the reversed Cobb Mountain short polarity event, having an age of about 1.12 m.y. On the basis of a very detailed subsampling every 0.6 cm, we found that the transition times for the Cobb Mountain geomagnetic polarity event, as seen in the three Lau Basin sediment records, appear to have been as short as 0.6-1.0 k.y., although the duration of the normal-polarity event itself lasted only about 17 ± 4 k.y. The older (R to N) transition as well as the younger (N to R) transition show virtual geomagnetic paths roughly along the Americas, but shifted some 30° ± 10° to the east. These paths conflict with Cobb Mountain transition paths recorded in sediments from the Labrador Sea and the North Atlantic, but they are in fair accordance with sediment records from the Celebes and Sulu seas when corrected for differences in site longitude, suggesting that the transitional fields are dominated by nonaxial, high-order spherical harmonics.

Age model and Nd isotope ratios of DSDO Hole 43-386 and ODP Hole 210-1276A

Modern thermohaline circulation plays a role in latitudinal heat transport and in deep-ocean ventilation, yet ocean circulation may have functioned differently during past periods of extreme warmth, such as the Cretaceous. The Late Cretaceous (100-65 Ma) was an important period in the evolution of the North Atlantic Ocean, characterized by opening ocean gateways, long-term climatic cooling and the cessation of intermittent periods of anoxia (oceanic anoxic events, OAEs). However, how these phenomena relate to deep-water circulation is unclear. We use a proxy for deep-water mass composition (neodymium isotopes; e-Nd) to show that, at North Atlantic ODP Site 1276, deep waters shifted in the early Campanian (~78-83 Ma) from e-Nd values of ~-7 to values of ~-9, consistent with a change in the style of deep-ocean circulation but >10 Myr after a change in bottom water oxygenation conditions. A similar, but more poorly dated, trend exists in e-Nd data from DSDP Site 386. The Campanian e-Nd transition observed in the North Atlantic records is also seen in the South Atlantic and proto-Indian Ocean, implying a widespread and synchronous change in deep-ocean circulation. Although a unique explanation does not exist for the change at present, we favor an interpretation that invokes Late Cretaceous climatic cooling as a driver for the formation of Southern Component Water, which flowed northward from the Southern Ocean and into the North Atlantic and proto-Indian Oceans.