Na 50 Nachlass Arthur Schopenhauer - 'Schopenhauer-Archiv', 276 - Antwortschreiben an Otto Hörth mit ausführlicher Beschreibung des hohen philosophischen Stellenwertes ihres Bruders Philipp Mainänder

u.a.: Minna Batz; Arthur Schopenhauer; Philipp Mainländer;

Na 50 Nachlass Arthur Schopenhauer - 'Schopenhauer-Archiv', 280 - Dankesschreiben an Otto Hörth wegen der geleisteten Hilfestellung zu ihrem Buch

u.a.: Minna Batz; Dr. Konrad; Theodor Grieben;

Familienblätter zur Erinnerung an unseren verewigten Vater Raphael J. Karger. Im Namen der Familie

hrsg. von S. Gronemann

Sterol, n-alcohol and n-alkane composition of living fen plants

In groundwater-fed fen peatlands, the surface biomass decays rapidly and, as a result, highly humified peat is formed. A high degree of humification constrains palaeoecological studies because reliable identification of plant remains is hampered. Organic geochemistry techniques as a means of identifying historical plant communities have been successfully applied tobog peat. The method has also been applied to fen peat, but without reference to the composition of fen plants. We have applied selected organic geochemistry methods to determine the composition of the neutral lipid fractions from 12 living fen plants, to investigate the potential for the distributions to characterize and separate different fen plants and plant groups. Our results show correspondence with previous studies, e.g. C23 and C25n-alkanes dominating Sphagnum spp. and C27 to C31 alkanes dominating vascular plants. However, we also found similarities in n-alkane distributions between Sphagnum spp. and the below ground parts of some vascular plants. We tested the efficiency of different n-alkane ratios to separate species and plant groups. The ratios used for bog studies (e.g. n-C23/n-C25 and n-C23/n-C29) did not work as consistently for fen plants. Some differences in sterol distribution were found between vascular plants and mosses; in general vascular plants had a higher concentration of sterols. When distributions of n-alkanes, n-alkane ratios and sterols were all included as variables, redundancy analysis (RDA) separated different plant groups into their own clusters. Our results imply that the pattern for bog biomarkers cannot directly be applied to fen environments. Nevertheless, they encourage further testing to determine whether or not the identification of plant groups, plants or plant parts from highly humified peat is possible by applying fen species-specific biomarker proxies.

The role of secretion systems and small molecules in soft-rot enterobacteriaceae pathogenicity

Soft-rot Enterobacteriaceae (SRE), which belong to the genera Pectobacterium and Dickeya, consist mainly of broad host-range pathogens that cause wilt, rot, and blackleg diseases on a wide range of plants. They are found in plants, insects, soil, and water in agricultural regions worldwide. SRE encode all six known protein secretion systems present in gram-negative bacteria, and these systems are involved in attacking host plants and competing bacteria. They also produce and detect multiple types of small molecules to coordinate pathogenesis, modify the plant environment, attack competing microbes, and perhaps to attract insect vectors. This review integrates new information about the role protein secretion and detection and production of ions and small molecules play in soft-rot pathogenicity.

Regulación del movimiento y anticipación en el resto del primer servicio en tenis

Aunque se han logrado importantes avances en estudios de laboratorio con diseños experimentales poco representativos (e.g., Farrow y Reid, 2012; Nieminen, Piirainen, Salmi, y Linnamo, 2013), a día de hoy, todavía se desconoce a cabalidad cómo los jugadores de tenis de diferente nivel de pericia calibran o ajustan sus movimientos a las demandas espacio-temporales presentes en la tarea de resto de un primer servicio. ! Escasos trabajos se han llevado a cabo in situ y a la mayoría se les puede cuestionar algún aspecto de la metodología empleada. Así pues, en varios estudios la frecuencia de grabación ha sido limitada (e.g., a 50 Hz en Jackson y Gudgeon, 2004; Triolet, Benguigui, Le Runigo y Williams, 2013), o la velocidad del saque ha sido visiblemente inferior a la habitual (cf. Carboch, Süss y Kocib, 2014; Williams, Singer y Weigelt, 1998). También, en algunos estudios los participantes experimentados no han sido jugadores de nivel internacional (e.g., Avilés, Ruiz, Sanz y Navia, 2014), y el tamaño muestral ha sido muy pequeño (e.g., Gillet, Leroy, Thouvarecq, Mégrot y Stein, 2010). ! Además, en los diferentes trabajos se han utilizado una diversidad de métodos e instrumentos de medida y los criterios de codificación del inicio de los movimientos y de las respuestas han diferido; como consecuencia el lapso visomotor de respuesta (LVMr) ha sido muy dispar variando considerablemente de 198 a 410 ms. Considerando los inconvenientes señalados anteriormente, el presente estudio tuvo como objetivo determinar un modelo técnico de regulación temporal de los movimientos y de la respuesta del restador, tomando en cuenta el flujo continuo de información proporcionado por el sacador. Para ello, se realizó un análisis cronométrico de los restos de doce jugadores de diferente nivel deportivo (seis internacionales y seis nacionales) que respondieron de forma natural enviando sus devoluciones hacia las dianas. Se grabaron las acciones de los restadores y sacadores con una cámara Casio Exilim Pro Ex-F1 de alta velocidad (300 Hz) y luego se realizó un análisis imagen por imagen cada 3.33 ms. Una vez obtenidos los datos de los vídeos se realizaron análisis con las pruebas de ANOVA de un factor, ANCOVA con la velocidad del saque como covariable, U de Mann-Whitney y Chi-cuadrado de Pearson. En cuanto a la regulación del movimiento hasta el momento del despegue, los jugadores internacionales iniciaron sus acciones antes que los jugadores nacionales lo que podría indicar una mejor preparación al ejecutar los movimientos como reflejo del nivel de pericia. Los jugadores internacionales iniciaron la elevación del pie posterior a -293 ms y los jugadores nacionales a -202 ms. Todas estas acciones se fueron enlazando unas con otras y fue en el momento del impacto del sacador donde los restadores demostraron una remarcable coordinación perceptivo-motriz. Por consiguiente, los jugadores internacionales despegaron e iniciaron el vuelo a tan solo -6.5 ms del impacto y los jugadores nacionales lo hicieron más tarde a +19.5 ms. A lo largo de la secuencia temporal, todo parece indicar que las informaciones que utilizan los restadores interactúan entre sí; información más temprana y menos fiable para anticipar o moverse antes e información más tardía y más fiable para regular la temporalización de las acciones. Los restadores de nivel internacional y nacional anticiparon a nivel espacial en un bajo porcentaje (7.7% vs. 13.6%) y en tiempos similares (-127 vs. -118 ms) sugiriendo que la utilización de variables ópticas tempranas y menos fiables solo se produce en contadas ocasiones. Por otra parte, estos datos se relacionan con una gran precisión en la respuesta ya que tanto los jugadores internacionales como los nacionales demostraron un alto porcentaje de acierto al responder (95.4% vs. 96.7%). Se había señalado que los jugadores internacionales y nacionales se diferenciarían en el tiempo de caída (i.e., aterrizaje) del primer pie del salto preparatorio, sin embargo ese efecto no fue encontrado (128 vs. 135 ms). Tampoco se hallaron diferencias en el porcentaje de caída con el pie contrario a la dirección de la pelota (58% vs. 62%). Donde sí ambos grupos se diferenciaron fue en el tiempo de caída del segundo pie (147 vs. 168 ms). Esta diferencia de 21 ms fue crucial y fue una prueba de la mayor rapidez de los jugadores internacionales; sugiriendo que ésta acción se podría relacionar con el momento del inicio de la respuesta. Aunque los jugadores internacionales hayan demostrado ser más rápidos en relación con sus capacidades funcionales, ambos grupos no se diferenciaron en todas las variables relacionadas con el LVMr. Ellos no utilizaron esos valiosos milisegundos ganados en el instante de la caída del segundo pie para responder más pronto, ya que el LVMr del miembro superior fue el mismo para ambos grupos (179 vs. 174 ms). Es como si hubiesen tenido todo el tiempo del mundo para seguir ajustando sus acciones hasta el propio golpeo. Además, estos tiempos largos sugieren que en la gran mayoría de los restos la información clave que determinó la respuesta fue detectada (extraída) en momentos cercanos al golpeo del sacador y en la primera parte del vuelo de la pelota. Asimismo, se constató que en general el LVMr se ve influenciado por el tipo de información utilizada. De esta manera, cuando se tomaron en cuenta los ensayos en los que hubo anticipación espacial reflejados en el LVMr del cuerpo entero los tiempos disminuyeron (152 vs. 136 ms). Por otra parte, existieron ocasiones (13%) en los que tanto los jugadores internacionales como los nacionales respondieron tarde recibiendo saques directos (208 vs. 195 ms). Es muy posible que en estos casos los jugadores hayan tenido problemas para detectar la información respondiendo fuera de los márgenes temporales de acción lo que mermó su rendimiento. Lo mismo pudo haber ocurrido cuando ambos grupos de jugadores corrigieron el movimiento del miembro superior tras el impacto (17% vs. 10%) lo que aumentó el tiempo en responder al redirigir la respuesta hacia el lado correcto (208 vs. 205 ms). Además, los jugadores internacionales obtuvieron tiempos de movimiento menores que el de los jugadores nacionales (509 vs. 531 ms) lo que se reflejó en un tiempo total de actuación menor (683 vs. 703 ms). Por último, en cuanto al rendimiento del resto, los jugadores internacionales obtuvieron valores superiores a los jugadores nacionales (1.3 vs. 0.9). ABSTRACT Although there have been significant advances in laboratory studies with unrepresentative experimental designs (e.g., Farrow y Reid, 2012; Nieminen, Piirainen, Salmi, y Linnamo, 2013), today it is still unknown to full extent how tennis players of different levels of expertise calibrate or adjust their movements to the spatial-temporal demands present in the return of a first serve. Few studies have been carried out in situ and some aspects of the methodology most of them used can be questioned. Thus, in several studies the recording frequency has been limited (e.g., a 50 Hz en Jackson y Gudgeon, 2004; Triolet, Benguigui, Le Runigo y Williams, 2013), or serve speed was visibly lower than the usual one (cf. Carboch, Süss y Kocib, 2014; Williams, Singer y Weigelt, 1998). Also, in some studies, experienced participants have not played at international level (e.g., Avilés, Ruiz, Sanz y Navia, 2014), and the sample size has been very small (e.g., Gillet, Leroy, Thouvarecq, Mégrot y Stein, 2010). Furthermore, different works have used a variety of methods and measurement instruments and coding criteria of the onset of movements and responses have differed; due to this, visuomotor response delay (LVMr) has been very uneven, varying considerably from 198-410 ms. Considering the drawbacks mentioned above, this study aimed to determine a technical model of temporal regulation of movements and returner’s response, taking into account the continuous flow of information provided by the server. For this, a chronometric analysis of the returns of twelve players (six international and six national) of different sports level, that naturally responded by hitting their returns towards the targets, was performed. Actions of servers and returners were recorded with a Casio Exilim Pro Ex-F1 high speed camera (300 Hz) and then every 3.33 ms analysis was made frame by frame. Once the data of the videos were obtained, analyses were performed using one factor ANOVA test, ANCOVA with the speed of the serve as a covariate, U of Mann- Whitney and Pearson’s Chi-square test. As for the regulation of movement until the moment of serve, international players began their actions before national players, which could indicate that they were better prepared to execute movements reflecting the level of their expertise. International players began raising the rear foot at -293 ms and national players at -202 ms. All these actions were being linked to each other and it was at the moment of impact of the server when the receivers demonstrated a remarkable perceptual-motor coordination. Therefore, international players took off and started their flight just -6.5 ms before the serve and national players did the same somewhat later: +19.5 ms after the serve. Along the timeline, everything seems to indicate that the information used by returners interact with each other; early information which is less reliable to anticipate or move before, and later information more reliable appears to regulate the timing of actions. Returners of international and national levels anticipated at spatial level in a low percentage (7.7% vs. 13.6%) and in similar times (-127 vs. -118 ms) suggesting that the use of early and less reliable optical variables is only produced on rare occasions. Moreover, these data relate to a precise response as both international and national players showed a high percentage of success in responding (95.4% vs. 96.7%). It had been noted that international and national players would differ in the time the fall (i.e., landing) of the first foot of the split-step, however, this effect was not found (128 vs. 135 ms). No differences in the percentage of fall with the opposite foot to the direction of the ball (58% vs. 62%) were found. Where the two groups differed was in the time of the fall of the second foot (147 vs. 168 ms). This difference of 21 ms was crucial and it was a proof of mayor speed of international players; suggesting that this action could be related to the onset time of response. Although international players have proven to be faster in relation to their functional capabilities, both groups did not differ in all variables related to LVMr. They did not use those precious milliseconds earned at the time of the fall of the second foot to respond as soon, since the LVMr of the upper limb was the same for both groups (179 vs. 174 ms). It is as if they had all the time in the world to continue to adjust their actions until the return itself. Furthermore, these long times suggest that in the vast majority of the returns, key information that determined the response was detected (pick-up) in moments close to the hit of the server and in the first part of the ball flight. It was also found that in general the LVMr is influenced by the type of information used. Thus, when taking into account the trials during which there was spatial anticipation, reflected in LVMr of the whole body, the times decreased (152 vs. 136 ms). On the other hand, there were occasions (13%) where both international and national players responded late, thus receiving aces (208 vs. 195 ms). It is quite possible that in these cases the players have had trouble to pick-up information, responding out of temporary margins of action, which affected their performance. The same could have occurred when both groups of players corrected upper limb movement after impact (17% vs. 10%), which increased the time to respond and to redirect the return towards the right side (208 vs. 205 ms). Moreover, international players scored lower movement times than the national players (509 vs. 531 ms), which was reflected in a shorter total response time (683 vs. 703 ms). Finally, as far as the performance of return is concerned, international players scored above the national players values (1.3 vs. 0.9).

Computerized polymorphic marker identification: Experimental validation and a predicted human polymorphism catalog

A computational system for the prediction of polymorphic loci directly and efficiently from human genomic sequence was developed and verified. A suite of programs, collectively called pompous (polymorphic marker prediction of ubiquitous simple sequences) detects tandem repeats ranging from dinucleotides up to 250 mers, scores them according to predicted level of polymorphism, and designs appropriate flanking primers for PCR amplification. This approach was validated on an approximately 750-kilobase region of human chromosome 3p21.3, involved in lung and breast carcinoma homozygous deletions. Target DNA from 36 paired B lymphoblastoid and lung cancer lines was amplified and allelotyped for 33 loci predicted by pompous to be variable in repeat size. We found that among those 36 predominately Caucasian individuals 22 of the 33 (67%) predicted loci were polymorphic with an average heterozygosity of 0.42. Allele loss in this region was found in 27/36 (75%) of the tumor lines using these markers. pompous provides the genetic researcher with an additional tool for the rapid and efficient identification of polymorphic markers, and through a World Wide Web site, investigators can use pompous to identify polymorphic markers for their research. A catalog of 13,261 potential polymorphic markers and associated primer sets has been created from the analysis of 141,779,504 base pairs of human genomic sequence in GenBank. This data is available on our Web site (pompous.swmed.edu) and will be updated periodically as GenBank is expanded and algorithm accuracy is improved.

Epigenetic phenotypes distinguish microsatellite-stable and -unstable colorectal cancers

Aberrant DNA methylation is a common phenomenon in human cancer, but its patterns, causes, and consequences are poorly defined. Promoter methylation of the DNA mismatch repair gene MutL homologue (MLH1) has been implicated in the subset of colorectal cancers that shows microsatellite instability (MSI). The present analysis of four MspI/HpaII sites at the MLH1 promoter region in a series of 89 sporadic colorectal cancers revealed two main methylation patterns that closely correlated with the MSI status of the tumors. These sites were hypermethylated in tumor tissue relative to normal mucosa in most MSI(+) cases (31/51, 61%). By contrast, in the majority of MSI(−) cases (20/38, 53%) the same sites showed methylation in normal mucosa and hypomethylation in tumor tissue. Hypermethylation displayed a direct correlation with increasing age and proximal location in the bowel and was accompanied by immunohistochemically documented loss of MLH1 protein both in tumors and in normal tissue. Similar patterns of methylation were observed in the promoter region of the calcitonin gene that does not have a known functional role in tumorigenesis. We propose a model of carcinogenesis where different epigenetic phenotypes distinguish the colonic mucosa in individuals who develop MSI(+) and MSI(−) tumors. These phenotypes may underlie the different developmental pathways that are known to occur in these tumors.

Potent and nontoxic antisense oligonucleotides containing locked nucleic acids

Insufficient efficacy and/or specificity of antisense oligonucleotides limit their in vivo usefulness. We demonstrate here that a high-affinity DNA analog, locked nucleic acid (LNA), confers several desired properties to antisense agents. Unlike DNA, LNA/DNA copolymers were not degraded readily in blood serum and cell extracts. However, like DNA, the LNA/DNA copolymers were capable of activating RNase H, an important antisense mechanism of action. In contrast to phosphorothioate-containing oligonucleotides, isosequential LNA analogs did not cause detectable toxic reactions in rat brain. LNA/DNA copolymers exhibited potent antisense activity on assay systems as disparate as a G-protein-coupled receptor in living rat brain and an Escherichia coli reporter gene. LNA-containing oligonucleotides will likely be useful for many antisense applications.

Cortical processing of change detection: Dissociation between natural vowels and two-frequency complex tones

We compared magnetoencephalographic responses for natural vowels and for sounds consisting of two pure tones that represent the two lowest formant frequencies of these vowels. Our aim was to determine whether spectral changes in successive stimuli are detected differently for speech and nonspeech sounds. The stimuli were presented in four blocks applying an oddball paradigm (20% deviants, 80% standards): (i) /α/ tokens as deviants vs. /i/ tokens as standards; (ii) /e/ vs. /i/; (iii) complex tones representing /α/ formants vs. /i/ formants; and (iv) complex tones representing /e/ formants vs. /i/ formants. Mismatch fields (MMFs) were calculated by subtracting the source waveform produced by standards from that produced by deviants. As expected, MMF amplitudes for the complex tones reflected acoustic deviation: the amplitudes were stronger for the complex tones representing /α/ than /e/ formants, i.e., when the spectral difference between standards and deviants was larger. In contrast, MMF amplitudes for the vowels were similar despite their different spectral composition, whereas the MMF onset time was longer for /e/ than for /α/. Thus the degree of spectral difference between standards and deviants was reflected by the MMF amplitude for the nonspeech sounds and by the MMF latency for the vowels.

A role for estrogen receptor β in the regulation of growth of the ventral prostate

In normal rats and mice, immunostaining with specific antibodies revealed that nuclei of most prostatic epithelial cells harbor estrogen receptor β (ERβ). In rat ventral prostate, 530- and 549-aa isoforms of the receptor were identified. These sediment in the 4S region of low-salt sucrose gradients, indicating that prostatic ERβ does not contain the same protein chaperones that are associated with ERα. Estradiol (E2) binding and ERβ immunoreactivity coincide on the gradient, with no indication of ERα. In prostates from mice in which the ERβ gene has been inactivated (BERKO), androgen receptor (AR) levels are elevated, and the tissue contains multiple hyperplastic foci. Most epithelial cells express the proliferation antigen Ki-67. In contrast, prostatic epithelium from wild-type littermates is single layered with no hyperplasia, and very few cells express Ki-67. Rat ventral prostate contains an estrogenic component, which comigrates on HPLC with the testosterone metabolite 5α-androstane-3β,17β-diol (3βAdiol). This compound, which competes with E2 for binding to ERβ and elicits an estrogenic response in the aorta but not in the pituitary, decreases the AR content in prostates of wild-type mice but does not affect the elevated levels seen in ERβ knockout (BERKO) mice. Thus ERβ, probably as a complex with 3βAdiol, is involved in regulating the AR content of the rodent prostate and in restraining epithelial growth. These findings suggest that ligands specific for ERβ may be useful in the prevention and/or clinical management of prostatic hyperplasia and neoplasia.

Tolerance of human MSH2+/− lymphoblastoid cells to the methylating agent temozolomide

Members of hereditary nonpolyposis colon cancer (HNPCC) families harboring heterozygous germline mutations in the DNA mismatch repair genes hMSH2 or hMLH1 present with tumors generally two to three decades earlier than individuals with nonfamilial sporadic colon cancer. We searched for phenotypic features that might predispose heterozygous cells from HNPCC kindreds to malignant transformation. hMSH2+/− lymphoblastoid cell lines were found to be on average about 4-fold more tolerant than wild-type cells to killing by the methylating agent temozolomide, a phenotype that is invariably linked with impairment of the mismatch repair system. This finding was associated with an average 2-fold decrease of the steady-state level of hMSH2 protein in hMSH2+/− cell lines. In contrast, hMLH1+/− heterozygous cells were indistinguishable from normal controls in these assays. Thus, despite the fact that HNPCC families harboring mutations in hMSH2 or hMLH1 cannot be distinguished clinically, the early stages of the carcinogenic process in hMSH2 and hMLH1 mutation carriers may be different. Should hMSH2+/− colonocytes and lymphoblasts harbor a similar phenotype, the increased tolerance of the former to DNA-damaging agents present in the human colon may play a key role in the initiation of the carcinogenic process.

The candidate tumor suppressor gene, RASSF1A, from human chromosome 3p21.3 is involved in kidney tumorigenesis

Clear cell-type renal cell carcinomas (clear RCC) are characterized almost universally by loss of heterozygosity on chromosome 3p, which usually involves any combination of three regions: 3p25-p26 (harboring the VHL gene), 3p12-p14.2 (containing the FHIT gene), and 3p21-p22, implying inactivation of the resident tumor-suppressor genes (TSGs). For the 3p21-p22 region, the affected TSGs remain, at present, unknown. Recently, the RAS association family 1 gene (isoform RASSF1A), located at 3p21.3, has been identified as a candidate lung and breast TSG. In this report, we demonstrate aberrant silencing by hypermethylation of RASSF1A in both VHL-caused clear RCC tumors and clear RCC without VHL inactivation. We found hypermethylation of RASSF1A's GC-rich putative promoter region in most of analyzed samples, including 39 of 43 primary tumors (91%). The promoter was methylated partially or completely in all 18 RCC cell lines analyzed. Methylation of the GC-rich putative RASSF1A promoter region and loss of transcription of the corresponding mRNA were related causally. RASSF1A expression was reactivated after treatment with 5-aza-2′-deoxycytidine. Forced expression of RASSF1A transcripts in KRC/Y, a renal carcinoma cell line containing a normal and expressed VHL gene, suppressed growth on plastic dishes and anchorage-independent colony formation in soft agar. Mutant RASSF1A had reduced growth suppression activity significantly. These data suggest that RASSF1A is the candidate renal TSG gene for the 3p21.3 region.