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Thomas Becker

Publications and source records attributed to Thomas Becker.

At least 19 recordsLinked to original sources
PubMed2025

The Myo2 adaptor Ldm1 and its receptor Ldo16 mediate actin-dependent lipid droplet motility.

Organelle motility enables strategic cellular reorganizations. In yeast, this process depends on the actin cytoskeleton, type V myosin motor proteins, and organelle-specific myosin adaptor proteins. While the myosin adaptors for most organelles are known, the coupling of myosin to lipid droplets (LDs), the cellular lipid storage organelles, remained enigmatic. Using genome-wide screening, we identified Ldm1 (lipid droplet motility 1/Yer085c) as a myosin adaptor. Ldm1 binds to the globular tail domain of the myosin Myo2 and to the LD surface protein Ldo16 to enable actin-dependent LD motility. Ldo16 has additional roles in LD contact sites to the vacuole and the endoplasmic reticulum, suggesting a coordination of LD motility and organelle tethering. Ldm1 has a second role in mitochondrial transport, and elevated Ldm1 levels rescue defects of the mitochondrial Myo2-adaptors Mmr1/Ypt11. Our work identifies the molecular machinery for LD motility and contributes to a comprehensive understanding of acto-myosin-based cellular reorganization.

Lipid Droplets↗
PubMed2007

Growth and pathfinding of regenerating axons in the optic projection of adult fish.

In contrast to mammals, teleost fish are able to regrow severed long-range projection axons in the central nervous system (CNS), leading to recovery of function. The optic projection in teleost fish is used to study neuron-intrinsic and environmental molecular factors that determine successful axon regrowth and navigation through a complex CNS pathway back to original targets. Here we review evidence for regeneration-specific regulation and robust expression of growth- and pathfinding-associated genes in regenerating retinal ganglion cell (RGC) axons of adult fish. The environment of the CNS in fish appears to contain few inhibitory molecules and at the same time a number of promoting molecules for axon regrowth. Finally, some environmental cues that are used as guidance cues for developing RGC axons are also present in continuously growing adult animals. These molecules may serve as guidance cues for the precise navigation of axons from newly generated RGCs in adult animals as well as of regenerating RGC axons after a lesion. The application of new molecular techniques especially to adult zebrafish, is likely to produce new insights into successful axonal regeneration in the CNS of fish and the absence thereof in mammals.

Animals↗
PubMed2007

Mental health care in Germany: current state and trends.

Germany turned towards community-based mental health care in the mid seventies, during a general climate of social and political reform. The continuing deinstitutionalisation process and the implementation of community mental health services was considerably affected by the reunification of East and West Germany in 1990, which required dramatic changes in the structure and quality of the mental health care system of the former German Democratic Republic (GDR). Overall, German mental health care is organised as a subsidiary system, where planning and regulating mental health care is the responsibility of the 16 federal states. So German mental health care provision is spread among many sectors and characterised by considerable regional differences. A key characteristic is the particularly wide gap between inpatient and outpatient services, which are funded separately and staffed by different teams. In 2003 the total number of psychiatric beds was a mere two thirds of the overall bed capacity in 1991, the first year as a re-unified Germany, when psychiatric beds in East and West Germany totalled 80,275. From 1970 onwards the number of psychiatric beds was cut by roughly half. So the momentum of the reform has been strong enough to assimilate the completely different mental health care system of the former German Democratic Republic and, in the course of a decade, to re-structure mental health services for an additional 17-18 million new inhabitants. In an ongoing struggle to adapt to changing administrative set-ups, legal frameworks, and financial constraints, psychiatry in Germany in currently facing specific problems and is seriously challenged to defend to considerable achievements of the past. A major obstacle to achieving this aim lies in the fragmented system of mental health care provision and mental health care funding.

Germany↗
PubMed2006

The cytohesin Steppke is essential for insulin signalling in Drosophila.

In metazoans, the insulin signalling pathway has a key function in regulating energy metabolism and organismal growth. Its activation stimulates a highly conserved downstream kinase cascade that includes phosphatidylinositol-3-OH kinase (PI(3)K) and the serine-threonine protein kinase Akt. This study identifies a new component of insulin signalling in Drosophila, the steppke gene (step). step encodes a member of the cytohesin family of guanine nucleotide exchange factors (GEFs), which have been characterized as activators for ADP-ribosylation factor (ARF) GTPases. In step mutant animals both cell size and cell number are reduced, resulting in decreased body size and body weight in larvae, pupae and adults. step acts upstream of PI(3)K and is required for the proper regulation of Akt and the transcription factor FOXO. Temporally controlled interference with the GEF activity of the Step protein by feeding the chemical inhibitor SecinH3 causes a block of insulin signalling and a phenocopy of the step mutant growth defect. Step represses its own expression and the synthesis of growth inhibitors such as the translational repressor 4E-BP. Our findings indicate a crucial role of an ARF-GEF in insulin signalling that has implications for understanding insulin-related disorders, such as diabetes and obesity.

Animals↗
PubMed2006

[Impact of structure and context on utilization of socio-psychiatric services in Saxony--a multi-level-analysis].

OBJECTIVE: To analyse the influence of structural (service) aspects and context (catchment area) variables on the individual use of socio-psychiatric services in Saxony. METHOD: Data collected in 34 services were used. For the analysis of the variance components a multi-level model with random effects was computed using data at two levels ([1] client, and [2] service/catchment area). RESULTS: Service use was substantially influenced by structural/context factors which accounted for a proportion of 10 to 50 % of the variance depending on the (sub-)group of users included in the analysis. The impact of service structure and context on service use was particularly strong in the subgroup of service users with very high service utilisation.

Adult↗
PubMed2006

Ex vivo microvesicle formation after prolonged ischemia in renal transplantation.

INTRODUCTION: Patients with chronic renal failure suffer from dysfunction in coagulation. Kidney transplantation induces inflammatory reactions and thus activation of platelets. Activated platelets, in turn, form microvesicles by shedding. These microvesicles have been shown to have coagulant activities. Activated platelets in prolonged cold ischemia were associated with delayed graft function and inferior survival. We investigated ex vivo formation of microvesicles in kidney transplantation and the influence of cold graft storage on microvesicles. METHODS: 20 patients (47.4+/-10.6 years (mean+/-SD)) undergoing transplantation were included in the study after written informed consent. Dependent on cold preservation time of transplanted kidneys, recipients were allocated into two groups with 10.4+/-6.1 h (group 1) and 23.7+/-3.8 h (group 2) preservation time, respectively. Blood samples were drawn before anesthesia, 12 h, 2, 7 and 14 days after transplantation. To evaluate microvesicle release, samples were activated with thrombin-receptor-activating-peptide-6 (TRAP) or adenosine-di-phosphate. Microvesicles were counted as percentage of platelets smaller than a predetermined size in flow cytometry. RESULTS: Platelet derived ex vivo microvesicle formation was significantly higher up to 48 h after transplantation when stimulated with TRAP in group 1. Platelet count was significantly higher compared to baseline values in the short-term ischemia group but not with long-term ischemia. Creatinine was significantly lower at study end compared to baseline with no differences between both groups. CONCLUSIONS: Lower platelet microvesicle formation after ex vivo stimulation with TRAP was associated with longer graft ischemia time. This may be a sign of former activation of platelets which could influence graft function and survival.

Adenosine Diphosphate↗
PubMed2006

Following the signal sequence from ribosomal tunnel exit to signal recognition particle.

Membrane and secretory proteins can be co-translationally inserted into or translocated across the membrane. This process is dependent on signal sequence recognition on the ribosome by the signal recognition particle (SRP), which results in targeting of the ribosome-nascent-chain complex to the protein-conducting channel at the membrane. Here we present an ensemble of structures at subnanometre resolution, revealing the signal sequence both at the ribosomal tunnel exit and in the bacterial and eukaryotic ribosome-SRP complexes. Molecular details of signal sequence interaction in both prokaryotic and eukaryotic complexes were obtained by fitting high-resolution molecular models. The signal sequence is presented at the ribosomal tunnel exit in an exposed position ready for accommodation in the hydrophobic groove of the rearranged SRP54 M domain. Upon ribosome binding, the SRP54 NG domain also undergoes a conformational rearrangement, priming it for the subsequent docking reaction with the NG domain of the SRP receptor. These findings provide the structural basis for improving our understanding of the early steps of co-translational protein sorting.

Animals↗
PubMed2006

Accurate quantification of dimethylamine (DMA) in human urine by gas chromatography-mass spectrometry as pentafluorobenzamide derivative: evaluation of the relationship between DMA and its precursor asymmetric dimethylarginine (ADMA) in health and disease.

Dimethylamine [DMA, (CH(3))(2)NH)] is abundantly present in human urine. Main sources of urinary DMA have been reported to include trimethylamine N-oxide, a common food component, and asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthesis. ADMA is excreted in the urine in part unmetabolized and in part after hydrolysis to DMA by dimethylarginine dimethylaminohydrolase (DDAH). Here we describe a GC-MS method for the accurate and rapid quantification of DMA in human urine. The method involves use of (CD(3))(2)NH as internal standard, simultaneous derivatization with pentafluorobenzoyl chloride and extraction in toluene, and selected-ion monitoring of m/z 239 for DMA and m/z 245 for (CD(3))(2)NH in the electron ionization mode. GC-MS analysis of urine samples from 10 healthy volunteers revealed a DMA concentration of 264+/-173 microM equivalent to 10.1+/-1.64 micromol/mmol creatinine. GC-tandem MS analysis of the same urine samples revealed an ADMA concentration of 27.3+/-15.3 microM corresponding to 1.35+/-1.2 micromol/mmol creatinine. In these volunteers, a positive correlation (R=0.83919, P=0.0024) was found between urinary DMA and ADMA, with the DMA/ADMA molar ratio being 10.8+/-6.2. Elevated excretion rates of DMA (52.9+/-18.5 micromol/mmol creatinine) and ADMA (3.85+/-1.65 micromol/mmol creatinine) were found by the method in 49 patients suffering from coronary artery disease, with the DMA/ADMA molar ratio also being elevated (16.8+/-12.8). In 12 patients suffering from end-stage liver disease, excretion rates of DMA (47.8+/-19.7 micromol/mmol creatinine) and ADMA (5.6+/-1.5 micromol/mmol creatinine) were found to be elevated, with the DMA/ADMA molar ratio (9.17+/-4.2) being insignificantly lower (P=0.46). Between urinary DMA and ADMA there was a positive correlation (R=0.6655, P<0.0001) in coronary artery disease, but no correlation (R=0.27339) was found in end-stage liver disease.

Acetazolamide↗
PubMed2006

Assessment of differentiation and progression of hepatic tumors using array-based comparative genomic hybridization.

BACKGROUND & AIMS: To gain more information about the molecular mechanisms leading to dedifferentiation of hepatocellular adenoma (HCA) and hepatocellular carcinoma (HCC), high-resolution array-based comparative genomic hybridization (array-CGH) was performed on 24 cases of HCC and 10 cases of HCA. METHODS: DNA chips containing 6251 individual bacterial artificial chromosome/plasmid artificial chromosome clones were used. They allowed for a genome-wide resolution of 1 Mb and an even higher resolution of up to 100 kb for chromosome regions recurrently involved in human tumors and for regions containing known tumor-suppressor genes and oncogenes. RESULTS: Copy number changes on the genomic scale were found by array-based comparative genomic hybridization in all cases. In HCC, gains of chromosomal regions 1q (91.6%), and 8q (58.3%), and losses of 8p (54%) were found most frequently. Hierarchic cluster analysis branched all HCA from HCC. However, in 2 adenomas with a known history of glycogenosis type I and adenomatosis hepatis gains of 1q were found, too. The critically gained region was narrowed down to bands 1q22-23. Although no significant differences in the mean number of chromosomal aberrations were seen between adenomas and well-differentiated carcinomas (2.7 vs 4.6), a significant increase accompanied the dedifferentiation of HCC (14.1 in HCC-G2 and 16.3 in HCC-G2/3; P < .02). Dedifferentiation of HCC also was correlated closely to losses of 4q and 13q (P <.001 and <.005, respectively). CONCLUSIONS: The increased chromosomal instability during dedifferentiation of HCC leads to an accumulation of structural chromosomal aberrations and losses and gains of defined chromosome regions.

Adenoma, Liver Cell↗
PubMed2006

Structure of eEF3 and the mechanism of transfer RNA release from the E-site.

Elongation factor eEF3 is an ATPase that, in addition to the two canonical factors eEF1A and eEF2, serves an essential function in the translation cycle of fungi. eEF3 is required for the binding of the aminoacyl-tRNA-eEF1A-GTP ternary complex to the ribosomal A-site and has been suggested to facilitate the clearance of deacyl-tRNA from the E-site. Here we present the crystal structure of Saccharomyces cerevisiae eEF3, showing that it consists of an amino-terminal HEAT repeat domain, followed by a four-helix bundle and two ABC-type ATPase domains, with a chromodomain inserted in ABC2. Moreover, we present the cryo-electron microscopy structure of the ATP-bound form of eEF3 in complex with the post-translocational-state 80S ribosome from yeast. eEF3 uses an entirely new factor binding site near the ribosomal E-site, with the chromodomain likely to stabilize the ribosomal L1 stalk in an open conformation, thus allowing tRNA release.

Adenosine Diphosphate↗
PubMed2006

Quality of life in adult transplant recipients more than 15 years after kidney transplantation.

BACKGROUND: With continuously rising survival rates following renal transplantation, health-related quality of life (HQOL) of long-term transplant survivors becomes increasingly important. METHODS: Recipients more than 15 years after successful renal transplantation were studied retrospectively. HQOL in 139 long-term transplant recipients was assessed using the SF-36 and the disease-specific kidney transplant questionnaire (KTQ-25). RESULTS: Long-term transplant recipients revealed satisfactory HQOL that was comparable to the healthy population in four of eight SF-36 categories (role physical, social functioning, role emotional and mental health). Other SF-36 categories such as physical functioning, physical pain, general health, and vitality were reduced. Among the study population, disease-specific HQOL was comparable or even improved to that of patients awaiting transplantation. In contrast to retired or unemployed patients, employed recipients revealed a highly significant improved HQOL in numerous SF-36 categories such as physical functioning (P<0.001), physical pain (P<0.001), general health (P<0.001), vitality (P<0.001), social functioning (P<0.005), and mental health (P<0.001), as well as for the KTQ-dimensions physical symptoms (P<0.001), fatigue (P>0.001), uncertainty/fear (P<0.01), and emotions (P<0.05). Other factors positively correlating with improved HQOL in certain dimensions were living situation, systolic blood pressure, and recipient age. CONCLUSIONS: More than 15 years after renal transplantation, recipients present satisfactory HQOL comparable to the general healthy population or at least to pretransplant patients. Vocational rehabilitation following renal transplantation is of highest importance among long-term survivors and is associated with improved HQOL.

Aging↗
PubMed2006

The molecular chaperone Hsp90 delivers precursor proteins to the chloroplast import receptor Toc64.

Precursor protein targeting toward organellar surfaces is assisted by different cytosolic chaperones. We demonstrate that the chloroplast protein translocon subunit Toc64 is the docking site for Hsp90 affiliated preproteins. Thereby, Hsp90 is recognised by the clamp type TPR domain of Toc64. The subsequent transfer of the preprotein from Toc64 to the major receptor of the Toc complex, namely Toc34, is affinity driven and nucleotide dependent. We propose that Toc64 acts as an initial docking site for Hsp90 associated precursor proteins. We outline a mechanism in which chaperones are recruited for a specific targeting event by a membrane-inserted receptor.

Amino Acid Sequence↗
PubMed2006

Molecular properties of Oep21, an ATP-regulated anion-selective solute channel from the outer chloroplast membrane.

The flux of phosphorylated carbohydrates, the major export products of chloroplasts, is regulated at the level of the inner and presumably also at the level of the outer membrane. This is achieved through modulation of the outer membrane Oep21 channel currents and tuning of its ion selectivity. Refined analysis of the Oep21 channel properties by biochemical and electrophysiological methods revealed a channel formed by eight beta-strands with a wider pore vestibule of dvest approximately 2.4 nm at the intermembrane site and a narrower filter pore of drestr approximately 1 nm. The Oep21 pore contains two high affinity sites for ATP, one located at a relative transmembrane electrical distance delta = 0.56 and the second close to the vestibule at the intermembrane site. The ATP-dependent current block and reduction in anion selectivity of the Oep21 channel is relieved by the competitive binding of phosphorylated metabolic intermediates like 3-phosphoglycerate and glycerinaldehyde 3-phosphate. Deletion of a C-terminal putative FX4K binding motif in Oep21 decreased the capability of the channel to tune its ion selectivity by about 50%, whereas current block remained unchanged.

Adenosine Triphosphate↗
PubMed2006

Outcome and quality of life in patients with polycystic liver disease after liver or combined liver-kidney transplantation.

In advanced stages of polycystic liver disease, often associated with polycystic kidney disease, a curative therapy is liver or combined liver-kidney transplantation. However, little is known about long-term outcome and quality of life. Between 1990 and 2003, 36 patients (32 female, 4 male) with polycystic liver or combined liver-kidney disease underwent liver (n = 21) or liver-kidney (n = 15) transplantation at our center. Main indications for liver transplantation were cachexia, muscle atrophy, loss of weight, recurrent cyst infections, portal hypertension, and ascites. Apart from clinical parameters, 2 anonymous questionnaires (standard short form 36 and self-designed) addressing quality of life and social status were evaluated. Five patients (14 %) died due to sepsis or myocardial infarction with pneumonia, all within 61 days after transplantation. The follow-up time of the remaining 31 patients ranged from 5 to 156 months, with a mean of 62 months. Of the 23 (74%) answered the questionnaires, 91% of patients felt "much better" or "better," only 9% felt "worse" than before, and 52% of patients participated in sports regularly. Fatigue, physical fitness, loss of appetite, and vomiting improved significantly after transplantation. Physical attractiveness and interest in sex increased as well. Professional occupation did not change for 71% of patients. Family situation before and after transplantation changed in 1 case only. Finally, 78% of patients said they would opt for transplantation again, while 17% were undecided; 1 patient would not repeat transplantation. In conclusion, patients with advanced polycystic liver or polycystic liver-kidney disease have an excellent survival rate and an improved quality of life after liver or combined liver-kidney transplantation.

Adult↗
PubMed2006

The value of reoperative procedures after unusual reconstructions in the gastrointestinal tract associated with substantial morbidity.

Reconstructive procedures of the gastrointestinal tract after resection or for bypass surgery are well established and almost completely standardized but still may cause significant morbidity. Deviations from standard reconstructive procedures have pitfalls, especially when complex reconstructions are required, and may lead to substantial morbidity. Scientific evidence for the indication to reoperate as well as the best methods to be applied is lacking and surgical experience indispensable. We report on 10 reoperative cases between 1999 and 2003 after uncommon reconstructive procedures in the gastrointestinal tract associated with substantial morbidity. In five cases (five of seven), operative correction of uncommon reconstructions in the upper gastrointestinal tract after gastrectomy, completion gastrectomy, or distal gastric resection could completely alleviate the complaints including reflux esophagitis, whereas incomplete relief of symptoms was achieved in the remaining two cases (two of seven). Corrective procedures used end-to-side esophagojejunostomy or end-to-side gastrojejunostomy with a retrocolic isoperistaltic jejunal Roux-en-Y loop and end-to-side jejunojejunostomy approximately 40 cm distal to the proximal anastomosis for biliary and exocrine pancreatic drainage. After biliodigestive anastomosis, problematic cholangitis could be completely alleviated in three cases (three of three) using end-to-side hepaticojejunostomy with a retrocolic isoperistaltic jejunal Roux-en-Y loop and end-to-side jejunojejunostomy 40 cm distal to the hepaticojejunostomy for reconstruction of the continuity of the gastrointestinal tract. Compliance with well-established standard reconstructive procedures is of elementary importance in the gastrointestinal tract. Operative correction of uncommon reconstructions associated with morbidity is usually indicated.

Aged↗
PubMed2006

[User involvement in mental health services research].

BACKGROUND: User involvement in mental health services research is discussed in Great Britain, and a number of user-led research initiatives can be found. In Germany, less attention is paid to the concept while virtually no initiatives can be found. METHOD: The concept of user involvement is introduced by reviewing the relevant literature. After discussion of theoretical and methodological implications, practicability of the concept for mental health services research is illustrated by some examples from Great Britain. RESULTS/DISCUSSION: User involvement in mental health services may promote the provision of user focused services. User involvement aims at the empowerment of mental health service users and can also improve the quality of mental health services research. Frequently, user-led/collaborative studies are focused on mental health service assessment. Some problematic aspects (e. g. representativeness, knowledge/skills of users) are discussed. Although more research is needed to document the additional benefit of user involvement in mental health services research it is conceivable that the concept will gain in importance.

Cross-Cultural Comparison↗