Drought and crop yield.

Episodes of water shortage occur in most agricultural regions of the world. Their durations and intensities increase, and their seasonal timing alters with changing climate. During the ontogenic cycle of crop plants, each development stage, such as seed germination, seedling establishment, vegetative root and shoot growth, flowering, pollination and seed and fruit development, is specifically sensitive to dehydration. Desiccation threatens yield and leads to specific patterns, depending on the type of crop plant and the harvested plant parts, e.g. leafy vegetables, tubers, tap roots or fruits. This review summarizes the effects of drought stress on crop plants and relates the dehydration-dependent yield penalty to the harvested organ and tissue. The control of shoot transpiration and the reorganization of root architecture are of core importance for maintaining proper plant water relationships. Upon dehydration, the provision and partitioning of assimilates and the uptake and distribution of nutrients define remaining growth activity. Domestication of crops by selection for high yield under high input has restricted the genetic repertoire for achieving drought stress tolerance. Introgression of suitable alleles from wild relatives into commercial cultivars might improve the ability to grow with less water. Future research activities should focus more on field studies in order to generate more realistic improvements to crops. Robotic field phenotyping should be integrated into genetic mapping for the identification of relevant traits.

Spatio-temporal deleted in colorectal cancer (DCC) and netrin-1 expression in human foetal brain development.

AIMS: Deleted in colorectal cancer (DCC) and its ligand netrin-1 are known as axonal guidance factors, being involved in angiogenesis, migration and survival of precursor cells in the embryonic mammalian central nervous system (CNS). So far, little is known about the distribution of those molecules in human CNS development. METHODS: We investigated 22 human foetal brain specimens (12th and 28th week of gestation) for DCC and netrin-1 expression by means of immunohistochemistry, immunofluorescence and confocal laser microscopy. Statistical analysis was performed by applying a semi-quantitative score, including staining intensity and frequency and correlation with foetal age. RESULTS: DCC and netrin-1 were differentially expressed throughout the developing human foetal telencephalic and cerebellar cortical layers. Netrin-1 exhibited the highest levels in telencephalic germinal layers, whereas the strongest DCC immunoreactivity was seen in the developing cortical plate. Netrin-1 and DCC were predominantly present on cerebellar external granule layer cells. Distinct co-expression was seen in maturing foetal brainstem nuclei, cerebellar external granular layer and the choroid plexus. In contrast, endothelial cells showed strong netrin-1 expression with subsidiary DCC immunoreactivity. Pontine and telencephalic axonal fibre tracts also demonstrated strong netrin-1 expression. CONCLUSIONS: We show that DCC and netrin-1 are ubiquitously expressed in the human foetal brain; however, both exhibit a distinct spatio-temporal expression pattern. Together with the data from animal experiments, our findings might indicate also an important role for DCC and netrin-1 in human foetal CNS development.

Professional risk for skin cancer development in male mountain guides--a cross-sectional study.

OBJECTIVE: For reasons of their outdoor work, mountain guides (MG) are heavily exposed to ultraviolet radiation during their work. METHODS: A standardized interview and examination were performed on 283 male MG (median 41 years) from Germany, Switzerland and Austria and 309 age-matched controls. The median occupation time as MG was 17 years; 39.9% were working full-time. RESULTS: The incidence of skin cancer and precancerous lesions was obtained. Precancerous lesions as solar keratosis (SK) were significantly more frequent in MG (25.4% vs. 7.4%). There was no skin cancer [BCC, SSC, melanoma (MEL)] in the control subjects. Basal cell carcinoma (BCC) was diagnosed in 20 MG (7.1%) and SSC in four MG (1.4%). There were 10 highly suspicious melanocytic lesions; one MG had a histologically confirmed malignant MEL. Risk factors for SK in the multivariate analysis included occupation (P < 0.0001), age (P < 0.0001) and skin type (P = 0.0002). Within the MG group, age (P < 0.0001) and hair colour (P = 0.0058) were independent risk factors for SK. Severe lifetime sunburns (P = 0.0007) and skin type (P = 0.041) were the significant risk factors for BCC, within the MG group in addition to the number of guiding days (P = 0.010). The risk factor for skin cancer (BCC, SCC and MEL) was the number of heavy sunburns during lifetime (P = 0.0014). CONCLUSION: The present study demonstrates an association between high occupational ultraviolet-exposure and an increased prevalence of precancerous skin lesions and skin cancer. MG may be considered as an example for other outdoor professionals. Skin cancer of outdoor workers is likely to be an occupational disease. Primary and secondary prevention should be enforced.

Immune depression syndrome following human spinal cord injury (SCI): a pilot study.

Experimental spinal cord injury (SCI) has been identified to trigger a systemic, neurogenic immune depression syndrome. Here, we have analyzed fluctuations of immune cell populations following human SCI by FACS analysis. In humans, a rapid and drastic decrease of CD14+ monocytes (<50% of control level), CD3+ T-lymphocytes (<20%, P<0.0001) and CD19+ B-lymphocytes (<30%, P=0.0009) and MHC class II (HLA-DR)+ cells (<30%, P<0.0001) is evident within 24 h after spinal cord injury reaching minimum levels within the first week. CD15+ granulocytes were the only leukocyte subpopulation not decreasing after SCI. A contributing, worsening effect of high dose methylprednisolone cannot be excluded with this pilot study. We demonstrate that spinal cord injury is associated with an early onset of immune suppression and secondary immune deficiency syndrome (SCI-IDS). Identification of patients suffering spinal cord injury as immune compromised is a clinically relevant, yet widely underappreciated finding.

Erythropoietin receptor is expressed in meningiomas and lower levels are associated with tumour recurrence.

AIMS: The Epo-EpoR pathway plays a role in tumour growth, metastasis and treatment resistance and is a potential target in oncological treatment. As the EpoR status in human meningiomas is unknown, our aim was to characterize EpoR expression in these tumours. METHODS: We examined 131 meningioma samples of all WHO grades from 116 patients by immunohistochemistry for EpoR. Among these, 25 meningiomas showed brain invasion and 29 patients had a further tumour recurrence. A group of 20 patients without tumour recurrence served as controls. In 12 cases we were able to compare both the primary and the following recurrent tumours. The presence of EpoR in meningiomas was confirmed by RT-PCR and Western blot. RESULTS: EpoR was expressed in all meningiomas. Statistical analysis revealed that the mean expression levels of EpoR were significantly lower in primary tumours with known recurrence compared with a recurrence-free control group. Additional matched pair analysis in individual cases showed no significant differences between primary and recurrent tumours. No significant correlation between EpoR expression and WHO grade, age, sex or brain invasion was detected. Using specific primer pairs for RT-PCR, we were able to detect all three known isoforms of EpoR: the full-length isoform EpoR-F, the truncated isoform EpoR-T and the soluble isoform EpoR-S. CONCLUSIONS: Our results demonstrate the expression of EpoR in meningiomas. Lower EpoR mean levels might be a useful marker for a higher recurrence risk, but further studies are needed to clarify the influence of EpoR on recurrences and the role of the different isoforms.

Molecular mechanisms of psychostimulant-induced structural plasticity.

Drug addiction is characterized by persistent behavioral and cellular plasticity throughout the brain's reward regions. Among the many neuroadaptations that occur following repeated drug administration are alterations in cell morphology including changes in dendritic spines. While this phenomenon has been well documented, the underlying molecular mechanisms are poorly understood. Here, within the context of drug abuse, we review and integrate several of the established pathways known to regulate synaptic remodeling, and discuss the contributions of neurotrophic and dopamine signaling in mediating this structural plasticity. Finally, we discuss how such upstream mechanisms could regulate actin dynamics, the common endpoint involved in structural remodeling in neurons.

Salinity and crop yield.

Thirty crop species provide 90% of our food, most of which display severe yield losses under moderate salinity. Securing and augmenting agricultural yield in times of global warming and population increase is urgent and should, aside from ameliorating saline soils, include attempts to increase crop plant salt tolerance. This short review provides an overview of the processes that limit growth and yield in saline conditions. Yield is reduced if soil salinity surpasses crop-specific thresholds, with cotton, barley and sugar beet being highly tolerant, while sweet potato, wheat and maize display high sensitivity. Apart from Na+ , also Cl- , Mg2+ , SO4 2- or HCO3 - contribute to salt toxicity. The inhibition of biochemical or physiological processes cause imbalance in metabolism and cell signalling and enhance the production of reactive oxygen species interfering with cell redox and energy state. Plant development and root patterning is disturbed, and this response depends on redox and reactive oxygen species signalling, calcium and plant hormones. The interlink of the physiological understanding of tolerance processes from molecular processes as well as the agronomical techniques for stabilizing growth and yield and their interlinks might help improving our crops for future demand and will provide improvement for cultivating crops in saline environment.

Regulation of thiol metabolism as a factor that influences the development and storage capacity of beech seeds.

Seeds are the basis of propagation for the common beech (Fagus sylvatica L.), but the seed set of the beech is unsteady, with 5-10 years between abundant crops. Beech seeds are very difficult to store and lose their viability quickly even in optimum storage conditions. To date, it has not been possible to determine factors indicative of the aging process and the loss of viability of beech seeds during storage. To address this important economic challenge and interesting scientific problem, we analyzed the adjustment of the redox state during the development and storage of seeds. Many metabolic processes are based on reduction and oxidation reactions. Thiol proteins control and react to the redox state in the cells. The level of thiol proteins increased during seed maturation and decreased during storage. Gel-based redox proteomics identified 17 proteins in beech seeds during development. The proteins could be assigned to processes like metabolism and antioxidant functions. During storage, the number of proteins decreased to only six, i.e., oxidoreductases, peptidases, hydrolases and isomerases. The occurrence of peroxiredoxins (PRX) as thiol peroxidases and redox regulators indicates an important role of cytosolic 1CysPRX and PRXIIC, mitochondrial PRXIIF, and plastidic PRXIIE, 2CysPRX, and PRXQ in beech seeds during development and storage. Particularly, 2CysPRX was present in beech seeds during development and storage and may perform an important function in regulation of the redox state during both seed development and storage. The role of thiol proteins in the regulation of the redox state during the development and storage of beech seeds is discussed.

The Residual Platelet Aggregation after Deployment of Intracoronary Stent (PREDICT) score.

BACKGROUND: Recent studies suggest a high interindividual variability of response to clopidogrel associated with adverse cardiovascular outcome. Different clinical factors are considered to influence a persistent residual platelet aggregation (RPA) despite conventional antiplatelet therapy. OBJECTIVES: To investigate clinical factors that affect RPA after 600-mg clopidogrel loading in a large unselected cohort of patients with symptomatic CAD. METHODS: The study population included a consecutive cohort of 1,092 patients treated with coronary stenting for stable angina and acute coronary syndromes (ACS). Residual platelet activity was assessed by ADP (20 micromol L(-1))-induced platelet aggregation >or= 6 h after LD. Eleven clinical factors were included in the primary analysis. RESULTS: In multivariate regression analysis increased RPA was significantly influenced by ACS, reduced LV-function, diabetes mellitus, renal failure (creatinine > 1.5 mg dL(-1)), and age > 65 years. In a factor-weighed model the risk for high RPA increased with higher score levels (OR for patients with a score of 1-3, 1.21, 95% CI 0.7-2.1; score 4-6, OR 2.0, 95% CI 1.17-3.5; P = 0.01; score 7-9, OR 3.3, 95% CI 1.8-6.0). During a 30-day follow-up the incidence of major adverse events was higher in patients with RPA in the upper tertile (4.8% vs. 2.5% in the 2nd and 1.5% in the 1st tertile; P < 0.05). CONCLUSIONS: The PREDICT score provides a good tool to estimate residual platelet activity after clopidogrel LD by easily available patient details. Additionally, we demonstrate its association with short-term outcome. Thus, patients with a high score may benefit from intensified antiplatelet therapy by improved platelet inhibition and risk reduction for thromboischemic events.

Repeated social defeat stress-induced sensitization to the locomotor activating effects of d-amphetamine: role of individual differences.

RATIONALE: In this study, we sought to examine individual differences in stress-induced behavioral sensitization to d-amphetamine after repeated social defeat stress. In an effort to understand what mechanisms underlie stress-induced sensitization to d-amphetamine, we examined striatal gene expression of the dopamine receptor D(2). Additionally, we investigated if repeated social defeat was associated with changes in dendritic spine density in the hippocampus, prefrontal cortex, and nucleus accumbens of rats that exhibit stress-induced sensitization. METHODS: Male rats were classified into high responders (HR) and low responders (LR) based on their locomotor response to a novel environment. Then, rats were either handled as a control or defeated on four occasions by aggressive rats. Two weeks after the last defeat, animals were challenged with one of three doses of d-amphetamine and their locomotor activity was recorded. RESULTS: Non-defeated HR rats exhibited higher locomotor activity in response to d-amphetamine when compared to LR non-defeated rats. Fourteen days from the last repeated social defeat, LR rats and HR rats were behaviorally identical in response to acute injections of amphetamine. Furthermore, HR non-defeated rats had less D(2) mRNA expression in the nucleus accumbens core and dorsal striatum than do LR non-defeated rats. However, after repeated social defeat, HR and LR rats had identical D(2) mRNA expression in both the core and dorsal striatum. Finally, there were no changes in dendritic spine density in any of the brain areas examined in LR rats. CONCLUSION: Repeated social defeat abolishes individual differences in behavioral responses to d-amphetamine which may be due to a down-regulation of striatal dopamine D(2) receptors in LR rats.

The SUI-homologous translation initiation factor eIF-1 is involved in regulation of ion homeostasis in rice.

Halophytes survive high salinity by using complex adaptive mechanisms. In a search for novel molecular mechanisms involved in salt acclimation, transcript analyses revealed increased expression of a SUI-homologous translation initiation factor eIF-1 in the salt-tolerant grass species Festuca rubra ssp. littoralis but not in rice. Upon analysis of the cell specificity of eIF-1 transcription by in situ polymerase chain reaction (PCR), predominant signals were detected in rice leaf mesophyll. To further examine the role of eIF-1 in salt tolerance, transgenic rice plants were generated that over-express this factor under the control of the CaMV-35S promoter. The eIF-1 over-expressing lines showed improved growth under salt stress that was correlated with maintenance of photosynthetic activity and reduced Na(+) and Cl(-) accumulation in leaves. The transgenic rice lines also activated expression of the vacuolar H(+)-ATPase. In addition, an oxidoreductase that belongs to the aldo/keto reductase family was identified as a gene with modified expression in the eIF-1 over-expressing lines, compared with wild-type rice. Our data suggest that eIF-1 has a central function in salt-stress adaptation in rice by regulating ion accumulation and the intracellular redox status.

Hypericin uptake: a prognostic marker for survival in high-grade glioma.

Currently adjuvant chemotherapy for glioblastoma patients can prolong survival time relative to patients who receive only surgery and radiotherapy. Despite these improvements and experimental and clinical efforts the prognosis for glioblastoma patients remains poor. At present, interest is focused on individual prognostic factors influencing patient responses to therapy. Photodynamic therapy may be a promising therapeutic option in the treatment of glioblastoma. In this investigation we examined whether uptake of hypericin (HY), a fluorescent photosensitization agent, by ex vivo glioblastoma cell lines correlates with prognosis of the individual from which the cell lines were derived. Twelve primary human glioma cell cultures were incubated with 20 micromol HY. Fluorescence intensity was measured using fluorescence microscopy. Three patients suffered from an anaplastic astrocytoma, WHO grade III, nine had a glioblastoma, WHO grade IV. In 6/12 patients complete tumour resection was possible. The mean survival time of the six patients in whom complete tumour resection was performed was 26 months, compared with 5 months for those who underwent incomplete resection. Eleven patients received radiation therapy. The five patients who received chemotherapy survived for a mean duration of 26 months, compared with the seven patients who survived for a mean duration of 5 months without chemotherapy. Statistical analysis using a parametric survival model based on the Weibull distribution showed that fluorescence intensity was the variable with the lowest p-value associated with survival (p=0.0225). An increase of 553 arbitrary units of fluorescence intensity is predicted to double survival time. Uptake of HY, a lipophilic molecule, is assumed to be related to low-density lipoprotein (LDL) uptake and metabolism. Cell proliferation is associated with a high turnover of cholesterol and membrane growth, which is related to cholesterol uptake by LDL. In summary, HY uptake by ex vivo glioblastoma cell cultures seems to be positively associated with survival of patients with malignant glioma.

Celebrating fifty years of the Biometrical Journal.

The publication of Volume 50 of the Biometrical Journal (formerly Biometrische Zeitschrift) in 2008 provides the perfect opportunity to describe the history of the present journal. We report on the long period of preparation for the journal within the German Region (DR) of the International Biometric Society (IBS). A special paragraph is dedicated to the first ten volumes. We emphasize the role of the journal as a bond between German biometricians on both sides of the border between the two German nations and IBS regions at that time. Furthermore, we report on the development of its thematic spectrum and impact factors and provide citation frequencies.

Comparative neuro tissue engineering using different nerve guide implants.

At the moment autologous nerve grafting remains the only reasonable technique for reconstruction of peripheral nerve defects. Unfortunately, this technique has a lot of complications and disadvantages. These problems are related to the autologous nerve that is harvested for this procedure. Donor site morbidity with loss of sensitivity, painful neuroma formation and of course the restricted availability of autologous nerves stimulates the idea for alternative techniques on that field. In this paper we describe our experience with different graft materials for reconstruction of a 2 cm nerve gap in a median nerve model in rats. After implantation of various materials (biological/synthetic) the main experiments were conducted with a synthetic, biodegradable nerve conduit seeded with autologous Schwann cells. With this material we were able to reconstruct successfully a 2 cm gap in the rat median nerve. Regeneration with this material was found to be equally to an autologous nerve graft.

A meta-analysis of hyperfractionated and accelerated radiotherapy and combined chemotherapy and radiotherapy regimens in unresected locally advanced squamous cell carcinoma of the head and neck.

BACKGROUND: Former meta-analyses have shown a survival benefit for the addition of chemotherapy (CHX) to radiotherapy (RT) and to some extent also for the use of hyperfractionated radiation therapy (HFRT) and accelerated radiation therapy (AFRT) in locally advanced squamous cell carcinoma (SCC) of the head and neck. However, the publication of new studies and the fact that many older studies that were included in these former meta-analyses used obsolete radiation doses, CHX schedules or study designs prompted us to carry out a new analysis using strict inclusion criteria. METHODS: Randomised trials testing curatively intended RT (> or =60 Gy in >4 weeks/>50 Gy in <4 weeks) on SCC of the oral cavity, oropharynx, hypopharynx, and larynx published as full paper or in abstract form between 1975 and 2003 were eligible. Trials comparing RT alone with concurrent or alternating chemoradiation (5-fluorouracil (5-FU), cisplatin, carboplatin, mitomycin C) were analyzed according to the employed radiation schedule and the used CHX regimen. Studies comparing conventionally fractionated radiotherapy (CFRT) with either HFRT or AFRT without CHX were separately examined. End point of the meta-analysis was overall survival. RESULTS: Thirty-two trials with a total of 10 225 patients were included into the meta-analysis. An overall survival benefit of 12.0 months was observed for the addition of simultaneous CHX to either CFRT or HFRT/AFRT (p < 0.001). Separate analyses by cytostatic drug indicate a prolongation of survival of 24.0 months, 16.8 months, 6.7 months, and 4.0 months, respectively, for the simultaneous administration of 5-FU, cisplatin-based, carboplatin-based, and mitomycin C-based CHX to RT (each p < 0.01). Whereas no significant gain in overall survival was observed for AFRT in comparison to CFRT, a substantial prolongation of median survival (14.2 months, p < 0.001) was seen for HFRT compared to CFRT (both without CHX). CONCLUSION: RT combined with simultaneous 5-FU, cisplatin, carboplatin, and mitomycin C as single drug or combinations of 5-FU with one of the other drugs results in a large survival advantage irrespective the employed radiation schedule. If radiation therapy is used as single modality, hyperfractionation leads to a significant improvement of overall survival. Accelerated radiation therapy alone, especially when given as split course radiation schedule or extremely accelerated treatments with decreased total dose, does not increase overall survival.

Distribution of survival times of deliberate Plasmodium falciparum infections in tertiary syphilis patients.

Survival time data of Plasmodium falciparum infections from deliberate infection of human subjects with P. falciparum between 1940 and 1963 as a treatment for neurosyphilis in the USA (Georgia) have been used to test the fits of five commonly used parametric distributions for survival times using quantile-quantile plots. Our results suggest that the best fit is obtained from the Gompertz or Weibull distributions. This result has important implications for mathematical modelling of malaria, which has for the past century exclusively assumed that the duration of malaria infections has an exponential distribution. It is desirable to know the correct distribution because its shape profoundly influences the length of monitoring needed in an intervention programme for eliminating or reducing malaria.

New standardised texts for assessing reading performance in four European languages.

AIMS: To develop standardised texts for assessing reading speed during repeated measurements and across languages for normal subjects and low vision patients. METHODS: 10 texts were designed by linguistic experts in English, Finnish, French, and German. The texts were at the level of a sixth grade reading material (reading ages 10-12 years) and were matched for length (830 (plus or minus 2) characters) and syntactic complexity, according to the syntactic prediction locality theory of Gibson. 100 normally sighted native speaking volunteers aged 18-35 years (25 per language) read each text aloud in randomised order. The newly designed text battery was then applied to test the reading performance of 100 normally sighted native speaking volunteers aged 60-85 years (25 per language). RESULTS: Reading speed was not significantly different with at least seven texts in all four languages. The maximum reading speed difference between texts, in the same language was 6.8% (Finnish). Average reading speeds (SD) in characters per minute are, for the young observer group: English 1234 (147), Finnish 1263 (142), French 1214 (152), German 1126 (105). The group of older readers showed statistically significant lower average reading speeds: English 951 (97), Finnish 1014 (179), French 1131 (160), German 934 (117). CONCLUSION: The authors have developed a set of standardised, homogeneous, and comparable texts in four European languages (English, Finnish, French, German). These texts will be a valuable tool for measuring reading speed in international studies in the field of reading and low vision research.

Freeze-thawing of breast milk does not prevent cytomegalovirus transmission to a preterm infant.

Freezing human milk is recommended to inactivate cytomegalovirus (CMV). A case of a preterm infant exclusively receiving frozen breast milk from his CMV seropositive mother showed that storage of breast milk for two months at -20 degrees C did not prevent symptomatic postnatal CMV infection.

Concepts and approaches towards understanding the cellular redox proteome.

The physiological activity of a significant subset of cell proteins is modified by the redox state of regulatory thiols. The cellular redox homeostasis depends on the balance between oxidation of thiols through oxygen and reactive oxygen species and reduction by thiol-disulfide transfer reactions. Novel and improved methodology has been designed during recent years to address the level of thiol/disulfide regulation on a genome-wide scale. The approaches are either based on gel electrophoresis or on chromatographic techniques coupled to high end mass spectrometry. The review addresses diagonal 2D-SDS-PAGE, targeted identification of specific redox-interactions, affinity chromatography with thioredoxins and glutaredoxins, gel-based and non-gel based labelling techniques with fluorophores (such as Cy3, Cy5, ICy), radioisotopes, or with isotope-coded affinity tags (ICAT), differential gel electrophoresis (DIGE) and combined fractional diagonal chromatography (COFRADIC). The extended methodological repertoire promises fast and new insight into the intricate regulation network of the redox proteome of animals, bacteria, and plants.

[Tissue engineering of peripheral nerves]. / Tissue Engineering peripherer Nerven.

BACKGROUND: In spite of considerable progress in microsurgical techniques, the treatment of long distance defects in peripheral nerves remains challenging for the surgeon. Autologous nerve grafting has been the only applicable procedure to overcome such defects in the past. Due to the known disadvantages of this procedure (neuroma formation and sensory deficits at the donor-site, limited availability of donor-material, etc.) and impaired regenerative results, different tubulisation techniques are discussed more frequently as alternatives to the autologous nerve grafts. AIM OF THE STUDY: In this work, the authors summarise their experiences and results with different synthetically developed materials, cellular and acellular tubes and venous conduits for the reconstruction of peripheral nerve defects. MATERIAL AND METHODS: To analyse peripheral nerve regeneration, we utilised a median nerve model in rats. In these studies nerve gaps up to 40 mm were induced. Guiding tubes of various materials (trimethylene carbonate-epsilon-caprolactone, polyethylene, veins, and collagen) were employed. Furthermore, we introduced Schwann cells as cellular elements into some of the trimethylene carbonate-epsilon-caprolactone tubes. The longest postoperative observation period was nine months. RESULTS: The results demonstrated that only in the case of cellular filled tubes (syngenic Schwann cells) did regeneration occur across the 20 mm gap. This regeneration was comparable to that induced after autologous grafting. Across a 40 mm gap the autologous graft demonstrated the best results.