The effect of an adaptation to hypoxia on cardiac tolerance to ischemia/reperfusion

The acute myocardial infarction(AMI)and sudden cardiac death(SCD),both associated with acute cardiac ischemia,are one of the leading causes of adult death in economically developed countries.The development of new approaches for the treatment and prevention of AMI and SCD remains the highest priority for medicine.A study on the cardiovascular effects of chronic hypoxia(CH)may contribute to the development of these methods.Chronic hypoxia exerts both positive and adverse effects.The positive effects are the infarct-reducing,vasoprotective,and antiarrhythmic effects,which can lead to the improvement of cardiac contractility in reperfusion.The adverse effects are pulmonary hypertension and right ventricular hypertrophy.This review presents a comprehensive overview of how CH enhances cardiac tolerance to ischemia/reperfusion.It is an in-depth analysis of the published data on the underlying mechanisms,which can lead to future development of the cardioprotective effect of CH.A better understanding of the CH-activated protective signaling pathways may contribute to new therapeutic approaches in an increase of cardiac tolerance to ischemia/reperfusion.

Effect of replacement of soybean oil by Hermetia illucens fat on performance,digestibility,cecal microbiome,liver transcriptome and liver and plasma lipidomes of broilers

Background In contrast to protein-rich insect meal,the feed potential of insect fat is generally less explored and knowledge about the suitability of insect fat as a fat source specifically in broiler diets is still limited.In view of this,the present study aimed to comprehensively investigate the effect of partial(50%) and complete replacement of soybean oil with insect fat from Hermetia illucens(HI) larvae in broiler diets on performance,fat digestibility,cecal microbiome,liver transcriptome and liver and plasma lipidomes.Thus,100 male,1-day-old Cobb 500 broilers were randomly assigned to three groups and fed three different diets with either 0(group HI-0,n cens(HI) larvae fat for 35 d.= 30),2.5%(group HI-2.5,n %(HI-5.0,n = 35) or 5.0= 35) Hermetia illuResults Body weight gain,final body weight,feed intake,and feed:gain ratio during the whole period and apparent ileal digestibility coefficient for ether extract were not different between groups.Cecal microbial diversity did not differ between groups and taxonomic analysis revealed differences in the abundance of only four low-abundance bacterial taxa among groups;the abundances of phylum Actinobacteriota,class Coriobacteriia,order Coriobacteriales and family Eggerthellaceae were lower in group HI-5.0 compared to group HI-2.5(P < 0.05).Concentrations of total and individual short-chain fatty acids in the cecal digesta were not different between the three groups.Liver transcriptomics revealed a total of 55 and 25 transcripts to be differentially expressed between groups HI-5.0 vs.HI-0 and groups HI-2.5 vs.HI-0,respectively(P < 0.05).The concentrations of most lipid classes,with the exception of phosphatidylethanolamine,phosphatidylglycerol and lysophosphatidylcholine in the liver and cholesterylester and ceramide in plasma(P < 0.05),and of the sum of all lipid classes were not different between groups.Conclusions Partial and complete replacement of soybean oil with HI larvae fat in broiler diets had no effect on growth performance and only modest,but no adverse effects on the cecal microbiome and the metabolic health of broilers.This suggests that HI larvae fat can be used as an alternative fat source in broiler diets,thereby,making broiler production more sustainable.

Blueberry and cranberry pangenomes as a resource for future genetic studies and breeding efforts

Domestication of cranberry and blueberry began in the United States in the early 1800s and 1900s,respectively,and in part owing to their f lavors and health-promoting benefits are now cultivated and consumed worldwide.The industry continues to face a wide variety of production challenges(e.g.disease pressures),as well as a demand for higher-yielding cultivars with improved fruit quality characteristics.Unfortunately,molecular tools to help guide breeding efforts for these species have been relatively limited compared with those for other high-value crops.Here,we describe the construction and analysis of the first pangenome for both blueberry and cranberry.Our analysis of these pangenomes revealed both crops exhibit great genetic diversity,including the presence-absence variation of 48.4%genes in highbush blueberry and 47.0%genes in cranberry.Auxiliary genes,those not shared by all cultivars,are significantly enriched with molecular functions associated with disease resistance and the biosynthesis of specialized metabolites,including compounds previously associated with improving fruit quality traits.The discovery of thousands of genes,not present in the previous reference genomes for blueberry and cranberry,will serve as the basis of future research and as potential targets for future breeding efforts.The pangenome,as a multiple-sequence alignment,as well as individual annotated genomes,are publicly available for analysis on the Genome Database for Vaccinium-a curated and integrated web-based relational database.Lastly,the core-gene predictions from the pangenomes will serve useful to develop a community genotyping platform to guide future molecular breeding efforts across the family.

1960-2005年长江流域降水极值概率分布特征

根据1960-2005年长江流域147个气象站逐日降水观测资料和ECHAM5/MPI-OM气候模式20世纪试验期(1941-2000年)79个格点逐日降水模拟资料,建立年最大强降水AM(annual maximum)序列及汛期日降水量<1.27mm的最长干旱持续天数MI(Munger index)序列,分析了长江流域降水极值序列的时空分布特征和概率分布模式。结果表明:1)长江流域强降水事件的强度和概率最大的地区位于岷沱江流域中游、洞庭湖湖区、长江中下游干流区与鄱阳湖东南部支流等地区,干旱事件强度和概率最大的地区位于金沙江流域中下游与嘉陵江流域;2)气候模式模拟的长江流域AM事件的多年平均值普遍高于观测值,但离差系数普遍低于观测值;3)气候模式模拟结果与观测的降水极值空间分布有一定的差异,但对气候模式和实际观测的降水极值概率分布的拟合,均证明Wakeby分布函数能够较好地拟合降水极值的概率分布。

人卵透明带蛋白huZP3a^(22～176)和huZP3b^(177～348)肽段在大肠杆菌中的表达及其纯化

目的:探索将huZP3a22~348蛋白编码基因拆分成两段,分别表达的可行性,并研究表达产物的免疫原性。方法:用PCR技术, 将去N-端信号肽和C-端跨膜区的huZP322~348蛋白编码基因拆成大小相近的两段, 以完整阅读框的形式分别重组插入热诱导型pBV221的多克隆区。结果:大肠杆菌分别特异地表达了可单独或复合应用的huZP3a22~176和huZP3b177~348,在经过抗人ZP3不同抗原区合成肽抗体的蛋白印迹鉴定后, 用改良的制备性PAGE方法分离纯化这两种表达产物。同时用兔抗猪ZP IgGs蛋白印迹试验表明, huZP3a和pZP3b的几个共同线性抗原表位都存在于其肽链的前半区域。结论:通过基因重组技术可获得足够量的huZP3a和huZP3b,这为开展huZP3a和huZP3b的免疫原性以及huZP3诱发人精子顶体胞吐的功能域等研究奠定了基础。

Foreign Direct Investment with Chinese Characteristics:A Middle Path Between Ownership-Location-Internalization Model and Linkage-Leverage-Learning Model

The majority of multinational enterprises(MNEs) traditionally originate from developed countries.In the last ten years,however,there has been dramatic growth in foreign direct investment(FDI) from China.It is a comparatively new phenomenon that challenges the classic FDI theories.In this paper,we review the pros and cons of two important theories,known as the Ownership-Location-Internalization(OLI) model and Linkage-Leverage-Learning(LLL) model,and use the statistical data and company case studies from China to test the plausibility of these two models.We believe that neither of them suits totally: the OLI model is quite useful for understanding FDI from China to developing economies,while the LLL model is more powerful for explaining the FDI to developed economies.We argue that the companies from China attain a very advantageous position as intermediates in the global economy.They may catch up with the first movers if they integrate OLI-led and LLL-led FDI within one firm.This combination can bring together the most advanced knowledge acquired in developed economies with the knowledge about adaptation needs and the needs for cost reduction in production as expressed in developing economies.It may also accelerate the knowledge transfer globally.We thus fill a gap in research into the geographical pattern of Chinese FDI and offer a deeper understanding of the internationalization of Chinese MNEs and revolving knowledge transfer.

Fertility and sexual life of men after their forties and in older age

Owing to the demographic development, the aging male will require more consideration in future. In contrast to arapid decline of estradiol during menopause in women, the process of aging in the male is retarded and subject to highindividual variations. Impairment of spermatogenesis is observed as a continuous process occurring over decades. How-ever, only about 50% of men in their eighties show complete loss of fertility. In principle, spermatogenesis may be re-tained well into senescence. Of importance for the individual health condition is the fact that the number of Leydig cellsdeclines with advancing age. Thus, altered sex hormone concentrations in aging men result from both functional distur-bances and a gradual reduction in Leydig cells. Furthermore, an impaired feed-back mechanism of the pituitary-gonadalaxis occurs, with disappearance of the circadian testosterone (T) rhythm. LH and FSH levels are increased, and a re-duced bioavailability of sex hormones is observed. Lower total testosterone concentrations in men over 60 years are ac-companied by clinical signs of reduced virility, such as decreased muscle mass and strength as well as reduced sexualhair growth and libido. An age-related decline in androgen secretion and plasma testosterone levels therefore suggeststhe use of androgen supplementation. However, there is a lack of risk-benefit long-term studies. Increased research inthe male is mandatory to meet the requirements of the aging population. This should include the availability of preciseepidemiological data about the frequency of partial androgen deficiency in aging males (PADAM).(Asian J Androl 2001 Mar; 3: 1-7)

Comprehensive evaluation of the metabolic effects of insect meal from Tenebrio molitor L.in growing pigs by transcriptomics, metabolomics and lipidomics

Background:The hypothesis was tested that insect meal(IM)as protein source influences intermediary metabolism of growing pigs.To test this,30 male,5-week-old crossbred pigs were randomly assigned to 3 groups of 10 pigs each with similar body weights(BW)and fed isonitrogenous diets either without(CON)or with 5%IM(IM5)or 10%IM(IM10)from Tenebrio molitor L.for 4 weeks and key metabolic tissues(liver,muscle,plasma)were analyzed using omics-techniques.Results:Most performance parameters did not differ across the groups,whereas ileal digestibilities of most amino acids were 6.7 to 15.6%-units lower in IM10 than in CON(P<0.05).Transcriptomics of liver and skeletal muscle revealed a total of 166 and 198,respectively,transcripts differentially expressed between IM10 and CON(P<0.05).Plasma metabolomics revealed higher concentrations of alanine,citrulline,glutamate,proline,serine,tyrosine and valine and a lower concentration of asparagine in IM10 than in CON(P<0.05).Only one out of fourteen quantifiable amino acid metabolites,namely methionine sulfoxide(MetS),in plasma was elevated by 45%and 71%in IM5 and IM10,respectively,compared to CON(P<0.05).Plasma concentrations of both,major carnitine/acylcarnitine species and bile acids were not different across groups.Lipidomics of liver and plasma demonstrated no differences in the concentrations of triacylglycerols,cholesterol and the main phospholipids,lysophospholipids and sphingolipids between groups.The percentages of all individual phosphatidylcholine(PC)and phosphatidylethanolamine(PE)species in the liver showed no differences between groups,except those with 6 double bonds(PC 38:6,PC 40:6,PE 38:6,PE 40:6),which were markedly lower in IM10 than in CON(P<0.05).In line with this,the percentage of C22:6n-3 in hepatic total lipids was lower in IM10 than in the other groups(P<0.05).Conclusions:Comprehensive analyzes of the transcriptome,lipidome and metabolome of key metabolic tissues indicate that partial or complete replacement of a conventional protein source by IM in the diet has only a weak impact on the intermediary metabolism of growing pigs.Thus,it is concluded that IM from Tenebrio molitor L.can be used as a dietary source of protein in pigs without causing adverse effects on metabolism.

Advancement in biochemical assays in andrology

Determination of markers of sperm function, accessory sex gland secretion and silent male genital tractinflammation is of considerable diagnostic value in the evaluation of male infertility. The introduction of biochemicaltests into the analysis of male factor has the advantage that standardized assays with a coefficient of variationcharacteristic of clinical chemistry are performed, in contrast to biological test systems with a large variability.Biochemical parameters may be used in clinical practice to evaluate the sperm fertilizing capacity (acrosin, aniline blue,ROS), to characterize male accessory sex gland secretions (fructose, α-glucosidase, PSA), and to identify men withsilent genital tract inflammation (elastase, C'3 complement component, coeruloplasmin, IgA, IgG, ROS).

Neutrophil extracellular traps in the intestinal mucosa of Eimeria-infected animals

Objective:To investigate the presence of neutrophil extracellular traps(NETs) in vivo by analysing intestinal sections from experimentally Eimeria bovis-and naturally Eimeria arloingi-infected animals.Methods:Intestinal samples of Eimeria arloingi-and Eimeria bovis-infected animals were analysed by using immunohistochemical and fluorescence approach by using monoclonal antibodies.Results:Classical NET components were confirmed by co-localization of extracellular DNA being decorated with neutrophil elastase and histones in Eimeria-infected tissue samples.Here,extrusion of NETs was exclusively detected in intestinal polymorphonuclear neutrophils infiltrating Eimeria-infected sites.In vivo NETs were either found in close proximity or in direct contact to different Eimeria stages suggesting a stage-independent process.NETs were also found within the gut lumen driven by polymorphonuclear neutrophils that were contacting released oocysts.Conclusions:We postulate that NETs might play an important role in innate defence reactions in coccidiosis therefore significantly altering the outcome of infection.

Genome-wide prediction for hybrids between parents with distinguished difference on exotic introgressions in Brassica napus

Extensive exotic introgression could significantly enlarge the genetic distance of hybrid parental populations to promote strong heterosis.The goal of this study was to investigate whether genome-wide prediction can support pre-breeding in populations with exotic introgressions.We evaluated seed yield,seed yield related traits and seed quality traits of 363 hybrids of Brassica napus (AACC) derived from two parental populations divergent on massive exotic introgression of related species in three environments.The hybrids presented strong heterosis on seed yield,which was much higher than other investigated traits.Five genomic best linear unbiased prediction models considering the exotic introgression and different marker effects (additive,dominance,and epistatic effects) were constructed to test the prediction ability for different traits of the hybrids.The analysis showed that the trait complexity,exotic introgression,genetic relationship between the training set and testing set,training set size,and environments affected the prediction ability.The models with best prediction ability for different traits varied.However,relatively high prediction ability (e.g.,0.728 for seed yield) was also observed when the simplest models were used,excluding the effects of the special exotic introgression and epistasis effect by5-fold cross validation,which would simplify the prediction for the trait with complex architecture for hybrids with exotic introgression.The results provide novel insights and strategies for genome-wide prediction of hybrids between genetically distinct parent groups with exotic introgressions.

Effect of genistein on acrosome reaction and zona pellucida binding independent of protein tyrosine kinase inhibition in bull

Aim： To investigate if the phytoestrogen, genistein, affects essential functions of cryopreserved bovine spermatozoa. Methods： The effect of genistein upon motility was assessed by computer-assisted motion analysis. Hemizona assay was performed to detect the ability of spermatozoa binding to the zona pellucida. The inducibility of the acrosome reaction using progesterone and ZP3-6 peptide was analysed by fluorescein-conjugated Pisum sativum agglutinin （FITC-PSA）/Hoechst 33258 double staining. Capacitation after incubation with genistein was assessed by the chlortetracycline （CTC） assay. Immunoblots showed the pattern of protein tyrosine phosphorylation of cryopreserved bovine spermatozoa. Results： Immunodetection of tyrosine-phosphorylated proteins showed that genistein did not affect tyrosine phosphorylation in cryopreserved bovine spermatozoa. However, genistein significantly reduced the progesterone- and ZP3-6 peptide-mediated induction of the acrosome reaction and led to a dose-dependent inhibition of sperm-zona pellucida binding; while sperm motility and capacitation were not affected by this phytoestrogen, as indicated by computer-assisted sperm motion analysis and the CTC assay, respectively. Conclusion： Our results suggest that in cryopreserved bovine spermatozoa, genistein affects a protein tyrosine phosphorylation-independent signal transduction pathway that is involved in sperm capacitation, the acrosome reaction and sperm-zona pellucida binding.

Hepatitis B virus subgenotype F3 reactivation with vaccine escape mutations:A case report and review of the literature

Hepatitis B represents a global health threat because its chronic course and sequelae contribute to a high morbidity and mortality. Hepatitis B virus(HBV) infection can be controlled by vaccines, antiviral treatment, and by interrupting transmission. Rare vaccine escape mutants are serious because they eliminate vaccine protection. Here, we present a 74-year-old vaccinated patient with HBV reactivation 11 years after kidney transplantation. The patient was HBV-positive but HBs Ag-negative prior to vaccination 6 years before transplantation. The reactivated virus was HBV genotype F3 with vaccine escape mutations G145 R, P120 Q, and Q129 P. The patient was successfully treated with entecavir. The epidemiological reasons for this subgenotype, which is extremely rare in Western Europe, were unclear. This case illustrates that second-generation vaccines are not always effective in a specific group of patients.

Effects of broccoli extract and various essential oils on intestinal and faecal microflora and on xenobiotic enzymes and the antioxidant system of piglets

Objective: Since the ban of antibiotics as growth promoting feed additives in the EU in 2006 research in alternatives has gained importance. Phytogenic feed additives represent a heterogenous class of different plant derived substances that are discussed to improve the health of farm animals by direct and indirect antioxidant effects and by influencing microbial eubiosis in the gastrointestinal tract. Consequently our study aimed to investigate the influence of broccoli extract and the essential oils of tur- meric, oregano, thyme and rosemary, as selected individual additives, on intestinal and faecal microflora, on xenobiotic enzymes, and on the antioxidant system of piglets. Methods: 48 four weeks old male weaned piglets were assigned to 6 groups of 8. The piglets were housed individually in stainless steel pens with slatted floor. The control group (Con) was fed a diet without an additive for 4 weeks. The diet of group BE contained 0.15 g/kg sulforaphane in form of a broccoli extract. 535, 282, 373 and 476 mg/kg of the essential oils of turmeric (Cuo), oregano (Oo), thyme (To) and rosemary (Ro) were added to the diets of the remaining 4 groups to stan-dardise supplementation to 150 mg/kg of the oils’ key terpene compounds ar-turmerone, carvacrol, thymol and 1,8-cineole. The composition of bacterial microflora was examined by cultivating samples of jejeunal and colonic mucosa and of faeces under specific conditions. The mRNA expression of xenobiotic and antioxidant enzymes was determined by reversing transcrip- tase real time detection PCR (RT-PCR). Total antioxidant status was assayed using the Trolox Equivalent Antioxidant Capacity (TEAC), and lipid peroxidation was determined by measuring thiobarbioturic acid reactive substances (TBA- RS). Results: Compared to Con piglets all additives positively influenced weight gain and feed conversion in week 1. Over the whole trial period no significant differences in performance parameters existed between the experimental groups. Compared to group Con performance of Ro piglets was, however, slightly impaired. Com- pared to Con piglets Cuo, Oo and To increased the ratio of Lactobacilli:E. coli attached to the jejunal mucosa, whereas BE and Ro impaired this ratio slightly. In contrast in colonic mucosa Ro improved Lactobacilli:E. coli ratio. In faecal samples an improvement of Lactobacilli:E. coli ratio could be analysed for To and Ro. Ro was the only additive that reduced the incidence rate of piglets tested positive for enterotoxic E. coli (ETEC). All additives significantly increased jejunal TEAC and reduced TBA-RS. In the liver BE, Cuo, Oo and To increased TEAC in tendency and Ro significantly. Liver TBA-RS were slightly reduced by all additives compared to Con piglets. Whereas the influence of BE, To and Ro on jejunal TEAC mainly was derived from the induction of xenobiotic and antioxidant enzymes (indirect antioxidant effects), Cuo and Oo influenced TEAC by direct antioxidant effects. Discussion and Conclusions: Our results have shown: That within the labiatae oils Oo and To have the potential to improve performance slightly. That phytogenic substances have a small but not sig- nificant influence on intestinal microflora. That phytogenic feed additives up-regulate the anti- oxidant system of piglets either by direct or by indirect antioxidant effects and that they may thereby improve health status. That within the labiatae oils Oo has a high direct antioxidant potential whereas Ro potently induces xenobiotic and antioxidant enzymes. That broccoli extract is an attractive new phytogenic additive, improving antioxidant status by indirect antioxidant effects. That defined combinations of selected phytogenic substances may produce additive effects. That health promoting effects of phytogenic additives in the future should be studied systematically under the challenge with pathogenic microorganisms or food derived to-xins.

Music in depression: Neural correlates of emotional experience in remitted depression

AIM: To investigate neural and behavioral correlates of emotional experiences as potential vulnerability markers in remitted depression. METHODS: Fourteen remitted participants with a history of major depression and fourteen closely matched healthy control participants took part in the study. We used two psychiatric interviews(Hamilton Depression Rating Scale, Montgomery-Asberg Depression Rating Scale) and one self-report scale(Beck Depression Inventory) to assess remission. Healthy control participants were interviewed by an experienced psychiatrist to exclude those who showed any current or lifetime psychiatric or neurological disorders. To explore psychosocialand cognitive-interpersonal underpinnings of potential vulnerability markers of depression, early life stress, coping styles and alexithymia were also assessed. We induced pleasant and unpleasant emotional states using congruent combinations of music and human emotional faces to investigate neural and behavioral correlates of emotional experiences; neutral stimuli were used as a control condition. Brain responses were recorded using functional magnetic resonance imaging. Behavioral responses of pleasantness, arousal, joy and fear were measured via button-press inside the resonance imaging scanner. RESULTS: The mean age of the sample was 54.9(± 11.3) years. There were no differences between remitted depressed(RD)(n = 14; 9 females and 5 males) and healthy participants(n = 14; 8 females and 6 males) regarding age, current degree of depression, early life stress, coping styles and alexithymia. On a neural level, RD participants showed reduced activations in the pregenual anterior cingulate cortex(pg ACC) in response to pleasant [parameter estimates:-0.78 vs 0.32; t(26) =-3.41, P < 0.05] and unpleasant [parameter estimates:-0.88 vs 0.56; t(26)=-4.02, P < 0.05] emotional stimuli. Linear regression analysis revealed that pg ACC activity was modulated by early life stress [β =-0.48; R2 = 0.23, F(1,27) = 7.83, P < 0.01] and taskoriented coping style [β = 0.63; R2 = 0.37, F(1,27) = 16.91, P < 0.001]. Trait anxiety modulated hippocampal responses to unpleasant stimuli [β = 0.62; R2= 0.38, F(1,27) = 15.95, P < 0.001]. Interestingly, in their reported experiences of pleasantness, arousal, happiness and fear in response to pleasant, unpleasant and neutral stimuli, RD participants did not differ significantly from healthy control participants. Adding trait anxiety or alexithymia as a covariate did not change the results.CONCLUSION: The present study indicates that, in euthymic individuals, depression history alters neural correlates, but not the subjective dimension of pleasant and unpleasant emotional experiences.

Is There a Future for 74 Gy Radiation Treatment of NSCLC after RTOG 0617?A Comparison of the RTOG Study Results with Our Own Department’s 74 Gy NSCLC Cohort

Background and Purpose: There have been a number of different efforts trying to improve the outcome of NSCLC patients treated with radiotherapy (RT). Contrary to most expectations, the long awaiting results of the RTOG 0617 trial didn’t show any benefit of dose escalation to 74 Gy. In this unicentric retrospective analysis we compare the RTOG 0617 result with the outcome of our own 74-Gy-NSCLC cohort. Methods and Material: Since October 2009, 80 patients with NSCLC were treated with 74 Gy in 37 fractions, of which 69 patients were eligible for a retrospective analysis of local and distant failure, survival time and treatment related toxicity. A subgroup analysis was done for patients with a possible follow-up of at least 18 month. Results: Complete local remission could be achieved in 18 patients (26.1%);26 patients (37.7%) had a partial remission and 3 patients (4.4%) a stable local disease. Local failure occurred in 12 patients (17.3%). Distant failure occurred in 27 patients (39.1%). The median survival time was 43.7 weeks (95% CI: 25.2 - 62.3 weeks). 5 patients (6.3%) developed RT induced side effects. As for the analyzed subgroup, a complete or partial local remission could be achieved in 29 patients (61.7%). Local failure occurred in 11 patients (23.4%) and 20 patients (42.6%) developed distant metastases. The 18-month overall survival was 38.3% and the median survival time was 51.7 weeks (95% CI: 27.2 - 76.3 weeks). Conclusion: The results of this retrospective analysis indicate that 74 Gy total radiation dose might not lead to results as bad as indicated by the RTOG 0617 trial. It might therefore be a suitable treatment concept for people with NSCLC.

Infectious Disease Research—What Role Is There for Hydrologists?

Numerous virulent and widespread diseases are related to water. The transmission and outbreak of water-related diseases are closely coupled to their hydrological environment. Changes in this environment and the associated hydrological processes may affect the occurrence and virulence of water-related diseases. Environmental changes can be manifold, including e.g. climate and land use, agricultural management or urbanization. Water fluxes and storages play a dominant role in describing disease outbreak, transmission and transport. New land cover types often alter landscape scale water storages. If the effects of changes could be better understood, predictions about the distribution, emergence or outbreak of water-related diseases would be possible. Furthermore, the collaboration of experts from different disciplines is essential for accurate spatial and temporal prediction of water-related disease outbreaks. Here we review the current state of knowledge of water-related diseases and present a general classification of these diseases, followed by a discussion of their major drivers. This review focuses particularly on hydrologists and how they can contribute with their understanding of hydrological processes.

How Safe Are Reduced Doses per Fraction in Target Volumes of 2^ndto 4^thOrder in the Simultaneous Integrated Boost Irradiation Technique in Head and Neck Carcinoma Patients?

Aim: The simultaneous irradiation of target volumes of different total dose levels using intensity modulated radiotherapy leads to reduced doses per fraction and longer treatment times in target volumes of 2nd?to 4th?order. Does the thereby caused reduced biological effectiveness induce an increased recurrence risk? The current work deals with the problem of recurrences of patients with head and neck carcinomas treated either with an intensitiy (IMRT) or with a volumetric modulated (VMAT) irradiation technique. Methods: From October 2002 to September 2014, 699 patients with carcinomas of the head and neck were irradiated using IMRT or VMAT. The median follow up of the patients was 21.9 months (2 to 145 months). Primary tumor regions (1st?order target volume) of 565 patients were treated with doses per fraction of 2 Gy. Accordingly, further 133 target volumes of the primary tumor received reduced doses per fraction. In 1 patient, the lymphatic drainage was treated solely without irradiation of the primary region. For the lympatic drainage, 854 1st?order target volumes were treated with a dose per fraction of 2 Gy. Reduced doses per fraction were applied to further 1780 target volumes. Results: 54 of 699 patients developed a recurrence in the primary tumor region after radio-(chemo) therapy, 4 patients developed a recurrence of the primary tumor and a unilateral recurrence of the lymphatic drainage, 2 patients a recurrence of the primary tumor and a bilateral lymph node recurrence. 18 patients showed an isolated unilateral recurrence and additionally 2 patients a bilateral recurrence of the lymphatic drainage. 619 patients stayed recurrence free. In primary tumor regions, receiving a dose per fraction of 2 Gy 55 patients (9.7%) developed a recurrence, whereas in target volumes receiving a reduced dose per fraction 5 patients (3.8%) developed a recurrence (p < 0.001). In lympatic drainage target volumes receiving a dose per fraction of 2 Gy, 25 target volumes (2.9%) developed a recurrence, whereas in target volumes receiving a reduced dose per fraction, 5 patients (0.3%) developed a recurrence (p = 0.001). Conclusion: The recurrence risk in target volumes of 2nd?to 4th?order was not increased due to reduced doses per fraction deposited by means of a simultaneous integrated boost technique. Therefore, the simultaneous irradiation of target volumes with different dose levels is safely applicable within one treatment plan.

High-level Expression and Purification of Human Zona Pellucida huZP3a^(22-176) and huZP3b^(177-348) Peptides in Escherichia coli

Objective To try making huZP3a^22-176 and huZP3b^177-348 polypeptides （representing an intact huZP^322-348 protein without its N-terminal signal peptide and C-terminal transmembrane domain ） express in E. coli at a higher level Methods The cDNAs encoding huZP3a and huZP3b were obtained with PCR method. The pBV221 plasmid was used to construct thermo-inducible recombinant expression vector. Purification of two target expression products employed an improved method of preparative gel polyacrylamide gel electrophoresis. Results Two polypeptides of recombinant huZP3a （rhuZP3a） and recombinant huZP3b （rhuZP3b） were all expressed respectively in an E. coli BL21（DE3）pLysS strain at a higher level, which were recognized by two specific polyclonal antisera in Western blotting test which recognize a linear B cell epitope present in rhuZP3a or rhuZP3b respectively. Using the shake-flask method, approximately 5 mg of rhuZP3a and rhuZP3b with more than 95% relative homogeneity were harvested from 1 L culture respectively. Conclusion The availability of two rhuZP3 polypeptides will help in detecting the immunogenicities of rhuZP3a and rhuZP3b through animal experiments and confirming the function domain of non-glycosylated huZP3 to induce acrosome reaction in vitro.