β-Hydroxy-L-valine and 4-Amino-3,6-dihydroxy-2-methylhexanoic Acid,Constitutional Amino Acids of the Antibiotic YA–56

From the acid hydrolyzate of the antibiotic YA–56 X (Zorbamycin) and Y belonging to the phleomycin-bleomycin group, 3 unique amino acids were isolated and their structures were determined to be β-hydroxy-L-valine and 2-(3′-amino-tetrahydrofuryl-2′-yl)-propionic acid and an isomer of the latter compound.

Considerations of NMR of the antibiotic YA-56 and of the reaction conditions led us to a view that the latter two new amino acids were not an integral part of the YA–56 molecule but were artifacts derived from 4-amino-3,6-dihydroxy-2-methyhexanoic acid constituting of YA–56 X and Y.     

Constitutional Amino Acids of the Antibiotic YA–56

Acid hydrolysis of the antibiotic YA-56 X (Zorbamycin) and Y belonging to the phleomycin-bleomycin group was carried out and the following constitutional amino acids were isolated from the hydrolyzate of YA–56 X: β-Amino-β-(4-amino-6-carboxy-5-methylpyrimidine-2-yl)- propionic acid, β-aminoalanine, L-erythro-β-hydroxyhistidine and 3 unidentified amino acids. Though the former 3 amino acids were known to be constituents of phleomycins and bleomycins, the latter three were not found in phleomycins and bleomycins. YA–56 Y gave one more unidentified amino acid.

Furthermore, isolation of β-alanine and 2-acetylthiazole-4-carboxylic acid from the hydrolyzate indicated the presence of 2-(2-(2-aminoethyl)-Δ²-thiazoline-4-yl)-thiazole-4-carboxylic acid in YA–56 X and Y as in phleomycins.     

2-O-(3-O-Carbamoyl-D-mannosyl)-6-deoxy-L-gulose The Constitutional Sugar of the Antibiotic YA-56

From the methanolysis product of the antibiotic YA–56 X (Zorbamycin) and Y belonging to phleomycin-bleomycin group, two monosaccharides and one disaccharide were isolated as their fully acetylated derivatives. The structures of these compounds were determined to be methyl 2,3,4-tri-O-acetyl-6-deoxy-β-L-gulopyranoside, methyl 2,4,6-tri-O-acetyl-3-O-carbamoyl-α-D-mannopyranoside and methyl 2-O-(2,4,6-tri-O-acetyl-3-O-carbamoyl-α-D-mannopyranosyl)-3,4-O-0-acetyl-6-deoxy-β-L-“gulopyranoside,

Based on these results, it was concluded that 2-O-(3-O-carbamoyl-α-D-mannosyl)-6-deoxy-L-gulose is present as a sugar moiety of the antibiotic YA–56.     

Mode of Action of Zorbamycin

Zorbamycin (U-30,604E) induces rapid degradation of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) in Bacillus subtilis cells. DNA degradation is initiated first and is closely followed by the degradation of RNA. No interaction between isolated DNA and zorbamycin is observed. Nucleic acid and protein syntheses are not inhibited by zorbamycin in cell-free systems. Since the initial effect of the antibiotic is expressed at the level of the cellular DNA fraction, we assume that zorbamycin somehow induces a change in the structure or function of the cellular DNA fraction which results in rapid breakdown of this fraction.     

Genetic Recombination in Streptomyces bikiniensis var. zorbonensis

A genetic recombination system in Streptomyces bikiniensis var. zorbonensis is described. This strain produces a mixture of antibiotics including zorbamycin and zorbonomycin B and C. A genetic map has been constructed from data obtained from an analysis of haploid recombinants which shows linkage relationships of 17 marker loci. Determination of map location has been made for three different loci affecting antibiotic biosynthesis in this strain.     

人胃癌细胞一种高表达基因的克隆及序列测定

采用DDRT-PCR法,以人胃上皮细胞GES-1为对照,从人胃癌细胞SGC-7901中克隆高表达基因,并对所克隆的基因进行斑点杂交分析, 序列测定,序列相似性分析及开放读框分析.斑点杂交分析结果表明所获克隆YA61为人胃癌细胞SGC-7901中高表达基因.序列相似性分析结果表明该基因序列为一新基因序列.GenBank收录号为AF220415.开放读框分析结果表明该基因序列有一完全开放读框.     

Health conditions associated with metabolic syndrome after cancer at a young age: A nationwide register-based study

PurposeChildhood cancer survivors are at risk for developing metabolic syndrome (MetS), which subsequently leads to cardiovascular morbidity and excess mortality. Our aim was to investigate the purchases of medications associated with MetS among 7551 early onset cancer patients compared to siblings.MethodsOur nationwide Finnish population-based registry study analyzed the drug purchase of medication among early onset cancer patients diagnosed with cancer below the age of 35 years between 1994 and 2004 compared to siblings by linkage to the drug purchase registry, allowing for a maximal follow-up of 18 years.ResultsThe hazard ratios (HRs) for purchasing antihypertensives and diabetes drugs were higher after both childhood (HR 4.6, 95%CI 3.1–7.0; HR 3.0, 95%1.5–6.1) and young adulthood (YA) cancer (HR 1.5, 95%CI 1.3–1.8; HR 1.6, 95%CI 1.1–2.2) compared to siblings. The HRs for purchasing lipid-lowering drugs were elevated both after childhood (HR 4.3,95%CI 0.9–19.5) and YA cancer (HR 1.6, 95%CI 1.04–2.5), but only reached significance in YA cancer patients. Among specific cancer diagnosis groups, highest HR values for antihypertensives were found in childhood acute lymphoblastic leukemia (ALL) (HR 6.1, 95%CI 3.7–10.3) and bone tumor (HR 4.3, 95%CI 1.9–9.4), and YA ALL (HR 4.8, 95%CI 3.1–7.0) and acute myeloid leukemia (AML) (HR 3.4, 95%CI 2.5–5.1) patients. Moreover, childhood ALL (HR 6.3, 95%CI 2.7–14.8), AML (HR 7.6, 95%CI 1.9–24.5) and central nervous system (CNS)-tumor (HR 3.5, 95%CI 1.3–9.2) and YA ALL (HR 3.7, 95%CI 1.2–9.5) patients showed the strongest likelihood of purchasing diabetes drugs compared to siblings.ConclusionThe purchase of medications associated with MetS was increased after early onset cancer and highly dependent on the age at cancer diagnosis and the cancer diagnosis. Prevention strategies are imperative for reducing potentially life-threatening cardiovascular complications after early onset cancer.     

Nuclear entry of the Drosophila melanogaster nuclear lamina protein YA correlates with developmentally regulated changes in its phosphorylation state.

The Drosophila melanogaster YA protein is a maternally provided nuclear lamina component that is essential during the transition from meiosis to mitosis at the beginning of embryogenesis. Localization of YA to the nuclear envelope is required for its function; this localization is cell cycle-dependent during embryogenesis. Here we show that the ability of YA to enter nuclei is modulated during development. In developing egg chambers, YA protein is made but excluded from nuclei of nurse cells and oocytes; upon egg activation, YA acquires the ability to enter nuclei and becomes incorporated into the nuclear lamina in unfertilized eggs and embryos. This localization switch correlates with changes in the phosphorylation state of YA. YA in ovaries is hyperphosphorylated relative to YA in unfertilized eggs and embryos. Through site-directed mutagenesis, we identified 443T, a potential phosphorylation site for both cyclin-dependent protein kinase and mitogen-activated-protein kinase, as one of the sites likely involved in this developmental control. Our results suggest that phosphorylation plays a role in modulating the localization of YA during development. A model for developmental regulation of the nuclear entry of YA is proposed and implications for understanding Drosophila egg activation are discussed.     

Young Adults' Performance in a Low‐Intensity Weight Loss Campaign

Young adults (YA) are underrepresented in behavioral weight loss programs and achieve poorer outcomes than older adults (OA). There has been a call to develop programs specifically targeting this age group. This study examined the performance of YA enrolled in a low‐intensity, team‐based weight loss campaign and compared their outcomes to OA to determine the utility of such an approach for weight loss in this population. Shape Up Rhode Island (SURI) 2009 was a 12‐week online team‐based weight loss and exercise competition (N = 6,795, 81% female, 94% white, age = 44.7 ± 11.2, BMI = 29.4 ± 5.9). YA was defined as 18–35 years and OA as >35 years; YA and OA were compared on enrollment, retention, weight loss, and change in steps. A total of 1,562 YA enrolled and 715 completed the program. Fewer YA completed compared with OA (46 vs. 62%, P < 0.001). However, among completers, YA achieved greater percent weight loss (‐4.5 ± 4.0 vs. ?3.8 ± 3.2%) and greater daily step change (+1,578.2 ± 3,877.2 vs. +1,342.2 ± 3,645.7) than OA (P's < 0.001). Further, more YA completers achieved a ≥5% weight loss (40 vs. 29%, P < 0.001). Findings were consistent in the overweight/obese (OW/OB) subsample, and using ≤25 years of age as the cut off for YA. Weight losses among YA in this low‐intensity weight loss campaign were quite promising, with over 700 YA completing the program and on average achieving a 4.5% weight loss. Indeed, the potential public health impact of such an approach is substantial; future efforts to develop programs for this age group may benefit from using a low‐intensity, team‐based approach.     

Functional Dissection of YA, an Essential, Developmentally Regulated Nuclear Lamina Protein in Drosophila melanogaster

The Drosophila YA protein is a nuclear lamina component whose function is essential to initiate embryonic development. To identify regions of YA required for its action in its normal cellular context, we made targeted mutations in the YA protein and tested their consequences in flies and embryos in vivo. We found that critical amino acids are distributed along the length of the YA molecule, with functionally important regions including the N- and the C-terminal ends, the cysteine residues in YA’s two potential zinc fingers, a serine/threonine-rich region, and a potential maturation-promoting factor or mitogen-activated protein kinase phosphorylation target site, ITPIR. In addition, several Ya mutations showed intragenic complementation, with N-terminal mutations complementing C-terminal mutations, suggesting that YA proteins interact with one another. In support of this interaction, we demonstrated by immunoprecipitation that YA molecules are present in complexes with each other. Finally, we showed that the C-terminal 179 amino acids of YA are necessary to target, or retain, YA in the nuclear envelope.     

Age and training effects on the lactate kinetics of master athletes during maximal exercise

To study the effects of age and training on lactate production in older trained subjects, the lactate kinetics of highly trained cyclists [HT, n = 7; 65 (SEM 1.2) years] and control subjects with low training (LT, n = 7) and of similar age were compared to those of young athletes [YA, n = 7; 26 (SEM 0.7) years], during an incremental exercise test to maximum power. The results showed that the lactacidaemia at maximal oxygen uptake (VO2max) was lower for HT than for LT (P < 0.05) and, in both cases, lower than that of YA (P < 0.001). The respective values were HT: 3.9 (SEM 0.51), LT: 5.36 (SEM 1.12), and YA: 10.3 (SEM 0.63) mmol.l-1. At submaximal powers, however, the difference in lactacidaemia was not significant between HT and YA, although the values for lactacidaemia at VO2max calculated per watt and per watt normalized by body mass were significantly lower for HT (P < 0.001) and LT (P < 0.02). These results would indicate that the decline in power with age induced a decline in lactacidaemia. Yet this loss in power was not the only causative factor; indeed, our results indicated a complementary metabolic influence. In the older subjects training decreased significantly the lactacidaemia for the same submaximal power (P < 0.01) and from 60% of VO2max onwards (P < 0.05); as for YA it postponed the increase and accumulation of lactates. The lactate increase threshold (Thla-,1) was found at 46% VO2max for LT and at 56% VO2max for HT.(ABSTRACT TRUNCATED AT 250 WORDS)     

A transferable plasmid associated with AS-48 production in Enterococcus faecalis.

Enterococcus faecalis S-48 produces a peptide antibiotic, AS-48, and a bacteriocin, Bc-48. We have isolated mutants that lack these inhibitory characteristics. Further analysis of the mutants indicates that a plasmid of 56 kilobases (pMB2) may harbor the genes for AS-48. In conjugation experiments, pMB2 has been transferred into a plasmid-free OG1X strain of E. faecalis. The OG1X(pMB2) transconjugant produces the antibiotic AS-48 in solid medium, and the MIC of AS-48 for this strain is the same as that of the donor strain.     

Interaction of the essential Drosophila nuclear protein YA with P0/AP3 in the cytoplasm and in vitro: implications for developmental regulation of YA's subcellular location

The Drosophila nuclear lamina protein YA is essential for the transition from female meiosis to embryo mitosis. Its localization and, hence, function is under developmental and cell cycle controls. YA protein is hyperphosphorylated and cytoplasmic in ovaries. Upon egg activation, YA is partially dephosphorylated and acquires the ability to enter nuclei. Its function is first detected at this time. To investigate the cytoplasmic retention machinery that keeps YA from entering nuclei, we used affinity chromatography and blot overlay assays to identify cytoplasmic proteins that associate with YA. Drosophila P0/AP3, a ribosomal protein that is also an apurinic/apyrimidinic endonuclease, binds to YA in ovary and embryo cytoplasms. P0 and YA bind specifically and directly in vitro and are present in a 20S complex in the cytoplasmic extracts. YA protein can be phosphorylated by MAPK, but not by p34(Cdc2) kinase, in vitro. This phosphorylation increases YA's binding to P0. We propose that the P0-containing 20S cytoplasmic complex retains hyperphosphorylated ovarian YA in the cytoplasm. In response to egg activation, YA is partially dephosphorylated and its binding to the 20S complex is reduced. Hence, some YA dissociates from the complex and enters nuclei. Consistent with this model, decreasing P0 levels partially suppress a hypomorphic Ya mutant allele.     

长期连作农田土壤细菌群落结构和共现网络拓扑性质对土壤理化性质的响应

【目的】为探究长期连作土壤细菌群落结构和分子生态网络与土壤环境演化的关联性。【方法】本研究利用16S rRNA基因高通量测序技术,解析了湖南省浏阳市两块连作十二年农田(表现连作障碍的GD和健康的YA)土壤微生物群落组成结构和分子生态网络拓扑性质与土壤理化性质的关系。【结果】GD土壤总氮和有效磷含量显著高于YA,而土壤硝态氮和速效钾含量显著低于YA(P<0.05)。GD土壤细菌群落多样性高于YA,两地土壤细菌群落结构存在显著差异(P<0.01),且与土壤pH和有效磷含量相关。进一步分析表明,GD土壤细菌群落之间比YA具有更复杂的生态网络,主要体现在能量代谢、碳循环和氮循环功能模块。【结论】综上所述,连作会引起土壤细菌群落多样性、组成结构和生态网络变化,这可能与土壤理化性质恶化、土壤肥力下降密切相关,进而影响作物生长发育。     

YA is needed for proper nuclear organization to transition between meiosis and mitosis in Drosophila

Background  

The Drosophila YA protein is required to initiate the embryonic cleavage divisions. After egg activation, YA enters nuclei and interacts with chromatin and the nuclear lamina. This study was designed to define more precisely the events prior to the first cleavage division that are dependent upon YA.     

Role of lipopolysaccharide and outer membrane protein of Escherichia coli K-12 in the receptor activity for bacteriophage T4.

Lipopolysaccharide isolated from Escherichia coli K-12 did not inactivate phage T4, although the cell envelopes with 1% sodium deoxycholate resulted in the release of cytoplasmic membrane proteins, 70% of the lipopolysaccharide, and almost all of the phospholipid. The reconstitution of phage receptor activity was achieved from deoxycholate-soluble and -insoluble fractions by dialysis against a solution of magnesium chloride. Lipopolysaccharide was the only essential component in the deoxycholate-soluble fraction. PhageT4-resistant mutants YA21-6 and YA21-82, having defects in the deoxycholate-soluble and -insoluble fractions, respectively, were isolated. The deoxycholate-soluble fraction of YA21-6 possessed heptoseless lipopolysaccharide, and this defect was responsible for the phage resistance. The deoxycholate-insoluble fraction of YA21-82 lacked outer membrane protein O-8. The addition of O-8 to this fraction together with the wild-type lipopolysaccharide resulted in the appearance of the receptor activity. Furthermore, the reconstitution was successfully achieved with only O-8 and the wild-type lipopolysaccharide, indicating that O-8 was an essential component in the deoxycholate-insoluble fraction.     

MBL在结肠直肠癌中的基因分型

目的：MBL是补体激活凝集素途径的关键因素。MBL基因多态性影响MBL血清水平。结肠直肠癌患者血清MBL水平升高。低水平的MBL则预示着术后肺炎的发生,目前还不清楚此相关性是否与遗传相关。本实验分析调查了结肠直肠癌患者和健康对照者的MBL基因分型,评估基因分析和复发率、生存率之间潜在的相关性。方法：使用TaqMan基因分型分析法和实时定量PCR分析MBL基因的4个SNP、启动子区2个SNP、非编码区1个SNP;ELISA测定标本血清MBL含量。结果：所有标本中发现了8种不同的MBL单体型,它们在患者和健康者中出现频率几乎是完全一样的;YA/YA基因型与高水平的MBL相关,YO／YO与低水平的MBL水平相关,6种不同基因型CRC患者的MBL水平存在着明显不同。结论：MBL基因型与血清MBL浓度显薯相关（P〈0．0001）;突变型B,C,D和启动子单体型Y,X对MBL含量的影响起主要作用;MBL基因型和术后感染并发症没有明显相关性（P=0．33）,与复发癌和存活时间也没有明显相关性（P=0．74）。因此,从基因水平还不能解释为何结肠直肠癌患者血清MBL水平增加。对比已经检测出的血清MBL水平,其基因型还不能预测结肠直肠癌患者的疾病进程。     

A case of an intersex horse with 63,X/64,XX/65,XX,del(Y)(q?) karyotype

Cytogenetic and molecular genetic studies of an intersex horse have been carried out. The investigated animal had overall male body conformation; however, its external genitalia consisted of incompletely developed vulva and penis. The X and Y chromosome painting probes detected three cell lines in the examined horse: 63,X, 64,XX and 65,XX with a fragment of a Y chromosome (del Y). The DNA analysis with the PCR and PCR/RFLP methods showed absence of SRY,AMELY and ZFY genes as well as of six Y microsatellite markers (YM2, YP9, YJ10, YE1, YH12, and YA16). These results suggest that the Y chromosome fragment detected in the investigated animal was the result of a deletion of a euchromatic fragment comprising the above-mentioned markers.     

The role of mechanically purified city sewers in the spread of antibiotic-resistant bacteria of the Enterobacteriaceae family

The aim of this study was to evaluate a degree of contribution of mechanically cleansed municipal sewage in a spread in on environment of bacteria of Enterobacteriaceae family with special regard to antibiotic resistant strains. High number of bacteria of Enterobacteriaceae family was found in 1 ml of sewage and the number of antibiotic-resistant bacteria was 0.5-50 X 10(3)/ml. Among the strains tested the resistance to more than one antibiotics was encountered. 78.3% of strains transferred antibiotic resistance to E. coli recipient strain, what indicate a participation of potentially pathogenic bacteria from Enterobacteriaceae family in a spread of antibiotic resistance in a environment.