Beyond natural antimicrobial peptides: multimeric peptides and other peptidomimetic approaches

Naturally occurring antimicrobial peptides (AMPs) present several drawbacks that strongly limit their development into therapeutically valuable antibiotics. These include susceptibility to protease degradation and high costs of manufacture. To overcome these problems, researchers have tried to develop mimics or peptidomimetics endowed with better properties, while retaining the basic features of membrane-active natural AMPs such as cationic charge and amphipathic design. Protein epitope mimetics, multimeric (dendrimeric) peptides, oligoacyllysines, ceragenins, synthetic lipidated peptides, peptoids and other foldamers are some of the routes explored so far. The synthetic approach has led to compounds that have already entered clinical evaluation for the treatment of specific conditions, such as Staphylococcus (MRSA) infections. Should these trials be successful, an important proof-of-concept would be established, showing that synthetic oligomers rather than naturally occurring molecules could bring peptide-based antibiotics to clinical practice and the drug market for local and systemic treatment of medical conditions associated with multi-drug resistant pathogens.     

Beta-carotene affects gene expression in lungs of male and female <Emphasis Type="Italic">Bcmo1</Emphasis><Superscript>−/−</Superscript> mice in opposite directions

Molecular mechanisms triggered by high dietary beta-carotene (BC) intake in lung are largely unknown. We performed microarray gene expression analysis on lung tissue of BC supplemented beta-carotene 15,15′-monooxygenase 1 knockout (Bcmo1 ^−/−) mice, which are—like humans—able to accumulate BC. Our main observation was that the genes were regulated in an opposite direction in male and female Bcmo1 ^−/− mice by BC. The steroid biosynthetic pathway was overrepresented in BC-supplemented male Bcmo1 ^−/− mice. Testosterone levels were higher after BC supplementation only in Bcmo1 ^−/− mice, which had, unlike wild-type (Bcmo1 ^+/+) mice, large variations. We hypothesize that BC possibly affects hormone synthesis or metabolism. Since sex hormones influence lung cancer risk, these data might contribute to an explanation for the previously found increased lung cancer risk after BC supplementation (ATBC and CARET studies). Moreover, effects of BC may depend on the presence of frequent human BCMO1 polymorphisms, since these effects were not found in wild-type mice.     

Mutations that silence constitutive signaling activity in the allosteric ligand-binding site of the thyrotropin receptor

The thyrotropin receptor (TSHR) exhibits elevated cAMP signaling in the basal state and becomes fully activated by thyrotropin. Previously we presented evidence that small-molecule ligands act allosterically within the transmembrane region in contrast to the orthosteric extracellular hormone-binding sites. Our goal in this study was to identify positions that surround the allosteric pocket and that are sensitive for inactivation of TSHR. Homology modeling combined with site-directed mutagenesis and functional characterization revealed seven mutants located in the allosteric binding site that led to a decrease of basal cAMP signaling activity. The majority of these silencing mutations, which constrain the TSHR in an inactive conformation, are found in two clusters when mapped onto the 3D structural model. We suggest that the amino acid positions identified herein are indicating locations where small-molecule antagonists, both neutral antagonists and inverse agonists, might interfere with active TSHR conformations.     

退火温度对5A06挤压型材组织及性能的影响

通过对型材微观组织的观察及维氏硬度、晶间腐蚀和剥落腐蚀等的测试,研究了退火温度对5A06挤压型材组织及性能的影响。结果表明,随着退火温度的升高,晶粒发生了回复、再结晶和晶粒长大三个阶段。当退火温度达到175 ℃时,型材发生低温回复,硬度变化不大,耐蚀性较差;在225～325 ℃退火,型材发生完全再结晶,硬度变化较明显,耐蚀性得到改善;当退火温度高于325 ℃时,晶粒长大,硬度略降低,耐蚀性变差。结合5A06挤压型材组织及性能研究可知,确定退火温度为225～325 ℃。     

基于LVQ神经网络的植物种类识别

提出一种基于学习矢量量化（LVQ）神经网络的计算机植物种类识别新方法. 使用2-D不变矩、 多尺度2-D Gabor滤波器等多种方法分别提取了叶片的几何特征和纹理特征, 应用LVQ神经网络识别植物种类. 实验结果表明, 该方法对植物种类的识别效率较高.     

关于卡方复形的强shellable性质

研究了卡方复形上的与强shellable相关的一些性质,证明了对任意一个复形Δ,若x是使基础集上每个点都染不同颜色的一个染色,那么Δx是一个强shellable复形;若Δ是一个TA复形,那么对Δ的任意一个染色x,Δx是一个强shellable复形;复形Δ在任意一个染色x下的卡方复形Δx是matroid的当且仅当Δ是一个...     

阿维拉霉素高产菌株的推理选育

为获得阿维拉霉素高产菌株,在研究菌株Streptomyces viridocbromogenes96(SV-96)葡萄糖及氨盐代谢的基础上,采用“NTG随机诱变 氨基乙酸和2-脱氧-D葡萄糖联合抗性”的试验方案进行阿维拉霉素高产菌株的推理选育,获得了氨基乙酸和2-脱氧-D-葡萄糖联合抗性高产突变株SV-GT-596.该菌株遗传性能良好,阿维拉霉素产量高达56.4mg/L,较出发菌株提高了162.3%.实验表明,氨基乙酸和2-脱氧-D-葡萄糖抗性推理选育可克服随机筛选的盲目性,提高筛选工作效率.     

云南曲靖下泥盆统桂家屯组一种新的工蕨类植物及栖生的微螺虫

记述发现于云南曲靖锅盖山剖面桂家屯组的一种早期维管植物。该植物茎轴裸露,根状茎以连续多次K型或H型分枝形成复杂的分枝系统,直立轴呈简单的二歧式分枝,孢子囊侧视呈匙形至卵形,螺旋状着生于穗轴上。该植物体型较小,保存较完整的根状茎,但孢子囊穗的保存状况较差,孢子囊结构不够清晰,无明显可见的孢子囊开裂线,因此将其暂定为cf. Zosterophyllum sp.。尽管如此,该植物展现的性状特征不同于典型的Zosterophyllum及其他相关属种,丰富了人们对早期维管植物形态变异及桂家屯组植物组合的认识。在cf.Zosterophyllumsp.的直立轴表面栖生大量微螺虫(microconchids)标本,直径为0.7～2.2 mm。微螺虫是一种已灭绝的水生无脊椎动物,发现于晚奥陶世到中侏罗世末期地层中,其壳体为螺旋状的钙质管,习惯固着在包括植物在内的各种硬质基体上。微螺虫在cf.Zosterophyllumsp.的直立轴栖生,表明该植物在生长期间曾被水体淹没,之后微螺虫伴随植物茎干被搬运和埋藏。