嗜黏蛋白阿克曼氏菌对高尿酸血症小鼠血清尿酸及组织炎症的影响及机制

目的：研究活的和巴氏杀菌处理的嗜黏蛋白阿克曼氏菌（Akkermansia muciniphila）对高尿酸血症小鼠血清尿酸水平及组织炎症的影响和潜在机制。方法：使用氧嗪酸钾和次黄嘌呤联合含20%（以体系质量计）酵母膏的饲料对ICR小鼠进行为期3周的高尿酸血症造模,同时分别灌胃活的和巴氏杀菌处理的嗜黏蛋白阿克曼氏菌作为处理组,采集小鼠血液和组织样品,测定小鼠血清尿酸浓度以及肝脏黄嘌呤氧化酶活力,并通过苏木精-伊红染色法进行小鼠肾和肠道病理分析。结果：不同形式的嗜黏蛋白阿克曼氏菌均能一定程度地降低小鼠血清尿酸浓度。肝脏黄嘌呤氧化酶活力检测以及蛋白印迹分析结果表明两种形式的嗜黏蛋白阿克曼氏菌能下调该酶活性及蛋白表达,从而减少肝脏尿酸的生成。肾和肠道组织病理分析结果表明模型组小鼠肾脏和肠道均有损伤,包括肾小球萎缩、肾间质炎性细胞浸润以及肠绒毛变短,嗜黏蛋白阿克曼氏菌处理能减轻这些症状。嗜黏蛋白阿克曼氏菌干预还能下调肾脏及肠道Toll样受体4和Caspase 1水平,从而抑制白细胞介素-1β表达,有效缓解小鼠脏器中的炎症反应。结论：嗜黏蛋白阿克曼氏菌能用于改善小鼠高尿酸血症,并且巴氏杀菌处理后的...     

Enzymatic Responses to Low-Intensity Radiation of Tritium

The present study considers a possible role of enzymatic reactions in the adaptive response of cells to the beta-emitting radionuclide tritium under conditions of low-dose exposures. Effects of tritiated water (HTO) on the reactions of bacterial luciferase and NAD(P)H:FMN-oxidoreductase, as well as a coupled system of these two reactions, were studied at radioactivity concentrations ≤ 200 MBq/L. Additionally, one of the simplest enzymatic reactions, photobiochemical proton transfer in Coelenteramide-containing Fluorescent Protein (CLM-FP), was also investigated. We found that HTO increased the activity of NAD(P)H:FMN-oxidoreductase at the initial stage of its reaction (by up to 230%); however, a rise of luciferase activity was moderate (<20%). The CLM-FP samples did not show any increase in the rate of the photobiochemical proton transfer under the exposure to HTO. The responses of the enzyme systems were compared to the ‘hormetic’ response of luminous marine bacterial cells studied earlier. We conclude that (1) the oxidoreductase reaction contributes significantly to the activation of the coupled enzyme system and bacterial cells by tritium, and (2) an increase in the organization level of biological systems promotes the hormesis phenomenon.     

Evaluation of adult and offspring thiamine deficiency in salmonine species from Lake Ontario

Thiamine Deficiency Complex (TDC) is an ongoing problem impacting salmonine health in various waterbodies, including Lake Ontario. The prevalence of TDC has been variable and explanations for differences are limited. In the current study, thiamine concentrations were measured in eggs, liver tissue, and muscle tissue sampled from brown trout (Salmo trutta), Chinook salmon (Oncorhynchus tshawytscha), coho salmon (O. kisutch), lake trout (Salvelinus namaycush), and steelhead trout (O. mykiss) that were collected from Lake Ontario and its surrounding tributaries. The occurrence of TDC was measured for each species based on TDC-induced offspring mortality rates under laboratory conditions. TDC-induced offspring mortality was observed for all species except brown trout. For affected species, egg free thiamine (Th) was consistently low compared to lake trout collected from Lake Superior that are considered thiamine replete. In addition, species with the lowest percentages of Th in their eggs were the most susceptible to TDC, suggesting that limited thiamine reserves in the form of Th may cause TDC-induced offspring mortality. Lastly, our results show that egg thiamine concentrations have yearly variation and increased for all species throughout the study. Reasons for such variation are undetermined; but, if egg thiamine concentrations continue to increase, the impacts of TDC on these salmonine species may lessen. Future monitoring is needed for determining if thiamine concentrations are increasing and the potential impacts that may have on the entire Lake Ontario fishery.     

Congenital Diseases of DNA Replication: Clinical Phenotypes and Molecular Mechanisms

Deoxyribonucleic acid (DNA) replication can be divided into three major steps: initiation, elongation and termination. Each time a human cell divides, these steps must be reiteratively carried out. Disruption of DNA replication can lead to genomic instability, with the accumulation of point mutations or larger chromosomal anomalies such as rearrangements. While cancer is the most common class of disease associated with genomic instability, several congenital diseases with dysfunctional DNA replication give rise to similar DNA alterations. In this review, we discuss all congenital diseases that arise from pathogenic variants in essential replication genes across the spectrum of aberrant replisome assembly, origin activation and DNA synthesis. For each of these conditions, we describe their clinical phenotypes as well as molecular studies aimed at determining the functional mechanisms of disease, including the assessment of genomic stability. By comparing and contrasting these diseases, we hope to illuminate how the disruption of DNA replication at distinct steps affects human health in a surprisingly cell-type-specific manner.     

Vitamin A fortification: Recent advances in encapsulation technologies

Vitamin A is an essential micronutrient whose deficiency is still a major health concern in many regions of the world. It plays an essential role in human growth and development, immunity, and vision, but may also help prevent several other chronic diseases. The total amount of vitamin A in the human diet often falls below the recommended dietary allowance of approximately 900–1000 $\mu$g/day for a healthy adult. Moreover, a significant proportion of vitamin A may be degraded during food processing, storage, and distribution, thereby reducing its bioactivity. Finally, the vitamin A in some foods has a relatively low bioavailability, which further reduces its efficacy. The World Health Organization has recommended fortification of foods and beverages as a safe and cost-effective means of addressing vitamin A deficiency. However, there are several factors that must be overcome before effective fortified foods can be developed, including the low solubility, chemical stability, and bioavailability of this oil-soluble vitamin. Consequently, strategies are required to evenly disperse the vitamin throughout food matrices, to inhibit its chemical degradation, to avoid any adverse interactions with any other food components, to ensure the food is palatable, and to increase its bioavailability. In this review article, we discuss the chemical, physical, and nutritional attributes of vitamin A, its main dietary sources, the factors contributing to its current deficiency, and various strategies to address these deficiencies, including diet diversification, biofortification, and food fortification.     

Frequency selective millimeter‐wave channel estimation based on subspace enhancement algorithms

In millimeter wave (mmW) communication systems, hybrid architecture, including the analog‐digital precoder and combiner matrices, is employed to take advantage of the multistream transceiver. In practice, mmW channel is assumed to be frequency‐selective, since the signal bandwidth is larger than the coherence bandwidth. Hence, orthogonal frequency‐division multiplexing signaling can be remedial. So far, most of the previous works on the frequency‐selective channel estimation have focused on the single measurement vector (SMV) form, whereas finding and exploiting the proper multimeasurement vector (MMV) model can improve upon the estimation procedure based on compressive sensing (CS) concepts. In fact, the estimation procedure based on the MMV model has a faster convergence speed than the SMV method specially, when the training frames are small. In this paper, we first extract the MMV model of the channel. In this model, the rank‐deficiency occurs as the number of training frames is less or equal to the sparsity level. Thus, the conventional estimation methods fail to provide the desirable performance. To overcome this issue, we propose two rank‐aware algorithms based on the enhancement of the observed signal subspace. The first algorithm assumes to know the sparsity level, while the second faces to the lack of knowledge about the sparsity level. The simulation results corroborate the fact that the proposed methods outperform the conventional CS algorithms such as Simultaneous Orthogonal Matching Pursuit.     

Natural Antioxidants in Anemia Treatment

Anemia, characterized by a decrease of the hemoglobin level in the blood and a reduction in carrying capacity of oxygen, is a major public health problem which affects people of all ages. The methods used to treat anemia are blood transfusion and oral administration of iron-based supplements, but these treatments are associated with a number of side effects, such as nausea, vomiting, constipation, and stomach pain, which limit its long-term use. In addition, oral iron supplements are poorly absorbed in the intestinal tract, due to overexpression of hepcidin, a peptide hormone that plays a central role in iron homeostasis. In this review, we conducted an analysis of the literature on biologically active compounds and plant extracts used in the treatment of various types of anemia. The purpose of this review is to provide up-to-date information on the use of these compounds and plant extracts, in order to explore their therapeutic potential. The advantage of using them is that they are available from natural resources and can be used as main, alternative, or adjuvant therapies in many diseases, such as various types of anemia.     

A missense mutation (p.Tyr452Cys) in the CAD gene compromises reproductive success in French Normande cattle

We scanned the genome of 77,815 Normande cattle with different Illumina SNP chips (Illumina Inc., San Diego, CA) to map recessive embryonic lethal mutations using homozygous haplotype deficiency. We detected 2 novel haplotypes on chromosomes 11 and 24 but did not confirm 6 previously reported haplotypes. The one on chromosome 11 showed a marked reduction in conception rates and moderate decrease in nonreturn rate in at-risk versus control mating, supporting late embryonic mortality. After fine mapping and analyzing whole-genome sequences, we prioritized a missense mutation in CAD (g.72399397T>C; p.Tyr452Cys)—a gene encoding a protein (carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase) essential for de novo pyrimidine biosynthesis—as a candidate causal variant. This transition mutation replaces a tyrosine residue, which is perfectly conserved among living organisms, with a cysteine residue in the carbamoyl-phosphate synthetase 2 domain of the protein. A single animal was confirmed to be homozygous for the mutation based on Sanger sequencing. However, large-scale genotyping of the candidate variant with the Illumina EuroG10k BeadChip revealed an absence of live homozygotes in a panel of 33,323 Normande animals and an absence of carriers in 348,593 animals from 19 other cattle breeds. These results support recessive embryonic lethality with nearly complete penetrance, as was previously reported in CAD mutants in several eukaryote species. The only homozygous cow had extremely poor udder conformation, suggesting a potential role of CAD in udder development, but no effect was detected when comparing daughter yield deviations of 250 heterozygous bulls with that of 2,912 homozygotes for the ancestral allele. Together, our results showed the importance of large-scale screening for homozygous haplotype deficiency with hundreds of thousands of animals, validating results with an independent data set, and considering unexpected live homozygotes, to avoid both false-positive and false-negative discoveries. These discoveries will be used primarily in mating decisions to avoid at-risk mating. In addition, we recommend including CAD in the breeding objectives of Normande cattle.     

基于Logistic回归模型的张掖市水资源供需风险研究

为缓解张掖市水资源供需矛盾,并为水资源科学管理提供决策依据,收集张掖市2006—2015年水资源相关数据,并选取张掖市供水量、需水量和缺水量3个变量,运用Logistic回归模型,得出张掖市水资源供需风险率及其影响程度;使用谱系聚类法评价其风险率并确定风险等级,最后得出张掖市在2种水平年可能存在的供需风险程度。结果表明:近10 a来,张掖市水资源均存在供需不平衡、供需矛盾的问题;张掖市未来经济发展与当地水资源供需状况有关,而供需风险的高低与供水保证率有直接关系。建议张掖市政府实行多措并举来保证水资源供应量充足,使得供需风险处于低风险。