Association analysis of HSP70A1A haplotypes with heat tolerance in Chinese Holstein cattle

Single-nucleotide polymorphisms (SNPs) in the coding and untranslated regions of heat shock 70 kDa protein 1A (HSP70A1A), an inducible molecular chaperone that is responsible for cellular protection against heat stress, have been reported as being associated with heat tolerance. A fragment of the HSP70A1A gene was amplified in Chinese Holstein cattle and eight novel mutations were found. We performed comprehensive linkage disequilibrium (LD) and haplotype analyses of the eight SNPs of the HSP70A1A gene and examined their involvement in heat resistance in 600 Chinese Holstein cattle. Our results revealed the presence of significant differences between individuals carrying haplotype 1 and those without haplotype 1 for most of the heat-tolerance traits. Haplotype 1 increased the risk of heat stress; however, association analysis of its combination with haplotype 2 showed the lowest rectal temperature and red blood cell K⁺ level, moderate respiratory rate, and the highest red blood cell NKA level, suggesting a heterozygote advantage in the penetration of the phenotype. Protein expression levels in white blood cells among haplotype combinations further confirmed the hypothesis that heterozygotes for haplotypes 1 and 2 are more sensitive to heat stress. We presume that these mutations may be useful in the future as molecular genetic markers to assist selection for heat tolerance in cattle.     

Ca 2+-induced self-assembly in designed peptides with optimally spaced gamma-carboxyglutamic acid residues

We have previously elucidated a new paradigm for the metal ion-induced helix-helix assembly in the natural γ-carboxyglutamic acid (Gla)-containing class of conantokin (con) peptides, typified by con-G and a variant of con-T, con-T[K7Gla], independent of the hydrophobic effect. In these “metallo-zipper” structures, Gla residues spaced at i, i + 4, i + 7, i + 11 intervals, which is similar to the arrangement of a and d residues in typical heptads of coiled-coils, coordinate with Ca²⁺ and form specific antiparallel helical dimers. In order to evaluate the common role of Gla residues in peptide self-assembly, we extend herein the same Gla arrangement to designed peptides: NH₂-(γLSγEAK)₃-CONH₂ (peptide 1) and NH₂-γLSγEAKγLSγQANγLSγKAE-CONH₂ (peptide 2). Peptide 1 and peptide 2 exhibit no helicity alone, but undergo structural transitions to helical conformations in the presence of a variety of divalent cations. Sedimentation equilibrium ultracentrifugation analyses showed that peptide 1 and peptide 2 form helical dimers in the presence of Ca²⁺, but not Mg²⁺. Folding and thiol-disulfide rearrangement assays with Cys-containing peptide variants indicated that the helical dimers are mixtures of antiparallel and parallel dimers, which is different from the strict antiparallel strand orientations of con-G and con-T[K7γGla] dimers. These findings suggest that the Gla arrangement, i, i + 4, i + 7, i + 11, i + 14, plays a key role in helix formation, without a strict adherence to strand orientation of the helical dimer.     

Potent, exceptionally selective, orally bioavailable inhibitors of TNF-alpha Converting Enzyme (TACE): novel 2-substituted-1H-benzo[d]imidazol-1-yl)methyl)benzamide P1' substituents

Novel ((2-substituted-1H-benzo[d]imidazol-1-yl)methyl)benzamides were found to be excellent P1' substituents in conjunction with unique constrained beta-amino hydroxamic acid scaffolds for the discovery of potent selective inhibitors of TNF-alpha Converting Enzyme (TACE). Optimized examples proved potent for TACE, exceptionally selective over a wide panel of MMP and ADAM proteases, potent in the suppression of LPS-induced TNF-alpha in human whole blood and orally bioavailable.     

Potent, selective, orally bioavailable inhibitors of tumor necrosis factor-alpha converting enzyme (TACE): discovery of indole, benzofuran, imidazopyridine and pyrazolopyridine P1' substituents

Potent and selective inhibitors of tumor necrosis factor-alpha converting enzyme (TACE) were discovered with several new heterocyclic P1' groups in conjunction with cyclic beta-amino hydroxamic acid scaffolds. Among them, the pyrazolopyridine provided the best overall profile when combined with tetrahydropyran beta-amino hydroxamic acid scaffold. Specifically, inhibitor 49 showed IC(50) value of 1 nM against porcine TACE and 170 nM in the suppression of LPS-induced TNF-alpha of human whole blood. Compound 49 also displayed excellent selectivity over a wide panel of MMPs as well as excellent oral bioavailability (F%>90%) in rat n-in-1 PK studies.     

Unexpected systematic affinities and geographic expansion of a marine alien hydroid (Cnidaria: Hydrozoa)

Biological systematics provides taxonomic information and expertise for biogeography and biological invasion research and management. However, the systematic classification of most taxa, including some alien and invasive species, relies only on morphology. This applies for example to Sertularella tongensis Stechow, 1919 Stechow, E. (1919). Zur Kenntnis der Hydroidenfauna des Mittelmeeres, Amerikas und anderer Gebiete, nebst Angaben über einige Kirchenpauer'sche Typen von Plumulariden. Zoologische Jahrbuecher (Systematik), 42, 1–172. [Google Scholar] (Cnidaria: Sertulariidae), an alien hydrozoan recently reported in the Mediterranean. Its genus affiliation is still unclear and controversial. Historically, it has been assigned to several existing genera. However, molecular data (COI, 16S, 18S, 28S) provided here do not support these previous assignments. Instead, integrative analyses combining morphological and molecular data support reassigning this species to a new genus, Bicaularia gen. nov. A biogeographic review revealed that this species is widely distributed in the mid- and low-latitude waters of the Indo-Pacific region, and is spreading to some tropical and temperate regions including the Mediterranean and Caribbean Seas, as well as Korea and Japan. This expansion may be attributable to human activity such as shipping through the Suez and the Panama Canals. However, the new record attached to a floating Sargassum algal fragment in the surface water of the open Pacific, might suggest a neglected cryptic spread pathway with the assistance of floating biological organisms. Our findings shed light on the complexity of the phylogeny and spread pathway of the investigated hydrozoan species. We regard the fine systematics as the first step towards future global sampling for molecular studies aiming to elucidate the origins and pathways for alien and invasive species.

http://zoobank.org/urn:lsid:zoobank.org: pub: 45AB0849-1E3B-477FB643-1B3B4603C1FF     

Removing of Disinfection By-Product Precursors from Surface Water by Using Magnetic Graphene Oxide

The magnetic graphene oxide (MGO) was successfully synthesised by the in situ chemical co-precipitation method with Fe³⁺, Fe²⁺ and graphene oxide (GO) in laboratory and, was used as an adsorbent for disinfection by-product (DBP) precursors removing from four natural surface water samples. The results indicate that various DBPs formation significantly decreased by 7–19% to 78–98% for the four samples after MGO treatment and, the treatment process was rapidly reached equilibrium within 20 minutes. The DBP precursors removal efficiency decreased with the increasing pH value from 4 to 10. Hydrophobic compounds (humic acid and fulvic acid) are more sensitive to MGO, whereas hydrophilic and nitrogenous compounds (aromatic proteins) are more insensitive. MGO could be regenerated by using 20% (v/v) ethanol and, the DBP precursors removal efficiency can stay stable after five cycles. These results indicate that MGO can be utilized as a promising adsorbent for the removal of DBP precursors from natural surface water.     

基于MaxEnt模型评估刺五加在东北地区的空间分布

研究刺五加(Acanthopanax senticosus)在东北地区的潜在分布区及生态适宜性,针对267个刺五加分布样点数据和17个环境因子数据,应用最大熵模型(Maximum Entropy Model,简称MaxEnt)和地理信息系统(Geographic Information System,GIS)评估刺五加的地理分布。结果表明:最大熵模型的AUC值为0.929,模型预测结果的准确性可信度高,可以用来预测刺五加的地理分布。刺五加生态适宜区主要集中在长白山山脉及小兴安岭东南地区,分布面积约为22.12万km~2,存在概率最高的区域主要在辽宁省东部、吉林省东南部以及黑龙江省中部。影响刺五加地理分布的主要环境因子依次为:年均降水量、森林类型、极端低温、生长季降水量及海拔。耦合了大尺度环境数据、植被群落类型数据与刺五加分布之间的关系,预测了东北地区刺五加的生态适宜区及主导环境因子,为其种群恢复与开发利用提供了科学依据。