A Human Skeleton from the Gillette Site (39ST23), Stanley County,South Dakota

Abstract

A skeleton excavated from a refuse area at the Gillette Site proved to be that of an adult male of advanced age.     

Probing the Structural Basis for Enzyme-Substrate Recognition In Cu,Zn Superoxide Dismutase

A full understanding of enzyme-substrate interactions requires a detailed knowledge of their structural basis at atomic resolution. Crystallographic and biochemical data have been analyzed with coupled computational and computer graphic approaches to characterize the molecular basis for recognition of the superoxide anion substrate by Cu. Zn superoxide dismutase (SOD). Detailed analysis of the bovine SOD structure aligned with SOD sequences from 15 species provides new results concerning the significance and molecular basis for sequence conservation. Specific roles have been assigned for all 23 invariant residues and additional residues exhibiting functional equivalence. Sequence invariance is dominated by 15 residues that form the active site stcreochemistry. supporting a primary biological function of superoxide dismutation. Using data from crystallographic structures and site-directed mutants, we are testing the role of individual residues in the active site channel, including (in human SOD) Glu132, Glu133, Lys136, Thr137, and Arg 143. Electrostatic calculations incorporating molecular flexibility suggest that the region of positive electrostatic potential in and over the active site channel above the Cu ion sweeps through space during molecular motion to enhance the facilitated diffusion responsible for the enzyme's rapid catalytic rate.     

In vitro cytotoxic,antibacterial, antifungal and urease inhibitory activities of some N4- substituted isatin-3-thiosemicarbazones

A series of 15 previously reported N⁴-substituted isatin-3-thiosemicarbazones 3a-o has been screened for cytotoxic, antibacterial, antifungal and urease inhibitory activities. Compounds 3b, 3e and 3n proved to be active in cytotoxicity assay; 3e exhibited a high degree of cytotoxic activity (LD₅₀ = 1.10 × 10^{? 5} M). Compound 3h exhibited significant antibacterial activity against B. subtilis, whereas compounds 3a, 3k and 3l displayed significant antifungal activity against one or more fungal strains i.e. T. longifusus, A. flavus and M. canis. In human urease enzyme inhibition assay, compounds 3g, 3k and 3m proved to be the most potent inhibitors, exhibiting relatively pronounced inhibition of the enzyme. These compounds, being non-toxic, could be potential candidates for orally effective therapeutic agents to treat certain clinical conditions induced by bacterial ureases like H. pylori urease. This study presents the first example of inhibition of urease by isatin-thiosemicarbazones and as such provides a solid basis for further research on such compounds to develop more potent inhibitors.     

Panamonon A and B,a pair of novel tetrahydrobenzofuran derivatives from Litsea panamonja (Nees) Hook. f.

A pair of novel tetrahydrobenzofuran derivatives with a unique C₁₈ carbon skeleton, panamonon A (1) and B (2), was isolated from the leaves and twigs of Litsea panamonja (Nees) Hook. f. These new compounds contain an unprecedented C₁₈ carbon skeleton consisting of a characteristic tetrahydrobenzofuran-2,5(3H,6H)-dione core with a biosynthetically extended geranyl side chain, designated as “panamonane”.

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Highlights? A pair of novel tetrahydrobenzofuran derivatives with a unique C₁₈ carbon skeleton was isolated. ? The new compounds possess an unprecedented C₁₈ carbon skeleton and are designated as “panamonane”. ? They are featured with a tetrahydrobenzofuran-2,5(3H,6H)-dione moiety and a geranyl side chain. ? The plausible biosynthetic pathways of them were discussed.     

New Horizons in Skeletal Physiology and Pathophysiology

ObjectiveTo review new discoveries that revisit our current thinking on the genesis of osteoporosis using hypogonadal and thyrotoxic bone loss as examples.MethodsWe focus on cell biologic, mouse genetic, and human studies that have established a direct action of the interior pituitary hormones follicle-stimulating hormone and thyrotropin on the skeleton and discuss emerging clinical evidence for a novel pituitary-bone axis in humans that bypasses master endocrine organs, namely the ovaries and thyroid gland.ResultsThe cataloguing of human mutations, the use of genetically modified mice that recapitulate human disease, and the rapid growth of genomic sciences have together had a profound impact on how basic research is translated into clinical practice. The skeleton has become a paradigm for the application of such advances to an extent that hitherto unrecognized physiologic and pathophysiologic findings have emerged. We propose that hypogonadal and thyrotoxic bone loss are not solely due to changes in the level of master hormones, but instead also arise from the direct action of anterior pituitary hormones on the skeleton.ConclusionsWe predict a pituitary-bone axis in which pituitary hormones bypass traditional endocrine targets to affect the skeleton directly with remarkable sensitivity. New therapeutic targets thus become a likely possibility. (Endocr Pract. 2010;16:874-881)     

Osteomesopyknosis: A Case Report and Review Of Sclerosing Bone Disorders

ObjectiveWe present a case of osteomesopyknosis, a nonmalignant sclerosing bone dysplasia of the axial skeleton, with unknown etiology and unknown prevalence.MethodsWe studied a 49-year-old female who suffered from back and pelvic pain. Her history was obtained, a physical examination performed, and the laboratory results and imaging diagnostics were studied to describe her disease.ResultsA 49-year-old, perimenopausal female suffered excruciating, intermittent, dull back and pelvic pain for 1.5 years. Nonmalignant blastic bone lesions along her spine and pelvis were discovered on computed tomography (CT) and confirmed by magnetic resonance imaging (MRI) and bone scans. Other metabolic/endocrine conditions were ruled out. Her son also has similar symptoms, and corresponding changes were observed on his vertebrae MRI. Both were diagnosed with osteomesopyknosis.ConclusionOsteomesopyknosis is a rare, autosomal dominant condition characterized by nonmalignant osteosclerosis restricted to the axial skeleton. The disease may produce chronic low-grade back pain in the thoracic and lumbar regions. (Endocr Pract. 2014;20:e106-e111)     

Late Woodland In The Kansas City Locality

Abstract

14WYB, situated near Edwardsville, Kansas, is a single-component site representative of terminal Kansas City Hopewell. Comparisons with other components with similar artifact assemblages, which are radiocarbon dated, demonstrates this terminal period to be from ca. A.D. 500 to A.D. BOO, and equivalent to early Late Woodland in the Illinois River Valley. Settlement and subsistence changes are not recognizable at this time, but do occur between A.D. BOO and A.D. 1000, perhaps as reflection of the adoption of agriculture as important to the subsistence base during the late Late Woodland period.     

A Late Woodland Burial from Platte County,Missouri

Abstract

A skeleton of a female discovered in a grave located on the west bank of Short Creek, Platte County, Missouri provides some of the first evidence for mortuary practices and human morphology for the Western Missouri-Eastern Kansas Late Woodland. The burial is a bundle type, with most of the bones placed in a central heap. Analysis of the distribution of the bones indicates that some soh tissue was still adhering to the skeleton at the time of the secondary burial. Bones of the right hand and foot and the vertebral column from cervical 7 to the coccyx are the only remains preserved in anatomical order. Many of the long bones appear to have been broken and there is also some evidence for burning and fleshing of the skeleton before final interment. Measurements of the cranial and post-cranial skeleton are given for comparison with future Late Woodland discoveries.     

家蚕核型多角体病毒lef-11基因RNA干扰策略的优化

【目的】家蚕核型多角体病毒(Bombyx mori nucleopolyhedrovirus,BmNPV)lef-11基因作为杆状病毒高度保守的晚期表达因子之一,对病毒晚期基因的表达极其重要。因此对lef-11基因进行有效RNA干扰将提高宿主细胞对BmNPV的抗性。【方法】本文基于经典的sh-RNA-loop骨架及家蚕内源性的miRNA骨架,构建以BmNPV lef-11基因为靶标的干扰载体pIZ-shRNA1、pIZ-shRNA2和pIZ-Ds RedamiR279;分别构建基于A4、IE1、IE1-295、IE2、IE2-339、hr3A4和hsp70启动子驱动的干扰载体,用以评价不同启动子驱动的干扰载体的抗病毒效果,并对干扰载体进行优化。【结果】首先,本文通过比较miRNA-based和shRNA-based RNAi载体对同一靶基因同一位点的干扰效率,发现pIZ-Ds Red-amiR279对BmNPV lef11基因的干扰效率超过90%,远优于shRNA-based RNAi载体的干扰效果;其次,通过对干扰载体进行优化,发现IE1启动子的效果最优,由其驱动的pIZ-Ds Red-milef11干扰载体也是本研究中的最优干扰载体,对病毒的增殖抑制效果最为明显。【结论】对目的基因的干扰效果并非启动子的活性越高、miRNA积累得越多就越好,只有综合考虑干扰片段的选择、启动子的活性以及靶基因自身的功能等多方面的因素,才能提高干扰效率,达到干扰目的。     

A Human Skeleton From The Pryor Creek Burial, 24YL404, Yellowstone County,Montana

Abstract

An adult human skeleton, found associated with artifacts of both Indian and White manufacture near Billings, Yellowstone County, Montana, is thought on the basis of cranial measurements and morphological features to be a prehistoric Crow Indian.     

Total Synthesis of the Thymidine Analogue of Sinefungin

Abstract

The carbon skeleton of “Sinethymidin” 4 was constructed by two radical coupling reaction. The first step was a coupling of the radical derived from 2 and the unsaturated amide 5. The olefin 6 thus obtained was added to the radical derived from the known N-hydroxy-2-thiopyridinone aspartic ester. “Sinethymidin”, tested for its antileismanial effect, was devoid of activity.     

A Human Skeleton from an Apache Baking Pit

Abstract

A human skeleton found in an Apache baking pit in Scott County, Kansas, is that of a 22 or 23 year old male, about 5 feet, 7 inches tall. It is probable that he was a Cuartelejo Apache of ca. 1700.     

Seven new triterpene glycosides from the pericarps of Stryphnodendron fissuratum

Seven new triterpene glycosides on the basis of the lupane skeleton (1–7) were isolated from the pericarps of Stryphnodendron fissuratum (Leguminosae). The structures of 1–7 were determined on the basis of extensive spectroscopic analysis, including two-dimensional NMR data, and the results of hydrolytic cleavage.     

The convenient synthesis and evaluation of the anticancer activities of new resveratrol derivatives

In the present study we report the simple synthesis and antitumour activity of novel stilbene derivatives 13–22. The key synthetic strategies involved Wadsworth-Horner-Emmons condensation and coupling reactions in high yields. All compounds showed significant growth inhibition on human tumour cell lines, with the most potent compound (19) exhibiting an IC₅₀ of 5.7 μM – 11.4 μM in vitro.     

SYNTHESIS AND ANTI-HCMV ACTIVITY OF NOVEL ACYCLIC NUCLEOSIDES

ABSTRACT

A series of novel acyclic nucleosides 10, 11, 21, and 22 were synthesized efficiently starting from D-lactose. The condensation of the mesylate 5 and 16 with an adenine and cytosine base under standard nucleophilic substitution conditions (K₂CO₃, 18-Crown-6, DMF) afforded a series of acyclic novel nucleosides. Compound 21 displayed moderate anti-HCMV activity in the AD-169 cells (EC₅₀=18.5 µg/mL) without exhibiting any cytotoxicity up to 100 µM.     

Ethnic Identification Of An Historic Sac Burial From Northeastern Kansas

Abstract

A partial human skeleton, associated with a number of white manufactured goods, has been excavated on a bluff overlooking the Missouri River. It is a male about 20 years of age and about five feet two inches in height. He is identified as a Sac Indian who was interred between 1840 and 1860.     

Taxusecone,a Novel Taxane with an Unprecedented 11,12-Secotaxane Skeleton,from Taxus cuspidata Needles

Taxusecone, 2α,7β,9α,10β-tetraacetoxy-5α,12-dihydroxy-11,12-secotax-4(20)-ene-11,13-dione (1), a novel taxane with an unprecedented skeleton, was isolated from the needles of Taxus cuspidata.     

基于主成分分析的双对比光学投影断层成像

目的 本文提出了一种基于主成分分析（PCA）的双对比光学投影断层成像（DC-OPT）方法,以获得活体中血流网络和骨骼的三维可视化。方法 使用主成分分析方法来提取吸收图像和血流图像,原始图像序列的第一主成分用于获取吸收图像;通过计算每个像素的调制深度来获得流动图像。不同投影位置的流动和吸收对比图像被用于三维血流网络和骨骼的同步重建。结果 采用PCA和OPT相结合的方法,通过将动态血流信号和静态背景信号分离,实现了对微生物样本的血流网络和骨骼的三维成像。结论 本文研究的新颖之处在于通过同一光学系统获得了快速、同步、双对比的血流网络和骨骼三维图像。实验结果可用于活体生物的生理发育研究。     

The Torpedo Electrocyte: A Model System for the Study of Receptor-Cytoskeleton Interactions

Abstract

We have used the electrocyte of Torpedo electric organ as a model system for the study of AchR stabilization in the post-synaptic membrane. Attention was focused on membrane cytoskeleton interactions in particular on a peripheral protein of 43 KD that is believed to participate in AchR immobilization.

Using immunocytochemical methods, we have shown that the cortical skeleton in Torpedo electrocyte displays a local differentiation proper for each specialized domain of the plasma membrane. In the postsynaptic membrane, characterized by an accumulation and a geometrical organization of the receptors in the plane of the membrane, the 43 KD protein participates in a submembraneous coating or “postsynaptic densities” that strictly codistribute with the AchR. The 43 KD protein might also account for the anchoring of intermediate-sized filaments.

The organization of the postsynaptic domain appears readily different from that of the non-innervated one where the membrane folds are maintained by a cortical meshwork of cytoskeletal proteins such as ankyrin, spectrin and oligomeric actin.

In conclusion, the asymmetrical organization of the cortical skeleton in the electrocyte offers a unique opportunity for the study of the specific aspects of membrane-skeleton interactions that take place in the postsynaptic domain.