Distribution of hereditary blood groups among Indians in South America. IV. In Chile with inferences concerning genetic connections between Polynesia and America

This is the fourth paper in a series on the distribution of blood groups among Indians of South America. It reports the findings on the Indians of Chile and the Polynesians of Chile's Easter Island. Blood specimens were procured from the following putatively pure Indians and unmixed Polynesians: 44 Alacaluf of Puerto Eden, Isla Wellington, 141 Mapuche (Araucanian) of Lonquimay, Malleco Province, 80 Atacameños of Antofagasta Province, and 45 Polynesians of Easter Island. These 310 samples were tested for blood factors in the A-B-O, M-N-S-s, P, Rh-Hr, Lutheran, K-k, Lewis, Duffy, Kidd and Diego systems, and for the Wright (Wr^a) agglutinogen. Serum samples were tested for haptoglobins and transferrins. Hemolysates prepared from the blood clots were tested for hemoglobin types. The results are presented as phenotype incidences and calculated gene frequencies in appropriate tables. Locations of the populations from which blood samples were procured are shown on two maps. The high frequencies for the O gene usually reported for South American Indians obtain in putatively pure Chilean Indians but A¹ is high in Easter Island Polynesians. In both Indians and Polynesians M, s, R¹ (CDe), R² (cDE), Lu^b, k, Le^H, and Fy^a gene frequencies are high and B, N, S, Mi^a, Vw, Rº (cDe), r (cde), Lu^a, K, Le¹, Fy^b, and Wr^a (Ca) are low or absent. The Diego (Di) gene is present in the Mapuche and Atacameños but absent in the Alacaluf and Polynesians. Hp¹ gene frequencies were determined only in the Alacaluf and Atacameños, in which they are 0.48 and 0.67 respectively. Transferrins were determined for the Alacaluf and Atacameños Indians and all were classified as Tf C. All Chilean Indian and Polynesian specimens were tested electrophoretically for hemoglobin types and all contained only hemoglobin (A) as a major component.     

Addressing the intrinsic disorder bottleneck in structural proteomics

The Center for Eukaryotic Structural Genomics (CESG), as part of the Protein Structure Initiative (PSI), has established a high-throughput structure determination pipeline focused on eukaryotic proteins. NMR spectroscopy is an integral part of this pipeline, both as a method for structure determinations and as a means for screening proteins for stable structure. Because computational approaches have estimated that many eukaryotic proteins are highly disordered, about 1 year into the project, CESG began to use an algorithm (the Predictor of Naturally Disordered Regions, PONDR to avoid proteins that were likely to be disordered. We report a retrospective analysis of the effect of this filtering on the yield of viable structure determination candidates. In addition, we have used our current database of results on 70 protein targets from Arabidopsis thaliana and 1 from Caenorhabditis elegans, which were labeled uniformly with nitrogen-15 and screened for disorder by NMR spectroscopy, to compare the original algorithm with 13 other approaches for predicting disorder from sequence. Our study indicates that the efficiency of structural proteomics of eukaryotes can be improved significantly by removing targets predicted to be disordered by an algorithm chosen to provide optimal performance.     

Theoretical study of hydrogenation of the doubly aromatic B 7 − cluster

We have studied the influence of hydrogenation on the relative stability of the low-lying isomers of the anionic B₇⁻ cluster, computationally. It is known that the pure-boron B₇⁻ cluster has a doubly (σ- and π-) aromatic C_6v (³A₁) quasi-planar wheel-type triplet global minimum (structure 1), a low-lying σ-aromatic and π-antiaromatic quasi-planar singlet C_2v (¹A₁) isomer 2 (0.7 kcal mol⁻¹ above the global minimum), and a planar doubly (σ- and π-) antiaromatic C_2v (¹A₁) isomer 3 (7.8 kcal mol⁻¹ above the global minimum). However, upon hydrogenation, an inversion in the stability of the species occurs. The planar B₇H₂⁻ (C_2v, ¹A₁) isomer 4, originated from the addition of two hydrogen atoms to the doubly antiaromatic B₇⁻ isomer 3, becomes the global minimum structure. The second most stable B₇H₂⁻ isomer 5, originated from the quasi-planar triplet wheel isomer 1 of B₇⁻, was found to be 27 kcal mol⁻¹ higher in energy. The inversion in stability occurs due to the loss of the doubly aromatic character in the wheel-type global minimum isomer (C_6v, ³A₁) of B₇⁻ upon H₂−addition. In contrast, the planar isomer of B₇⁻ (C_2v, ¹A₁) gains aromatic character upon addition of two hydrogen atoms, which makes it more stable. Figure The B₇H₂-global minimum structure and its σ-aromatic and π-antiaromatic MOs Dedicated to Professor Dr. Paul von Ragué Schleyer on the occasion of his 75th birthday.     

Coalescent processes when the distribution of offspring number among individuals is highly skewed

We report a complex set of scaling relationships between mutation and reproduction in a simple model of a population. These follow from a consideration of patterns of genetic diversity in a sample of DNA sequences. Five different possible limit processes, each with a different scaled mutation parameter, can be used to describe genetic diversity in a large population. Only one of these corresponds to the usual population genetic model, and the others make drastically different predictions about genetic diversity. The complexity arises because individuals can potentially have very many offspring. To the extent that this occurs in a given species, our results imply that inferences from genetic data made under the usual assumptions are likely to be wrong. Our results also uncover a fundamental difference between populations in which generations are overlapping and those in which generations are discrete. We choose one of the five limit processes that appears to be appropriate for some marine organisms and use a sample of genetic data from a population of Pacific oysters to infer the parameters of the model. The data suggest the presence of rare reproduction events in which approximately 8% of the population is replaced by the offspring of a single individual.     

Novel racemosin B derivatives as new therapeutic agents for aggressive breast cancer

Carbazole derivatives show anti-cancer activity and are of great interest for drug development. In this study, we synthesized and analyzed several new alkylamide derivatives of racemocin B, a natural indolo[3,2-a]carbazole molecule originally isolated from the green alga Caulerpa racemose. Several alkylamide derivatives were found to exhibit moderate to strong growth inhibition against human breast cancer cell lines. They induced G2/M cell cycle arrest and apoptosis in the aggressive triple-negative breast cancer cell line MDA-MB-231. Among these derivatives, compound 25 with the lowest IC₅₀ induced cell death by suppressing autophagy. This was accompanied by inhibition of autophagic flux and accumulation of autophagy protein 1 light chain 3, LC3II, and p62. The novel alkylamide derivative offers a potential new treatment for human breast cancer.     

Microanatomy of the renal cortex in the domestic fowl

Two aspects of the avian renal cortical microanatomy previously were unclear. The precise in situ folding patterns and orientations of the nephrons with respect to the other cortical elements had not been demonstrated. It also was not known whether certain nephron segments are supplied exclusively by either the arterial or the portal blood flow. In the present study, a new casting compound was developed to allow selective examination of the cortical components by light microscopy. Cortical nephrons at the surface of the kidney were serially sectioned and reconstructed in order to determine: (a) their relationships to the vasculature and collecting ducts; (b) the location and characteristics of the tubule segments; and (c) the primary and secondary folding patterns of the tubules. The anatomical findings were documented individually and then summarized in a comprehensive diagram of the superficial cortical microanatomy. In addition, an in vivo method was used to determine the extent of portal blood distribution to the nephron segments. It was demonstrated that renal portal blood suffuses all of the segments except for the loops of Henle.