HIV-1 nef suppression by virally encoded microRNA

BACKGROUND: MicroRNAs (miRNAs) are 21~25-nucleotides (nt) long and interact with mRNAs to trigger either translational repression or RNA cleavage through RNA interference (RNAi), depending on the degree of complementarity with the target mRNAs. Our recent study has shown that HIV-1 nef dsRNA from AIDS patients who are long-term non-progressors (LTNPs) inhibited the transcription of HIV-1. RESULTS: Here, we show the possibility that nef-derived miRNAs are produced in HIV-1 persistently infected cells. Furthermore, nef short hairpin RNA (shRNA) that corresponded to a predicted nef miRNA (~25 nt, miR-N367) can block HIV-1 Nef expression in vitro and the suppression by shRNA/miR-N367 would be related with low viremia in an LTNP (15-2-2). In the 15-2-2 model mice, the weight loss, which may be rendered by nef was also inhibited by shRNA/miR-N367 corresponding to suppression of nef expression in vivo. CONCLUSIONS: These data suggest that nef/U3 miRNAs produced in HIV-1-infected cells may suppress both Nef function and HIV-1 virulence through the RNAi pathway

Genetic heterogeneity within an electrophoretic phenotype of phosphoglucose isomerase in a Japanese population

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65884/1/j.1469-1809.1979.tb00662.x.pd

The frequency in Japanese of genetic variants of 22 proteins III. Phosphoglucomutase-1, phosphoglucomutase-2, 6-phosphogluconate dehydrogenase, adenylate kinase, and adenosine deaminase

Five enzyme systems, PGM 1 , PGM 2 , ADA, 6-PGD and AK, were examined by electrophoresis in over 4000 samples from Hiroshima and Nagasaki for the frequencies of common and rare variants. In the PGM 1 , system, the PGM 2 1 allele and PGM 7 1 ; allele were found in polymorphic proportions. I n addition, five kinds of slow variants and three types of fast variants of PGM 1 were detected. The PGM 3 NGS 1 1 allele was found in five individuals from Nagasaki, but was not observed in samples from Hiroshima. There were no variants of PGM 2 . Three kinds of fast variants of 6-PGD were detected. NO variation in AK was observed. There were no rare variants of ADA. The 6-PGD c allele had a frequency of 0.084 in Hiroshima, and 0.093 in Nagasaki, and the ADA 2 allele frequencies of 0.025 in Hiroshima and 0.032 in Nagasaki.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65524/1/j.1469-1809.1977.tb01912.x.pd

The optimal elastic flagellum

Motile eukaryotic cells propel themselves in viscous fluids by passing waves of bending deformation down their flagella. An infinitely long flagellum achieves a hydrodynamically optimal low-Reynolds number locomotion when the angle between its local tangent and the swimming direction remains constant along its length. Optimal flagella therefore adopt the shape of a helix in three dimensions (smooth) and that of a sawtooth in two dimensions (non-smooth). Physically, biological organisms (or engineered micro-swimmers) must expend internal energy in order to produce the waves of deformation responsible for the motion. Here we propose a physically-motivated derivation of the optimal flagellum shape. We determine analytically and numerically the shape of the flagellar wave which leads to the fastest swimming while minimizing an appropriately-defined energetic expenditure. Our novel approach is to define an energy which includes not only the work against the surrounding fluid, but also (1) the energy stored elastically in the bending of the flagellum, (2) the energy stored elastically in the internal sliding of the polymeric filaments which are responsible for the generation of the bending waves (microtubules), and (3) the viscous dissipation due to the presence of an internal fluid. This approach regularizes the optimal sawtooth shape for two-dimensional deformation at the expense of a small loss in hydrodynamic efficiency. The optimal waveforms of finite-size flagella are shown to depend upon a competition between rotational motions and bending costs, and we observe a surprising bias towards half-integer wave-numbers. Their final hydrodynamic efficiencies are above 6%, significantly larger than those of swimming cells, therefore indicating available room for further biological tuning

Anthropology and GIS: Temporal and Spatial Distribution of the Philippine Negrito Groups

The Philippine negrito groups comprise a diverse group of populations speaking over 30 different languages, who are spread all over the archipelago, mostly in marginal areas of Luzon Island in the north, the central Visayas islands, and Mindanao in the south. They exhibit physical characteristics that are different from more than 100 Philippine ethnolinguistic groups that are categorized as non-negritos. Given their numbers, it is not surprising that Philippine negritos make up a major category in a number of general ethnographic maps produced since the nineteenth century. Reports from various ethnological surveys during this period, however, have further enriched our understanding regarding the extent and distribution of negrito populations. Using the data contained in these reports, it is possible to plot and create a map showing the historical locations and distribution of negrito groups. Using geographic information systems (GIS), the location and distribution of negrito groups at any given time can be overlaid on historical or current maps. In the present study, a GIS layer was compiled and extracted from the 2000 Philippine Census of population at the village level and overlaid on existing maps of the Philippines. The maps that were generated from this project will complement ongoing anthropological and genetic studies of negrito groups that inhabit different locations within the Philippine archipelago

Application Of The Hsu Model To Soybean Grain Hydration [aplicação Do Modelo De Hsu à Hidratação De Grãos De Soja]

A comparative analysis of the theoretical-experimental study, developed by Hsu on the hydration of Amsoy 71 soybean grain, was performed through several soaking experiments using CD 202 soybean at 10, 20, 30, 40, and 50 °C, measuring moisture content over time. The results showed that CD 202 soybean equilibrium moisture content, Xeq, does not depend on temperature and is 21% higher than that found by Hsu, suggesting that soybean cultivar exerts great influence on Xeq. The Hsu model was numerically solved and its parameters were adjusted by the least squares method, with maximum deviations of +/- 10% relative to the experimental values. The limiting step in the mass transfer process during hydration corresponds to water diffusion inside the grain, leading to radial moisture gradients that decrease over time and with an increase in temperature. Regardless of the soybean cultivar, diffusivity increases as temperature or moisture content increases. However, the values of this transport property for Amsoy 71 were superior to those of CD 202, very close at the beginning of hydration at 20 °C and almost three times higher at the end of hydration at 50 °C.301Adeyemi, I.A., Dry-milling of sorghum for ogi manufacture (1983) Journal of Cereal Science, 1 (3), pp. 221-227Ahromrit, A., Ledward, D.A., Niranjan, K., High pressure induced water uptake characteristics of Thai glutinous rice (2006) Journal of Food Engineering, 72 (3), pp. 225-233Barrozo, M.A.S., Calado, V.M.A., Calçada, L.A., Secagem de soja em leito deslizante e recirculação pneumática: Influência da umidificação artificial (1991) ENCONTRO SOBRE ESCOAMENTO EM MEIOS POROSOS, 1, pp. 327-337. , Campinas. Anais... São Paulo: UNICAMP, 1991Beckert, O.P., Miguel, M.H., Marcos Filho, J., Absorção de água e potencial fisiológico em sementes de soja de diferentes tamanhos (2000) Scientia Agrícola, 57 (4), pp. 671-675Calado, V.M.A., (1993) Modelagem E Simulação De Secadores Em Leitos Fixo E Deslizante, , Tese (Doutorado em Engenharia Química) - Universidade Federal doRio de Janeiro - UFRJ, Rio de JaneiroChopra, R., Prasad, D.N., Standardization of soaking conditions for soybean seeds/cotyledons for improved quality of soymilk (1994) Indian Journal of Animal Sciences, 64 (4), pp. 405-410Ciabotti, S., Características sensoriais e físicas de extratos e tofus de soja comum processada termicamente e livre de lipoxigenase (2007) Ciência E Tecnologia De Alimentos, 27 (3), pp. 643-648Coutinho, M.R., Modelagem e validação da hidratação de grãos de soja (2005) Ciência E Tecnologia De Alimentos, 25 (3), pp. 603-610Coutinho, M.R., Novo modelo de parâmetros concentrados aplicado à hidratação de grãos (2007) Ciência E Tecnologia De Alimentos, 27 (3), pp. 451-455Crank, J., (1975) The Mathematics of Diffusion, , 2 ed. London: Oxford University PressEngels, C., Modelling water diffusion during long-grain rice soaking (1986) Journal of Food Engineering, 5 (1), pp. 55-73Hsu, K.H., A diffusion model with a concentration-dependent diffusion coefficient for describing water movement in legumes during soaking (1983) Journal of Food Science, 48 (2), pp. 618-622+645Hsu, K.H., Effect of temperature on water diffusion in soybean (1983) Journal of Food Science, 48 (4), pp. 1364-1365INSTITUTO ADOLFO LUTZ - IAL. Normas analíticas do Instituto Adolfo Lutz. 3 ed. São Paulo, 1985. (v. 1)Klamczynska, B., Czuchajowska, Z., Baik, B., Composition, soaking, cooking properties and thermal characteristics of starch of chickpeas, wrinkled peas and smooth peas (2001) International Journal of Food Science and Technology, 36 (5), pp. 563-572Lo, W.Y.L., Soaking soybeans before extraction as it affects chemical composition and yield of soymilk (1968) Food Technology, 22 (9), pp. 1188-1190Long, F.A., Richman, D., Concentration gradients for diffusion of vapor in glassy polymers and their relation to time dependent diffusion phenomena (1960) Journal of The American Chemical Society, 82 (3), pp. 513-519Nelson, A.I., Steinberg, M.P., Wei, L.S., Illinois process for preparation of soymilk (1976) Journal of Food Science, 41 (1), pp. 57-61Pan, Z., Tangratanavalee, W., Characteristics of soybeans as affected by soaking conditions (2003) Lebensmittel-Wissenschaft Und-Technologie, 36 (1), pp. 143-151Peleg, M., An empirical model for the description of moisture sorption curves (1988) Journal of Food Science, 53 (4), pp. 1216-1219Singh, B.P.N., Kulshrestha, S.P., Kinetics of water sorption by soybean and pigeonpea grains (1987) Journal of Food Science, 52 (6), pp. 1538-1544Sopade, P.A., Obekpa, J.A., Modelling water absorption in soybean, cowpea and peanuts at three temperatures using Peleg's equation (1990) Journal of Food Science, 55 (4), pp. 1084-1087Wang, H.L., Hydration of whole soybeans affects solids losses and cooking quality (1979) Journal of Food Science, 44 (5), pp. 1510-151

The Discovery of a Potent, Selective, and Peripherally Restricted Pan-Trk Inhibitor (PF-06273340) for the Treatment of Pain

The neurotrophin family of growth factors, comprised of nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), and neurotrophin 4 (NT4), is implicated in the physiology of chronic pain. Given the clinical efficacy of anti-NGF monoclonal antibody (mAb) therapies, there is significant interest in the development of small molecule modulators of neurotrophin activity. Neurotrophins signal through the tropomyosin related kinase (Trk) family of tyrosine kinase receptors, hence Trk kinase inhibition represents a potentially “druggable” point of intervention. To deliver the safety profile required for chronic, nonlife threatening pain indications, highly kinase-selective Trk inhibitors with minimal brain availability are sought. Herein we describe how the use of SBDD, 2D QSAR models, and matched molecular pair data in compound design enabled the delivery of the highly potent, kinase-selective, and peripherally restricted clinical candidate PF-06273340

Modulation of gene-specific epigenetic states and transcription by non-coding RNAs

Emerging evidence points to a role for long non-coding RNAs in the modulation of epigenetic states and transcription in human cells. New insights, using various forms of small non-coding RNAs, suggest that a mechanism of action is operative in human cells, which utilizes non-coding RNAs to direct epigenetic marks to homology containing loci resulting ultimately in the epigenetic-based modulation of gene transcription. Importantly, insights into this mechanism of action have allowed for certain target sequences, which are either actively involved in RNA mediated epigenetic regulation or targets for non-coding RNA based epigenetic regulation, to be selected. As such, it is now feasible to utilize small antisense RNAs to either epigenetically silence a gene expression or remove epigenetic silencing of endogenous non-coding RNAs and essentially turn on a gene expression. Knowledge of this emerging RNA-based epigenetic regulatory network and our ability to cognitively control gene expression has deep implications in the development of an entirely new area of pharmacopeia

Terror from the Sky: Unconventional Linguistic Clues to the Negrito Past

Within recorded history. most Southeast Asian peoples have been of southern Mongoloid physical type, whether they speak Austroasiatic, Tibeto-Burman, Austronesian, Tai-Kadai, or Hmong-Mien languages. However, population distributions suggest that this is a post-Pleistocene phenomenon and that for tens of millennia before the last glaciation ended Greater Mainland Southeast Asia, which included the currently insular world that rests on the Sunda Shelf, was peopled by short, dark-skinned, frizzy-haired foragers whose descendants in the Philippines came to be labeled by the sixteenth-century Spanish colonizers as negritos, a term that has since been extended to similar groups throughout the region. There are three areas in which these populations survived into the present so as to become part of written history: the Philippines, the Malay Peninsula, and the Andaman Islands. All Philippine negritos speak Austronesian languages, and all Malayan negritos speak languages in the nuclear Mon-Khmer branch of Austroasiatic, but the linguistic situation in the Andamans is a world apart. Given prehistoric language shifts among both Philippine and Malayan negritos, the prospects of determining whether disparate negrito populations were once a linguistically or culturally unified community would appear hopeless. Surprisingly, however, some clues to a common negrito past do survive in a most unexpected way