The Role of Vitamin E in Slowing Down Mild Cognitive Impairment: A Narrative Review.

With the aging population, dementia emerges as a public health concern. In 2012, the Health and Retirement Study found that 8.8% of adults over 65 years suffered from dementia. The etiopathogenesis and treatment of dementia are not well understood. Antioxidant properties of Vitamin E and its major elements tocopherols and tocotrienols have been reported to be effective in slowing down the progression of dementia from its initial stage of Mild cognitive impairment (MCI). Therefore, the current review aims to explore the role of vitamin E on MCI. A literature search using the key words "Vitamin E, tocopherols, tocotrienols, and mild cognitive impairment" was conducted in MEDLINE (PubMed), CINAHL, and Google Scholar. The inclusion criteria were: (1) articles published in the past ten years; (2) published in English language; (3) published in peer-reviewed journals; and (4) descriptive and epidemiological or evaluation studies. Articles published prior to 2010, focused on other forms of dementia than MCI, grey literature and non-peer-reviewed articles were excluded. A total of 22 studies were included in the narrative synthesis. The results were equivocal. Eleven studies showed some level of the neuroprotective effect of Vitamin E, tocopherols and tocotrienols on the progression of MCI. The mixed results of this review suggest further exploration of the possible protective effects of Vitamin E on the development of dementia. Future studies can be conducted to decipher antioxidant properties of vitamin E and its association with slowing down the cognitive decline.

Identification of young-of-the-year great hammerhead shark Sphyrna mokarran in northern Florida and South Carolina.

Two sharks, visually identified in the field as young-of-the-year (YOY) scalloped hammerhead Sphyrna lewini, were identified as great hammerhead Sphyrna mokarran based on nuclear-encoded single nucleotide polymorphisms (SNP) and sequences of mtDNA. Individuals were captured and released in Bulls Bay, SC, and Saint Joseph Bay, FL, in 2013 and 2014, respectively. These findings indicate S. mokarran may be pupping in or around these areas and highlight new regions that may be a productive focus for future research on early life history of S. mokarran.

Contemporary population structure and post-glacial genetic demography in a migratory marine species, the blacknose shark, Carcharhinus acronotus.

Patterns of population structure and historical genetic demography of blacknose sharks in the western North Atlantic Ocean were assessed using variation in nuclear-encoded microsatellites and sequences of mitochondrial (mt)DNA. Significant heterogeneity and/or inferred barriers to gene flow, based on microsatellites and/or mtDNA, revealed the occurrence of five genetic populations localized to five geographic regions: the southeastern U.S Atlantic coast, the eastern Gulf of Mexico, the western Gulf of Mexico, Bay of Campeche in the southern Gulf of Mexico and the Bahamas. Pairwise estimates of genetic divergence between sharks in the Bahamas and those in all other localities were more than an order of magnitude higher than between pairwise comparisons involving the other localities. Demographic modelling indicated that sharks in all five regions diverged after the last glacial maximum and, except for the Bahamas, experienced post-glacial, population expansion. The patterns of genetic variation also suggest that the southern Gulf of Mexico may have served as a glacial refuge and source for the expansion. Results of the study demonstrate that barriers to gene flow and historical genetic demography contributed to contemporary patterns of population structure in a coastal migratory species living in an otherwise continuous marine habitat. The results also indicate that for many marine species, failure to properly characterize barriers in terms of levels of contemporary gene flow could in part be due to inferences based solely on equilibrium assumptions. This could lead to erroneous conclusions regarding levels of connectivity in species of conservation concern.

Validated age, growth and maturity of the bonnethead Sphyrna tiburo in the western North Atlantic Ocean.

The age, growth and maturity of bonnetheads Sphyrna tiburo inhabiting the estuarine and coastal waters of the western North Atlantic Ocean (WNA) from Onslow Bay, North Carolina, south to West Palm Beach, Florida, were examined. Vertebrae were collected and aged from 329 females and 217 males ranging in size from 262 to 1043 mm and 245 to 825 mm fork length, LF , respectively. Sex-specific von Bertalanffy growth curves were fitted to length-at-age data. Female von Bertalanffy parameters were L∞ = 1036 mm LF , k = 0·18, t0 = -1·64 and L0 = 272 mm LF . Males reached a smaller theoretical asymptotic length and had a higher growth coefficient (L∞ = 782 mm LF , k = 0·29, t0 = -1·43 and L0 = 266 mm LF ). Maximum observed age was 17·9 years for females and 16·0 years for males. Annual deposition of growth increments was verified by marginal increment analysis and validated for age classes 2·5+ to 10·5+ years through recapture of 13 oxytetracycline-injected specimens at liberty in the wild for 1-4 years. Length (LF50 ) and age (A50 ) at 50% maturity were 819 mm and 6·7 years for females, and 618 mm and 3·9 years for males. Both female and male S. tiburo in the WNA had a significantly higher maximum observed age, LF50 , A50 and L∞ , and a significantly lower k and estimated L0 than evident in the Gulf of Mexico (GOM). These significant differences in life-history parameters, as well as evidence from tagging and genetic studies, suggest that S. tiburo in the WNA and GOM should be considered separate stocks.

African Americans and Caucasian Americans: differences in glucocorticoid-induced insulin resistance.

African Americans are more insulin resistant than Caucasian Americans and this discrepancy cannot be explained by measures of body weight or body composition. The aim of the study was to compare the sensitivity of African Americans and Caucasian Americans to glucocorticoids by measuring glucose and insulin responses to a meal challenge under conditions of placebo and glucocorticoid. A total of 160 healthy or overweight/obese African American and Caucasian American participants completed exercise testing and a liquid meal challenge during separate laboratory visits. Participants were evaluated following treatments with placebo and dexamethasone (4 mg). Main outcome measures were correlation between body composition measures (body mass index, percent body fat, waist circumference) and insulin responses; insulin and glucose responses after a liquid meal challenge; and calculated HOMA. After dexamethasone treatment African Americans were significantly more hyperinsulinemic after a meal as indicated by higher peak insulin (p=0.02) and postprandial insulin areas under the curve (p=0.006) than Caucasians. Additionally, African Americans were more insulin resistant than Caucasian Americans under both placebo and dexamethasone as determined by fasting insulin and HOMA (p=0.05). Waist circumference correlated with post-dexamethasone insulin AUC and HOMA in Caucasian Americans (p<0.05), but none of the body composition measures were predictive of IR for African Americans. African Americans are more sensitive to glucocorticoids (dexamethasone) than Caucasian Americans, as indicated by significantly greater peak insulin and postprandial insulin areas under the curve. The glucocorticoid receptor and its potential interactions with stress may contribute to this ethnic disparity.

Noninvasive measurement of effective diffusivities in cell immobilization gels through use of near-infrared spectroscopy.

Encapsulated cell systems provide some advantages over typical suspension cell cultivations as higher cell densities may be obtained; however, the supply of nutrients to the cells often is a limiting factor in productivity. In this study, we describe the development of a new approach to characterize the effective diffusivity of nutrients in immobilized cell materials. Near-infrared spectroscopy is employed to measure nutrient concentrations within a specially designed diffusion chamber that permits noninvasive sampling at ten spatial positions and multiple timepoints. To demonstrate this technique, we measured the effective diffusivity of glutamine in a cell-free 3% (w/w) agarose gel and determined the effective diffusivity (D(eff)) = 6.46 x 10(-10) m(2)/s, which is in good agreement with theoretical values.

Microelectromechanical system programmable aberration generator for adaptive optics.

Adaptive optics systems and control algorithms can be tested in the laboratory with controlled disturbances. We have a micromachined deformable mirror that we use as a programmable aberration generator. We present a method of programming the actuator amplitudes so that the wave front reflecting from the surface will simulate atmospheric turbulence. We present experimental results that show that we can simulate the Kolmogorov spatial spectrum within the constraints of the useful region of the deformable mirror.

Rapid calibration of near-infrared spectroscopic measurements of mammalian cell cultivations.

Near-infrared (NIR) spectroscopy is a flexible method that can be employed to noninvasively monitor the concentrations of multiple nutrients and wastes in mammalian cell bioreactors. Development of suitable calibrations can be a labor- and time-intensive process that must be repeated when process conditions are altered significantly. To address this difficulty, we have produced a new approach for generating NIR spectroscopic calibrations that requires significantly less time compared with standard calibration schemes. This method reduces development time from the present level of several weeks to several hours. A small number of experimentally collected spectra serve as inputs to a computational procedure that yields a large number of simulated spectra, each containing both analyte-specific and analyte-independent information. Such simulated spectra may be employed as a calibration set for quantifying analytes in experimentally collected spectra. Spectroscopic measurements of the concentrations of five components (ammonia, glucose, glutamate, glutamine, and lactate) can be accomplished with levels of error similar to those obtained with full experimental calibrations. A key to this process is the utilization of random numbers, which randomizes the influence of natural variations, present in each experimentally collected spectrum, on the resultant composite spectrum. This approach may increase the feasibility of employing NIR spectroscopy to monitor bioreactors and other biological processes subjected to varying operating conditions.

Minimally invasive aortic valve replacement.

During a consecutive 12-month period from January 1996 to January 1997 inclusive, 108 aortic valve replacements were performed by one group of surgeons in two community hospitals The majority of the valve replacements were done in combination with other procedures or were redo surgeries. Thirty-one patients had primary isolated aortic valve replacement. Fourteen patients underwent aortic valve replacement via a standard sternotomy, and seventeen patients underwent aortic valve replacement using a minimally invasive parasternal approach, as described by Dr. Cosgrove. There were no operative deaths in either group; however there was one hospital death in each of the two groups. Blood loss and postoperative pain were less in the minimally invasive group. Although the cross-clamp times were longer in the minimally invasive group, with a mean of 82.7 min as compared with 63.1 min in the standard group, the length of stay was shortened, with a median of 5 days in the minimally invasive group as compared to 7 days in the sternotomy group. In the follow-up which ranges from 4-15 months, all patients in the minimally invasive group were New York Heart Class I or II. Patients with the parasternal incisions are permitted to return to work much earlier than those with a standard sternotomy incision. The decreased blood loss and postoperative pain, combined with the anticipated ease of re-entry via a median sternotomy in the future (should redo aortic valve replacement become necessary), make this approach our procedure of choice in isolated primary aortic valve replacement.

Patients with HIV/AIDS: physicians' knowledge, attitudes, and referral practices.

BACKGROUND: This study investigated Massachusetts family physicians' current care and referral practices with respect to HIV/AIDS patients and examined actors that might influence family physicians in referring these patients to specialists. Educational opportunities for physicians with regard to HIV were also examined. METHODS: In 1994, a 2-page survey was mailed to the 468 members of the Massachusetts Academy of Family Physicians. The survey questionnaire examined such factors as whether the respondents were teaching or nonteaching, rural or urban; number of years since medical school or residency training; and knowledge and attitudes with regard to HIV/AIDS patients. The data were analyzed using Student's t test, chi-square, and correlation analysis. RESULTS: Usable responses were returned by 281 (60%) of the physicians surveyed. Of these, 65% reported having HIV patients in their practice, and 46% reported having AIDS patients was being managed alone by 53% of these physicians, and 11% managed their patients with AIDS. Physicians providing care for HIV/AIDS patients were more likely to be practicing in urban locations, have three or more HIV/AIDS patients in their practice, or recently graduated from residency. Additionally, they were more likely to be involved in residency teaching programs. Those who did not care for HIV/AIDS patients felt less knowledgeable about HIV/AIDS care, and felt that they had no time in their practice to care for this population of patients. Physicians with HIV patients learn more about HIV care from their colleagues than those without HIV patients. CONCLUSIONS: Family physicians are increasingly seeing HIV/AIDS patients in their offices. The majority are continually caring for these patients, either by themselves or co-managing their care with a specialist. Local CME programs relying on colleagues and community resources to discuss management of these patients may be one of the best ways of ensuring that increasing numbers of family physicians obtain the appropriate knowledge to care for these patients within their own communities.

Genetic and linguistic differentiation in the Americas.

The relationship between linguistic differentiation and evolutionary affinities was evaluated in three tribes of the Pacific Northwest. Two tribes (Nuu-Chah-Nulth and Bella Coola) speak Amerind languages, while the language of the third (Haida) belongs to a different linguistic phylum--Na-Dene. Construction of a molecular phylogeny gave no evidence of clustering by linguistic affiliation, suggesting a relatively recent ancestry of these linguistically divergent populations. When the evolutionary affinities of the tribes were evaluated in terms of mitochondrial sequence diversity, the Na-Dene-speaking Haida had a reduced amount of diversity compared to the two Amerind tribes and thus appear to be a biologically younger population. Further, since the sequence diversity between the two Amerind-speaking tribes is comparable to the diversity between the Amerind tribes and the Na-Dene Haida, the evolutionary divergence within the Amerind linguistic phylum may be as great as the evolutionary divergence between the Amerind and Na-Dene phyla. Hence, in the New World, rates of linguistic differentiation appear to be markedly faster than rates of biological differentiation, with little congruence between linguistic hierarchy and the pattern of evolutionary relationships.

mtDNA sequences suggest a recent evolutionary divergence for Beringian and northern North American populations.

Conventional descriptions of the pattern and process of human entry into the New World from Asia are incomplete and controversial. In order to gain an evolutionary insight into this process, we have sequenced the control region of mtDNA in samples of contemporary tribal populations of eastern Siberia, Alaska, and Greenland and have compared them with those of Amerind speakers of the Pacific Northwest and with those of the Altai of central Siberia. Specifically, we have analyzed sequence diversity in 33 mitochondrial lineages identified in 90 individuals belonging to five Circumpolar populations of Beringia, North America, and Greenland: Chukchi from Siberia, Inupiaq Eskimos and Athapaskans from Alaska, Eskimos from West Greenland, and Haida from Canada. Hereafter, we refer to these five populations as "Circumarctic peoples." These data were then compared with the sequence diversity in 47 mitochondrial lineages identified in a sample of 145 individuals from three Amerind-speaking tribes (Bella Coola, Nuu-Chah-Nulth, and Yakima) of the Pacific Northwest, plus 16 mitochondrial lineages identified in a sample of 17 Altai from central Siberia. Sequence diversity within and among Circumarctic populations is considerably less than the sequence diversity observed within and among the three Amerind tribes. The similarity of sequences found among the geographically dispersed Circumarctic groups, plus the small values of mean pairwise sequence differences within Circumarctic populations, suggest a recent and rapid evolutionary radiation of these populations. In addition, Circumarctic populations lack the 9-bp deletion which has been used to trace various migrations out of Asia, while populations of southeastern Siberia possess this deletion. On the basis of these observations, while the evolutionary affinities of Native Americans extend west to the Circumarctic populations of eastern Siberia, they do not include the Altai of central Siberia.

Paracrystalline inclusions of a novel ferritin containing nonheme iron, produced by the human gastric pathogen Helicobacter pylori: evidence for a third class of ferritins.

An abundant 19.3-kDa Helicobacter pylori protein has been cloned, and the sequence is homologous with a ferritin-like protein produced by Escherichia coli K-12. Homologies are also present with a number of eucaryotic ferritins, as well as with the heme group-containing bacterioferritins. All amino acids involved in chelation of inorganic iron by ferritins from humans and other higher species are conserved in the H. pylori protein. Consistent with the structural data indicating an iron-binding function, E. coli overexpressing the H. pylori ferritin-like protein accumulates almost 10 times more nonheme iron than vector controls, and the iron-binding activity copurifies with the 19.3-kDa protein. Immunoelectron microscopy of H. pylori, as well as of E. coli overexpressing the H. pylori gene, demonstrates that the gene product has a cytoplasmic location where it forms paracrystalline inclusions. On the basis of these structural and functional data, we propose that the H. pylori gene product (termed Pfr) forms the basis for a second class of bacterial ferritins designed to store nonheme iron.

Extensive mitochondrial diversity within a single Amerindian tribe.

Sequencing of a 360-nucleotide segment of the mitochondrial control region for 63 individuals from an Amerindian tribe, the Nuu-Chah-Nulth of the Pacific Northwest, revealed the existence of 28 lineages defined by 26 variable positions. This represents a substantial level of mitochondrial diversity for a small local population. Furthermore, the sequence diversity among these Nuu-Chah-Nulth lineages is greater than 60% of the mitochondrial sequence diversity observed in major ethnic groups such as Japanese or sub-Saharan Africans. It was also observed that the majority of the mitochondrial lineages of the Nuu-Chah-Nulth fell into phylogenetic clusters. The magnitude of the sequence difference between the lineage clusters suggests that their origin predates the entry of humans into the Americas. Since a single Amerindian tribe can contain such extensive molecular diversity, it is unnecessary to presume that substantial genetic bottlenecks occurred during the formation of contemporary ethnic groups. In particular, these data do not support the concept of a dramatic founder effect during the peopling of the Americas.

Structural requirements for C3d,g/Epstein-Barr virus receptor (CR2/CD21) ligand binding, internalization, and viral infection.

The structure of CR2, the human C3d,g/EBV receptor (CR2/CD21) consists of 15 or 16 60-70 amino acid repeats called short consensus repeats (SCRs) followed by a transmembrane and a 34-amino acid intracytoplasmic domain. Functions of CR2 include binding the human complement component C3d,g when it is covalently attached to targets or cross-linked in the fluid phase. In addition, CR2 binds the Epstein-Barr virus (EBV) and mediates internalization of EBV and subsequent infection of cells. In order to explore functional roles of the repetitive extracytoplasmic SCR structure and the intracytoplasmic domain of CR2, we have created truncated CR2 (rCR2) mutants bearing serial deletions of extracytoplasmic SCRs and also the intracytoplasmic tail. We then stably transfected these rCR2 mutants into two cell lines, murine fibroblast L cells and human erythroleukemic K562 cells. Phenotypic analysis of these expressed mutants revealed that 1) The C3d,g- and EBV-binding sites are found in the two amino-terminal SCRs of CR2, 2) expression of SCRs 3 and 4 is further required for high affinity binding to soluble cross-linked C3d,g, 3) the intracytoplasmic domain of CR2 is not required for binding C3d,g or EBV but is necessary for internalization of cross-linked C3d,g as well as for EBV infection of cells, 4) monoclonal anti-CR2 antibodies with similar activities react with single widely separated epitopes, and 5) no functional roles can yet be clearly assigned to SCRs 5-15, as rCR2 mutants not containing these SCRs show no major differences from wild-type rCR2 in binding or internalizing cross-linked C3d,g or mediating EBV binding and infection.

Analysis of epitope expression and the functional repertoire of recombinant complement receptor 2 (CR2/CD21) in mouse and human cells.

We transfected human complement receptor 2 (CR2/CD21) cDNA containing eukaryotic expression constructs into CR2-negative mouse L cells and human K562 erythroleukemia cells. We subsequently selected stably transformed cells that expressed human CR2, as assessed by flow microfluorimetry analysis and immunoprecipitation of 125I-labeled surface membranes using the monoclonal anti-CR2 antibody, HB5. Utilizing flow microfluorimetry analysis, epitopes recognized by anti-CR2 mAb HB5, OKB7, B2, and four other anti-CR2 antibodies were detected on CR2 expressing transfectants but not parental cells. In addition, CR2 expressing transfected cells efficiently formed rosettes with sheep erythrocyte intermediates bearing human C3bi and C3d, but not C4b or C3b, consistent with the known ligand specificity of CR2. CR2 containing transfectants were also demonstrated to specifically bind EBV. Infection with EBV of CR2 expressing L cells and K562 cells resulted in mean expression of Epstein-Barr nuclear Ag (EBNA) at 48 h in 0.35% of CR2 expressing L cells and 3.7% of CR2 expressing K562 cells. Parental L cells and K562 cells did not express EBNA after EBV infection. These results indicate that CR2 alone is sufficient to transfer both C and EBV receptor functions to heterologous cells. In addition, expression of EBNA was found to be significantly higher in human K562 than mouse L cells, both expressing the same recombinant receptor. These results suggest that mechanisms other than CR2 binding lead to inefficient EBV infection and/or EBNA synthesis in mouse fibroblasts.

Genetic variation in an inbred plant: variation in tissue cultures of soybean [Glycine max (L.) Merrill].

Although soybean [Glycine max (L.) Merrill] grows as an inbreeding, generally homozygous, plant, the germplasm of the species contains large amounts of genetic variation. Analysis of soybean DNA has indicated that variation of RFLP (restriction fragment length polymorphism) markers within the species usually entails only two alleles at any one locus and that mixtures of such dimorphic loci account for virtually all of the restriction fragment variation seen in soybean (G. max), and in its ancestors, G. soja and G. gracilis. We report here that tissue cultures prepared from root tissue of individual soybean plants develop RFLP allelic differences at various loci. However, these newly generated alleles are almost always the same as ones previously found and characterized in other varieties of cultivated soybean (cultivars). This repeated generation of particular alleles suggests that much of the genetic variation seen in soybean could be the consequence of specific, relatively frequently employed, recombinational events. Such a mechanism would allow inbred cultivars to generate genetic variation (in the form of alternative alleles) in a controlled manner, perhaps in response to stress.

Genomic organization and polymorphisms of the human C3d/Epstein-Barr virus receptor.

The human C3d/Epstein-Barr virus receptor (CR2/CD21) is a 145-kDa protein primarily expressed on mature B lymphocytes. CR2 is a member of the regulators of complement activation (RCA) gene family found on band q32 of chromosome 1. The RCA proteins are characterized by the presence of 60-70 amino acid short consensus repeats (SCR). A full length CR2 cDNA was cloned and used to identify overlapping cosmid genomic clones. Analysis of CR2 exon-intron junctions revealed the presence of three types of exons in the short consensus repeat region of CR2. First, four exons each of which encodes two SCR are present. Five exons encode a single SCR. Six exons encode SCRs which are split in identical positions. The order of these types of exons is in a repeated array of four SCRs, indicating that the contemporary CR2 gene likely evolved from a more primitive gene containing four SCRs. The CR2 full length cDNA clone was used to find restriction fragment length polymorphisms (RFLPs). Restriction enzyme TaqI generated 2.55- and 2.10-kilobase (kb) polymorphic bands. This RFLP was mapped near the exon containing the first two SCRs. HaeIII digestion generated polymorphic bands of 1.45, 1.55, and 1.75 kb. The HaeIII 1.45-kb RFLP band maps near the exon containing the 15th SCR. The TaqI and HaeIII RFLPs will provide tools for the genetic analysis of CR2. The organization of the CR2 gene provides insights into the evolution of human CR2 and the RCA gene family.

Complete thrombospondin mRNA sequence includes potential regulatory sites in the 3' untranslated region.

The nucleotide sequence of human thrombospondin (TS) mRNA has been determined from human fibroblast and endothelial cDNAs. The sequence of 5802 bp begins 110 bp upstream from the initiator codon and includes the entire 3' untranslated region (UTR) of the mRNA. The coding region (3510 bp) specifies a protein of 1170 amino acids with all of the known features of the TS subunit (Frazier, W. A. 1987. J. Cell Biol. 105:625-632). The long 3' UTR of 2166 nucleotides is extremely A/T-rich, particularly in the latter half. It contains 37 TATT or ATTT(A) sequences that have been suggested as mediators of the stability of mRNAs for cytokines, lymphokines, and oncogenes (Shaw, G., and R. Kamen. 1986. Cell. 46:659-667). Another unusual feature of the 3' UTR of TS mRNA is a stretch of 42 nucleotides of which 40 are thymidines (uridine in the mRNA) including an uninterrupted sequence of 26 thymidines. This region is flanked by two sets of direct repeats suggesting that it may be an insertion element of retrotranscriptional origin. Comparison of the 3' untranslated region of TS mRNA with the GenBank data base indicates the greatest degree of similarity with an alpha-interferon gene which contains a number of the TATT/ATTT consensus sites. The degree of similarity between the TS and interferon sequences is the same in regions of the interferon gene corresponding to its coding and noncoding regions suggesting that most of the TS 3' UTR may be derived from an interferon gene or pseudogene. The features of the TS mRNA 3' UTR provide a potential explanation for the rapid regulation of TS message observed in cultured cells in response to PDGF and suggest that TS is a member of a group of proteins which are intimately involved in the control of cell growth and differentiation.