William Zamboni, PharmD, PhD
 https://pharmacy.unc.edu/news/directory/zamboni/ Studies that measured perfluoroalkyls in maternal and fetal cord blood of matched mother-infant pairs found relatively strong correlations (r>0 hiv infection questions order 250mg famvir. With some exceptions symptoms of hiv reinfection buy famvir 250mg line, longer fluoroalkyl chain length and a terminal sulfonate group are associated with lower fetal/maternal ratios (Glynn et al anti virus programs discount famvir 250mg. Serum (or Plasma) Concentrations in Matched Human Maternal-Infant Pairs Perfluoro Perfluoroalkyl Maternal Cord Study alkyl chain length N (ng/mL) (ng/mL) Ratioa r Glynn et al antiviral drug for herpes proven 250mg famvir. Serum (or Plasma) Concentrations in Matched Human Maternal-Infant Pairs Perfluoro Perfluoroalkyl Maternal Cord Study alkyl chain length N (ng/mL) (ng/mL) Ratioa r Kato et al. Serum (or Plasma) Concentrations in Matched Human Maternal-Infant Pairs Perfluoro Perfluoroalkyl Maternal Cord Study alkyl chain length N (ng/mL) (ng/mL) Ratioa r Yang et al. Studies that measured perfluoroalkyls in maternal serum (or plasma) and breast milk in matched mother-infant pairs found highly variable correlations (Table 3-3). Transfer to breast milk appears to be a significant route of elimination of perfluoroalkyls during breastfeeding. Concentrations of perfluoroalkyls in breast milk also decrease with breastfeeding duration (Tao et al. Serum concentrations in breastfed infants can be higher than maternal levels (Fromme et al. Matched Serum (or Plasma) and Breast Milk Concentrations in Humans Perfluoroalkyl Serum Milk Study Perfluoroalkyl chain length N (ng/mL) (ng/mL) Ratioa r Cariou et al. Perfluoroalkyls in plasma bind to serum albumin and various other plasma proteins including gamma-globulin, alpha-globulin, alpha-2-macroglobulin, transferrin, and beta lipoproteins (Bischel et al. Noncovalent binding appears to be at the same sites as fatty acids (Chen and Guo 2009). Mechanisms by which perfluoroalkyls enter the liver have not been elucidated and may involve interactions with organic anion transporters that function in the distribution of fatty acids or other organic anions (Andersen et al. Although no studies examining metabolism of perfluoroalkyls following inhalation, oral, or dermal exposure were identified, metabolism by these exposure routes is not anticipated. Findings suggest that the route of absorption has no substantial effect of rates of elimination of absorbed perfluoroalkyls (Butenhoff et al. As discussed in this section, perfluoroalkyls are primarily eliminated in the urine, with smaller amounts eliminated in the feces and breast milk (see Section 3. Perfluoroalkyls undergo biliary excretion, but substantial reabsorption occurs; therefore, biliary excretion does not represent a major elimination pathway. Perfluoroalkyls are eliminated in menstrual fluid, which appears to contribute to sex differences in serum elimination rates (Wong et al. Urinary excretion of perfluoroalkyls may show sex and age differences (Zhang et al. Rates of elimination of perfluoroalkyls vary substantially across chemical species and animal species, and show sex differences and age-dependencies within certain species. Table 3-5 summarizes estimates of the elimination t1/2 for perfluoroalkyls in humans and experimental animals. In compiling the estimates presented in Table 3-5, preference was given to the terminal t1/2 when multiple t1/2 values were reported. The significance of the terminal t1/2 is that it determines the time required for complete elimination of the perfluoroalkyl as well as the exposure duration required to achieve a steady state. Most of the t1/2 values in Table 3-5 were estimated from analyses of data on declining serum concentrations of perfluoroalkyls after a single dose or following cessation of a period of repeated dosing. Estimates of the terminal t1/2 based on serum concentrations can vary with the length of the observation period following the last dose and with the modeling approach used to estimate the t1/2. Longer observation times are required to estimate the slowest phases of elimination. Direct comparisons of t1/2 values should be made with consideration of whether or not the observation periods were comparable. Differences in estimation methodology can also contribute to differences in t1/2 values. Values reported in Table 3-5 are based on fitting data to single or multi compartment models, or noncompartmental modeling of the data. While the terminal t1/2 provides a metric for comparing times required for complete elimination and steady state, it does not always provide a measure of how rapidly the perfluoroalkyl is cleared from the body. Estimates of systemic clearance based on pharmacokinetics analyses of serum data from animal studies are presented in Table 3-6. Summary Elimination Half-Lives for Perfluoroalkyls Estimated in Humans and Experimental Animals Species, age, and Exposure Elimination half sex Route Dose durationa lifeb Reference Rat (Sprague Oral 50 mg/kg 1 day 2. Summary Elimination Half-Lives for Perfluoroalkyls Estimated in Humans and Experimental Animals Species, age, and Exposure Elimination half sex Route Dose durationa lifeb Reference Rat (Sprague Oral 30 mg/kg 1 day 7. Estimates in humans are based on measurements of the decline in serum perfluoroalkyl concentrations following cessation or an abrupt decrease in exposure, or on measurements of renal plasma clearance from serum in a general population sample from Japan (Harada et al. The latter clearance estimates were converted to t1/2 values, for display in Table 3-5 as follows (Equations 3-4 and 3-5): Cl ke = Eq. In general, these studies show that longer chain length is associated with slower elimination rates. Perfluoroalkyl sulfonates are eliminated more slowly in humans than corresponding carboxylates of the same chain length (Zhang et al. Analytical methods typically used to measure serum perfluoroalkyls do not discriminate between linear and branched isomers and, as a result, these studies estimate elimination rates for the isomer mixture. However, the estimated serum t1/2 of 27 years is much higher than values calculated from other studies; Zhang et al. The estimated mean serum t1/2 for a group of 200 adults followed for 1 year after filtration was initiated was 2. In one population (n=643), the serum t1/2 increased with increasing elapsed time since leaving the water district. In a second population with an elapsed time since residence of <9 years, the t1/2 was 8. Temporal trends in perfluoroalkyl serum concentrations have also been used to estimate population halving times (Glynn et al. Population halving times are influenced by temporal trends in intakes and may therefore not accurately reflect clearance. Elimination of perfluoroalkyls in monkeys is multiphasic and, as a result, estimates of the terminal t1/2 can vary with the duration of the observation period and assumptions made in modeling elimination kinetics (Chang et al. Studies in monkeys confirm general trends observed in humans that perfluoroalkyl sulfonates are more slowly eliminated than perfluoroalkyl carboxylates and that elimination of longer-chain perfluoroalkyls occurs more slowly than short-chain perfluoroalkyls. Consistent with observations made in humans and Cynomolgus monkeys, perfluoroalkyl sulfonates are more slowly eliminated than perfluoroalkyl carboxylates and short-chain perfluoroalkyls. Elimination of perfluoroalkyls exhibits pronounced sex differences in rats, with faster elimination in females than in males (Benskin et al. Steady-state plasma concentrations in male rats were approximately 10 times that of daily peak concentrations in female rats. With increasing dose, plasma elimination kinetics in female rats converts from monophasic to biphasic. Although sex differences for elimination of perfluoroalkyls have been detected in laboratory animals, human monitoring studies have not consistently detected sex differences in elimination t1/2 of perfluoroalkyls; this may reflect limitations in the studies, including numbers and age of subjects (Bartell et al. The effect of menstruation or other variables related to menstruation appear to contribute to faster elimination in younger (50 years) women compared to men and older women (Zhang et al. The model was based, in part, on a multi-compartmental model developed by Tan et al. Complete lists of parameters and parameter values and the bases for parameter values and evaluations of model predictions in comparison to observations are described in Loccisano et al.
Sequence x /y x /y x /y 10918/4 1 2/2 24 acute hiv yeast infection buy 250 mg famvir with amex, aspiration hiv infection french kissing famvir 250 mg low cost,penileinjection 1/1 (neosynephrine) 10918/5 1 1/1 24 penileinjection(saline antiviral bell's palsy discount famvir 250 mg overnight delivery, 1/1 neosynephrine) antiviral gene therapy research unit generic 250mg famvir with mastercard,irrigationand drainage 10918/23 1 1/1 72 penileinjection(hepariniz edsaline, 1/1 prosthesislaterinserted neosynephrine),irrigationand drainage 11038/4 1 3/3 >6. Sequence x /y x /y x /y 12589/2 1 1/3 72 idiopathic,after penileinjection(diluteadrenergic 0/1 suddenonsetof a agent),irrigationanddrainage headache 12613/1 1 2/4, sicklecelldisease penileinjection(alpha-adrenergic 0/1 Agent/dosenotspecified. Sequence x /y x /y x /y 12722/22 2 1/1 penileinjection(metaraminol) 2/2 12902/1 1 1/2 10 diagnosticpenile penileinjection(metaraminoldilute) 0/1 injection[papaverine 60mg. Sequence x /y x /y x /y 10918/4 1 1/2 24 penileinjection(neosynephrine) 0/1 10918/16 1 1/3 40 penileinjection(neosynephrine) 0/1 12637/1 1 1/1 30 druginduced penileinjection 1/1 0/1 0/1 multipleinjections(unspecified [thioridiz ine(mellaril)] (phenylephrine[1. Sequence x /y x /y x /y 10918/6 1 1/1 24 penileinjection(saline, 1/1 epinephrine),irrigationanddrainage 10918/7 1 1/1 27 penileinjection(saline, 1/1 epinephrine),irrigationanddrainage 10918/12 1 1/2 24 aspiration,penileinjection 0/1 (epinephrine) 10918/14 1 1/1 36 penileinjection(saline, 1/1 epinephrine),irrigationanddrainage 10918/17 1 1/2 48 penileinjection(saline, 0/1 epinephrine),irrigationanddrainage 10918/20 1 1/2 48 aspiration,penileinjection 0/1 (epinephrine) 10918/22 1 1/2 72 aspiration,penileinjection 0/1 (epinephrine) 10918/22 1 2/2 72, penileinjection(epinephrine), 1/1 prosthesislaterinserted E bbehojshunt 12575/1 14 1/3 3-28 sicklecelldisease penileinjection(epinephrine), 13/14 0/6 0/10 Somepatientsreceivedmultiple irrigationanddrainage treatments-upto15. Sequence x /y x /y x /y 12790/1 1 1/1 2 diagnosticpenile penileinjection(epinephrine[. Sequence x /y x /y x /y 12836/1 15 1/1 0-36 penileinjection(epinephrinein 15/15 / 0/15 allpatientswhowerepotentprior saline[1ml]),irrigationanddrainage totreatmentcontinuedtobe potent,butsomeunknown numberwereimpotentpriorto priapism. Total]) possiblyfluphenaz ine, phenobarbital, phenytoinorother] 12895/1 9 1/1 penileinjection penileinjection(epinephrinein 9/9 ptsimpotentprepriapism therapy[papaverine saline20-30ml[1mcg/ml]),irrigation +/-phentolamine] anddrainage 12895/2 45 1/1 diagnosticpenile penileinjection(epinephrinein 45/45 pts. Sequence x /y x /y x /y 10918/15 1 1/1 40 penileinjection(saline, 1/1 metaraminol),irrigationand drainage 10918/19 1 1/2 48 aspiration,penileinjection 0/1 (metaraminol) 12722/22 2 1/1 penileinjection(metaraminol) 2/2 12723/1 1 3/5,12/0, penileinjection(metaraminol), 0/1 markeddetumescence irrigationanddrainage 12742/1 1 1/2 8 anticoagulation penileinjection(metaraminol, 0/1 [heparinand heparin),irrigationanddrainage coumadin] 12823/1 1 1/3 48 penileinjection penileinjection(metaraminol), 0/1 partialresponseforshortduration therapy[papaverint,80 irrigationanddrainage mg. Sequence x /y x /y x /y 12945/1 1 1/1 20 penileinjection penileinjection 0/1 F laccidity3. Sequence x /y x /y x /y 10918/8 1 1/1 30 aspiration,penileinjection 1/1 (norepinephrine) 10918/9 1 1/2 30 aspiration,penileinjection 0/1 (norepinephrine) 10918/18 1 1/2 48 aspiration,penileinjection 0/1 (norepinephrine) 10918/21 1 1/1 72 aspiration,penileinjection 1/1 (norepinephrine) 10918/24 1 1/2 96 penileinjection(hepariniz edsaline, 0/1 norepinephrine),irrigationand drainage 12722/24 13 1/1 penileinjection(norepinephrine) 7/13 12819/3 1 2/2 6-28, penileinjection penileinjection(norepinephrinein 1/1 impotentpre-treatmentand therapy[papaverine15 saline[1mg/ml]),irrigationand continuedtorespondto 30mg. Sequence x /y x /y x /y 10918/4 1 1/2 24 penileinjection(neosynephrine) 0/1 10918/4 1 2/2 24, aspiration,penileinjection 1/1 (neosynephrine) 10918/5 1 1/1 24 penileinjection(saline, 1/1 neosynephrine),irrigationand drainage 10918/16 1 1/3 40 penileinjection(neosynephrine) 0/1 10918/23 1 1/1 72 penileinjection(hepariniz edsaline, 1/1 prosthesislaterinserted neosynephrine),irrigationand drainage 11038/4 1 3/3 >6. Sequence x /y x /y x /y 12823/1 1 2/3 48, penileinjection penileinjection 0/1 multipledosesgiven-number therapy[papaverint,80 (phenylephrine[1mg]) unspecified mg. Sequence x /y x /y x /y 12722/20 13 1/1 penileinjection(heparin),irrigation 4/13 anddrainage 12819/1 3 1/3 13-36 druginduced penileinjection(hepariniz edsaline), 0/3 Allrecurredrapidly,presumably [traz odone200-300 irrigationanddrainage within24hours. Sequence x /y x /y x /y 13135/1 1 2/3 336, druginduced penileinjection(hepariniz edsaline, 0/1 transientimprovement [aldomet,navidrex for procaine[. Sequence x /y x /y x /y 10918/12 1 2/2 24, Al-G horabshunt 1/1 / 1/1 openshuntlaterclosedsurgically ex tractedasimpotent. E rectile functionunknown 12589/5 1 2/2 10, recurrentpriapism Al-G horabshunt 1/1 / 0/1 resolutionover3weeks over20years 12722/17 10 1/1 Al-G horabshunt 7/10 12734/1 1 3/4 72, idiopathic Al-G horabshunt 0/1 12819/1 1 3/3 13-36, druginduced Al-G horabshunt 1/1 [traz odone200-300 mg. Splitintotwotreatments E bbehojfollowedbysaphenous shuntperpaneldecision4/02 12902/5 1 4/4,96/0, idiopathic E bbehojshunt 1/1 / 0/1 ptreportederectionadequatefor intercourse,butpenisis shorter/thinnerthanbefore episode. Sequence x /y x /y x /y 10918/11 1 3/3 26, W intershunt 1/1 10918/17 1 2/2 48, W intershunt 1/1 10918/19 1 2/2 48, W intershunt 1/1 10918/24 1 2/2 96, W intershunt 1/1 prosthesislaterinserted 12589/2 1 2/3 72, idiopathic,after W intershunt 0/1 suddenonsetof a headache 12613/1 1 3/4, sicklecelldisease W intershunt 0/1 Unclearif recurredorunresolved. Sequence x /y x /y x /y 12692/1 1 5/8 24,72,108,828 sicklecelldisease aspiration,penileinjection 1/1 1/1 /, (phenylephrine[100mg]),W inter shunt 12722/16 40 1/1 W intershunt 26/40 12740/1 2 2/4, W intershunt 0/2 12781/1 1 3/3, idiopathic W intershunt 1/1 1/1 0/1 12800/1 1 3/7 72,24 sicklecelldisease W intershunt 0/1 ReclassifiedasW intershuntonly perpaneldecision4/02. Sequence x /y x /y x /y 12849/4 5 1/4 W intershunt 2/5 12849/4 2 2/4, W intershunt 2/2 12896/1 1 1/1 <12 W intershunt 1/1 / 0/1 12896/2 1 1/1 <12 W intershunt 1/1 / 0/1 12896/3 1 1/1 <12 W intershunt 1/1 / 0/1 12896/4 1 1/3 <12 W intershunt 0/1 12896/4 1 2/3 <12, W intershunt 0/1 12897/1 4 1/1 8-18 irrigationanddrainage,W intershunt 4/4 0/4 0/4 Allpatientsfailedirrigationand drainage.
Those false positive cases did not move forward to the case abstraction or review process symptoms of hiv infection mayo clinic buy famvir master card. Out of the 98 cases identified as potential pregnancy-associated deaths hiv aids infection rates for south africa generic famvir 250mg amex, 78 (80%) were verified deaths of women while pregnant or within one year of pregnancy; the remaining 20 (20%) were false positives (See Figure 2) hiv infection rate us buy famvir from india. These 78 confirmed cases were elevated for case abstraction and subsequent review by the Maternal Mortality Review Committee hiv infection how early symptoms cheap 250 mg famvir. The effect this verification process had on the overall estimate of the burden of pregnancy-associated mortality is substantial. Efforts to improve data collection and case identification processes have been initiated based on the case verification findings. Data sources: Tennessee Department of Health, Office of Vital Records and Health Statistics, Death Statistical File, 2013-2017. Tennessee Department of Health, Division of Family Health and Wellness, Maternal Mortality Review Program. Case Review After each death is fully abstracted, the Maternal Mortality Nurse Consultant and Program Coordinator assigns each case to either the Internal Team or the Full Review Team. This decision form provides guidance on key decisions required for each case, including: Was the death pregnancy-related Additionally, cases that have limited records are also assigned to the Internal Team. These cases are reviewed intensively by the Internal Team prior to the Full Team Review. Each internal case is presented in summary at the Full Team Review, with the Full Team providing consensus for each element of the decision form. If there are substantial questions raised on internal cases, they are held over for a more comprehensive Full Team Review. The primary and secondary reviewers are members who present the case to the committee. Initially, once the case was presented, the decision form was filled by the entire committee. The committee discusses the form and comes to a consensus about each element on the form. Table 1 provides a description of these women by age, race/ethnicity, educational level, insurance type, and residence, in comparison to maternal characteristics of all Tennessee births in 2017. The table describes frequencies and percentages of all women who died as well as ratios that compare these deaths to maternal characteristics of the total birth population. Social determinants of health such as education level, housing status, and poverty often are a factor in these deaths. Disparities were also seen by insurance status, which is reflective of poverty and other risk factors. Additional years of data will enable us to study racial and ethnic disparities in subsets of pregnancy-associated deaths. Data sources: Tennessee Department of Health, Division of Family Health and Wellness, Maternal Mortality Review Program. Tennessee Department of Health, Office of Vital Records and Health Statistics, Birth Statistical File, 2017. The remaining deaths occurred either during pregnancy (22%) or within 42 days of pregnancy (22%) (Figure 5). Timing of All Pregnancy Associated Deaths in Relation to Pregnancy, Tennessee, 2017 Data Source: Tennessee Department of Health, Division of Family Health and Wellness, Maternal Mortality Review Program. The large majority (81%) of these deaths occurred in the late post-partum period, between 43 and 365 days postpartum. Among these deaths, the majority were to non-Hispanic White women (81%), women with TennCare coverage (62%), and women who lived in metropolitan areas (69%). Mental Health Conditions the Committee determined that mental health conditions were a contributing factor in 18% of all pregnancy-associated deaths (Figure 6). These deaths mostly occurred among non-Hispanic White 26 P a g e women (86%), women with TennCare coverage (57%), and women living in metropolitan areas (64%). Obesity Eight percent of all pregnancy-associated deaths reviewed were determined to have obesity as a contributing factor (Figure 6). There were no differences in the percentage of deaths occurring by timing of death (33% of deaths occurred during pregnancy, within 42 days of pregnancy and within 43-365 days of pregnancy). Half of these deaths were to non-Hispanic Black women (50%) and women with TennCare coverage (50%). The majority of these deaths occurred to women who resided in metropolitan areas (83%). Figure 6: Contributing Factors for All Pregnancy-Associated Deaths, Tennessee, 2017 Data Source: Tennessee Department of Health, Division of Family Health and Wellness, Maternal Mortality Review Program. Also, the majority of violent deaths (62%) occurred between 43 days and one year of pregnancy. Committee Determination of Pregnancy-Relatedness, Pregnancy-Associated Deaths, Tennessee, 2017 Data Source: Tennessee Department of Health, Division of Family Health and Wellness, Maternal Mortality Review Program. Preventability Deaths were considered preventable if there was at least some chance of the death being averted by one or more reasonable changes to patient, community, provider, 7 facility, and/or systems factors. Preventability of All Pregnancy-Associated Deaths, Tennessee, 2017 Critical FactorsData Source: Tennessee Department of Health, Division of Family Health and Wellness, Maternal Mortality Review Program. For each of the 66 preventable deaths, the Committee identified critical factors that contributed to each death and categorized them into one of five factor levels in which change in the outcome could have occurred. The five factor levels are patient/family, provider, facility, systems of care, and community. Figure 9 provides the percentage of critical factors affecting preventable deaths. Critical Factors Contributing to Preventable Pregnancy-Associated Deaths, Tennessee, 2017 Data Source: Tennessee Department of Health, Division of Family Health and Wellness, Maternal Mortality Review Program. A total of 22 deaths were classified as pregnancy-related by the committee (28% of all pregnancy-associated deaths). Table 2 describes these decedents by demographic characteristics, including age, race/ethnicity, educational level, insurance type, and place of residence. The majority of deaths occurred among women under 30 years old (45%) and between 30 and 39 years of age (41%). More than half of the women were non-Hispanic White (55%) and half received more than a high school education (college graduates and non graduates) (50%). A large percentage of deaths occurred among women with TennCare insurance (55%) and who resided in metropolitan areas of the state (50%). In regards to TennCare coverage, pregnancy is a primary eligibility category for TennCare. Women who become pregnant may become eligible for TennCare and often apply for coverage at different points in their pregnancy. As such, TennCare Coverage is not reflective of the length of time that the pregnant women may have had health insurance coverage by TennCare. Figure 10: Timing of Pregnancy-Related Deaths, Tennessee, 2017 Data Source: Tennessee Department of Health, Division of Family Health and Wellness, Maternal Mortality Review Program. Figure 11 provides the number of pregnancy-related deaths by each of the underlying cause of death categories. The leading causes of pregnancy related deaths were embolism (4 deaths) and cardiovascular and coronary conditions (4 deaths). Leading causes of death by race and ethnicity are not provided due to very small numbers. Figure 11: Leading Underlying Causes of Pregnancy-Related Deaths, Tennessee, 2017 Data Source: Tennessee Department of Health, Division of Family Health and Wellness, Maternal Mortality Review Program. Critical Factors of Pregnancy-Related Deaths If a pregnancy-related death was deemed preventable, the Committee then assessed critical factors that contributed to the death.
The cell plate hiv infection by gender order genuine famvir, which is synthesized by the Golgi apparatus pictures of hiv infection symptoms generic 250mg famvir amex, supplies the plasma membrane that will separate the two daughter cells antiviral mushrooms purchase famvir with a mastercard. Synthesis of a new cell wall between the daughter cells also occurs at the cell plate hiv infection and aids pictures famvir 250mg for sale. Meiosis Meiosis is the type of cell division by which germ cells (eggs and sperm) are produced. Four stages can be described for each nuclear division: 30 Molecular Biology and Applied Genetics 2. Meiosis I Prophase of meiosis I (prophase I) is a more elaborate process than prophase of mitosis (and usually takes much longer). Daughter cells have half the number of chromosomes found in the original parent cell and with crossing over, are genetically different. Organisms with 35 Molecular Biology and Applied Genetics more than two sets of chromosomes are termed polyploid. Meiosis and Genetic Recombination While genes determine most of our physical characteristics, the exact combination of genes we inherit, and thus our physical traits, is in part due to a process our chromosomes undergo, known as genetic recombination. Genetic recombination happens during meiosis, a special type of cell division that occurs during formation of sperm and egg cells and gives them the correct number of chromosomes. Since a sperm and egg unite during fertilization, each must have only half the number of chromosomes other body cells have. While they are pressed together, the chromosomes may break, and each may swap a portion of its genetic material for the matching portion from its mate. This form of recombination is 36 Molecular Biology and Applied Genetics called crossing-over. When the chromosomes glue themselves back together and separate, each has picked up new genetic material from the other. The constellation of physical characteristics it determines is now different than before crossing-over. Tracking the movement of genes during crossing-over helps geneticists determine roughly how far apart two genes are on a chromosome. Since there are more chances for a break to occur between two genes that lie far apart, it is more likely that one gene will stay on the original chromosome, while the other crosses over. On the other hand, genes that lie very close together are less likely to be separated by a break and crossing-over. Sometimes, one gene in a linked pair serves as a "marker" that can be used by geneticists to infer the presence of the other (often, a disease-causing gene). Each chromosome moves independently of all the others a phenomenon called independent assortment. So, for example, the copy of chromosome 1 that an egg cell receives in no way influences which of the two possible copies of chromosome 5 it gets. So, any single human egg receives one of two possible chromosomes 23 times, and the total number of different possible chromosome combinations is over 8 million (2 raised to the 23rd power). Thus, when a sperm fertilizes an egg, the resulting zygote contains a combination of genes arranged in an order that has never occurred before and will never occur again. Meiosis not only preserves the genome size of sexually reproducing eukaryotes but also provides three mechanisms to diversify the genomes of the offspring. Meiosis and Sexual Reproduction Meiosis: Sexual reproduction occurs only in eukaryotes. During the formation of gametes, the number of chromosomes is reduced by half, and returned to the full amount when the two gametes fuse during fertilization. Meiosis is a special type of nuclear division which segregates one copy of each homologous chromosome into each new "gamete". Meiosis, on the other hand, reduces the number of sets of chromosomes by half, so that when gametic recombination (fertilization) occurs the ploidy of the parents will be reestablished. The vast majority of cell divisions in the human body are mitotic, with meiosis being restricted to the gonads. Introduction There are three major types of biological macromolecules in mammalian systems. It has two important types of functional group: 1) A carbonyl group (aldehydes in glucose, some other sugars have a ketone group instead, 2) Hydroxyl groups on the other carbons. Free anomeric carbons have the chemical reactivity of carbonyl carbons because they spend part of their time in the open chain form. The point is, a monosaccharide can therefore be thought of as having polarity, with one end consisting of the anomeric carbon, and the other end consisting of the rest of the molecule. Monosaccharide can polymerize by elimination of the elements of water between the anomeric hydroxyl and a hydroxyl of another sugar. If two anomeric hydroxyl groups react (head to head condensation) the product has no reducing end (no free anomeric carbon). If the anomeric hydroxyl reacts with a non-anomeric hydroxyl 43 Molecular Biology and Applied Genetics of another sugar, the product has ends with different properties. Since most monosaccharide has more than one hydroxyl, branches are possible, and are common. If the branch ends are the reactive sites, more branches provide more reactive sites per molecule. A base 44 Molecular Biology and Applied Genetics the bases are categorized in two groups: Purine Pyrimidine Adenine Cytosine Guanine Uracil (in Ribonucleotides) or Thymine (in Deoxyribonucleotides) Nucleotides polymerize to form nucleic acids. The last sequence is written in reverse order, but the ends are appropriately designated. The amino groups are usually attached to the carbons which are alpha to the carboxyl carbons, so they are called alpha-amino acids. There are many ways of classifying amino acids, but one very useful way is on the basis of how well or poorly the R-group interacts with water: 1. The hydrophobic R-groups which can be aliphatic (such as the methyl group of alanine) or aromatic (such as the phenyl group of phenylalanine). Polymerization of amino acids Amino acids polymerize to form polypeptides or proteins. Amino acids polymerize by eliminating the elements of water to form an amide between the amino and carboxyl groups. Conventions for writing sequences of amino acids Abbreviations for the amino acids are usually used; most of the three letter abbreviations are self evident, such as gly for glycine, asp for aspartate, etc. Many of the one-letter abbreviations are straightforward, for example: G = glycine L = leucine H = histidine Others require a little imagination to justify: F = phenylalanine ("ph" sounds like "F"). Y = tyrosine (T was used for threonine, so it was settled by the second letter in the name). D = aspartate (D is the fourth letter in the alphabet, and aspartate has four carbons). Still others are rather difficult to justify: W = tryptophan (The bottom half of the two aromatic rings look sort of like a "W"). The sequence of monomer units in a macromolecule is called the primary structure of that macromolecule. Helix A helical structure consists of repeating units that lie on the wall of a cylinder such that the structure is super-imposable upon itself if moved along the cylinder axis. These helical conformations of macromolecules persist in solution only if they are stabilized. Helices in carbohydrates Carbohydrates with long sequences of alpha (1 -> 4) links have a weak tendency to form helices. The starch helix is not very stable in the absence of other interactions (iodine, which forms a purple complex with starch, stabilized the starch helix), and it commonly adopts a random coil conformation in solution. Cellulose is a degenerate helix consisting of glucose units in alternating orientation stabilized by intrachain hydrogen bonds. Cellulose chains lying side by side can form sheets stabilized by interchain hydrogen bonds. Buy generic famvir 250 mg on line. HIV/AIDS: Progress and Promise in Stem Cell Research. |
