Inherited Biochemical Variation in DROSOPHILA MELANOGASTER: Noise or Signal? I. Single-Locus Analyses

A study was conducted using small effective population size as an experimental design to test selective neutrality of seven isozyme polymorphisms. Loci varied as to the degree to which the decay of heterozygosity over 21 generations was retarded. Selection for heterozygotes, overdominance, is implicated for at least four of seven loci. Of these ADH gave the largest heterozygote excess in the presence of inbreeding. An interaction between the small population size treatment and excess heterozygosity suggests that (1) the loci studied may be selectively neutral and linked to other loci which are under the influence of selection or (2) the selection coefficients for the loci studied are not independent of the background genotype. In either case four of the seven enzymes studied are signaling the operation of selection. The problem of distinguishing the effect of a single marker from that of a chromosome segment is emphasized. The identification of the genetic unit of selection is crucial to any interpretation of the meaning of enzyme polymorphisms.     

Analysis of genetic and environmental sources of variation in serum cholesterol in Tecumseh,Michigan. III. Identification of genetic effects using 12 polymorphic genetic blood marker systems.

Four of 12 unlinked polymorphic marker systems were identified as predictors of normal serum cholesterol levels. Consistent effects between males and females and with other studies suggest that these marker loci are themselves involved in cholesterol determination or are closely linked to the involved loci. Two-locus combinations suggest that an 8-9 mg/100 ml difference in nonfasting serum cholesterol may be predicted between phenotypic classes which are not rare in frequency.     

HLA antigens, phytohemagglutinin stimulation, and corticosteroid response.

Although it is clear that the major histocompatibility complex is associated with lymphocyte glucocorticoid sensitivity in mice, there has been less evidence for a similar relationship in man. We have typed 158 individuals for: (1) 13 A locus and 16 B locus antigens, (2) degree of stimulation of their purified lymphocytes by phytohemagglutinin A (PHA), and (3) degree of inhibition of the PHA stimulation by prednisolone and prednisolone-21-hemisuccinate. In contrasts of individuals with a particular antigen (homozygous or heterozygous) with all remaining individuals, HLA-B7 was found to be associated with an enhancing effect on the log stimulation by PHA while other antigens of these series did not have significant associations. In similar contrasts, A10 was associated with a decrease in sensitivity to glucocorticoid inhibition of PHA stimulation as measured by the log I50 of the suppression of PHA stimulation. Other antigens of these series were not found to have significant associations with the glucocorticoid sensitivity of lymphocytes in this assay.     

Computational methods for the design of effective therapies against drug resistant HIV strains

The development of drug resistance is a major obstacle to successful treatment of HIV infection. The extraordinary replication dynamics of HIV facilitates its escape from selective pressure exerted by the human immune system and by combination drug therapy. We have developed several computational methods whose combined use can support the design of optimal antiretroviral therapies based on viral genomic data.     

Sustained release of proteins from electrospun biodegradable fibers

Electrospinning is a simple and versatile technique of producing polymeric fibers ranging from submicron to micron in diameter. Incorporation of bioactive agents into the fibers could make a biofunctional tissue engineering scaffold. In this study, we investigated the feasibility of encapsulating human beta-nerve growth factor (NGF), which was stabilized in a carrier protein, bovine serum albumin (BSA) in a copolymer of epsilon-caprolactone and ethyl ethylene phosphate (PCLEEP) by electrospinning. Partially aligned protein encapsulated fibers were obtained and the protein was found to be randomly dispersed throughout the electrospun fibrous mesh in aggregate form. A sustained release of NGF via diffusion process was obtained for at least 3 months. PC12 neurite outgrowth assay confirmed that the bioactivity of electrospun NGF was retained, at least partially, throughout the period of sustained release, thus clearly demonstrating the feasibility of encapsulating proteins via electrospinning to produce biofunctional tissue scaffolds.     

Yersinia V antigen induces both TLR homo- and heterotolerance in an IL-10-involving manner

The virulence antigen (LcrV) of pathogenic yersiniae "silences" macrophages against stimulation with the TLR2-agonist zymosan A in a CD14/TLR2-dependent fashion via IL-10 induction. This pathogenically important "silencing" resembles TLR tolerance phenomena; in these, pre-exposure to a primary tolerizing TLR-agonist renders macrophages unresponsive to stimulation with a secondary challenging TLR-agonist which may involve either the same (TLR homotolerance) or a different TLR (TLR heterotolerance) as the primary TLR-agonist. Here, we show that rLcrV induces TLR homo- and heterotolerance against TLR2- or TLR4-agonists both in human and murine macrophages, respectively. The underlying mechanism of LcrV-induced tolerance is most likely not due to changes in TLR2- or TLR4 expression, but involves LcrV-mediated IL-10 production, since LcrV-induced TLR homo- and heterotolerance is highly impaired in IL-10(-/-) macrophages. Moreover, the involvement of IL-10 in TLR tolerance induction seems to be a more general phenomenon as shown by experiments using different TLR-agonists in IL-10(-/-) macrophages. Since LcrV acts as a secreted protein upon macrophages without requiring direct cell contact, as shown in transwell assays, we propose that yersiniae exploit IL-10-involving TLR tolerance mechanisms by the virulence factor LcrV.     

Alkyl Chain Regiochemistry of Benzotriazole‐Based Donor Polymers Influencing Morphology and Performances of Non‐Fullerene Organic Solar Cells

The effects of alkyl chain regiochemistry on the properties of donor polymers and performances of non‐fullerene organic solar cells are investigated. Two donor polymers (PfBTAZ and PfBTAZS) are compared that have nearly identical chemical structures except for the regiochemistry of alkyl chains. The optical properties and crystallinity of two polymers are nearly identical yet the PfBTAZ:O‐IDTBR blend exhibits nearly double domain size compared to the blend based on PfBTAZS:O‐IDTBR. To reveal the origins of the very different domain size of two blends, the morphology of neat polymer films is characterized, and it is found that PfBTAZ tends to aggregate into much larger polymer fibers without the presence of O‐IDTBR. This indicates that it is not the polymer:O‐IDTBR interactions but the intrinsic aggregation properties of two polymers that determine the morphology features of neat and blend films. The stronger aggregation tendency of PfBTAZ could be explained by its more co‐planar geometry of the polymer backbone arising from the different alkyl chain regiochemistry. Combined with the similar trend observed in another set of donor polymers (PTFB‐P and PTFB‐PS), the results provide an important understanding of the structure–property relationships that could guide the development of donor polymers for non‐fullerene organic solar cells.     

Rethinking neurasthenia: The illness concepts of Shenjing Shuairuo among Chinese undergraduates in Hong Kong

Neurasthenia is both a Western disease construct and a popular Chinese illness concept (shenjing shuairuo, SJSR). Using a self-report questionnaire, we examined 148 Hong Kong Chinese undergraduates' concept of its epidemiology, symptomatology, etiology and treatment. Notwithstanding that fatigue is thesine qua non of neurasthenia in Western nosology, subjects believed that SJSR was compatible with a diversity of symptoms which fell, on factor analysis, into the neurotic, psychotic, somatic and dysfunctional subgroups. Contrary to the popular portrayal of SJSR as a physical or chronic fatigue disorder, the most common perceived symptoms were anxiety, insomnia, depression and fright. Logically, psychological etiology and remedy were highly emphasized. The perceived high prevalence, non-aggressive nature and symptomatic diversity of SJSR attested to the notion that it might camouflage and destigmatize psychiatric labels of insanity. The contextual study of neurasthenia illustrates how in its search for legitimacy an originally Western concept adapts, transforms, and acquires distinctive local meanings in a non-Western culture.