Ancient Human Parasites in Ethnic Chinese Populations

Whilst archaeological evidence for many aspects of life in ancient China is well studied, there has been much less interest in ancient infectious diseases, such as intestinal parasites in past Chinese populations. Here, we bring together evidence from mummies, ancient latrines, and pelvic soil from burials, dating from the Neolithic Period to the Qing Dynasty, in order to better understand the health of the past inhabitants of China and the diseases endemic in the region. Seven species of intestinal parasite have been identified, namely roundworm, whipworm, Chinese liver fluke, oriental schistosome, pinworm, Taenia sp. tapeworm, and the intestinal fluke Fasciolopsis buski. It was found that in the past, roundworm, whipworm, and Chinese liver fluke appear to have been much more common than the other species. While roundworm and whipworm remained common into the late 20th century, Chinese liver fluke seems to have undergone a marked decline in its prevalence over time. The iconic transport route known as the Silk Road has been shown to have acted as a vector for the transmission of ancient diseases, highlighted by the discovery of Chinese liver fluke in a 2,000 year-old relay station in northwest China, 1,500 km outside its endemic range.     

Real time visualization of protein kinase activity in living cells.

A library of fluorescently labeled protein kinase C (PKC) peptide substrates was prepared to identify a phosphorylation-induced reporter of protein kinase activity. The lead PKC substrate displays a 2.5-fold change in fluorescence intensity upon phosphorylation. PKC activity is readily sampled in cell lysates containing the activated PKCs. Immunodepletion of conventional PKCs from the cell lysate eliminates the fluorescence response, suggesting that this peptide substrate is selectively phosphorylated by PKCalpha, beta, and gamma. Finally, living cells microinjected with the peptide substrate exhibit a 2-fold increase in fluorescence intensity upon exposure to a PKC activator. These results suggest that peptide-based protein kinase biosensors may be useful in monitoring the temporal and spatial dynamics of PKC activity in living cells.     

Integrating across neuroimaging modalities boosts prediction accuracy of cognitive ability

Variation in cognitive ability arises from subtle differences in underlying neural architecture. Understanding and predicting individual variability in cognition from the differences in brain networks requires harnessing the unique variance captured by different neuroimaging modalities. Here we adopted a multi-level machine learning approach that combines diffusion, functional, and structural MRI data from the Human Connectome Project (N = 1050) to provide unitary prediction models of various cognitive abilities: global cognitive function, fluid intelligence, crystallized intelligence, impulsivity, spatial orientation, verbal episodic memory and sustained attention. Out-of-sample predictions of each cognitive score were first generated using a sparsity-constrained principal component regression on individual neuroimaging modalities. These individual predictions were then aggregated and submitted to a LASSO estimator that removed redundant variability across channels. This stacked prediction led to a significant improvement in accuracy, relative to the best single modality predictions (approximately 1% to more than 3% boost in variance explained), across a majority of the cognitive abilities tested. Further analysis found that diffusion and brain surface properties contribute the most to the predictive power. Our findings establish a lower bound to predict individual differences in cognition using multiple neuroimaging measures of brain architecture, both structural and functional, quantify the relative predictive power of the different imaging modalities, and reveal how each modality provides unique and complementary information about individual differences in cognitive function.     

Modulation of the expression of interleukin 2 receptors of human thymocytes by recombinant interleukin 2

The effect of purified recombinant interleukin 2 on the expression of the receptors for interleukin 2 by human thymocytes was examined. Interleukin 2 augmented the expression of interleukin 2 receptors and interferon-gamma synthesis by thymocytes activated with concanavalin A, and it was required to maintain the growth of thymocytes in vitro and the expression of interleukin 2 receptors. The increase observed in the number of receptor bearing thymocytes and in the density of receptors due to interleukin 2 occurred within the first 2 days of culture. Dexamethasone inhibited the expression of interleukin 2 receptors, the synthesis of interferon-gamma, and the early proliferation and protein synthesis of lectin-activated thymocytes during the first 2 days of culture. The inhibitory effect of dexamethasone on the expression of interleukin 2 receptors and on the synthesis of interferon-gamma was reversed by interleukin 2, whereas its effect on proliferation and on protein synthesis during the first two days of culture was not reversed by interleukin 2. Interleukin 2 induced the proliferation of thymocytes in vitro, even in the absence of activation by lectin; however, the number of cells displaying receptors which could be detected with anti-Tac remained low throughout the first week of culture and interferon-gamma synthesis was not observed. Nonetheless, interleukin 2-induced proliferation was inhibited by anti-Tac on a dose dependent manner. The results of the study document that recombinant interleukin 2, like purified natural interleukin 2, is required for the expression of interleukin 2 receptors, for interferon-gamma synthesis, and for the growth of thymocytes in vitro.     

Identification of the probable coding region for exon 2 of cytochrome oxidase polypeptide I from Aspergillus nidulans mitochondrion

Hypothetical protein URFe of Aspergillus nidulans mitochondrion is homologous with the amino end of cytochrome oxidase (EC 1.9.3.1) polypeptide I. Unidentified reading frame URFe does not contain a suitable initiation codon and codes for a protein with a length of only 91 residues, corresponding to about 20% of cytochrome oxidase polypeptide I. It is proposed that this region codes for the second exon of the cox 1 gene of Aspergillus mitochondrion. Possible candidates for the 2- to 3-residue amino-terminal exon 1 are discussed.     

Inhibition of glycosylphosphatidylinositol anchor formation by mannosamine.

Many eucaryotic cell surface proteins are anchored to the plasma membrane via a glycosylphosphatidylinositol (GPI), of which the core region is highly conserved from protozoa to mammalian cells. Previous studies (Lisanti, M. P., Field, M. C., Caras, I. W., Menon, A. K., and Rodiguez-Boulan, E. (1991) EMBO J. 10, 1969-1977) showed that mannosamine blocked the expression of a recombinant GPI-anchored protein in Madin-Darby canine kidney cells and converted this protein to an unpolarized secretory product. In the present study, we examined the effect of mannosamine on the formation of the glycan portion of the GPI anchor precursors. This amino sugar inhibited the incorporation of mannose into the glycan portion, and the inhibition was dose-dependent. Mannosamine was shown to be incorporated into the glycan as mannosamine, probably mostly in the second mannose position and thereby to block the further addition of mannose and other anchor components. The products formed in the presence of this drug were characterized by gel filtration and high resolution TLC both before and after deamination with nitrous acid and dephosphorylation by HF. Galactosamine and trehalosamine were inactive in this system, whereas glucosamine also inhibited mannose incorporation into GPI intermediates.