The non-random distribution of intronless human genes across molecular function categories

It has been proposed that one function of introns is to coordinate expression across/within networks of related genes. This same hypothesis also predicts that intronless genes will not be uniformly distributed among the functional categories of human genes, but will be found most frequently in those categories that have less need to communicate changes in their expression. Statistical analysis demonstrates significant clustering of single exon genes among those with binding or signal transduction/receptor activities and fewer than expected among those with catalytic function.     

CXCL1: A new diagnostic biomarker for human tuberculosis discovered using Diversity Outbred mice

More humans have died of tuberculosis (TB) than any other infectious disease and millions still die each year. Experts advocate for blood-based, serum protein biomarkers to help diagnose TB, which afflicts millions of people in high-burden countries. However, the protein biomarker pipeline is small. Here, we used the Diversity Outbred (DO) mouse population to address this gap, identifying five protein biomarker candidates. One protein biomarker, serum CXCL1, met the World Health Organization’s Targeted Product Profile for a triage test to diagnose active TB from latent M.tb infection (LTBI), non-TB lung disease, and normal sera in HIV-negative, adults from South Africa and Vietnam. To find the biomarker candidates, we quantified seven immune cytokines and four inflammatory proteins corresponding to highly expressed genes unique to progressor DO mice. Next, we applied statistical and machine learning methods to the data, i.e., 11 proteins in lungs from 453 infected and 29 non-infected mice. After searching all combinations of five algorithms and 239 protein subsets, validating, and testing the findings on independent data, two combinations accurately diagnosed progressor DO mice: Logistic Regression using MMP8; and Gradient Tree Boosting using a panel of 4: CXCL1, CXCL2, TNF, IL-10. Of those five protein biomarker candidates, two (MMP8 and CXCL1) were crucial for classifying DO mice; were above the limit of detection in most human serum samples; and had not been widely assessed for diagnostic performance in humans before. In patient sera, CXCL1 exceeded the triage diagnostic test criteria (>90% sensitivity; >70% specificity), while MMP8 did not. Using Area Under the Curve analyses, CXCL1 averaged 94.5% sensitivity and 88.8% specificity for active pulmonary TB (ATB) vs LTBI; 90.9% sensitivity and 71.4% specificity for ATB vs non-TB; and 100.0% sensitivity and 98.4% specificity for ATB vs normal sera. Our findings overall show that the DO mouse population can discover diagnostic-quality, serum protein biomarkers of human TB.     

Which 3-ribofuranosyl-substituted purine 5′-phosphates undergo template-directed oligomerization?

Summary We have studied the oligomerization reactions of the 2-methylimidazolide derivatives of 3-isoisoguanosine 5-phosphate (2) and 3-isoxanthosine 5-phosphate (5) in the presence of a variety of homopolynucleotide templates. In no case did we observe a substantial template-facilitated production of long oligomers. Polyuridylic acid directed the synthesis of low molecular-weight products from both monomers. Polycytidylic acid, polyadenylic acid, polyinosinic acid, and polyguanylic acid were ineffective as templates in the systems that we investigated.     

Calmodulin and the cell cycle: Involvement in regulation of cell-cycle progression

Calmodulin levels are elevated twofold at late G1 and/or early S phases during the growth cycle of CHO-K1 cells. These levels are maintained throughout the remainder of the cell cycle until cytokinesis. The G1 daughter cells then contain half the intracellular calmodulin level found prior to cell division. Elevation of calmodulin at the G1-S boundary is independent of the length of G1, and the increase in calmodulin appears to be related to progression into S phase. The importance of calmodulin for G1-S progression is suggested by the ability of the anticalmodulin drug W13 to elicit specific and reversible progression delays into and through S phase.     

Immunoreactive growth hormone production by human lymphocyte cell lines

1. Two human lymphocyte cell lines, a T-cell line and a B-cell line, were shown to produce and secrete immunoreactive growth hormone (irGH). The irGH molecules secreted by the two cell lines appeared to be de novo synthesized and their molecular size was similar to that of pituitary GH as well as irGH secreted by peripheral blood lymphocytes. 2. Affinity-purified irGH molecules had human growth hormone (hGH)-like mitogenic activity on Nb2 cells. These findings indicate that the irGH molecules produced by H9 and IM9 were similar to hGH in structure. 3. However, the irGH messages could not be amplified by polymerase chain reaction (PCR) primers which had been demonstrated to be able to amplify reverse-transcribed hGH messenger RNA successfully, suggesting that the lymphocyte-derived irGH and pituitary hGH are not exactly identical molecules. 4. We conclude that the H9 and IM9 cells produce a growth hormone-related molecule whose structure is different from that in the anterior pituitary.     

Root xylem CO<Subscript>2</Subscript> flux: an important but unaccounted-for component of root respiration

Key message

In tree roots, a large fraction of root-respired CO ₂ remains within the root system rather than diffusing into the soil. This CO ₂ is transported in xylem sap into the shoot, and because respiration is almost always measured as the flux of CO ₂ into the atmosphere from plant tissues, it represents an unaccounted-for component of tree root metabolism.

Abstract

Root respiration has been considered a large component of forest soil CO₂ efflux, but recent findings indicate that it may be even more important than previous measurements have shown because a substantial fraction of root-respired CO₂ remains within the tree root system and moves internally with the transpiration stream. The high concentration of CO₂ in roots appears to originate mainly within the root. It has been suggested that plants can take up dissolved inorganic carbon (DIC) from soil, but under most conditions uptake from soil is minimal due to the root-to-soil diffusion gradient, which suggests that most of the CO₂ in root xylem is derived from root respiration. Estimates of the internal flux of CO₂ through root xylem are based on combined measurements of sap flow and internal [CO₂]. Results quantifying root xylem CO₂ flux, obtained for a limited number of species, have raised important concerns regarding our understanding of tree respiration. Taken together, the results of these studies call into question the partitioning of ecosystem respiration into its above- and belowground components, and redefine the energetic costs of tree root metabolism and hence estimates of belowground carbon allocation. Expanding our observations of root xylem CO₂ flux to more species and at longer time scales, as well as improving the techniques used to study this process, could be fruitful avenues for future research, with the potential to substantially revise our understanding of root respiration and forest carbon cycles.

     

Stimulation by thyrotropin of synthesis of poly(A)-RNA and non-poly(A)-RNA in rat thyroid tissue

The $\text{in vivo}$ stimulation by thyrotropin of the synthesis of poly(A)-RNA and non-poly(A)-RNA in thyroid tissue was studied in 18 day old male rats. Each rat was injected with 0.25 ml of saline or of thyrotropin (0.25 unit) 4 hr or 8 hr before killing. Rats were injected with ³H-uridine 2 to 4 hr before sampling of thyroid tissue. Poly(A)-RNA and non-poly(A)-RNA were isolated by oligo (dT)-cellulose chromatography. Poly(A)-RNA accounts for about 3.5% of total cellular RNA; the specific activity of labeled poly(A)-RNA was 4–7 fold greater than that of non-poly(A)-RNA. A stimulation of about 40% and 90% over the control values was observed in the incorporation of ³H-uridine into poly(A)-RNA and non-poly(A)-RNA, respectively, in thyroid 4 to 8 hr after hormonal injection. The RNA contents of thyroid from hormone-treated rats did not change during the same time period. The stimulation of synthesis of poly(A)-RNA and non-poly(A)-RNA in thyroid was tissue specific insofar as these phenomena were not seen in liver or brain tissues.