Evidence of a rudimentary colon in the elasmobranch, Leucoraja erinacea

The transition from aquatic to terrestrial life presented tetrapodamorphs with the challenge of maintaining water homeostasis and preventing desiccation on land. The colon evolved in terrestrial vertebrates to help maintain fluid balance. Although marine elasmobranchs lack a colon, their spiral intestine contains a subregion that histologically appears to be colon-like, possibly representing an evolutionary precursor to terrestrial digestive tracts. The distal-most region of the spiral intestine of elasmobranchs has no villi and a large number of acid mucins: hallmarks of water absorption in the colons of terrestrial animals. To determine if histologically distinct regions of the elasmobranch digestive tract correspond to functional differences, we compared water absorption in different subregions of the skate, Leucoraja erinacea digestive tract. Water absorption in stomach and spiral intestinal sacs was linear with time and not hydrostatic pressure-dependent. The histologically distinct distal portion of the spiral intestine had a threefold higher rate of water absorption than the proximal portion of the spiral intestine. In addition, the water-selective, colon-specific aquaporin 4 is expressed strongly in the distal spiral intestine epithelia, correlating with the region of the spiral intestine exhibiting the greatest rate of water absorption. We demonstrate that the distal spiral intestine is histologically and functionally distinct from the rest of the spiral intestine and represents a rudimentary colon within the vertebrate lineage.     

Origin of immunoglobulin isotype switching

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Highlights? Switching in sharks consistent with immunization and cytidine deaminase expression ? Isotype switching can be reciprocal between genes of established positions ? Switch joints show DNA double-strand breakage repaired by nonhomologous end-joining ? Unlike in tetrapods, switching in shark is bidirection between IgM and IgW     

Reliability of maternal-reports regarding the use of household pesticides: experience from a case-control study of childhood leukemia

Introduction: Self-reported household pesticide use has been associated with higher risk of childhood leukemia in a number of case–control studies. The aim of this study is to assess the reliability of self-reported household use of pesticides and potential differences in reliability by case–control status, and by socio-demographic characteristics. Methods: Analyses are based on a subset of the Northern California Childhood Leukemia Study population. Eligible households included those with children less than 8 years old who lived in the same residence since diagnosis (reference date for controls). The reliability was based on two repeated in-person interviews. Kappa, percent positive and negative agreements were used to assess reliability of responses to ever/never use of six pesticides categories. Results: Kappa statistics ranged from 0.31 to 0.61 (fair to substantial agreement), with 9 out of the 12 tests indicating moderate agreement. The percent positive agreement ranged from 46 to 80% and the percent negative agreement from 54 to 95%. Reliability for all pesticide types as assessed by the three reliability measures did not differ significantly for cases and controls as confirmed by bootstrap analysis. For most pesticide types, Kappa and percent positive agreement were higher for non-Hispanics than Hispanics and for households with higher income vs. lower income. Conclusions: Reproducibility of maternal-reported pesticide use was moderate to high and was similar among cases and controls suggesting that differential recall is not likely to be a major source of bias.     

Hemocompatible poly(NIPAm-MBA-AMPS) colloidal nanoparticles as carriers of anti-inflammatory cell penetrating peptides

Anionic copolymer systems containing sulfated monomers have great potential for delivery of cationic therapeutics, but N-isopropylacrylamide (NIPAm) 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS) copolymer nanoparticles have seen limited characterization to date with regard to physical properties relevant to loading and release of therapeutics. Characterization of polymeric nanoparticles incorporating AMPS showed an increased size and decreased thermodynamic swelling ratios of AMPS containing particles as compared to NIPAm nanoparticles lacking AMPS. Particles with increasing AMPS addition showed an increased propensity for uniformity, intraparticle colloidal stability, and drug loading capacity. Peptide encapsulated in particles was shielded from peptide degradation in serum. Particles were shown not impede blood coagulation or to cause hemolysis. This study has demonstrated that AMPS incorporation into traditional NIPAm nanoparticles presents a tunable parameter for changing particle LCST, size, swelling ratio, ζ potential, and cationic peptide loading potential. This one-pot synthesis results in a thermosensitive anionic nanoparticle system that is a potentially useful platform to deliver cationic cell penetrating peptides.     

Establishing epithelial glandular polarity: interlinked roles for ARF6, Rac1, and the matrix microenvironment

Epithelial cysts comprise the structural units of the glandular epithelium. Although glandular inversion in epithelial tumors is thought to be a potential mechanism for the establishment of metastatic disease, little is known about the morphogenic cues and signaling pathways that govern glandular polarity and organization. Using organotypic cultures of Madin-Darby canine kidney cells in reconstituted basement membrane, we show that cellular depletion of the small GTP-binding protein ARF6 promotes the formation of inverted cysts, wherein the apical cell membrane faces the cyst exterior, and the basal domain faces the central lumen, while individual cell polarity is maintained. These cysts are also defective in interactions with laminin at the cyst–matrix interface. This inversion of glandular orientation is accompanied by Rac1 inactivation during early cystogenesis, and temporal activation of Rac1 is sufficient to recover the normal cyst phenotype. In an unnatural collagen I microenvironment, ARF6-depleted, inverted epithelial cysts exhibit some loss of cell polarity, a marked increase in Rho activation and Rac1 inactivation, and striking rearrangement of the surrounding collagen I matrix. These studies demonstrate the importance of ARF6 as a critical determinant of glandular orientation and the matrix environment in dictating structural organization of epithelial cysts.     

Dynamic reorganization of Eg5 in the mammalian spindle throughout mitosis requires dynein and TPX2

Kinesin-5 is an essential mitotic motor. However, how its spatial-temporal distribution is regulated in mitosis remains poorly understood. We expressed localization and affinity purification-tagged Eg5 from a mouse bacterial artificial chromosome (this construct was called mEg5) and found its distribution to be tightly regulated throughout mitosis. Fluorescence recovery after photobleaching analysis showed rapid Eg5 turnover throughout mitosis, which cannot be accounted for by microtubule turnover. Total internal reflection fluorescence microscopy and high-resolution, single-particle tracking revealed that mEg5 punctae on both astral and midzone microtubules rapidly bind and unbind. mEg5 punctae on midzone microtubules moved transiently both toward and away from spindle poles. In contrast, mEg5 punctae on astral microtubules moved transiently toward microtubule minus ends during early mitosis but switched to plus end-directed motion during anaphase. These observations explain the poleward accumulation of Eg5 in early mitosis and its redistribution in anaphase. Inhibition of dynein blocked mEg5 movement on astral microtubules, whereas depletion of the Eg5-binding protein TPX2 resulted in plus end-directed mEg5 movement. However, motion of Eg5 on midzone microtubules was not altered. Our results reveal differential and precise spatial and temporal regulation of Eg5 in the spindle mediated by dynein and TPX2.     

Sex differences in spatial cognition among Hadza foragers

This paper describes sex differences in spatial competencies among the Hadza, a mobile hunter–gatherer population in Tanzania. It addresses the following questions: (a) Is the usual male advantage in Euclidean spatial abilities found in this population, where both women and men are highly mobile? (b) Do Hadza women have better object location memory than men, as the gathering hypothesis predicts? (c) Do women who are nominated by others as being good at finding bushfoods excel at the object location memory task? We tested object location memory with a version of the memory game using cards of local plants and animals. This allowed us to also ask whether women and men would have better spatial memory for the plant and animal cards, respectively. We found that Hadza men were significantly better than women in three tests of spatial ability: the water-level test, targeting, and the ability to point accurately to distant locations (the latter only in the less mobile groups). There was a trend toward a male advantage at the object location memory task, in contrast to results found previously in nonforaging populations, and women's performance at the task deteriorated with age, while that of men did not. The women who were nominated by peers as being good at finding bushfoods were consistently older women. We discuss the probable hormonal causes and functional consequences of age changes in the spatial competencies of female foragers.