Rhesus macaque brain morphometry: A methodological comparison of voxel-wise approaches

Voxel-based morphometry studies have become increasingly common in human neuroimaging over the past several years; however, few studies have utilized this method to study morphometry changes in non-human primates. Here we describe the application of voxel-wise morphometry methods to the rhesus macaque (Macaca mulatta) using the 112RM-SL template and priors (McLaren et al. (2009) [42]) and as an illustrative example we describe age-associated changes in grey matter morphometry. Specifically, we evaluated the unified segmentation routine implemented using Statistical Parametric Mapping (SPM) software and the FMRIB’s Automated Segmentation Tool (FAST) in the FMRIB Software Library (FSL); the effect of varying the smoothing kernel; and the effect of the normalization routine. We found that when studying non-human primates, brain images need less smoothing than in human studies, 2–4 mm FWHM. Using flow field deformations (DARTEL) improved inter-subject alignment leading to results that were more likely due to morphometry differences as opposed to registration differences.     

Comparison of the host ranges and antigenicity of Cryptosporidium parvum and Cryptosporidium wrairi from guinea pigs.

Oocysts of a Cryptosporidium isolate from guinea pigs were not infectious for adult mice, but were infectious for two of three newborn calves and for suckling mice. However, oocysts isolated from calves or mice infected with guinea pig Cryptosporidium were not infectious for guinea pigs. Four isolates of C. parvum from calves were incapable of infecting weanling guinea pigs. Microscopic examination of tissue from the colon and cecum of suckling guinea pigs inoculated with C. parvum revealed sparse infection of some pups. These host range studies and previously described differences in 125I-labeled oocyst surface protein profiles between Cryptosporidium sp. from guinea pigs and C. parvum suggest they are distinct species. We propose the name Cryptosporidium wrairi be retained. Studies with monoclonal antibodies indicate that C. wrairi and C. parvum are antigenically related.     

Ecological Niche Conservatism in Doucs (Genus Pygathrix)

The impressive diversity and unique distribution of primate taxa in Southeast Asia creates a region of interesting biogeography and evolutionary history that remains poorly understood. The three species in the Asian colobine genus Pygathrix (P. cinerea, P. nemaeus, and P. nigripes) appear to follow the unique distribution pattern, replacing one another along the north–south axis. However, the evolutionary history and taxonomic status within Pygathrix is currently debated. We constructed climate-based ecological niche models (ENMs) for the three species, using six environmental variables, to confirm that the bioclimate envelopes of Pygathrix cinerea, P. nemaeus, and P. nigripes follow the north–south gradient. We also used the ENMs to test whether the three species lack ecological exchangeability, meaning differentiation among factors that define the fundamental niche, and whether they exhibit ecological niche conservatism, or the tendency for related species to differ less ecologically than might be expected by the climate available to each species. Our ENMs for Pygathrix followed a north–south gradient as expected, with P. nemaeus extending from ca. 14°N to 21°N, P. cinerea from 14°N to 16°N, and P. nigripes from 11°N to 13.5°N. This study presents the first use of ENMs for doucs that yield significant predictive ability based only on climatic variables. The models are significantly different for all three species, supporting a lack of ecological exchangeability between them, as well as the recent elevation of Pygathrix cinerea to species status. Importantly, Pygathrix cinerea and P. nemaeus show evidence of ecological niche conservatism, which lends support to the occurrence of an allopatric speciation event. This result also suggests that the current overlapping distribution of Pygathrix cinerea and P. nemaeus is the result of secondary contact. The north–south distribution gradient, which exists in similar form among other groups of sister taxa in the region, may be attributed to a zoogeographic barrier, vicariance, or current or historical climatic shifts.     

3, 3′-diindolylmethane Enhances the Effectiveness of Herceptin against HER-2/Neu-Expressing Breast Cancer Cells

Herceptin failure is a major clinical problem in breast cancer. A subset of breast cancer patients with high HER-2/neu levels eventually experience metastatic disease progression when treated with Herceptin as a single agent. Mechanistic details of development of this aggressive disease are not clear. Therefore, there is a dire need to better understand the mechanisms by which drug resistance develops and to design new combined treatments that benefit patients with aggressive breast cancer and have minimal toxicity. We hypothesized that 3, 3′-diindolylmethane (DIM), a non-toxic agent can be combined with Herceptin to treat breast cancers with high levels of HER-2/neu. Here, we evaluated the effects of Herceptin alone and in combination with DIM on cell viability, apoptosis and clonogenic assays in SKBR3 (HER-2/neu-expressing) and MDA-MB-468 (HER-2/neu negative) breast cancer cells. We found that DIM could enhance the effectiveness of Herceptin by significantly reducing cell viability, which was associated with apoptosis-induction and significant inhibition of colony formation, compared with single agent treatment. These results were consistent with the down-regulation of Akt and NF-kB p65. Mechanistic investigations revealed a significant upregulation of miR-200 and reduction of FoxM1 expression in DIM and Herceptin-treated breast cancer cells. We, therefore, transfected cells with pre-miR-200 or silenced FoxM1 in these cells for understanding the molecular mechanism involved. These results provide experimental evidence, for the first time, that DIM plus Herceptin therapy could be translated to the clinic as a therapeutic modality to improve treatment outcome of patients with breast cancer, particularly for the patients whose tumors express high levels of HER-2/neu.     

COMPARATIVE MORPHOLOGY OF THE CARPEL IN THE ROSACEAE VII. POMOIDEAE: CHAENOMELES,CYDONIA, DOCYNIA

The multi-ovulate pomoids, Chaenomeles, Cydonia, and Docynia, all have closed sutures and extensive fusion between carpel and floral cup and between ovular and wing bundles. Although the ovules in Docynia are generally apotropic and few in number (4–7), the ovules in the other two genera are pleurotropic and numerous (15–48). A statistical treatment of the whole tribe of Pomoideae shows that in carpels with open sutures ovular and wing bundles definitely tend to be separate while in those with closed sutures these bundles tend to be fused. To a lesser degree carpels with open sutures also tend to have bitegmic ovules, separate carpels, and a lesser extent of fusion between carpel and floral cup, while carpels with closed sutures tend to have monotegmic ovules, united carpels, and a greater extent of fusion between carpel and floral cup.     

Does Auxin Binding Protein 1 Control Both Cell Division and Cell Expansion?

The Auxin-Binding Protein 1 (ABP1) was identified over 30 years ago thanks to it''s high affinity for active auxins. ABP1 plays an essential role in plant life yet to this day, its function remains ‘enigmatic.’ A recent study by our laboratory shows that ABP1 is critical for regulation of the cell cycle, acting both in G₁ and at the G₂/M transition. We showed that ABP1 is likely to mediate the permissive auxin signal for entry into the cell cycle. These data were obtained by studying a conditional functional knock-out of ABP1 generated by cellular immunization in the model tobacco cell line, Bright Yellow 2.Key Words: auxin responses, auxin-binding protein 1, immunomodulation, cellular immunisation