Molecular systematics and paleobiogeography of the South American sigmodontine rodents [published erratum appears in Mol Biol Evol 1998 Feb;15(2):224]

The murid rodent subfamily Sigmodontinae contains 79 genera which are distributed throughout the New World. The time of arrival of the first sigmodontines in South America and the estimated divergence time(s) of the different lineages of South American sigmodontines have been controversial due to the lack of a good fossil record and the immense number of extant species. The "early-arrival hypothesis" states that the sigmodontines must have arrived in South America no later than the early Miocene, at least 20 MYA, in order to account for their vast present-day diversity, whereas the "late-arrival hypothesis" includes the sigmodontines as part of the Plio-Pleistocene Great American Interchange, which occurred approximately 3.5 MYA. The phylogenetic relationships among 33 of these genera were reconstructed using mitochondrial DNA (mtDNA) sequence data from the ND3, ND4L, arginine tRNA, and ND4 genes, which we show to be evolving at the same rate. A molecular clock was calibrated for these genes using published fossil dates, and the genetic distances were estimated from the DNA sequences in this study. The molecular clock was used to estimate the dates of the South American sigmodontine origin and the main sigmodontine radiation in order to evaluate the "early-" and "late-arrival" scenarios. We estimate the time of the sigmodontine invasion of South America as between approximately 5 and 9 MYA, supporting neither of the scenarios but suggesting two possible models in which the invading lineage was either (1) ancestral to the oryzomyines, akodonts, and phyllotines or (2) ancestral to the akodonts and phyllotines and accompanied by the oryzomyines. The sigmodontine invasion of South America provides an example of the advantage afforded to a lineage by the fortuitous invasion of a previously unexploited habitat, in this case an entire continent.      

Over-Expression of Ephrin-A5 in Mice Results in Decreasing the Size of Progenitor Pool through Inducing Apoptosis

Eph receptors and their ligands, ephrins, mediate cell-to-cell contacts in a specific brain region and their bidirectional signaling is implicated in the regulation of apoptosis during early brain development. In this report, we used the alpha(α)-Cre transgenic line to induce ephrin-A5 over-expression in the distal region of the neural retina. Using this double transgenic embryo, we show that the over-expression of ephrin-A5 was responsible for inducing massive apoptosis in both the nasal and temporal retinas. In addition, the number of differentiated retinal neurons with the exception of the bipolar neuron was significantly reduced, whereas the laminar organization of the mature retina remained intact. Consistent with this finding, an analysis of the mature retina revealed that the size of the whole retina— particularly the nasal and temporal regions—is markedly reduced. These results strongly suggest that the level of ephrin-A5 expression plays a role in the regulation of the size of the retinal progenitor pool in the neural retina.     

Iron promotes the survival and neurite extension of serum-starved PC12 cells in the presence of NGF by enhancing cell attachment

Delayed death of serum-starved PC12 cells on a poly-L-lysine (PLL) matrix was observed, even in the presence of NGF. NGF blocked the apoptotic death of attached but not detached cells, which suggests that delayed death may be related to cell detachment from the PLL matrix. Iron selectively blocked this anoikis-like death by increasing cell attachment. Interestingly, the addition of > 10 microM FeCl2 to the culture medium generated gelatinous iron precipitates, and the removal of the precipitates abolished the iron effect. Attachment experiments using poly-HEMA supported the role of iron precipitates on cell-to-matrix adhesion. The expression of integrin beta1, neither N-cadherin nor alpha/beta-catenin, was also significantly increased by iron. In addition to its effect on cell viability, iron promoted the outgrowth of neurites. Our results collectively indicate that iron functions as a necessary co-element for NGF by enhancing cell attachment, survival, and neurite extension.     

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     

In Vivo Tumor Growth Rate Measured by US in Preoperative Period and Long Term Disease Outcome in Breast Cancer Patients

Objective

The aim of our study was to evaluate the effect of tumor growth rate, calculated from tumor size measurements by US, on breast cancer patients’ outcome.

Patients and Methods

Breast cancer patients who received at least two serial breast ultrasonographies (US) in our institution during preoperative period and were surgically treated between 2002 and 2010 were reviewed. Tumor growth rate was determined by specific growth rate (SGR) using the two time point tumor sizes by US.

Results

A total of 957 patients were analyzed. The median duration between initial and second US was 28 days (range, 8–140). The median initial tumor size was 1.7cm (range, 0.4–7.0) and median second size was 1.9cm (range, 0.3–7.2). 523(54.6%) cases had increase in size. The median SGR(x10^-2) was 0.59 (range, -11.90~31.49) and mean tumor doubling time was 14.51 days. Tumor growth rate was higher when initial tumor size was smaller. Lymphovascular invasion, axillary lymph node metastasis, and higher histologic grade were significantly associated with higher SGR. SGR was significantly associated with disease-free survival (DFS) in a univariate analysis (p = 0.04), but not in a multivariate Cox analysis (p>0.05). High SGR was significantly associated with worse DFS in a subgroup of initial tumor size >2cm (p = 0.018), but not in those with tumor size <2cm (p>0.05).

Conclusion

Our results showed that tumor growth rate measured by US in a relatively short time interval was associated with other worse prognostic factors and DFS, but it was not an independent prognostic factor in breast cancer patients.