Jennifer McNally

Biomineralization has mostly been studied in the class Anthozoa (Phylum Cnidaria), but very little is known about the evolution of the calcified skeleton in the class Hydrozoa or about the processes leading to its formation. The evolution of the calcified skeleton is here investigated in the hydrozoan family Hydractiniidae. A phylogenetic analysis of ribosomal, mitochondrial, and nuclear-protein-coding DNA sequences supported two independent origins of the calcified skeleton within the Hydractiniidae and indicates a case of parallel evolution, as suspected in the Anthozoa. Neither of the two origins of skeleton in the Hydractiniidae has led to either speciose or numerically abundant species, in contrast with other skeletonized hydrozoan families. Finally, we show that the origin of calcified skeletons in the Hydractiniidae is significantly correlated with the distribution of species with calcium carbonate granules within a polyp's gastrodermal cells. This suggests that the presence of these granules precedes the origin of a full skeleton.

<jats:title>ABSTRACT</jats:title><jats:p>Multiple lines of evidence suggest that inflammation and glutamate dysfunction contribute to the pathophysiology of depression. In this review we provide an overview of how these two systems may interact. Excess levels of inflammatory mediators occur in a subgroup of depressed patients. Studies of acute experimental activation of the immune system with endotoxin and of chronic activation during interferon-α treatment show that inflammation can cause depression. Peripheral inflammation leads to microglial activation which could interfere with excitatory amino acid metabolism leading to inappropriate glutamate receptor activation. Loss of astroglia, a feature of depression, upsets the balance of anti- and pro-inflammatory mediators and further impairs the removal of excitatory amino acids. Microglia activated by excess inflammation, astroglial loss, and inappropriate glutamate receptor activation ultimately disrupt the delicate balance of neuroprotective versus neurotoxic effects in the brain, potentially leading to depression.</jats:p>

In humans, a subset of placental cytotrophoblasts (CTBs) invades the uterus and its vasculature, anchoring the pregnancy and ensuring adequate blood flow to the fetus. Appropriate depth is critical. Shallow invasion increases the risk of pregnancy complications, e.g., severe preeclampsia. Overly deep invasion, the hallmark of placenta accreta spectrum (PAS), increases the risk of preterm delivery, hemorrhage, and death. Previously a rare condition, the incidence of PAS has increased to 1:731 pregnancies, likely due to the rise in uterine surgeries (e.g., Cesarean sections). CTBs track along scars deep into the myometrium and beyond. Here we compared the global gene expression patterns of CTBs from PAS cases to gestational age-matched control cells that invaded to the normal depth from preterm birth (PTB) deliveries. The messenger RNA (mRNA) encoding the guanine nucleotide exchange factor, DOCK4, mutations of which promote cancer cell invasion and angiogenesis, was the most highly up-regulated molecule in PAS samples. Overexpression of DOCK4 increased CTB invasiveness, consistent with the PAS phenotype. Also, this analysis identified other genes with significantly altered expression in this disorder, potential biomarkers. These data suggest that CTBs from PAS cases up-regulate a cancer-like proinvasion mechanism, suggesting molecular as well as phenotypic similarities in the two pathologies.

<jats:sec><jats:title>Objective</jats:title><jats:p>Given the relative chemo-resistant nature of clear-cell gynecologic cancers, we investigated the utility of radiation therapy (RT) to treat recurrent clear-cell carcinoma (CCC) of the ovary.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>A retrospective chart review of patients with recurrent CCC managed from 1994–2012 was conducted at 2 academic medical centers. Demographic and clinicopathologic factors were abstracted and evaluated using Pearson χ<jats:sup>2</jats:sup> or <jats:italic>t</jats:italic> tests, Kaplan-Meier and Cox regression analyses.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Fifty-three patients had recurrent CCC, and 24 (45.3%) of these patients received RT. There were no significant differences in age, stage, optimal cytoreduction, platinum response, or the percentage of patients that received more than 3 regimens of chemotherapy between the 2 groups. Patients who received RT for recurrent CCC were more likely to have had a focal recurrence (62.5% vs 10.3%, <jats:italic>P</jats:italic> ≤ 0.001) and to have undergone secondary cytoreduction (70.8% vs 10.3%, <jats:italic>P</jats:italic> ≤ 0.001). Of patients who received RT, 73.9% underwent surgery with or before their treatment. Five-year survival after recurrence was significantly higher in the group that received RT, 62.9% versus 18.8% (<jats:italic>P</jats:italic> = 0.002). In a multivariate analysis, platinum-sensitive disease and RT were associated with improved survival from recurrence, (hazard ratio, 0.26; 95% confidence interval, 0.08-0.81; <jats:italic>P</jats:italic> = 0.02 and hazard ratio, 0.28; 95% confidence interval, 0.09–0.90, <jats:italic>P</jats:italic> = 0.03, respectively).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>In this cohort of patients with recurrent CCC, platinum-sensitive disease and RT are associated with improved survival. However, it is important to note that the majority of these patients underwent surgery along with RT, and it may be that the benefit of RT is limited to those who undergo secondary cytoreduction.</jats:p></jats:sec>