Distribution of \u3cem\u3ePlethodon cinereus\u3c/em\u3e Color Morphs in New England: 40 Years Later

Global climate change is threatening species with habitat loss and extinction, but specific mechanisms driving changes in species abundance are unclear, partly due to a lack of time-series data sets documenting population changes. In order to study these effects on amphibian species, we revisited Lotter and Scott’s 1977 study of color morph frequency in relation to climate in Plethodon cinereus (eastern red-backed salamander). 25 Massachusetts, New Hampshire, and Vermont localities were resampled during summer 2016, to quantify any changes in morph frequency since 1977. At 19 of the 25 localities, we were able to find ≥100 salamanders, and of those 19, five localities had significant changes in morph frequency since 1977. Previous work suggests that the unstriped morph is more heat- and drought-tolerant, and thus should be the morph that increases in relative abundance over time in areas where global climate change results in either higher temperatures, decreased precipitation, more prolonged periods of drought, or some combination of these factors. Collection of fine-scale climate data at each location from 1977 to today was beyond the scope of this study, so I only documented the patterns of morph frequency change. Despite a general warming trend in New England, I found a higher proportion of the unstriped morph at only 1 of the 5 localities with significant change; the others showed an increase in the striped or erythristic morphs. Lotter and Scott also suggested that there was differential mortality between striped and unstriped morphs, with unstriped morphs suffering higher juvenile mortality. We found no evidence of this pattern at 9 MA localities with 2016 age data, suggesting that the current morph frequency distribution is stable. I continue to work with collaborators to resample all 50 Lotter and Scott localities. Once all sites have been resampled, we plan to explore potential climate or land-use changes that may be driving changes in morph frequency

The t Complex Distorter 2 Candidate Gene, Dnahc8, Encodes at Least Two Testis-Specific Axonemal Dynein Heavy Chains That Differ Extensively at Their Amino and Carboxyl Termini

AbstractHomozygosity for the t haplotype allele of the testis-specifically expressed axonemal dynein heavy chain (axDHC) gene, Dnahc8, has been linked to male sterility resulting from aberrant sperm motility. However, the near absence of Dnahc8 expression has been associated with male sterility resulting from an early breakdown in sperm flagellar development. Although axDHCs are integral participants in flagellar motility, a role in flagellar morphogenesis has never been attributed to a member of this highly conserved gene family. To gain a better understanding of this presumed novel role for Dnahc8, we have studied the organization and expression of full-length Dnahc8+ and Dnahc8t transcripts. Our results demonstrate the existence of at least two alternatively spliced, testis-specific Dnahc8 mRNAs transcribed from both the + and t alleles. A highly expressed isoform encodes a protein with significant homology nearly throughout to the γ heavy chain of the Chlamydomonas axonemal outer arm dynein, while a more poorly expressed isoform codes for a protein whose sequence diverges significantly from that of other axDHCs at both its N and C termini. While in situ hybridization studies demonstrate that both mRNA species accumulate exclusively in mid to late spermatocytes, each isoform shows spatial independence. Additional experiments demonstrate the existence of a testis-expressed mRNA with no significant open reading frame, a portion of which is antisense to the 5′-untranslated region of the highly divergent Dnahc8 isoform. The cumulative data imply that Dnahc8 may have acquired functional plasticity in the testis through the tightly controlled expression of both typical and unusual isoforms

Assessing the molecular genetics of attention networks

BACKGROUND: Current efforts to study the genetic underpinnings of higher brain functions have been lacking appropriate phenotypes to describe cognition. One of the problems is that many cognitive concepts for which there is a single word (e.g. attention) have been shown to be related to several anatomical networks. Recently, we have developed an Attention Network Test (ANT) that provides a separate measure for each of three anatomically defined attention networks. RESULTS: In this study we have measured the efficiency of neural networks related to aspects of attention using the ANT in a population of 200 adult subjects. We then examined genetic polymorphisms in four candidate genes (DRD4, DAT, COMT and MAOA) that have been shown to contribute to the risk of developing various psychiatric disorders where attention is disrupted. We find modest associations of several polymorphisms with the efficiency of executive attention but not with overall performance measures such as reaction time. CONCLUSIONS: These results suggest that genetic variation may underlie inter-subject variation in the efficiency of executive attention. This study also shows that genetic influences on executive attention may be specific to certain anatomical networks rather than affecting performance in a global or non-specific manner. Lastly, this study further validates the ANT as an endophenotypic assay suitable for assessing how genes influence certain anatomical networks that may be disrupted in various psychiatric disorders

The Differential Efficacy of Pemetrexed According to NSCLC Histology: A Review of Two Phase III Studies

Abstract Background. Recent studies of pemetrexed have identified a predictive role for non-small cell lung cancer (NSCLC) histology. We further reviewed the differential efficacy of pemetrexed according to histology in two large, phase III NSCLC trials. Methods. One study tested pemetrexed versus docetaxel in previously treated patients (n = 571) and the other tested cisplatin plus pemetrexed versus cisplatin plus gemcitabine in chemotherapy-naive patients (n = 1,725) with advanced NSCLC. Cox proportional hazard models were used to test for covariate-adjusted treatment-by-histology interactions (THIs) for overall survival (OS) and progression-free survival (PFS). For each histologic subgroup, the Kaplan–Meier method was used to estimate unadjusted within-arm medians, and Cox models were used to estimate covariate-adjusted between-arm hazard ratios (HRs). Results. In both studies, treatment arms were well balanced for histology. THIs were statistically significant (p < .005) for both OS and PFS. Nonsquamous patients treated with pemetrexed-based therapy experienced longer survival than the comparators (HR, 0.78 and 0.84, respectively), whereas squamous patients had shorter survival (HR, 1.56 and 1.23, respectively). Whereas the efficacy of pemetrexed regimens differed according to histology, it did not differ for docetaxel or for cisplatin plus gemcitabine. Pemetrexed was well tolerated across histologic groups. Conclusions. The consistency of these results across studies confirms the predictive effect of histology for pemetrexed and the survival advantage for pemetrexed in patients with nonsquamous histology. These analyses suggest pemetrexed should not be recommended for the treatment of squamous cell carcinoma, but, because of efficacy and safety advantages, pemetrexed may be preferable to other agents for treatment of patients with nonsquamous NSCLC

The impact of induction chemotherapy on the outcome of second-line therapy with pemetrexed or docetaxel in patients with advanced non-small-cell lung cancer

Background: Using data from a large phase III study of previously treated advanced non-small-cell lung cancer (NSCLC) that showed similar efficacy for pemetrexed and docetaxel, this retrospective analysis evaluates the impact of first-line chemotherapy on the outcome of second-line chemotherapy. Patients and methods: In all, 571 patients with advanced NSCLC were randomly assigned to receive pemetrexed 500 mg/m2 or docetaxel 75 mg/m2 on day 1 of a 21-day cycle. Comparisons were made based on type of first-line therapy [gemcitabine + platinum (GP), taxane + platinum (TP), or other therapies (OT)], response to initial therapy, time since initial therapy, and clinical characteristics. The two second-line treatment groups were pooled for this analysis due to similar efficacy and were assumed to have no interaction with the first-line therapies. Results: Baseline characteristics were generally balanced. By multivariate analysis, gender, stage at diagnosis, performance status (PS), and best response to first-line therapy significantly influenced overall survival (OS). Additional factors by univariate analysis, histology, and time elapsed from first- to second-line therapy significantly influenced OS. Conclusions: Future trials in the second-line setting should stratify patients by gender, stage at diagnosis, PS, and best response to first-line therap

Mitomycin C and Vinorelbine for second-line chemotherapy in NSCLC – a phase II trial

Single-agent therapy with Docetaxel or Pemetrexed is the current therapy of choice for second-line treatment in advanced non-small-cell lung cancer (NSCLC). The role of older agents was underattended over the last years. This study presents the combination of Mitomycin C and Vinorelbine in pretreated patients. Forty-two patients (stage IIIB and IV, pretreated with platinum-based chemotherapy) received 8 mg m−2 Mitomycin C on day 1 and 25 mg m−2 Vinorelbine on days 1 and 8 of a 28-day cycle. End points were objective tumour response, survival, and toxicity. Additionally, quality of life (QoL) was assessed. Five patients (11.9 %) achieved partial responses and 13 patients (31.9%) stable disease. Progression-free survival was 16 weeks. The median overall survival was 8.5 month. Eleven patients (26.2 %) suffered from grade 3 or 4 neutropenia and four patients (9.52%) from grade 3 or 4 anaemia. Evaluation of QoL showed that some items ameliorated during therapy. The therapeutic concept including Mitomycin C and Vinorelbine offers an efficacious and well-tolerated regimen, with relatively low toxicity. Objective response and survival data correlate with other second-line studies using different medication. As costs of Mitomycin C and Vinorelbine are lower compared with current drugs of choice, this regimen is likely to be cost-saving

A randomised phase II trial of docetaxel vs docetaxel and irinotecan in patients with stage IIIb–IV non-small-cell lung cancer who failed first-line treatment

Response rate and toxicity of second-line therapy with docetaxel (75 mg m−2) or docetaxel, irinotecan, and lenogastrim (60 mg m−2, 200 mg m−2, and 150 μg m−2 day−1, respectively) were compared in 108 patients with stage IIIb–IV non-small-cell lung cancer. Addition of irinotecan to docetaxel does not improve response rate, and increases gastrointestinal toxicity