Identification of Thresholds in Benthic Macroinvertebrate Communities Associated with Agricultural Land Cover

Agricultural land use affects benthic macroinvertebrate (BMI) community structure but riparian forest may mitigate its impact to within a specific threshold. BMI communities were sampled in small streams within the Grand River, Thames River, and Long Point watersheds in southwestern Ontario. The study assessed the location and amount of agricultural land use associated with variation in BMI assemblage structure. Three land use distribution scenarios were evaluated to isolate specific ranges of agricultural land use at either the riparian or catchment scale, with the adjoining scale covering as wide a gradient of agricultural land use as possible. We did identify thresholds but the amount of variation associated with our thresholds would not enable us to suggest specific target ranges for land use managers looking to incorporate them into their stream biomonitoring programs. Further studies that assess various geologies and share wider gradients will improve upon our findings

Telomere erosion in NF1 tumorigenesis

Neurofibromatosis type 1 (NF1; MIM# 162200) is a familial cancer syndrome that affects 1 in 3,500 individuals worldwide and is inherited in an autosomal dominant fashion. Malignant Peripheral Nerve Sheath Tumors (MPNSTs) represent a significant cause of morbidity and mortality in NF1 and currently there is no treatment or definite prognostic biomarkers for these tumors. Telomere shortening has been documented in numerous tumor types. Short dysfunctional telomeres are capable of fusion and it is considered that the ensuing genomic instability may facilitate clonal evolution and the progression to malignancy. To evaluate the potential role of telomere dysfunction in NF1-associated tumors, we undertook a comparative analysis of telomere length in samples derived from 10 cutaneous and 10 diffused plexiform neurofibromas, and 19 MPNSTs. Telomere length was determined using high-resolution Single Telomere Length Analysis (STELA). The mean Xp/Yp telomere length detected in MPNSTs, at 3.282 kb, was significantly shorter than that observed in both plexiform neurofibromas (5.793 kb; [p = 0.0006]) and cutaneous neurofibromas (6.141 kb; [p = 0.0007]). The telomere length distributions of MPNSTs were within the length-ranges in which telomere fusion is detected and that confer a poor prognosis in other tumor types. These data indicate that telomere length may play a role in driving genomic instability and clonal progression in NF1-associated MPNSTs

Meformin and insulin treatment prevent placental telomere attrition in boys exposed to maternal diabetes

Shortened leukocyte and placental telomeres associated with gestational diabetes mellitus (GDM) suggest this exposure triggers telomere attrition contributing to adverse outcomes. We applied high resolution Single Telomere Length Analysis (STELA) to placenta from GDM pregnancies with different treatment pathways to determine their effectiveness at preventing telomere attrition. Differences in telomere length between control (N = 69), GDM lifestyle intervention (n = 14) and GDM treated with metformin and/or insulin (n = 17) was tested by Analysis of Covariance (ANCOVA) followed by group comparisons using Fisher’s least significant difference. For male placenta only, there were differences in mean telomere length (F(2,54) = 4.98, P = 0.01) and percentage of telomeres under 5 kb (F(2,54) = 4.65, P = 0.01). Telomeres were shorter in the GDM lifestyle intervention group compared to both controls (P = 0.02) and medically treated pregnancies (P = 0.003). There were more telomeres under 5 kb in the GDM lifestyle intervention group compared to the other two groups (P = 0.03 and P = 0.004). Although further work is necessary, we suggest that early adoption of targeted medical treatment of GDM pregnancies where the fetus is known to be male may be an effective strategy for ameliorating adverse outcomes for children

Haptic-driven, interactive drug design: implementing a GPU-based approach to evaluate the induced fit effect

In this paper, we describe a hybrid meta-heuristics method of energy minimization and conformational sampling and its application into our haptic-driven molecular modelling simulator. The proposed method has been designed to suit real-time molecular docking simulations, where the time-lapse between two successive ligand poses is relatively small. In these situations, the energy minimization problem becomes increasingly complex and chaotic. The algorithm is tuned to take advantage of recent advances in GPU computing with asynchronous kernel execution, which has allowed us to include full protein flexibility in the real-time interactive, haptic-driven simulations. Finally, in this paper, we will also discuss the implementation of such high-performance computing approaches in our software, discussing the results of our initial validation studies, highlighting the advantages and limitations of such interactive methodology

Telomere dysfunction accurately predicts clinical outcome in chronic lymphocytic leukaemia, even in patients with early stage disease

© 2014 John Wiley & Sons Ltd. Defining the prognosis of individual cancer sufferers remains a significant clinical challenge. Here we assessed the ability of high-resolution single telomere length analysis (STELA), combined with an experimentally derived definition of telomere dysfunction, to predict the clinical outcome of patients with chronic lymphocytic leukaemia (CLL). We defined the upper telomere length threshold at which telomere fusions occur and then used the mean of the telomere 'fusogenic' range as a prognostic tool. Patients with telomeres within the fusogenic range had a significantly shorter overall survival (P  <  0·0001; Hazard ratio [HR] = 13·2, 95% confidence interval [CI]  = 11·6-106·4) and this was preserved in early-stage disease patients (P  <  0·0001, HR=19·3, 95% CI = 17·8-802·5). Indeed, our assay allowed the accurate stratification of Binet stage A patients into those with indolent disease (91% survival at 10 years) and those with poor prognosis (13% survival at 10 years). Furthermore, patients with telomeres above the fusogenic mean showed superior prognosis regardless of their IGHV mutation status or cytogenetic risk group. In keeping with this finding, telomere dysfunction was the dominant variable in multivariate analysis. Taken together, this study provides compelling evidence for the use of high-resolution telomere length analysis coupled with a definition of telomere dysfunction in the prognostic assessment of CLL

Koinonia

College Student IssuesCampus Suicide: Lessons Learned, Caryn Grimstead, Bob Neideck, Ann Snow, and Skip Trudeau Conference SpotlightOne Church Many Tribes: Following Jesus the Way God Made You, Richard Twiss Pursuing the Pearl, Ken Fong Residence Life & BeyondBuilding Inclusive Communities in the Residence Hall, Stephen J. Pasiciel Faculty Involvement in Student Development: Teaching Does Not End in the Classroom, Neil Friesland FeaturesThe President\u27s Corner Editor\u27s Disk ACSD Ballot NEW COLUMN: Thinking Theologically, Todd Ream My Senior Year; A Reflection on the First Four Years, Adela Huffordhttps://pillars.taylor.edu/acsd_koinonia/1020/thumbnail.jp

Telomere length heterogeneity in placenta revealed with high-resolution telomere length analysis

Introduction Telomeres, are composed of tandem repeat sequences located at the ends of chromosomes and are required to maintain genomic stability. Telomeres can become shorter due to cell division and specific lifestyle factors. Critically shortened telomeres are linked to cellular dysfunction, senescence and aging. A number of studies have used low resolution techniques to assess telomere length in the placenta. In this study, we applied Single Telomere Length Analysis (STELA) which provides high-resolution chromosome specific telomere length profiles to ask whether we could obtain more detailed information on the length of individual telomeres in the placenta. Methods Term placentas (37–42 weeks) were collected from women delivering at University Hospital of Wales or Royal Gwent Hospital within 2 h of delivery. Multiple telomere-length distributions were determined using STELA. Intraplacental variation of telomere length was analysed (N = 5). Telomere length distributions were compared between labouring (N = 10) and non-labouring (N = 11) participants. Finally, telomere length was compared between female (N = 17) and male (N = 20) placenta. Results There were no significant influences of sampling site, mode of delivery or foetal sex on the telomere-length distributions obtained. The mean telomere length was 7.7 kb ranging from 5.0 kb to 11.7 kb across all samples (N = 42) and longer compared with other human tissues at birth. STELA also revealed considerable telomere length heterogeneity within samples. Conclusions We have shown that STELA can be used to study telomere length homeostasis in the placenta regardless of sampling site, mode of delivery and foetal sex. Moreover, as each amplicon is derived from a single telomeric molecule, from a single cell, STELA can reveal the full detail of telomere-length distributions, including telomeres within the length ranges observed in senescent cells. STELA thus provides a new tool to interrogate the relationship between telomere length and pregnancy complications linked to placental dysfunction

Telomere length heterogeneity in placenta revealed with high-resolution telomere length analysis

Introduction Telomeres, are composed of tandem repeat sequences located at the ends of chromosomes and are required to maintain genomic stability. Telomeres can become shorter due to cell division and specific lifestyle factors. Critically shortened telomeres are linked to cellular dysfunction, senescence and aging. A number of studies have used low resolution techniques to assess telomere length in the placenta. In this study, we applied Single Telomere Length Analysis (STELA) which provides high-resolution chromosome specific telomere length profiles to ask whether we could obtain more detailed information on the length of individual telomeres in the placenta. Methods Term placentas (37–42 weeks) were collected from women delivering at University Hospital of Wales or Royal Gwent Hospital within 2 h of delivery. Multiple telomere-length distributions were determined using STELA. Intraplacental variation of telomere length was analysed (N = 5). Telomere length distributions were compared between labouring (N = 10) and non-labouring (N = 11) participants. Finally, telomere length was compared between female (N = 17) and male (N = 20) placenta. Results There were no significant influences of sampling site, mode of delivery or foetal sex on the telomere-length distributions obtained. The mean telomere length was 7.7 kb ranging from 5.0 kb to 11.7 kb across all samples (N = 42) and longer compared with other human tissues at birth. STELA also revealed considerable telomere length heterogeneity within samples. Conclusions We have shown that STELA can be used to study telomere length homeostasis in the placenta regardless of sampling site, mode of delivery and foetal sex. Moreover, as each amplicon is derived from a single telomeric molecule, from a single cell, STELA can reveal the full detail of telomere-length distributions, including telomeres within the length ranges observed in senescent cells. STELA thus provides a new tool to interrogate the relationship between telomere length and pregnancy complications linked to placental dysfunction

UPF1 promotes the formation of R loops to stimulate DNA double-strand break repair

DNA-RNA hybrid structures have been detected at the vicinity of DNA double-strand breaks (DSBs) occurring within transcriptional active regions of the genome. The induction of DNA-RNA hybrids strongly affects the repair of these DSBs, but the nature of these structures and how they are formed remain poorly understood. Here we provide evidence that R loops, three-stranded structures containing DNA-RNA hybrids and the displaced single-stranded DNA (ssDNA) can form at sub-telomeric DSBs. These R loops are generated independently of DNA resection but are induced alongside two-stranded DNA-RNA hybrids that form on ssDNA generated by DNA resection. We further identified UPF1, an RNA/DNA helicase, as a crucial factor that drives the formation of these R loops and DNA-RNA hybrids to stimulate DNA resection, homologous recombination, microhomology-mediated end joining and DNA damage checkpoint activation. Our data show that R loops and DNA-RNA hybrids are actively generated at DSBs to facilitate DNA repair

Reduced aggression and foraging efficiency of invasive signal crayfish (Pacifastacus leniusculus) infested with non-native branchiobdellidans (Annelida: Clitellata)

Background Biological invasions are a principal threat to global biodiversity and identifying the determinants of non-native species’ success is a conservation priority. Through their ability to regulate host populations, parasites are increasingly considered as important in determining the outcome of species’ invasions. Here, we present novel evidence that the common crayfish ecto-symbiont, Xironogiton victoriensis (Annelida: Clitellata) can affect the behaviour of a widespread and ecologically important invader, the signal crayfish (Pacifastacus leniusculus). Methods To assess the signal crayfish–X. victoriensis relationship naïve crayfish were infested with an intensity of worms typically observed under natural conditions. Over a 10-week period the growth rate and survivorship of these animals was monitored and compared to those of uninfested counterparts. Complementary dyadic competition and foraging experiments were run to assess the behaviour of infested compared to uninfested animals. These data were analysed using General Linear Models and Generalized Linear Mixed Models. Results Whilst X. victoriensis did not affect the growth rate or survivorship of signal crayfish under laboratory conditions, infested animals were significantly less aggressive and poorer foragers than uninfested individuals. Conclusions Through reducing aggression and foraging efficiency, infestation with X. victoriensis may disrupt the social structure, and potentially growth rate and/or dispersal of afflicted crayfish populations, with potential effects on their invasion dynamics. This is important given the widespread invasive range of crayfish and their functional roles as ecosystem engineers and keystone species