Loss, resilience and recovery of kelp forests in a region of rapid ocean warming.

BACKGROUND AND AIMS: Changes in kelp abundances on regional scales have been highly variable over the past half-century owing to strong effects of local and regional drivers. Here, we assess patterns and dominant environmental variables causing spatial and interspecific variability in kelp persistence and resilience to change in Nova Scotia over the past 40 years. METHODS: We conducted a survey of macrophyte abundance at 251 sites spanning the Atlantic coast of Nova Scotia from 2019 to 2022. We use this dataset to describe spatial variability in kelp species abundances, compare species occurrences to surveys conducted in 1982 and assess changes in kelp abundance over the past 22 years. We then relate spatial and temporal patterns in abundance and resilience to environmental metrics. KEY RESULTS: Our results show losses of sea urchins and the cold-tolerant kelp species Alaria esculenta, Saccorhiza dermatodea and Agarum clathratum in Nova Scotia since 1982 in favour of the more warm-tolerant kelps Saccharina latissima and Laminaria digitata. Kelp abundances have increased slightly since 2000, and Saccharina latissima and L. digitata are widely abundant in the region today. The highest kelp cover occurs on wave-exposed shores and at sites where temperatures have remained below thresholds for growth (21 °C) and mortality (23 °C). Moreover, kelp has recovered from turf dominance following losses at some sites during a warm period from 2010 to 2012. CONCLUSIONS: Our results indicate that dramatic changes in kelp community composition and a loss of sea urchin herbivory as a dominant driver of change in the system have occurred in Nova Scotia over the past 40 years. However, a broad-scale shift to turf-dominance has not occurred, as predicted, and our results suggest that resilience and persistence are still a feature of kelp forests in the region despite rapid warming over the past several decades.

Calcification Volume Reduces Stretch Capability and Predisposes Plaque to Rupture in an in vitro Model of Carotid Artery Stenting.

OBJECTIVE/BACKGROUND: Carotid artery stenting (CAS) in calcified arteries carries a higher peri-operative risk. This study investigates the relationship between the stretching limits of carotid plaque samples and calcification in order to determine a stretch tolerance criterion for endovascular intervention. METHODS: Seventeen carotid plaque samples were acquired from standard endarterectomy procedures. The maximum stretch capability of the global plaque was determined by circumferentially extending the tissue to complete failure. Quantitative assessment of calcification was performed using high resolution computed tomography, including measures of percent calcification volume fraction (%CVF) and calcification configuration. Maximum stretch properties were then related to calcification measures in order to evaluate the predictive power of calcification for determining plaque stretching limits. RESULTS: A strong negative correlation was found between %CVF and stretch ratio with respect to specific calcification configuration types. All plaques with < 70% stenosis superseded the minimum required stretch threshold. Severe stenosis (> 70%) warrants a stretch of at least 2.33 during revascularisation and only plaques containing concentric calcifications with < 20% CVF successfully reached this minimum required stretch threshold. CONCLUSION: The addition of calcification measures to the stenosis classification may help in guiding endovascular intervention techniques to achieve a balance between an acceptable residual patency level while avoiding plaque rupture in calcified carotid plaques.

Vaginal progesterone decreases preterm birth ≤ 34 weeks of gestation in women with a singleton pregnancy and a short cervix: an updated meta-analysis including data from the OPPTIMUM study.

OBJECTIVE: To evaluate the efficacy of vaginal progesterone administration for preventing preterm birth and perinatal morbidity and mortality in asymptomatic women with a singleton gestation and a mid-trimester sonographic cervical length (CL) ≤ 25 mm. METHODS: This was an updated systematic review and meta-analysis of randomized controlled trials comparing the use of vaginal progesterone to placebo/no treatment in women with a singleton gestation and a mid-trimester sonographic CL ≤ 25 mm. Electronic databases, from their inception to May 2016, bibliographies and conference proceedings were searched. The primary outcome measure was preterm birth ≤ 34 weeks of gestation or fetal death. Two reviewers independently selected studies, assessed the risk of bias and extracted the data. Pooled relative risks (RRs) with 95% confidence intervals (CI) were calculated. RESULTS: Five trials involving 974 women were included. A meta-analysis, including data from the OPPTIMUM study, showed that vaginal progesterone significantly decreased the risk of preterm birth ≤ 34 weeks of gestation or fetal death compared to placebo (18.1% vs 27.5%; RR, 0.66 (95% CI, 0.52-0.83); P = 0.0005; five studies; 974 women). Meta-analyses of data from four trials (723 women) showed that vaginal progesterone administration was associated with a statistically significant reduction in the risk of preterm birth occurring at < 28 to < 36 gestational weeks (RRs from 0.51 to 0.79), respiratory distress syndrome (RR, 0.47 (95% CI, 0.27-0.81)), composite neonatal morbidity and mortality (RR, 0.59 (95% CI, 0.38-0.91)), birth weight < 1500 g (RR, 0.52 (95% CI, 0.34-0.81)) and admission to the neonatal intensive care unit (RR, 0.67 (95% CI, 0.50-0.91)). There were no significant differences in neurodevelopmental outcomes at 2 years of age between the vaginal progesterone and placebo groups. CONCLUSION: This updated systematic review and meta-analysis reaffirms that vaginal progesterone reduces the risk of preterm birth and neonatal morbidity and mortality in women with a singleton gestation and a mid-trimester CL ≤ 25 mm, without any deleterious effects on neurodevelopmental outcome. Clinicians should continue to perform universal transvaginal CL screening at 18-24 weeks of gestation in women with a singleton gestation and to offer vaginal progesterone to those with a CL ≤ 25 mm. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Characterization of the avian aryl hydrocarbon receptor 1 from blood using non-lethal sampling methods.

The amino acid sequence of the aryl hydrocarbon receptor 1 ligand binding domain (AHR1 LBD) is an important determinant of sensitivity to dioxin-like compounds in avian species. We are interested in surveying AHR1 LBD sequences in a large number of birds as a means of identifying species that are particularly sensitive to dioxin-like compounds. Our original method for determining AHR1 LBD genotype used liver tissue and required lethal sampling. Here we present two alternate methods for determining AHR1 LBD genotype which use non-lethal sampling and are more appropriate for ecologically sensitive species. First, we establish that AHR1 LBD mRNA is expressed in avian blood and test a variety of blood collection and handling protocols in order to establish a method that is convenient for field collections. Our findings also identify which types of archival blood samples might be appropriate for AHR1 LBD sequence determination. Second, we present a method for obtaining AHR1 LBD coding sequences from DNA. A DNA-based method is advantageous because DNA can be isolated from many tissue types, is more stable than RNA, and requires less specific sample handling and preservation. This work extends applicability of a genetic screen for dioxin sensitivity to a larger number of species and sample types including endangered species and potentially museum specimens.

A noninvasive eye fixation monitoring system for CyberKnife radiotherapy of choroidal and orbital tumors.

A new noninvasive monitoring system for fixing the eye has been developed to treat orbital and choroidal tumors with CyberKnife-based radiotherapy. This device monitors the eye during CT/MRI scanning and during treatment. The results of this study demonstrate the feasibility of the fixation light system for CyberKnife-based treatments of orbital and choroidal tumors and supports the idea that larger choroidal melanomas and choroidal metastases could be treated with CyberKnife without implanting fiducial markers.

Effect of progesterone on cervical shortening in women at risk for preterm birth: secondary analysis from a multinational, randomized, double-blind, placebo-controlled trial.

OBJECTIVES: To determine whether progesterone supplementation alters cervical shortening in women at increased risk for preterm birth. METHODS: We performed a planned secondary analysis from a large, multinational preterm birth prevention trial of daily intravaginal progesterone gel, 90 mg, compared with placebo in women with a history of spontaneous preterm birth or premature cervical shortening. Transvaginal cervical length measurements were obtained in all randomized patients at baseline (18 + 0 to 22 + 6 weeks' gestation) and at 28 weeks' gestation. For this secondary analysis, the difference in cervical length between these time points was compared for the study population with a history of spontaneous preterm birth and for a population with premature cervical shortening (< or = 30 mm) at randomization. Differences between groups in cervical length for the 28-week examination were analyzed using ANCOVA, including adjustment for relevant clinical parameters and maternal characteristics. RESULTS: Data were analyzed from 547 randomized patients with a history of preterm birth. The progesterone-treated patients had significantly less cervical shortening than the placebo group (difference 1.6 (95% CI, 0.3-3.0) mm; P = 0.02, ANCOVA). In the population of 104 subjects with premature cervical shortening at randomization, the cervical length also differed significantly on multivariable analysis, with the treatment group preserving more cervical length than the placebo group (difference 3.3 (95% CI, 0.3-6.2) mm; P = 0.03, ANCOVA), with adjustment for differences in cervical length at screening. A significant difference was also observed between groups for categorical outcomes including the frequency of cervical length progression to < or = 25 mm and a > or = 50% reduction in cervical length from baseline in this subpopulation. CONCLUSIONS: Intravaginal progesterone enhances preservation of cervical length in women at high risk for preterm birth.

Form and motion coherence activate independent, but not dorsal/ventral segregated, networks in the human brain.

There is much evidence in primates' visual processing for distinct mechanisms involved in object recognition and encoding object position and motion, which have been identified with 'ventral' and 'dorsal' streams, respectively, of the extra-striate visual areas [1] [2] [3]. This distinction may yield insights into normal human perception, its development and pathology. Motion coherence sensitivity has been taken as a test of global processing in the dorsal stream [4] [5]. We have proposed an analogous 'form coherence' measure of global processing in the ventral stream [6]. In a functional magnetic resonance imaging (fMRI) experiment, we found that the cortical regions activated by form coherence did not overlap with those activated by motion coherence in the same individuals. Areas differentially activated by form coherence included regions in the middle occipital gyrus, the ventral occipital surface, the intraparietal sulcus, and the temporal lobe. Motion coherence activated areas consistent with those previously identified as V5 and V3a, the ventral occipital surface, the intraparietal sulcus, and temporal structures. Neither form nor motion coherence activated area V1 differentially. Form and motion foci in occipital, parietal, and temporal areas were nearby but showed almost no overlap. These results support the idea that form and motion coherence test distinct functional brain systems, but that these do not necessarily correspond to a gross anatomical separation of dorsal and ventral processing streams.

Mutational analysis of CDC42Sc, a Saccharomyces cerevisiae gene that encodes a putative GTP-binding protein involved in the control of cell polarity.

The Saccharomyces cerevisiae CDC42 gene product, a member of the ras superfamily of low-molecular-weight GTP-binding proteins, is involved in the control of cell polarity. We have analyzed the effects of three CDC42 mutations (Gly to Val-12, Gln to Leu-61, and Asp to Ala-118) in the putative GTP-binding and hydrolysis domains and one mutation (Cys to Ser-188) in the putative isoprenylation site. The first three mutations resulted in either a dominant-lethal or dose-dependent dominant-lethal phenotype when present on plasmids in haploid cdc42-1ts or wild-type strains. Both wild-type and cdc42-1ts cells carrying plasmids (pGAL) with either the CDC42Val-12 or CDC42Leu-61 alleles under the control of a GAL promoter were arrested with a novel phenotype of large cells with elongated or multiple buds. Cells carrying pGAL-CDC42Ala-118 were arrested as large, round, unbudded cells reminiscent of cdc42-1ts arrested cells. The different phenotype of the CDC42Ala-118 mutant versus the CDC42Val-12 and CDC42Leu-61 mutants was unexpected since the phenotypes of all three analogous ras mutants were similar to each other. This suggests that aspects of the biochemical properties of the Cdc42 protein differ from those of the Ras protein. The cdc42Ser-188 mutant gene was incapable of complementing the cdc42-1ts mutation and was recessive to both wild-type and cdc42-1ts. In double-mutant alleles, the cdc42Ser-188 mutation was capable of suppressing the dominant lethality associated with the three putative GTP-binding and hydrolysis mutations, suggesting that isoprenylation is necessary for the activity of the wild-type and mutant proteins.

Subcellular localization of Cdc42p, a Saccharomyces cerevisiae GTP-binding protein involved in the control of cell polarity.

The Saccharomyces cerevisiae Cdc42 protein, a member of the Ras superfamily of low-molecular-weight GTP-binding proteins, is involved in the control of cell polarity during the yeast cell cycle. This protein has a consensus sequence (CAAX) for geranylgeranyl modification and is likely to be associated, at least in part, with cell membranes. Using cell fractionation and immunolocalization techniques, we have investigated the subcellular localization of Cdc42p. Cdc42p was found in both soluble and particulate pools, and neither its abundance nor its distribution varied through the cell cycle. The particulate form of Cdc42p could be solubilized with detergents but not with NaCl or urea, suggesting that it is tightly associated with membranes. An increase in soluble Cdc42p was observed in a geranylgeranyltransferase mutant strain (cdc43-2ts) grown at the restrictive temperature. In addition, Cdc42p from a cdc42C188S mutant strain (that has an alteration at the prenylation consensus site) was almost exclusively in the soluble fraction, suggesting that membrane localization is dependent on geranylgeranyl modification at Cys-188. Immunofluorescence and immunoelectron microscopy experiments demonstrated that Cdc42p localizes to the plasma membrane in the vicinity of secretory vesicles that were found at the site of bud emergence, at the tips and sides of enlarging buds, and within mating projections (shmoo tips) in alpha-factor-arrested cells. These results indicate that Cdc42p is localized to the bud site early in the cell cycle and suggest that this localization is critical for the selection of the proper site for bud emergence and for polarized cell growth.

Increased birth weight is associated with altered gene expression in neonatal foreskin.

Elevated birth weight is linked to glucose intolerance and obesity health-related complications later in life. No studies have examined if infant birth weight is associated with gene expression markers of obesity and inflammation in a tissue that comes directly from the infant following birth. We evaluated the association between birth weight and gene expression on fetal programming of obesity. Foreskin samples were collected following circumcision, and gene expression analyzed comparing the 15% greatest birth weight infants (n=7) v. the remainder of the cohort (n=40). Multivariate linear regression models were fit to relate expression levels on differentially expressed genes to birth weight group with adjustment for variables selected from a list of maternal and infant characteristics. Glucose transporter type 4 (GLUT4), insulin receptor substrate 2 (IRS2), leptin receptor (LEPR), lipoprotein lipase (LPL), low-density lipoprotein receptor-related protein 1 (LRP1), matrix metalloproteinase 2 (MMP2), plasminogen activator inhibitor-1 (PAI-1) and transcription factor 7-like 2 (TCF7L2) were significantly upregulated and histone deacetylase 1 (HDAC1) and thioredoxin (TXN) downregulated in the larger birth weight neonates v. CONTROLS: Multivariate modeling revealed that the estimated adjusted birth weight group difference exceeded one standard deviation of the expression level for eight of the 10 genes. Between 25 and 50% of variation in expression level was explained by multivariate modeling for eight of the 10 genes. Gene expression related to glycemic control, appetite/energy balance, obesity and inflammation were altered in tissue from babies with elevated birth weight, and these genes may provide important information regarding fetal programming in macrosomic babies.

On the effect of computed tomography resolution to distinguish between abdominal aortic aneurysm wall tissue and calcification: A proof of concept.

PURPOSE: The purpose of this study is to determine the optimal target CT spatial resolution for accurately imaging abdominal aortic aneurysm (AAA) wall characteristics, distinguishing between tissue and calcification components, for an accurate assessment of rupture risk. MATERIALS AND METHODS: Ruptured and non-ruptured AAA-wall samples were acquired from eight patients undergoing open surgical aneurysm repair upon institutional review board approval and informed consent was obtained from all patients. Physical measurements of AAA-wall cross-section were made using scanning electron microscopy. Samples were scanned using high resolution micro-CT scanning. A resolution range of 15.5-155µm was used to quantify the influence of decreasing resolution on wall area measurements, in terms of tissue and calcification. A statistical comparison between the reference resolution (15.5µm) and multi-detector CT resolution (744µm) was also made. RESULTS: Electron microscopy examination of ruptured AAAs revealed extremely thin outer tissue structure <200µm in radial distribution which is supporting the aneurysm wall along with large areas of adjacent medial calcifications far greater in area than the tissue layer. The spatial resolution of 155µm is a significant predictor of the reference AAA-wall tissue and calcification area measurements (r=0.850; p<0.001; r=0.999; p<0.001 respectively). The tissue and calcification area at 155µm is correct within 8.8%±1.86 and 26.13%±9.40 respectively with sensitivity of 87.17% when compared to the reference. CONCLUSION: The inclusion of AAA-wall measurements, through the use of high resolution-CT will elucidate the variations in AAA-wall tissue and calcification distributions across the wall which may help to leverage an improved assessment of AAA rupture risk.

Comparative genomic hybridization in the detection of DNA copy number abnormalities in uveal melanoma.

Genomic instability appears to play an important role in the development, growth, invasiveness, and eventual metastasis of the neoplastic cell. We have used a powerful new technique, comparative genomic hybridization, to evaluate genetic alterations in 10 fresh frozen uveal melanomas. Comparative genomic hybridization utilizes dual fluorescence in situ hybridization to characterize chromosome deletions and duplications, allowing for simultaneous evaluation of the entire human genome. Several consistent chromosomal abnormalities were detected. This study confirmed previous findings obtained using standard cytogenetic techniques but demonstrated an increased incidence in abnormalities of chromosomes 3 and 8; there was loss of chromosome 3 and duplication of 8q. In addition, we identified, although less frequently, other recurrent abnormal regions including alterations on chromosomes 6p, 7q, 9p, and 13q.

Effects of celecoxib in human retinoblastoma cell lines and in a transgenic murine model of retinoblastoma.

BACKGROUND/AIM: Celecoxib, a cyclooxygenase-2 inhibitor and antiangiogenic agent, has demonstrated potent anticancer effects in preclinical studies and in human clinical trials. To evaluate the potential utility of this agent in the treatment of retinoblastoma, the authors investigated the effects of celecoxib in retinoblastoma cell lines and in a murine model of this disease. METHODS: Growth inhibitory effects of celecoxib were evaluated in Y79 and Weri-RB1 human retinoblastoma cell lines by WST-1 cell proliferation assay. For animal study, two groups of 24, 8 week old LHbeta-TAg transgenic mice were treated with celecoxib (250 mg/kg, orally once a day) or vehicle control, 5 days/week for 6 weeks. Mice were sacrificed on day 43. Enucleated eyes were serially sectioned and ocular tumour burden was quantified by histopathological analysis. RESULTS: Celecoxib did not inhibit proliferation of Y79 or Weri-RB1 cells, even at concentrations far exceeding clinically achievable levels. No significant difference in ocular tumour burden between celecoxib treated and control mice (p=0.73) was found. CONCLUSION: Celecoxib was ineffective at inhibiting proliferation of retinoblastoma cells in vitro and was ineffective at controlling retinoblastoma tumour growth in a murine model of this disease. On the basis of these findings, oral celecoxib therapy is unlikely to have clinical utility in the treatment of retinoblastoma.