Socioecology Explains Individual Variation in Urban Space Use in Response to Management in Cape Chacma Baboons (Papio ursinus)

The presence of wildlife adjacent to and within urban spaces is a growing phenomenon globally. When wildlife’s presence in urban spaces has negative impacts for people and wildlife, nonlethal and lethal interventions on animals invariably result. Recent evidence suggests that individuals in wild animal populations vary in both their propensity to use urban space and their response to nonlethal management methods. Understanding such interindividual differences and the drivers of urban space use could help inform management strategies. We use direct observation and high-resolution GPS (1 Hz) to track the space use of 13 adult individuals in a group of chacma baboons (Papio ursinus) living at the urban edge in Cape Town, South Africa. The group is managed by a dedicated team of field rangers, who use aversive conditioning to reduce the time spent by the group in urban spaces. Adult males are larger, more assertive, and more inclined to enter houses, and as such are disproportionately subject to “last resort” lethal management. Field rangers therefore focus efforts on curbing the movements of adult males, which, together with high-ranking females and their offspring, comprise the bulk of the group. However, our results reveal that this focus allows low-ranking, socially peripheral female baboons greater access to urban spaces. We suggest that movement of these females into urban spaces, alone or in small groups, is an adaptive response to management interventions, especially given that they have no natural predators. These results highlight the importance of conducting behavioral studies in conjunction with wildlife management, to ensure effective mitigation techniques

How attractive is the girl next door? An assessment of spatial mate acquisition and paternity in the solitary Cape Dune mole-rat, Bathyergus suillus

Behavioural observations of reproduction and mate choice in wild fossorial rodents are extremely limited and consequently indirect methods are typically used to infer mating strategies. We use a combination of morphological, reproductive, spatial, and genetic data to investigate the reproductive strategy of a solitary endemic species, the Cape dune mole-rat Bathyergus suillus. These data provide the first account on the population dynamics of this species. Marked sexual dimorphism was apparent with males being both significantly larger and heavier than females. Of all females sampled 36% had previously reproduced and 12% were pregnant at the time of capture. Post-partum sex ratio was found to be significantly skewed in favour of females. The paternity of fifteen litters (n = 37) was calculated, with sires assigned to progeny using both categorical and full probability methods, and including a distance function. The maximum distance between progeny and a putative sire was determined as 2149 m with males moving between sub-populations. We suggest that above-ground movement should not be ignored in the consideration of mate acquisition behaviour of subterranean mammals. Estimated levels of multiple paternity were shown to be potentially as high as 26%, as determined using sibship and sire assignment methods. Such high levels of multiple paternity have not been found in other solitary mole-rat species. The data therefore suggest polyandry with no evidence as yet for polygyny.The Department of Science and Technology and the National Research Foundation for funding from the South African Research Chairs Initiative Chair for Mammal Behavioural Ecology and Physiology awarded to NB. Funding was also provided by the University of Pretoria in provision of TB’s postdoctoral fellowship.http://www.plosone.orgab201

The development and growth of the software industry in Ireland: an institutionalized relationship approach

peer-reviewedIreland's software industry emerged in the 1970s and 1980s due to significant international developments and, more importantly, the industrial policy approach adopted in Ireland. The attraction of software foreign direct investment during these decades was followed by the emergence of an internationally competitive Irish software sector. A multitude of factors combine to explain the trajectory of software in Ireland: from developments related to globalization and international trade, to policy makers' efforts to promote an industry where Ireland could forge a comparative advantage internationally. An analysis of industrial dynamics and institutionalized relationships (IRs) furthers our understanding of significant developments in the industry in terms of interactions between firms, government and other stakeholders. This paper makes a novel contribution by analysing Ireland's software industry within the IR framework. The IR approach we employ focuses on the finance IR, the purchase IR, the employment IR, and the commercial IR. The adoption of the IR framework approach is particularly insightful in the Irish case as it facilitates a multifaceted analysis of the complex relationships that have moulded the Irish software industry. Such an approach also facilitates a study of the policy implications and policy prescriptions that are pertinent to the software sector.ACCEPTEDpeer-reviewe

CD10−/ALDH− cells are the sole cisplatin-resistant component of a novel ovarian cancer stem cell hierarchy

It is long established that tumour-initiating cancer stem cells (CSCs) possess chemoresistant properties. However, little is known of the mechanisms involved, particularly with respect to the organisation of CSCs as stem-progenitor-differentiated cell hierarchies. Here we aimed to elucidate the relationship between CSC hierarchies and chemoresistance in an ovarian cancer model. Using a single cell-based approach to CSC discovery and validation, we report a novel, four-component CSC hierarchy based around the markers cluster of differentiation 10 (CD10) and aldehyde dehydrogenase (ALDH). In a change to our understanding of CSC biology, resistance to chemotherapy drug cisplatin was found to be the sole property of CD10−/ALDH− CSCs, while all four CSC types were sensitive to chemotherapy drug paclitaxel. Cisplatin treatment quickly altered the hierarchy, resulting in a three-component hierarchy dominated by the cisplatin-resistant CD10−/ALDH− CSC. This organisation was found to be hard-wired in a long-term cisplatin-adapted model, where again CD10−/ALDH− CSCs were the sole cisplatin-resistant component, and all CSC types remained paclitaxel-sensitive. Molecular analysis indicated that cisplatin resistance is associated with inherent- and adaptive-specific drug efflux and DNA-damage repair mechanisms. Clinically, low CD10 expression was consistent with a specific set of ovarian cancer patient samples. Collectively, these data advance our understanding of the relationship between CSC hierarchies and chemoresistance, which was shown to be CSC- and drug-type specific, and facilitated by specific and synergistic inherent and adaptive mechanisms. Furthermore, our data indicate that primary stage targeting of CD10−/ALDH− CSCs in specific ovarian cancer patients in future may facilitate targeting of recurrent disease, before it ever develops

Prevalence of tumor BRCA1 and BRCA2 dysfunction in unselected patients with ovarian cancer

Objective The therapeutic benefits of poly(ADP-ribose) polymerase inhibitors highlight the need to evaluate BRCA1/2 defects in tubal/ovarian cancer (OC). We sought to determine the pattern and disease characteristics associated with tumor BRCA1/2 mutations and BRCA1 methylation in women with OC. Methods We obtained 111 OC specimens from 2 university hospitals and assessed BRCA1/2 mutations and BRCA1 methylation in tumor DNA. The frequency and pattern of BRCA1/2 defects were examined. Associations between patient/disease characteristics and BRCA1/2 defects were ascertained (Fisher’s exact test). Platinum-free interval (PFI), progression-free survival (PFS), and overall survival (OS) based on the underlying BRCA1/2 defect were determined (Kaplan-Meier analysis [log-rank test]). Results We observed a BRCA1/2 dysfunction rate of 40% (28/70) in high-grade serous tubal/ovarian cancer (HGSC), including 14.3% BRCA1 methylation (n=10), 7.1% BRCA1 mutation (n=5), and 18.6% BRCA2 mutation (n=13). Defects in BRCA1/2 genes were associated with stage III/IV HGSC (BRCA1 methylation: P=0.005 [stage III/IV] and P=0.004 [HGSC]; BRCA1/2 mutation: P=0.03 [stage III/IV] and P<0.001 [HGSC]). Patients with BRCA1/2-mutated cancers showed improved OS (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.43–0.99; P=0.045) and a trend toward improved PFI (HR, 0.48; 95% CI, 0.22–1.06; P=0.07) and PFS (HR, 0.72; 95% CI, 0.51–1.03; P=0.07). No survival differences were observed between BRCA1-methylated and BRCA1/2 wild-type non-BRCA1-methylated cancers. Conclusion We observed a high tumor BRCA1/2 dysfunction rate in HGSC with a unique predominance of BRCA2 over BRCA1 mutations. While BRCA1/2 mutations conferred survival benefits in OC, no such association was observed with BRCA1 methylation

Perilous state of critically endangered Northwest African cheetah (Acinonyx jubatus hecki) across the Sudano‐Sahel

Northwest African cheetah populations have declined precipitously, with expert opinion estimating that <420 individuals persist across parts of Algeria, Benin, Burkina Faso, Chad, Niger and Mali. However, no reliable density estimates exist in the remaining subspecies strongholds throughout the Sudano‐Sahel Zone, including the W‐Arly‐Pendjari Complex and Greater Zakouma Ecosystem within the Bahr/Salamat landscape. Camera trap surveys were combined with spatially explicit capture–recapture methodologies in both regions to estimate the cheetah density and detectable demographic composition of these populations. Following 15 429 camera trap nights, we detected nine individuals during the dry season and four individuals during the wet season in Pendjari (2021), nine individuals (dry season; 2023) in Zakouma and none in Siniaka Minia. Cheetah densities were thus estimated at 0.17–0.24 and 0.37 cheetah per 100 km2 in Pendjari and Zakouma, respectively. While marginally higher than predicted, such low‐density estimates are concerning in the last remaining habitats harbouring this critically endangered subspecies. Considering the substantial contraction of regional cheetah distribution, we estimate an overall population size of 68 ± 29 individuals across the studied areas. These novel estimates are among the lowest formally determined densities throughout cheetah range in Africa, where a high frequency of people and livestock detected on camera traps highlight the ongoing risks to large carnivores in these protected areas. Subsequent management recommendations include implementation of the established regional conservation strategies that encompass the distributional range of these cheetah, continuous monitoring of populations, genetic analyses to inform management, curbing illegal trade and increasing international awareness around the plight of the subspecies

BRCA1 promoter methylation and clinical outcomes in ovarian cancer: an individual patient data meta-analysis

BACKGROUND BRCA1 methylation has been associated with homologous recombination deficiency, a biomarker of platinum sensitivity. Studies evaluating BRCA1-methylated tubal/ovarian cancer (OC) do not consistently support improved survival following platinum chemotherapy. We examine the characteristics of BRCA1-methylated OC in a meta-analysis of individual participant data. METHODS 2636 participants' data across 15 studies were analyzed. BRCA1-methylated tumors were defined according to their original study. Associations between BRCA1 methylation and clinico-pathological characteristics were evaluated. The effects of methylation on overall survival (OS) and progression-free survival (PFS) were examined using mixed-effects models. All statistical tests were two-sided. RESULTS 430 (16.3%) tumors were BRCA1-methylated. BRCA1 methylation was associated with younger age and advanced-stage high-grade serous OC. There were no survival differences between BRCA1-methylated and non-BRCA1-methylated OC (median PFS = 20.0 vs 18.5 months, HR = 1.01, 95% CI = 0.87-1.16, P=0.98; median OS = 46.6 vs 48.0 months, HR = 1.02, 95% CI = 0.87-1.18, P=0.96). Where BRCA1/2 mutations were evaluated (n = 1248), BRCA1 methylation displayed no survival advantage over BRCA1/2 intact (BRCA1/2 wild type non-BRCA1-methylated) OC. Studies used different methods to define BRCA1 methylation. Where BRCA1 methylation was determined using methylation-specific PCR and gel electrophoresis (n = 834), it was associated with improved survival (PFS: HR = 0.80, 95% CI = 0.66-0.97, P=0.02; OS: HR = 0.80, 95% CI = 0.63-1.00, P=0.05) on mixed-effects modelling. CONCLUSION BRCA1-methylated OC displays similar clinico-pathological features to BRCA1-mutated OC, but is not associated with survival. Heterogeneity within BRCA1 methylation assays influences associations. Refining these assays may better identify cases with silenced BRCA1 function and improved patient outcomes

Comprehensive profiling of DNA methylation in colorectal cancer reveals subgroups with distinct clinicopathological and molecular features

<p>Abstract</p> <p>Background</p> <p>Most previous studies of the CpG island methylator phenotype (CIMP) in colorectal cancer (CRC) have been conducted on a relatively small numbers of CpG sites. In the present study we performed comprehensive DNA methylation profiling of CRC with the aim of characterizing CIMP subgroups.</p> <p>Methods</p> <p>DNA methylation at 1,505 CpG sites in 807 cancer-related genes was evaluated using the Illumina GoldenGate^®methylation array in 28 normal colonic mucosa and 91 consecutive CRC samples. Methylation data was analyzed using unsupervised hierarchical clustering. CIMP subgroups were compared for various clinicopathological and molecular features including patient age, tumor site, microsatellite instability (MSI), methylation at a consensus panel of CpG islands and mutations in <it>BRAF </it>and <it>KRAS</it>.</p> <p>Results</p> <p>A total of 202 CpG sites were differentially methylated between tumor and normal tissue. Unsupervised hierarchical clustering of methylation data from these sites revealed the existence of three CRC subgroups referred to as CIMP-low (CIMP-L, 21% of cases), CIMP-mid (CIMP-M, 14%) and CIMP-high (CIMP-H, 65%). In comparison to CIMP-L tumors, CIMP-H tumors were more often located in the proximal colon and showed more frequent mutation of <it>KRAS </it>and <it>BRAF </it>(<it>P </it>< 0.001).</p> <p>Conclusions</p> <p>Comprehensive DNA methylation profiling identified three CRC subgroups with distinctive clinicopathological and molecular features. This study suggests that both <it>KRAS </it>and <it>BRAF </it>mutations are involved with the CIMP-H pathway of CRC rather than with distinct CIMP subgroups.</p

Molecular subtypes of breast cancer are associated with characteristic DNA methylation patterns

Introduction: Five different molecular subtypes of breast cancer have been identified through gene expression profiling. Each subtype has a characteristic expression pattern suggested to partly depend on cellular origin. We aimed to investigate whether the molecular subtypes also display distinct methylation profiles. Methods: We analysed methylation status of 807 cancer-related genes in 189 fresh frozen primary breast tumours and four normal breast tissue samples using an array-based methylation assay. Results: Unsupervised analysis revealed three groups of breast cancer with characteristic methylation patterns. The three groups were associated with the luminal A, luminal B and basal-like molecular subtypes of breast cancer, respectively, whereas cancers of the HER2-enriched and normal-like subtypes were distributed among the three groups. The methylation frequencies were significantly different between subtypes, with luminal B and basal-like tumours being most and least frequently methylated, respectively. Moreover, targets of the polycomb repressor complex in breast cancer and embryonic stem cells were more methylated in luminal B tumours than in other tumours. BRCA2-mutated tumours had a particularly high degree of methylation. Finally, by utilizing gene expression data, we observed that a large fraction of genes reported as having subtype-specific expression patterns might be regulated through methylation. Conclusions: We have found that breast cancers of the basal-like, luminal A and luminal B molecular subtypes harbour specific methylation profiles. Our results suggest that methylation may play an important role in the development of breast cancers