The Role of Landscape Connectivity in Planning and Implementing Conservation and Restoration Priorities. Issues in Ecology

Landscape connectivity, the extent to which a landscape facilitates the movements of organisms and their genes, faces critical threats from both fragmentation and habitat loss. Many conservation efforts focus on protecting and enhancing connectivity to offset the impacts of habitat loss and fragmentation on biodiversity conservation, and to increase the resilience of reserve networks to potential threats associated with climate change. Loss of connectivity can reduce the size and quality of available habitat, impede and disrupt movement (including dispersal) to new habitats, and affect seasonal migration patterns. These changes can lead, in turn, to detrimental effects for populations and species, including decreased carrying capacity, population declines, loss of genetic variation, and ultimately species extinction. Measuring and mapping connectivity is facilitated by a growing number of quantitative approaches that can integrate large amounts of information about organisms’ life histories, habitat quality, and other features essential to evaluating connectivity for a given population or species. However, identifying effective approaches for maintaining and restoring connectivity poses several challenges, and our understanding of how connectivity should be designed to mitigate the impacts of climate change is, as yet, in its infancy. Scientists and managers must confront and overcome several challenges inherent in evaluating and planning for connectivity, including: •characterizing the biology of focal species; •understanding the strengths and the limitations of the models used to evaluate connectivity; •considering spatial and temporal extent in connectivity planning; •using caution in extrapolating results outside of observed conditions; •considering non-linear relationships that can complicate assumed or expected ecological responses; •accounting and planning for anthropogenic change in the landscape; •using well-defined goals and objectives to drive the selection of methods used for evaluating and planning for connectivity; •and communicating to the general public in clear and meaningful language the importance of connectivity to improve awareness and strengthen policies for ensuring conservation. Several aspects of connectivity science deserve additional attention in order to improve the effectiveness of design and implementation. Research on species persistence, behavioral ecology, and community structure is needed to reduce the uncertainty associated with connectivity models. Evaluating and testing connectivity responses to climate change will be critical to achieving conservation goals in the face of the rapid changes that will confront many communities and ecosystems. All of these potential areas of advancement will fall short of conservation goals if we do not effectively incorporate human activities into connectivity planning. While this Issue identifies substantial uncertainties in mapping connectivity and evaluating resilience to climate change, it is also clear that integrating human and natural landscape conservation planning to enhance habitat connectivity is essential for biodiversity conservation

Pennsylvania Folklife Vol. 14, No. 1

• The Oley Valley Basketmaker • The Sheen of Copper • Pennsylvania Corncribs • Land-Clearing in Lycoming County, Pennsylvania • Funerals in My Childhood Days • Folk Medicine from Western Pennsylvania • Peddlers I Rememberhttps://digitalcommons.ursinus.edu/pafolklifemag/1017/thumbnail.jp

Par-4 Links Dopamine Signaling and Depression

SummaryProstate apoptosis response 4 (Par-4) is a leucine zipper containing protein that plays a role in apoptosis. Although Par-4 is expressed in neurons, its physiological role in the nervous system is unknown. Here we identify Par-4 as a regulatory component in dopamine signaling. Par-4 directly interacts with the dopamine D2 receptor (D2DR) via the calmodulin binding motif in the third cytoplasmic loop. Calmodulin can effectively compete with Par-4 binding in a Ca2+-dependent manner, providing a route for Ca2+-mediated downregulation of D2DR efficacy. To examine the importance of the Par-4/D2DR interaction in dopamine signaling in vivo, we used a mutant mouse lacking the D2DR interaction domain of Par-4, Par-4ΔLZ. Primary neurons from Par-4ΔLZ embryos exhibit an enhanced dopamine-cAMP-CREB signaling pathway, indicating an impairment in dopamine signaling in these cells. Remarkably, Par-4ΔLZ mice display significantly increased depression-like behaviors. Collectively, these results provide evidence that Par-4 constitutes a molecular link between impaired dopamine signaling and depression

Ending AIDS as a public health threat by 2030: Time to reset targets for 2025.

Paul De Lay and co-authors introduce a Collection on the design of targets for ending the AIDS epidemic

Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk.

Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Pennsylvania Folklife Vol. 12, No. 2

• The Township Weavers of Pennsylvania • Amish Funerals • The Bush-Meeting Dutch • Steep Roofs and Red Tiles • Carpet Rag Parties • Fences in Rural Pennsylvania • Folk Festival Program • A Study of the Dialect Terminology of the Plain Sects of Montgomery County, Pa. • Henry Chapman Mercer, Pennsylvania Folklife Pioneer • The Glingelsock • Sauerkraut in the Pennsylvania Folk-Culture • Collectaneahttps://digitalcommons.ursinus.edu/pafolklifemag/1010/thumbnail.jp

Identification of new genetic susceptibility loci for breast cancer through consideration of gene-environment interactions

Genes that alter disease risk only in combination with certain environmental exposures may not be detected in genetic association analysis. By using methods accounting for gene-environment (G × E) interaction, we aimed to identify novel genetic loci associated with breast cancer risk. Up to 34,475 cases and 34,786 controls of European ancestry from up to 23 studies in the Breast Cancer Association Consortium were included. Overall, 71,527 single nucleotide polymorphisms (SNPs), enriched for association with breast cancer, were tested for interaction with 10 environmental risk factors using three recently proposed hybrid methods and a joint test of association and interaction. Analyses were adjusted for age, study, population stratification, and confounding factors as applicable. Three SNPs in two independent loci showed statistically significant association: SNPs rs10483028 and rs2242714 in perfect linkage disequilibrium on chromosome 21 and rs12197388 in ARID1B on chromosome 6. While rs12197388 was identified using the joint test with parity and with age at menarche (P-values = 3 × 10(−07)), the variants on chromosome 21 q22.12, which showed interaction with adult body mass index (BMI) in 8,891 postmenopausal women, were identified by all methods applied. SNP rs10483028 was associated with breast cancer in women with a BMI below 25 kg/m(2) (OR = 1.26, 95% CI 1.15–1.38) but not in women with a BMI of 30 kg/m(2) or higher (OR = 0.89, 95% CI 0.72–1.11, P for interaction = 3.2 × 10(−05)). Our findings confirm comparable power of the recent methods for detecting G × E interaction and the utility of using G × E interaction analyses to identify new susceptibility loci