Subsurface planning: Towards a common understanding of the subsurface as a multifunctional resource

In response to powerful trends in technology, resource and land supply and demand, socioeconomics and geopolitics, cities are likely to increase use of the subsurface in the near future. Indeed, the subsurface and its appropriate use have been put forward as being of crucial importance if we are to achieve resilient and sustainable cities. In recent years, quite apart from being seen primarily as a construction basis to provide physical space for infrastructure and to create a better surface living environment, the subsurface has been recognised as a multifunctional natural resource, one which provides physical space, water, energy, materials, habitats for ecosystems, support for surface life, and a repository for cultural heritage and geological archives. Currently, the subsurface is often utilised according to the “first-come-first-served” principle, which hinders possibilities to take strategic decisions on prioritisation and optimisation of competing subsurface uses, as well as fair inter- and intragenerational distribution of limited natural resources. Taking a broad international perspective, this paper investigates the subsurface as a multifunctional resource from five focal points: (1) what professionals with different backgrounds mean when using different terms related to the subsurface; (2) how professionals describe the subsurface and its multiple resources, functions and services; (3) how planning of subsurface use is supported in policy and regulations; (4) how the subsurface is included in the planning process; and (5) frameworks that can support decision-making on responsible use of the subsurface. The study reveals that the subsurface must be recognised (not only by scientists but also by decision- and policy-makers and other stakeholders) as a precious and multifunctional resource requiring careful planning and sensitive management in accordance with its potential and its value to society. Utilisation of the different subsurface functions to yield services requires careful planning and a framework to support decision-makers in achieving a balance between utilisation and preservation, and between the subsurface functions themselves in the case of outright utilisation. Further, to facilitate the necessary change towards transdisciplinary work settings in the planning process and form a platform for knowledge exchange and capacity building, there is an urgent need for a common language, i.e. mutually understandable terminology, and a common understanding, i.e. an all-inclusive view on the subsurface as a complex multifunctional resource

Dynamics of the normal gut microbiota: A longitudinal one-year population study in Sweden

Temporal dynamics of the gut microbiota potentially limit the identification of microbial features associated with health status. Here, we used whole-genome metagenomic and 16S rRNA gene sequencing to characterize the intra- and inter-individual variations of gut microbiota composition and functional potential of a disease-free Swedish population (n = 75) over one year. We found that 23% of the total compositional variance was explained by intra-individual variation. The degree of intra-individual compositional variability was negatively associated with the abundance of Faecalibacterium prausnitzii (a butyrate producer) and two Bifidobacterium species. By contrast, the abundance of facultative anaerobes and aerotolerant bacteria such as Escherichia coli and Lactobacillus acidophilus varied extensively, independent of compositional stability. The contribution of intra-individual variance to the total variance was greater for functional pathways than for microbial species. Thus, reliable quantification of microbial features requires repeated samples to address the issue of intra-individual variations of the gut microbiota

Lunds kommuns klimatpolitiska råd : Rapport 2021

Lunds kommuns klimatpolitiska råd (Rådet) bildades hösten 2018 med uppdrag att utvärdera hur Lunds kommuns samlade politik är förenlig med de klimatmål som antagits av kommunfullmäktige. Rådet, som består av forskare från Lunds universitet (LU) och SLU Alnarp, har sammantaget en bred tvär- och mångvetenskaplig kompetens och en gedigen erfarenhet av samverkan med olika samhällsaktörer.Samarbetet mellan Lunds kommun och akademin har sedan länge stimulerat utvecklingen i Lund och utgör en viktig källa till nytänkande och problemlösning.Rådet uppskattar förtroendet att utvärdera kommunens klimatarbete men uttrycker samtidigt en ödmjukhet inför komplexiteten i detta arbete. Rådets ambition är att sträva efter att vara kritiskt granskande men också konstruktiv och lösningsorienterad för att kunna bidra till utvecklingen av det lokala klimatarbetet.Rådet presenterar årligen en rapport i vilken Lunds kommuns klimatarbete granskas. Detta är Rådets tredje rapport i vilken Rådet valt att fokusera på Lunds kommuns förslag till nya klimatmål i miljömålsprogrammet LundaEko. Denna granskningkompletteras med en uppföljning av de klimatmål som antagits i den tidigare versionen av LundaEko (LundaEko II 2014-2020) inom områdena Minstamöjliga klimatpåverkan och Klimatanpassning. Rådet har i sin granskning utgått från tillgängliga planer, dokument, redovisningar och data. Detta material har kompletterats med samtal med ansvariga tjänstepersoner. Under arbetets gång har Rådet även fört dialog med Ungdomspolitiken i Lund, som på egen hand granskat LundaEko ur ett ungdomsperspektiv.Under 2020 har mandatet för några rådsledamöter löpt ut – Lena Hiselius (LU), Anna Peterson (SLU Alnarp), Markku Rummukainen (LU) och Catharina Sternudd (LU) – och de har avtackats för sina insatser under de inledande två åren. Samtidigt har nya ledamöter tillkommit – Cecilia Akselsson (LU), Susanne Arvidsson (LU), Anders Larsson (SLU Alnarp) och Lars J Nilsson (LU) – som tillsammans med övriga ledamöter har deltagit i den granskning som presenteras i denna rapport

Integration of molecular profiles in a longitudinal wellness profiling cohort

An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, we sample a longitudinal wellness cohort with 100 healthy individuals and analyze blood molecular profiles including proteomics, transcriptomics, lipidomics, metabolomics, autoantibodies and immune cell profiling, complemented with gut microbiota composition and routine clinical chemistry. Overall, our results show high variation between individuals across different molecular readouts, while the intra-individual baseline variation is low. The analyses show that each individual has a unique and stable plasma protein profile throughout the study period and that many individuals also show distinct profiles with regards to the other omics datasets, with strong underlying connections between the blood proteome and the clinical chemistry parameters. In conclusion, the results support an individual-based definition of health and show that comprehensive omics profiling in a longitudinal manner is a path forward for precision medicine

Antibodies against a Surface Protein of Streptococcus pyogenes Promote a Pathological Inflammatory Response

Streptococcal toxic shock syndrome (STSS) caused by Streptococcus pyogenes is a clinical condition with a high mortality rate despite modern intensive care. A key feature of STSS is excessive plasma leakage leading to hypovolemic hypotension, disturbed microcirculation and multiorgan failure. Previous work has identified a virulence mechanism in STSS where M1 protein of S. pyogenes forms complexes with fibrinogen that activate neutrophils to release heparin-binding protein (HBP), an inducer of vascular leakage. Here, we report a marked inter-individual difference in the response to M1 protein–induced HBP release, a difference found to be related to IgG antibodies directed against the central region of the M1 protein. To elicit massive HBP release, such antibodies need to be part of the M1 protein–fibrinogen complexes. The data add a novel aspect to bacterial pathogenesis where antibodies contribute to the severity of disease by promoting a pathologic inflammatory response

The genetic architecture of type 2 diabetes

The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of heritability. To test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole genome sequencing in 2,657 Europeans with and without diabetes, and exome sequencing in a total of 12,940 subjects from five ancestral groups. To increase statistical power, we expanded sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support a major role for lower-frequency variants in predisposition to type 2 diabetes

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

A genome-wide association search for type 2 diabetes genes in African Americans.

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations