The obligation of States to repair victims of violations of economic, social and cultural rights perpetrated by non-State actors

The present research was inspired by the chance encounter of an important dissonance between the Basic Principles and Guidelines on the Right to a Remedy and Reparation for Victims of Gross Violations of International Human Rights Law and Serious Violations of International Humanitarian Law and Uganda’s nascent transitional justice policy. The latter foresaw reparations for all victims of Uganda’s civil wars while the former stated that customary international law merely encouraged but did not oblige States to repair victims of non-State actors, the victims of others. Was Uganda’s policy gratuitous? Or has public international law evolved beyond the economy of the Basic Principles and Guidelines? It is the purpose of the present text to answer these questions. The thesis is divided into three substantive chapters that are preceded by an Introduction and tied together by a brief Conclusion. The Introduction articulates the hypothesis and highlights that if correct, i.e., if there exists a rule of public international law obliging States to repair victims not their own, there exist two candidates for the content of that rule. The candidates are explored in Chapters 1 and 2. Before turning to them, the Introduction demonstrates that avenues typically proposed today are insufficient juxtaposed with the aim of making reparations a reality for victims of non-State actors. It thereby underlines that the hypothesis is not just thought-provoking but also of immense practical value. Chapter 1 first investigates the nature of the States’ obligation to protect economic, social and cultural rights, and concludes that the existing consensus as it is contained in the Basic Principles and Guidelines is that the obligation is a qualified obligation of result. It then examines the historical origins of the rule, demonstrates why it is inappropriate to apply it to the situation at hand and proposes that the obligation to protect be understood as an unqualified obligation of result instead, meaning that the State would find itself in a position of wrongfulness at the exact moment a non-State actor committed a violation. This would ipso facto create the State’s secondary obligation to repair. Lacking a conventional articulation to that effect, such a rule would have to exist in the sphere of customary international law. Chapter 2 takes under the magnifying glass the International Covenant on Economic, Social and Cultural Rights and explores the potential of the obligation of progressive realisation, the prohibition against discrimination and studies the work of the Committee on Economic, Social and Cultural Rights, substantiating the argument that the obligation to repair could be understood as a primary obligation. What we do not yet know at this point in the thesis is whether either proposition corresponds to the States’ understanding of the law. Chapter 3 therefore examines a dozen countries that have experienced a non-international armed conflict in their more or less recent past. It looks at their practice in regard to reparations, paying particular attention to whether States discriminate between victims of the State and those not of the State. As far as it can be discerned, it also analyses their understanding of public international law. The Conclusion suggests an affirmation of the hypothesis

Genome-wide screening for genetic variants in polyadenylation signal (PAS) sites in mouse selection lines for fatness and leanness

Alternative polyadenylation (APA) determines mRNA stability, localisation, translation and protein function. Several diseases, including obesity, have been linked to APA. Studies have shown that single nucleotide polymorphisms in polyadenylation signals (PAS-SNPs) can influence APA and affect phenotype and disease susceptibility. However, these studies focussed on associations between single PAS-SNP alleles with very large effects and phenotype. Therefore, we performed a genome-wide screening for PAS-SNPs in the polygenic mouse selection lines for fatness and leanness by whole-genome sequencing. The genetic variants identified in the two lines were overlapped with locations of PAS sites obtained from the PolyASite 2.0 database. Expression data for selected genes were extracted from the microarray expression experiment performed on multiple tissue samples. In total, 682 PAS-SNPs were identified within 583 genes involved in various biological processes, including transport, protein modifications and degradation, cell adhesion and immune response. Moreover, 63 of the 583 orthologous genes in human have been previously associated with human diseases, such as nervous system and physical disorders, and immune, endocrine, and metabolic diseases. In both lines, PAS-SNPs have also been identified in genes broadly involved in APA, such as Polr2c, Eif3e and Ints11. Five PAS-SNPs within 5 genes (Car, Col4a1, Itga7, Lat, Nmnat1) were prioritised as potential functional variants and could contribute to the phenotypic disparity between the two selection lines. The developed PAS-SNPs catalogue presents a key resource for planning functional studies to uncover the role of PAS-SNPs in APA, disease susceptibility and fat deposition. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00335-022-09967-8

Theoretical and Experimental Study of (Ba,Sr)TiO 3 Perovskite Solid Solutions and BaTiO 3 /SrTiO 3 Heterostructures

This study was supported by the ERA-NET HarvEnPiez project. The authors would like to thank their national funding agencies (Latvian State Education Development Agency, Slovenian Ministry of Higher Education, Science and Technology, Romanian National Authority for Scientific Research and Innovation, CCCDI-UEFISCDI, project number 49/2016 within PNCDI III – M-ERA NET Program).The results of experimental and theoretical ab initio study of structural and piezoelectric properties of (Ba,Sr)TiO3 perovskite solid solutions are discussed and compared. Experimentally, plate-like (Ba,Sr)TiO3 particles were synthesized by the topochemical conversion in the molten salt from Bi4Ti3O12 template plates. All dimensions (side length ≈ 1 µm, thickness ≈ 200–400 nm) were well above the critical size necessary for observation of piezo- and ferroelectricity. The first-principles computations of the structural and electromechanical properties of solid solutions were performed with CRYSTAL14 computer code within the linear combination of atomic orbitals (LCAO) approximation, using three advanced hybrid functionals of the density-functional-theory (DFT). Different chemical compositions are considered for the ferroelectric and paraelectric phases. Calculated structural properties of solid solutions in tetragonal and cubic phases are in a very good agreement with experimental data. Experimentally obtained and calculated band gaps are compared for cubic SrTiO3 and tetragonal BaTiO3. BaTiO3/SrTiO3 heterostructures were considered theoretically for different chemical compositions. The calculated piezoelectric properties of solid solutions and heterostructures in ferroelectric phase are compared. It is predicted that both solid solutions and heterostructures improve the piezoelectric properties of the bulk BaTiO3, but solid solutions are more preferable for equal Sr concentrations.ERA-NET HarvEnPiez project; Latvian State Education Development Agency, Slovenian Ministry of Higher Education, Science and Technology, Romanian National Authority for Scientific Research and Innovation, CCCDI-UEFISCDI, project number 49/2016 within PNCDI III – M-ERA NET Program; Institute of Solid State Physics, University of Latvia as the Center of Excellence has received funding from the European Union’s Horizon 2020 Framework Programme H2020-WIDESPREAD-01-2016-2017-TeamingPhase2 under grant agreement No. 739508, project CAMART

Vascular endothelial growth factor (VEGF)-related polymorphisms rs10738760 and rs6921438 are not risk factors for proliferative diabetic retinopathy (PDR) in patients with type 2 diabetes mellitus (T2DM)

Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis and has been investigated as a candidate gene in a number of conditions, including diabetes and its microvascular complications (e.g., retinopathy and nephropathy). Several VEGF-related polymorphisms have been shown to contribute to nearly half of the variability in circulating VEGF levels in healthy individuals. Our aim was to assess the association between VEGF-related rs10738760 and rs6921438 polymorphisms and proliferative diabetic retinopathy (PDR) in Slovenian patients with type 2 diabetes mellitus (T2DM). We also investigated the effect of these polymorphisms on VEGF receptor 2 (VEGFR-2) expression in fibrovascular membranes (FVMs) from patients with PDR. This case-control study enrolled 505 unrelated patients with T2DM: 143 diabetic patients with PDR as a study group, and 362 patients with T2DM of >10 years duration and with no clinical signs of PDR as a control group. Patient clinical and laboratory data were obtained from their medical records. rs10738760 and rs6921438 polymorphisms were genotyped using TaqMan SNP Genotyping assay. VEGFR-2 expression was assessed by immunohistochemistry in 20 FVMs from patients with PDR, and numerical areal density of VEGFR-2-positive cells was calculated. The occurrence of PDR was 1.7 times higher in diabetic patients carrying GA genotype of rs6921438 compared to patients with GG genotype, with a borderline statistical significance (OR = 1.7, 95% CI = 1.00 – 2.86, p = 0.05). In addition, A allele of rs6921438 was associated with increased VEGFR-2 expression in FVMs from PDR patients. However, we observed no association between AA genotype of rs6921438 nor between rs10738760 variants and PDR, indicating that the two polymorphisms are not genetic risk factors for PDR

Use of SNP Markers Within the Fat Mass and Obesity-associated (FTO) Gene to Verify Pedigrees and Determine Haplotypes in Paternal Half-sib Families of Slovenian Simmental Cattle

The objective of this preliminary study was to identify SNP markers within the FTO gene for evaluation of pedigree data accuracy and determination of haplotypes in paternal half-sib families of Slovenian Simmental cattle. Out of 23 polymorphic SNPs identified ten most informative SNPs for genotyping 31 sires and 56 half-sib progeny were used. The ATLAS program was used for paternity testing. Haplotype analysis revealed three haplotype blocks. The effect of SNPs “ex2 T>C” and “int2 indel*>T” was significant on three correlated carcass traits: live weight at slaughter (P= 0.03), carcass weight (P= 0.038), and lean weight (P= 0.048). The FTO gene can thus be regarded as a candidate for the marker assisted selection programs in our and possibly other populations of cattle. Future studies in cattle might also reveal novel roles of the FTO gene in carcass traits on livestock species as well as fatness control in other mammals

How Can We Advance Integrative Biology Research in Animal Science in 21st Century?:Experience at University of Ljubljana from 2002 to 2022

In this perspective analysis, we strive to answer the following question: how can we advance integrative biology research in the 21st century with lessons from animal science? At the University of Ljubljana, Biotechnical Faculty, Department of Animal Science, we share here our three lessons learned in the two decades from 2002 to 2022 that we believe could inform integrative biology, systems science, and animal science scholarship in other countries and geographies. Cultivating multiomics knowledge through a conceptual lens of integrative biology is crucial for life sciences research that can stand the test of diverse biological, clinical, and ecological contexts. Moreover, in an era of the current COVID-19 pandemic, animal nutrition and animal science, and the study of their interactions with human health (and vice versa) through integrative biology approaches hold enormous prospects and significance for systems medicine and ecosystem health

Association of Peroxisome Proliferator-Activated Receptors (PPARs) with Diabetic Retinopathy in Human and Animal Models: Analysis of the Literature and Genome Browsers

Diabetic retinopathy (DR) is a condition that develops after long-lasting and poorly handled diabetes and is presently the main reason for blindness among elderly and youth. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that are involved in carbohydrate and fatty-acid metabolism and have also been associated with DR. Three PPAR isoforms are known: PPARG, PPARA, and PPARD. In the present study, we retrieved articles reporting associations between PPARs and DR from PubMed database and compiled the data in two catalogues, for human and animal models. Extracted data was then complemented with additional relevant genomic information. Seven retrieved articles reported testing an association between PPARs with DR in human. Four of them concluded association of PPARG and PPARA with DR in European and Asian populations, having a protective role on DR development. One study reported pathogenic role of PPARG, while two articles reported no association between PPARG and DR among Indian and Chinese populations. Six retrieved articles reported testing of involvement of PPARG and PPARA in DR in animal models, including mouse and rat. The review includes case-control studies, meta-analysis, expression studies, animal models, and cell line studies. Despite a large number of documented sequence variants of the PPAR genes available in genome browsers, researchers usually focus on a small set of previously reported variants. Data extraction from Ensembl genome browser revealed several sequence variants with predicted deleterious effect on protein function which present candidates for further experimental validation. Results of the present analysis will enable more holistic approach for understanding of PPARs in DR development. Additionally, developed catalogues present a baseline for standardized reporting of PPAR-phenotype association in upcoming studies

The effect of phytosulfokine alpha on haploid embryogenesis and gene expression of Brassica napus microspore cultures

Microspore embryogenesis (ME) is the most powerful tool for creating homozygous lines in plant breeding and molecular biology research. It is still based mainly on the reprogramming of microspores by temperature, osmotic and/or nutrient stress. New compounds are being sought that could increase the efficiency of microspore embryogenesis or even induce the formation of haploid embryos from recalcitrant genotypes. Among these, the mitogenic factor phytosulfokine alpha (PSK-α) is promising due to its broad spectrum of activity in vivo and in vitro. The aim of our study was to investigate the effect of PSK-α on haploid embryogenesis from microspores of oilseed rape (Brassica napus L., DH4079), one of the most important oil crops and a model plant for studying the molecular mechanisms controlling embryo formation. We tested different concentrations (0, 0.01, 0.1 and 1 µM) of the peptide and evaluated its effect on microspore viability and embryo regeneration after four weeks of culture. Our results showed a positive correlation between addition of PSK-α and cultured microspore viability and a positive effect also on the number of developed embryos. The analysis of transcriptomes across three time points (day 0, 2 and 4) with or without PSK-α supplementation (15 RNA libraries in total) unveiled differentially expressed genes pivotal in cell division, microspore embryogenesis, and subsequent regeneration. PCA grouped transcriptomes by RNA sampling time, with the first two principal components explaining 56.8% variability. On day 2 with PSK, 45 genes (15 up- and 30 down-regulated) were differentially expressed when PSK-α was added and their number increased to 304 by day 4 (30 up- and 274 down-regulated). PSK, PSKR, and PSI gene expression analysis revealed dynamic patterns, with PSK2 displaying the highest increase and overall expression during microspore culture at days 2 and 4. Despite some variations, only PSK1 showed significant differential expression upon PSK-α addition. Of 16 ME-related molecular markers, 3 and 15 exhibited significant differential expression in PSK-supplemented cultures at days 2 and 4, respectively. Embryo-specific markers predominantly expressed after 4 days of culture, with higher expression in medium without PSK, while on day 0, numerous sporophyte-specific markers were highly expressed

Syndromic male subfertility

BACKGROUND: Male infertility is a disorder of the reproductive system with a highly complex genetic landscape. In most cases, the reason for male infertility remains unknown; however, the importance of genetic abnormalities in the diagnosis of subfertility/infertility is becoming increasingly recognized. Several syndromes include impaired male fertility in the clinical picture, although a comprehensive analysis of genetic causes of the syndromology perspective of male reproduction is not yet available. OBJECTIVES: (1) To develop a catalog of syndromes and corresponding genes associated with impaired male fertility and (2) to visualize an up‐to‐date genome–phenome network of syndromic male subfertility. MATERIALS AND METHODS: Published literature was retrieved from the Online Mendelian Inheritance in Man, Orphanet, Human Phenotype Ontology and PubMed databases using keywords “male infertility,” “syndrome,” “gene,” and “case report”; time period from 1980 to September, 2021. Retrieved data were organized as a catalog and complemented with identification numbers of syndromes (MIM ID) and genes (Gene ID). The genome–phenome network and the phenome network were visualized using Cytoscape and Gephi software platforms. Protein–protein interaction analysis was performed using STRING tool. RESULTS: Retrieved syndromes were presented as (1) a catalog containing 63 syndromes and 93 associated genes, (2) a genome–phenome network including CHD7 and WT1 genes and Noonan and Kartagener syndromes, and (3) a phenome network including 63 syndromes, and 25 categories of clinical features. DISCUSSION: The developed catalog will contribute to the advances and translational impact toward understanding the factors of syndromic male infertility. Visualized networks provide simple, flexible tools for clinicians and researchers to quickly generate hypotheses and gain a deeper understanding of underlying mechanisms affecting male reproduction. CONCLUSION: Recognition of the significance of genome–phenome visualization as part of network medicine can help expedite efforts toward unravelling molecular mechanisms and enable advances personal/precision medicine of male reproduction and other complex traits