Introduction

Since the 1990s, Albania has aimed to introduce democratic values into its legislation. This process can come to fruition only by the recognition and protection of private property. As a result, a new Civil Code was enacted at the beginning of the 1990s through intensive collaboration between Albanian and foreign scholars. Book II of the Albanian Civil Code of 1994 highlights the importance of private property. This book fills the gap in the national and international scientific literature since there is no scientific contribution written in English that examines the development of the Albanian law of property showing the similarities and differences between the Albanian and the Italian civil codes. Another novelty rests on its identification of the rules of the Albanian Civil Codes of 1929 and of 1982 that regulate the various legal institutional parts of the property law. Furthermore, this research summarizes the EU impact on Albanian property law by examining the differences between the legal institutions established at the supranational level such as Dir. 2014/60/EU, Dir. 2008/122/EC, Dir. 1346/2000/EC, and Reg. 2015/848 with the current Albanian system. In the conclusions, this research demonstrates that the Albanian law of property of 1994 is similar, sometimes identical, to the rules established in the Italian Civil Code of 1942

The DO-KB Knowledgebase: a 20-year journey developing the disease open science ecosystem.

In 2003, the Human Disease Ontology (DO, https://disease-ontology.org/) was established at Northwestern University. In the intervening 20 years, the DO has expanded to become a highly-utilized disease knowledge resource. Serving as the nomenclature and classification standard for human diseases, the DO provides a stable, etiology-based structure integrating mechanistic drivers of human disease. Over the past two decades the DO has grown from a collection of clinical vocabularies, into an expertly curated semantic resource of over 11300 common and rare diseases linking disease concepts through more than 37000 vocabulary cross mappings (v2023-08-08). Here, we introduce the recently launched DO Knowledgebase (DO-KB), which expands the DO\u27s representation of the diseaseome and enhances the findability, accessibility, interoperability and reusability (FAIR) of disease data through a new SPARQL service and new Faceted Search Interface. The DO-KB is an integrated data system, built upon the DO\u27s semantic disease knowledge backbone, with resources that expose and connect the DO\u27s semantic knowledge with disease-related data across Open Linked Data resources. This update includes descriptions of efforts to assess the DO\u27s global impact and improvements to data quality and content, with emphasis on changes in the last two years

Comparison of electrohysterogram signal measured by surface electrodes with different designs: A computational study with dipole band and abdomen models

Non-invasive measurement of uterine activity using electrohysterogram (EHG) surface electrodes has been attempted to monitor uterine contraction. This study aimed to computationally compare the performance of acquiring EHG signals using monopolar electrode and three types of Laplacian concentric ring electrodes (bipolar, quasi-bipolar and tri-polar). With the implementation of dipole band model and abdomen model, the performances of four electrodes in terms of the local sensitivity were quantifed by potential attenuation. Furthermore, the efects of fat and muscle thickness on potential attenuation were evaluated using the bipolar and tri-polar electrodes with diferent radius. The results showed that all the four types of electrodes detected the simulated EHG signals with consistency. That the bipolar and tri-polar electrodes had greater attenuations than the others, and the shorter distance between the origin and location of dipole band at 20dB attenuation, indicating that they had relatively better local sensitivity. In addition, ANOVA analysis showed that, for all the electrodes with diferent outer ring radius, the efects of fat and muscle on potential attenuation were signifcant (all p<0.01). It is therefore concluded that the bipolar and tri-polar electrodes had higher local sensitivity than the others, indicating that they can be applied to detect EHG efectively

Formin 1-Isoform IV Deficient Cells Exhibit Defects in Cell Spreading and Focal Adhesion Formation

Background: Regulation of the cytoskeleton is a central feature of cell migration. The formin family of proteins controls the rate of actin nucleation at its barbed end. Thus, formins are predicted to contribute to several important cell processes such as locomotion, membrane ruffling, vesicle endocytosis, and stress fiber formation and disassociation. Methodology/Principal Findings: In this study we investigated the functional role of Formin1-isoform4 (Fmn1-IV) by using genetically null primary cells that displayed augmented protrusive behaviour during wound healing and delayed cell spreading. Cells deficient of Fmn1-IV also showed reduced efficiency of focal adhesion formation. Additionally, we generated an enhanced green fluorescence protein (EGFP)-fused Fmn1-IV knock-in mouse to monitor the endogenous subcellular localization of Fmn1-IV. Its localization was found within the cytoplasm and along microtubules, yet it was largely excluded from adherens junctions. Conclusions/Significance: It was determined that Fmn1-IV, as an actin nucleator, contributes to protrusion of the cell’s leading edge and focal adhesion formation, thus contributing to cell motility

Interaction between genetic and epigenetic variation defines gene expression patterns at the asthma-associated locus 17q12-q21 in lymphoblastoid cell lines

Phenotypic variation results from variation in gene expression, which is modulated by genetic and/or epigenetic factors. To understand the molecular basis of human disease, interaction between genetic and epigenetic factors needs to be taken into account. The asthma-associated region 17q12-q21 harbors three genes, the zona pellucida binding protein 2 (ZPBP2), gasdermin B (GSDMB) and ORM1-like 3 (ORMDL3), that show allele-specific differences in expression levels in lymphoblastoid cell lines (LCLs) and CD4+ T cells. Here, we report a molecular dissection of allele-specific transcriptional regulation of the genes within the chromosomal region 17q12-q21 combining in vitro transfection, formaldehyde-assisted isolation of regulatory elements, chromatin immunoprecipitation and DNA methylation assays in LCLs. We found that a single nucleotide polymorphism rs4795397 influences the activity of ZPBP2 promoter in vitro in an allele-dependent fashion, and also leads to nucleosome repositioning on the asthma-associated allele. However, variable methylation of exon 1 of ZPBP2 masks the strong genetic effect on ZPBP2 promoter activity in LCLs. In contrast, the ORMDL3 promoter is fully unmethylated, which allows detection of genetic effects on its transcription. We conclude that the cis-regulatory effects on 17q12-q21 gene expression result from interaction between several regulatory polymorphisms and epigenetic factors within the cis-regulatory haplotype region

IL-15 Participates in the Respiratory Innate Immune Response to Influenza Virus Infection

Following influenza infection, natural killer (NK) cells function as interim effectors by suppressing viral replication until CD8 T cells are activated, proliferate, and are mobilized within the respiratory tract. Thus, NK cells are an important first line of defense against influenza virus. Here, in a murine model of influenza, we show that virally-induced IL-15 facilitates the trafficking of NK cells into the lung airways. Blocking IL-15 delays NK cell entry to the site of infection and results in a disregulated control of early viral replication. By the same principle, viral control by NK cells can be therapeutically enhanced via intranasal administration of exogenous IL-15 in the early days post influenza infection. In addition to controlling early viral replication, this IL-15-induced mobilization of NK cells to the lung airways has important downstream consequences on adaptive responses. Primarily, depletion of responding NK1.1+ NK cells is associated with reduced immigration of influenza-specific CD8 T cells to the site of infection. Together this work suggests that local deposits of IL-15 in the lung airways regulate the coordinated innate and adaptive immune responses to influenza infection and may represent an important point of immune intervention

RAGE Mediates Accelerated Diabetic Vein Graft Atherosclerosis Induced by Combined Mechanical Stress and AGEs via Synergistic ERK Activation

Aims/Hypothesis: Diabetes with hypertension rapidly accelerates vascular disease, but the underlying mechanism remains unclear. We evaluated the hypothesis that the receptor of advanced glycation end products (RAGE) might mediate combined signals initiated by diabetes-related AGEs and hypertension-induced mechanical stress as a common molecular sensor. Methods: In vivo surgical vein grafts created by grafting vena cava segments from C57BL/6J mice into the common carotid arteries of streptozotocin (STZ)-treated and untreated isogenic mice for 4 and 8 weeks were analyzed using morphometric and immunohistochemical techniques. In vitro quiescent mouse vascular smooth muscle cells (VSMCs) with either knockdown or overexpression of RAGE were subjected to cyclic stretching with or without AGEs. Extracellular signalregulated kinase (ERK) phosphorylation and Ki-67 expression were investigated. Results: Significant increases in neointimal formation, AGE deposition, Ki-67 expression, and RAGE were observed in the vein grafts of STZ-induced diabetic mice. The highest levels of ERK phosphorylation and Ki-67 expression in VSMCs were induced by simultaneous stretch stress and AGE exposure. The synergistic activation of ERKs and Ki-67 in VSMCs was significantly inhibited by siRNA-RAGE treatment and enhanced by over-expression of RAGE. Conclusion: RAGE may mediate synergistically increased ERK activation and VSMC proliferation induced by mechanica

Prevalence, Features and Risk Factors for Malaria Co-Infections amongst Visceral Leishmaniasis Patients from Amudat Hospital, Uganda

Visceral leishmaniasis (VL) and malaria are two major parasitic diseases sharing a similar demographic and geographical distribution. In areas where both diseases are endemic, such as Sudan, Uganda, India and Bangladesh, co-infection cases have been reported, but features and risk factors associated with these co-morbidities remain poorly characterized. In the present study, routinely collected data of VL patients admitted to Amudat Hospital, Uganda, were used to investigate the magnitude of VL-malaria co-infections and identify possible risk factors. Nearly 20% of the patients included in this study were found to be co-infected with VL and malaria, indicating that this is a common condition among VL patients living in malaria endemic areas. Young age (≤9 years) was identified as an important risk factor for contracting the VL-malaria co-infection, while being anemic or carrying a skin infection appeared to negatively correlate with the co-morbidity. Co-infected patients presented with slightly more severe symptoms compared to mono-infected patients, but had a similar prognosis, possibly due to early diagnosis of malaria as a result of systematic testing. In conclusion, these results emphasize the importance of performing malaria screening amongst VL patients living in malaria-endemic areas and suggest that close monitoring of co-infected patients should be implemented

Global Analysis of the Impact of Environmental Perturbation on cis-Regulation of Gene Expression

Genetic variants altering cis-regulation of normal gene expression (cis-eQTLs) have been extensively mapped in human cells and tissues, but the extent by which controlled, environmental perturbation influences cis-eQTLs is unclear. We carried out large-scale induction experiments using primary human bone cells derived from unrelated donors of Swedish origin treated with 18 different stimuli (7 treatments and 2 controls, each assessed at 2 time points). The treatments with the largest impact on the transcriptome, verified on two independent expression arrays, included BMP-2 (t = 2h), dexamethasone (DEX) (t = 24h), and PGE2 (t = 24h). Using these treatments and control, we performed expression profiling for 18,144 RefSeq transcripts on biological replicates of the complete study cohort of 113 individuals (ntotal = 782) and combined it with genome-wide SNP-genotyping data in order to map treatment-specific cis-eQTLs (defined as SNPs located within the gene ±250 kb). We found that 93% of cis-eQTLs at 1% FDR were observed in at least one additional treatment, and in fact, on average, only 1.4% of the cis-eQTLs were considered as treatment-specific at high confidence. The relative invariability of cis-regulation following perturbation was reiterated independently by genome-wide allelic expression tests where only a small proportion of variance could be attributed to treatment. Treatment-specific cis-regulatory effects were, however, 2- to 6-fold more abundant among differently expressed genes upon treatment. We further followed-up and validated the DEX–specific cis-regulation of the MYO6 and TNC loci and found top cis-regulatory variants located 180 kb and 250 kb upstream of the transcription start sites, respectively. Our results suggest that, as opposed to tissue-specificity of cis-eQTLs, the interactions between cellular environment and cis-variants are relatively rare (∼1.5%), but that detection of such specific interactions can be achieved by a combination of functional genomic approaches as described here