Policing in a Democratic Constitution

Most constitutions contain provisions relating to or impacting policing. Separate from the armed forces and intelligence services, the police are the state’s internal security apparatus, and codifying issues related to policing within a constitution can ensure efficient service delivery and human rights protections. Originating from the Libyan constitution making process, this paper provides a taxonomy of options for constitution drafters and scholars. More so than other issues, such as separation of powers or human rights protections generally, policing sections are very country specific. While not advocating for specific best practices, the work gives ample justifications for certain policing principles and concepts, particularly regarding due process and gender matters. In any case, local constitution drafters will need to consider a wide breadth of options for what to include on policing and what to leave to legislative bodies. The constitutions in some countries, such as South Africa, Brazil, the Dominican Republic, Fiji, Kenya, and Nigeria, contain significant detail regarding the policing principles, mandates, and governance. In many other states, the constitution contains very limited detail and defers to national legislation for police formation and oversight. Many factors contribute to these variations, including the security status of the country, the context of the democratic transition, and the chosen overall government structure. Generally, modern constitutional representative democracies require police to serve and protect civilians. The current social movements in the United States addressing mistreatment of people of color and militarization of the police highlight the challenges of managing and training police. Constitution drafters must grapple with complex issues like the potential for misuse of force, the politicization of police, and the relationship between the police and the military. These themes are borne out around the world with constitutional language options as diverse as the States themselves

Detailed phylogenetic analysis tracks transmission of distinct SARS-COV-2 variants from China and Europe to West Africa

SARS-CoV-2, the virus causing the COVID-19 pandemic emerged in December 2019 in China and raised fears it could overwhelm healthcare systems worldwide. Mutations of the virus are monitored by the GISAID database from which we downloaded sequences from four West African countries Ghana, Gambia, Senegal and Nigeria from February 2020 to April 2020. We subjected the sequences to phylogenetic analysis employing the nextstrain pipeline. We found country-specific patterns of viral variants and supplemented that with data on novel variants from June 2021. Until April 2020, variants carrying the crucial Europe-associated D614G amino acid change were predominantly found in Senegal and Gambia, and combinations of late variants with and early variants without D614G in Ghana and Nigeria. In June 2021 all variants carried the D614G amino acid substitution. Senegal and Gambia exhibited again variants transmitted from Europe (alpha or delta), Ghana a combination of several variants and in Nigeria the original Eta variant. Detailed analysis of distinct samples revealed that some might have circulated latently and some reflect migration routes. The distinct patterns of variants within the West African countries point at their global transmission via air traffic predominantly from Europe and only limited transmission between the West African countries

Transcriptome-based analysis of blood samples reveals elevation of DNA damage response, neutrophil degranulation, cancer and neurodegenerative pathways in Plasmodium falciparum patients

Background: Malaria caused by Plasmodium falciparum results in severe complications including cerebral malaria (CM) especially in children. While the majority of falciparum malaria survivors make a full recovery, there are reports of some patients ending up with neurological sequelae or cognitive deficit.// Methods: An analysis of pooled transcriptome data of whole blood samples derived from two studies involving various P. falciparum infections, comprising mild malaria (MM), non-cerebral severe malaria (NCM) and CM was performed. Pathways and gene ontologies (GOs) elevated in the distinct P. falciparum infections were determined.// Results: In all, 2876 genes were expressed in common between the 3 forms of falciparum malaria, with CM having the least number of expressed genes. In contrast to other research findings, the analysis from this study showed MM share similar biological processes with cancer and neurodegenerative diseases, NCM is associated with drug resistance and glutathione metabolism and CM is correlated with endocannabinoid signalling and non-alcoholic fatty liver disease (NAFLD). GO revealed the terms biogenesis, DNA damage response and IL-10 production in MM, down-regulation of cytoskeletal organization and amyloid-beta clearance in NCM and aberrant signalling, neutrophil degranulation and gene repression in CM. Differential gene expression analysis between CM and NCM showed the up-regulation of neutrophil activation and response to herbicides, while regulation of axon diameter was down-regulated in CM.// Conclusions: Results from this study reveal that P. falciparum-mediated inflammatory and cellular stress mechanisms may impair brain function in MM, NCM and CM. However, the neurological deficits predominantly reported in CM cases could be attributed to the down-regulation of various genes involved in cellular function through transcriptional repression, axonal dysfunction, dysregulation of signalling pathways and neurodegeneration. It is anticipated that the data from this study, might form the basis for future hypothesis-driven malaria research

Free Bilirubin Induces Neuro-Inflammation in an Induced Pluripotent Stem Cell-Derived Cortical Organoid Model of Crigler-Najjar Syndrome

Bilirubin-induced neurological damage (BIND), which might progress to kernicterus, occurs as a consequence of defects in the bilirubin conjugation machinery, thus enabling albumin-unbound free bilirubin (BF) to cross the blood-brain barrier and accumulate within. A defect in the UGT1A1 enzyme-encoding gene, which is directly responsible for bilirubin conjugation, can cause Crigler-Najjar syndrome (CNS) and Gilbert's syndrome. We used human-induced pluripotent stem cell (hiPSC)-derived 3D brain organoids to model BIND in vitro and unveil the molecular basis of the detrimental effects of BF in the developing human brain. Healthy and patient-derived iPSCs were differentiated into day-20 brain organoids, and then stimulated with 200 nM BF. Analyses at 24 and 72 h post-treatment point to BF-induced neuro-inflammation in both cell lines. Transcriptome, associated KEGG, and Gene Ontology analyses unveiled the activation of distinct inflammatory pathways, such as cytokine-cytokine receptor interaction, MAPK signaling, and NFκB activation. Furthermore, the mRNA expression and secretome analysis confirmed an upregulation of pro-inflammatory cytokines such as IL-6 and IL-8 upon BF stimulation. This novel study has provided insights into how a human iPSC-derived 3D brain organoid model can serve as a prospective platform for studying the etiology of BIND kernicterus

Natural Products in Renal-Associated Drug Discovery

The global increase in the incidence of kidney failure constitutes a major public health problem. Kidney disease is classified into acute and chronic: acute kidney injury (AKI) is associated with an abrupt decline in kidney function and chronic kidney disease (CKD) with chronic renal failure for more than three months. Although both kidney syndromes are multifactorial, inflammation and oxidative stress play major roles in the diversity of processes leading to these kidney malfunctions. Here, we reviewed various publications on medicinal plants with antioxidant and anti-inflammatory properties with the potential to treat and manage kidney-associated diseases in rodent models. Additionally, we conducted a meta-analysis to identify gene signatures and associated biological processes perturbed in human and mouse cells treated with antioxidants such as epigallocatechin gallate (EGCG), the active ingredient in green tea, and the mushroom Ganoderma lucidum (GL) and in kidney disease rodent models. We identified EGCG- and GL-regulated gene signatures linked to metabolism; inflammation (NRG1, E2F1, NFKB1 and JUN); ion signalling; transport; renal processes (SLC12A1 and LOX) and VEGF, ERBB and BDNF signalling. Medicinal plant extracts are proving to be effective for the prevention, management and treatment of kidney-associated diseases; however, more detailed characterisations of their targets are needed to enable more trust in their application in the management of kidney-associated diseases

Wasco Notice of Adopted Amendment (2009-01-22)

52 pp. Adopted 2009-01-22. Department of Land Conservation and Development Notice of Adopted AmendmentApplicant requested to rezone 7.8 acres from F-2 (80) to FF (10). Planning Staff recommended denial, Planning Commission hearing held on December 2, 2008 and recommended denial, County Court hearing held on January 7. 2009 and denied requested rezone, goal exception, and comp plan amendment

Unveiling Angiotensin II and Losartan-Induced Gene Regulatory Networks Using Human Urine-Derived Podocytes

Podocytes are highly specialized cells that play a pivotal role in the blood filtration process in the glomeruli of the kidney, and their dysfunction leads to renal diseases. For this reason, the study and application of this cell type is of great importance in the field of regenerative medicine. Hypertension is mainly regulated by the renin–angiotensin–aldosterone system (RAAS), with its main mediator being angiotensin II (ANG II). Elevated ANG II levels lead to a pro-fibrotic, inflammatory, and hypertrophic milieu that induces apoptosis in podocytes. The activation of RAAS is critical for the pathogenesis of podocyte injury; as such, to prevent podocyte damage, patients with hypertension are administered drugs that modulate RAAS signaling. A prime example is the orally active, non-peptide, selective angiotensin-II-type I receptor (AGTR1) blocker losartan. Here, we demonstrate that SIX2-positive urine-derived renal progenitor cells (UdRPCs) and their immortalized counterpart (UM51-hTERT) can be directly differentiated into mature podocytes. These podocytes show activation of RAAS after stimulation with ANG II, resulting in ANG II-dependent upregulation of the expression of the angiotensin-II-type I receptor, AGTR1, and the downregulated expression of the angiotensin-II-type II receptor 2 (AGTR2). The stimulation of podocytes with losartan counteracts ANG II-dependent changes, resulting in a dependent favoring of the specific receptor from AGTR1 to AGTR2. Transcriptome analysis revealed 94 losartan-induced genes associated with diverse biological processes and pathways such as vascular smooth muscle contraction, the oxytocin signaling pathway, renin secretion, and ECM-receptor interaction. Co-stimulation with losartan and ANG II induced the exclusive expression of 106 genes associated with DNA methylation or demethylation, cell differentiation, the developmental process, response to muscle stretch, and calcium ion transmembrane transport. These findings highlight the usefulness of UdRPC-derived podocytes in studying the RAAS pathway and nephrotoxicity in various kidney diseases

Wasco County Notice of Adopted Amendment (2007-01-11)

47 pp. Adopted 2007-01-11. Department of Land Conservation and Development Notice of Adopted AmendmentDevelop County wide fire standards that will be incorporated into the County's Land Use and Development Ordinances in order to reduce threats to life, safety, property, and resources by improving access to and defensibility of development and resources in rural areas of Wasco County

Wasco County Notice of Adopted Amendment (2008-10-31)

58 pp. Adopted 2008-10-31. Department of Land Conservation and Development Notice of Adopted AmendmentAmend Chapter 13, Nonconforming Uses, Buildings & Lots and related chapters. The primary purpose is to include language in ORS 215.130 that is not currently included. The secondary purpose is to clarify review critiera and streamline Chapter. Please note - original Local File Number was PLALUA-08-06-0001. This was replaced by the current file number listed above

Wasco County Notice of Adopted Amendment (2008-10-31)

58 pp. Adopted 2008-10-31. Department of Land Conservation and Development Notice of Adopted AmendmentAmend Chapter 13, Nonconforming Uses, Buildings & Lots and related chapters. The primary purpose is to include language in ORS 215.130 that is not currently included. The secondary purpose is to clarify review critiera and streamline Chapter. Please note - original Local File Number was PLALUA-08-06-0001. This was replaced by the current file number listed above