Vulnerabling People: Dementia and the Making of Embodied Agency

In dementia research and care practice and there has been a turn to try to offer approaches that acknowledge the patient’s personhood and agency and protect the rights of the vulnerable. Yet while defining people as demented or vulnerable, the focus is on the disabilities of and dysfunctions in the patient, and the strengths are left undiscussed, thus ignoring an important part of being a person. I move the focus from disabilities to strengths and call for more attention to be paid to other ways of interaction with vulnerable people. As an example, I consider ‘making’ as a form of creative interaction and how this applies to people living with dementia. My focus is on the phenomenological experience of the world. I argue that this offers a perspective that shows the value in embodied knowledge and making practices in a manner that acknowledges the agency and ability to interact with the world, even when other forms of interaction might not seem possible. Keywords: agency, art, dementia, making, phenomenology, vulnerabilit

Hospital-Based Buprenorphine-Focused Interventions for the Treatment of Opioid Use Disorder: A Scoping Literature Review and Case Study

The United States continues to struggle to find meaningful solutions to the opioid epidemic. Because they save lives, medications for the treatment of opioid use disorder (OUD), such as buprenorphine, are recommended to be made available in all practice settings. Yet the treatment of opioid use disorder appears to be rarely offered during hospitalization. However, a 220-bed academic hospital in Texas achieved this goal without the presence of an addiction medicine consultation service. This study sought to illuminate this growing area of work through an extensive literature review and case study of the program in Texas. For the case study, key informant interviews took place of stakeholders engaged in the program in addition to document review from the program’s inception. Over 4,500 computer files and over 9,400 emails were reviewed from November 2017 to December 2019. Eleven key informant interviews were conducted. The findings show key areas for integration of OUD treatment within the walls of U.S. hospitals including stakeholder engagement, executive support, interprofessional collaboration, widespread education, stigma reduction, advocacy and institutional policy reform, and sharing of patient stories. As a result, a dedicated group of interprofessional hospital-based healthcare professionals working in a consultative model is one feasible method of increasing access to life-saving treatment and harm reduction for patients with opioid use disorder and likely substance use disorders as a whole

The phosphorylation of Prp1p by Prp4p-kinase is required for the activation of pre-catalytic spliceosomes

Die Rolle von Prp1p und seiner Phosphorylierung durch die Prp4p-Kinase beim Aufbau und der Aktivierung von Spleißosomen wurde untersucht. Prp1p und Prp31p werden unabhängig von der Prp4p-Kinaseaktivität an prä-katalytische Komplexe gebunden, die entweder alle fünf snRNAs (U1.U2.U5.U4/U6) oder nur vier snRNAs (U2.U5.U4/U6) enthalten. In einer konditional letalen prp1-Mutante, wird Prp31p in prä-katalytischen Komplexen mit U1.U2.U5.U4/U6 und U2.U5.U4/U6 in gleichen Mengen wie unter permissiven Bedingungen nachgewiesen. Diese Ergebnisse demonstrieren, dass in S. pombe Spleißosomen unabhängig von Prp1p aufgebaut werden. Sie sind ein Hinweis auf eine regulatorische Funktion der Phosphorylierung von Prp1p bei der Aktivierung des Spleißosoms. Die Analysen von Deletionsmutationen im N-Terminus von Prp1p in vivo ergaben, dass die strukturelle Integrität des N-Terminus zwar für die Funktion von Prp1p essentiell ist, dass er aber für die Assoziation mit prä-katalytischen Spleißosomen keine wesentliche Rolle spielt. In vitro wurden im N-Terminus von Prp1p mehrere Phosphorylierungsstellen der Prp4p-Kinase identifiziert, von denen das Threonin in Position 244 auch in vivo phosphoryliert wird. Die Analysen der mutierten in vitro Phosphorylierungsstellen in vivo bestätigen, dass weder die hochkonservierte Region in den Positionen 20-33 im N-Terminus von Prp1p, noch die Phosphorylierung des Threonins an Position 244 für die Assoziation von Prp1p mit prä-katalytischen Spleißkomplexen notwendig sind. Das ist ein weiterer Hinweis darauf, dass die Phosphorylierung von Prp1p durch die Prp4p-Kinase an prä-katalytischen Spleißosomen erfolgt. Auf der Grundlage dieser Ergebnisse wird ein Modell der Regulation des prä-mRNA Spleißens in vivo vorgeschlagen, in dem die Phosphorylierung von Prp1p durch die Prp4p-Kinase an der Aktivierung von prä-katalytischen Spleißosomen beteiligt ist. Für den Aufbau von Spleißosomen wird Prp1p nicht benötigt.The significance of phosphorylation of Prp1p by Prp4p-kinase in assembling and activation of splicesomes was investigated. Independent of the activity of Prp4p-kinase, Prp1p and Prp31p associate with pre-catalytic splicesomal complexes which contain either five (U1.U2.U5.U4/U6) or four snRNAs (U2.U5.U4/U6). In a conditional lethal mutant of prp1, the amounts of Prp31p present in precatalytic splicesomal complexes containing either U1.U2.U5.U4/U6 or U2.U5.U4/U6 are identical to those seen under permissive conditions. These results demonstrate that in S. pombe the assembly of spliceosomes was independent of Prp1p, indicating a regulatory function of phosphorylation of Prp1p for activation of spliceosomes. In vivo investigations of mutants harbouring deletions in the N-terminus of Prp1p showed that the structural integrity of the N-terminus is essential for the function of Prp1p but it does not play a considerable role in the association of Prp1p with pre-catalytic spliceosomes. We identified several in vitro phosphorylation sites of Prp4p-kinase in the N-terminus of Prp1p of which threonin in position 244 is also phosphorylated in vivo. Analysis of the in vitro phosphorylation sites in vivo confirmed, that neither the highly conserved region in position 20-30 in the N-terminus of Prp1p nor the phosphorylation of threonin 244 is necessary for association of Prp1p with pre-catalytic spliceosomal complexes, indicating that phosphorylation of Prp1p by Prp4p-kinase may proceed in pre-catalytic spliceosomes.On the basis of these experiments, we suggest a model for regulation of pre-mRNA splicing in vivo, in which the phosphorylation of Prp1p by Prp4p-kinase is essential for the activation of pre-catalytical spliceosomes but not for their assembly

Modelling microbial exchanges between forms of soil nitrogen in contrasting ecosystems

Although nitrogen (N) is often combined with carbon (C) in organic molecules, C passes from the air to the soil through plant photosynthesis, whereas N passes from the soil to plants through a chain of microbial conversions. However, dynamic models do not fully consider the microorganisms at the centre of exchange processes between organic and mineral forms of N. This study monitored the transfer of ¹⁴C and ¹⁵N between plant materials, microorganisms, humified compartments, and inorganic forms in six very different ecosystems along an altitudinal transect. The microbial conversions of the ¹⁵N forms appear to be strongly linked to the previously modelled C cycle, and the same equations and parameters can be used to model both C and N cycles. The only difference is in the modelling of the flows between microbial and inorganic forms. The processes of mineralization and immobilization of N appear to be regulated by a two-way microbial exchange depending on the C : N ratios of microorganisms and available substrates. The MOMOS (Modelling of Organic Matter of Soils) model has already been validated for the C cycle and also appears to be valid for the prediction of microbial transformations of N forms. This study shows that the hypothesis of microbial homeostasis can give robust predictions at global scale. However, the microbial populations did not appear to always be independent of the external constraints. At some altitudes their C : N ratio could be better modelled as decreasing during incubation and increasing with increasing C storage in cold conditions. The ratio of potentially mineralizable-¹⁵N/inorganic-¹⁵N and the ¹⁵N stock in the plant debris and the microorganisms was modelled as increasing with altitude, whereas the ¹⁵N storage in stable humus was modelled as decreasing with altitude. This predicts that there is a risk that mineralization of organic reserves in cold areas may increase global warming

The N-terminus of Prp1 (Prp6/U5-102 K) is essential for spliceosome activation in vivo

The spliceosomal protein Prp1 (Prp6/U5-102 K) is necessary for the integrity of pre-catalytic spliceosomal complexes. We have identified a novel regulatory function for Prp1. Expression of mutations in the N-terminus of Prp1 leads to the accumulation of pre-catalytic spliceosomal complexes containing the five snRNAs U1, U2, U5 and U4/U6 and pre-mRNAs. The mutations in the N-terminus, which prevent splicing to occur, include in vitro and in vivo identified phosphorylation sites of Prp4 kinase. These sites are highly conserved in the human ortholog U5-102 K. The results presented here demonstrate that structural integrity of the N-terminus is required to mediate a splicing event, but is not necessary for the assembly of spliceosomes

Comparison of five soil organic matter decomposition models using data from a 14C and 15N labeling field experiment

Five alternatives of the previously published MOMOS model (MOMOS-2 to -6) are tested to predict the dynamics of carbon (C) and nitrogen (N) in soil during the decomposition of plant necromass. 14C and 15N labeled wheat straw was incubated over 2 years in fallow soils of the high Andean Paramo of Venezuela. The following data were collected: soil moisture, total 14C and 15N and microbial biomass (MB)-14C and -15N, daily rainfall, air temperature and total radiation. Daily soil moisture was predicted using the SAHEL model. MOMOS-2 to -4 (type 1 models) use kinetic constants and flow partitioning parameters. MOMOS-2 can be simplified to MOMOS-3 and further to MOMOS-4, with no significant changes in the prediction accuracy and robustness for total-14C and -15N as well as for MB-14C and -15N. MOMOS-5 (type 2 models) uses only kinetic constants: three MB-inputs (from labile and stable plant material and from humified compounds) and two MB-outputs (mortality and respiration constants). MOMOS-5 did not significantly change the total-14C and -15N predictions but markedly improved the predictive quality and robustness of MB-14C and -15N predictions (with a dynamic different from the predictions by other models). Thus MOMOS-5 is proposed as an accurate and ecologically consistent description of decomposition processes. MOMOS-6 extends MOMOS-5 by including a stable humus compartment for long-term simulations of soil native C and N. The improvement of the predictions is not significant for this 2-year experiment, but MOMOS-6 enables prediction of a sequestration in the stable humus compartment of 2% of the initially added 14C and 5.4% of the added 15

Immunohistochemical Expression Analysis of Caldesmon Isoforms in Colorectal Carcinoma Reveals Interesting Correlations with Tumor Characteristics

Colorectal cancer is a notorious disease, with almost half of the patients succumbing to the disease. The prevalence and incidence rates of colorectal cancer are increasing in many parts of the world, highlighting the need to discover new biomarkers for diagnosis and therapy. Caldesmon (CaD), an actin-binding protein that plays a significant role in controlling cell motility, has emerged as a promising biomarker. The CALD1 gene encodes CaD as multiple transcripts that mainly encode two protein isoforms: High-molecular-weight (h-CaD), expressed in smooth muscle, and low-molecular-weight (l-CaD), expressed in nonsmooth muscle cells. Most studies have suggested an oncogenic role of CaD in colorectal cancer, but the exact subcellular localization of the two CaD isoforms in tumor cells and stroma have not been clarified yet. Here, we analyzed tissue samples from 262 colorectal cancer patients by immunohistochemistry analysis using specific antibodies for l-CaD and h-CaD. The results showed elevated cytoplasmic expression levels of l-Cad in 187/262 (71.4%) cases. l-Cad was expressed at low levels in the normal colon mucosa and was also consistently expressed in the cancer-associated stroma of all cases, suggesting that it could play a role in modulating the tumor microenvironment. l-CaD expression in cancer cells was associated with preinvasive stages of cancer. Survival analysis indicated that patients with high l-CaD expression in tumor cells could respond poorly to selective chemotherapeutic 5FU, but not combination chemotherapy. h-CaD was expressed in colonic and vascular smooth muscle cells as expected and to a lesser extent in the tumor-associated stroma, but it was not expressed in the cancer cells or normal colon mucosal epithelial cells. Collectively, these data clarify how the expression patterns of CaD isoforms in colorectal cancer can have applications in the management of colorectal cancer patients

Proteomic analysis of the U1 snRNP of Schizosaccharomyces pombe reveals three essential organism-specific proteins

Characterization of spliceosomal complexes in the fission yeast Schizosaccharomyces pombe revealed particles sedimenting in the range of 30–60S, exclusively containing U1 snRNA. Here, we report the tandem affinity purification (TAP) of U1-specific protein complexes. The components of the complexes were identified using (LC-MS/MS) mass spectrometry. The fission yeast U1 snRNP contains 16 proteins, including the 7 Sm snRNP core proteins. In both fission and budding yeast, the U1 snRNP contains 9 and 10 U1 specific proteins, respectively, whereas the U1 particle found in mammalian cells contains only 3. Among the U1-specific proteins in S. pombe, three are homolog to the mammalian and six to the budding yeast Saccharomyces cerevisiae U1-specific proteins, whereas three, called U1H, U1J and U1L, are proteins specific to S. pombe. Furthermore, we demonstrate that the homolog of U1-70K and the three proteins specific to S. pombe are essential for growth. We will discuss the differences between the U1 snRNPs with respect to the organism-specific proteins found in the two yeasts and the resulting effect it has on pre-mRNA splicing