Vaccination Strategies and Herd Immunity Thresholds in Small World Models

Infectious diseases pose a serious threat to humans, plants, and animals. Though vaccines can help control outbreaks of infectious diseases, there is typically not enough vaccine available for the entire population. In this case, certain vaccination strategies can be employed to maximize the benefits for the entire population. Using results from graph theory and the simulation tool lONTW (Infections On NeTWorks), we investigated various vaccination strategies on certain types of so-called contact networks that model the patterns of interactions within a population. In particular, we focused on a certain class of contact networks known as small world models, where individuals are randomly connected, i.e., can transmit and/or contract an infectious disease, along paths that are relatively small in relation to the overall population size. These types of networks tend to provide good estimations of the interactions of real populations when the exact contact network is unknown. However, the complexity and stochasticity of such networks create challenges in determining the best vaccination strategy. Here we discuss our preliminary results for vaccination strategies on small world models, including how many vaccines are needed (a notion related to a concept called the herd immunity threshold) and, for a given amount of vaccine, which individuals should be vaccinated in order to prevent major outbreaks

Teaching in Tumultuous Times: Unraveling Teachers’ Experiences amidst the COVID-19 Pandemic

Teachers are the most significant assets in any educational institution. They serve as an avenue for conveying knowledge, skills, and values to students. They play a vital role in reforming and strengthening the education system of any country. However, education in the new normal requires numerous adaptations, as teachers were unprepared when the pandemic struck. This qualitative study sought to discover the strengths, weaknesses, opportunities, and threats (SWOT) from teachers' lived experiences in teaching during the pandemic. A total of 28 participants were involved, who had first-hand experiences of teaching tertiary level in the new normal in a university. The qualitative phenomenological research design was used in this study. Thus, teaching in the wake of the COVID-19 pandemic provided teachers’ deficiencies in some course delivery; however, they worked diligently to transform and demonstrate resilience in teaching in the new normal amidst pandemics, converting them into strengths and opportunities. On the other hand, instructors' and professors’ strengths should be recognized, and professional development opportunities should be provided to help them become more competent educators

Frontotemporal dementia causative CHMP2B impairs neuronal endolysosomal traffic-rescue by TMEM106B knockdown.

Mutations in the endosome-associated protein CHMP2B cause frontotemporal dementia and lead to lysosomal storage pathology in neurons. We here report that physiological levels of mutant CHMP2B causes reduced numbers and significantly impaired trafficking of endolysosomes within neuronal dendrites, accompanied by increased dendritic branching. Mechanistically, this is due to the stable incorporation of mutant CHMP2B onto neuronal endolysosomes, which we show renders them unable to traffic within dendrites. This defect is due to the inability of mutant CHMP2B to recruit the ATPase VPS4, which is required for release of CHMP2B from endosomal membranes. Strikingly, both impaired trafficking and the increased dendritic branching were rescued by treatment with antisense oligonucleotides targeting the well validated frontotemporal dementia risk factor TMEM106B, which encodes an endolysosomal protein. This indicates that reducing TMEM106B levels can restore endosomal health in frontotemporal dementia. As TMEM106B is a risk factor for frontotemporal dementia caused by both C9orf72 and progranulin mutations, and antisense oligonucleotides are showing promise as therapeutics for neurodegenerative diseases, our data suggests a potential new strategy for treating the wide range of frontotemporal dementias associated with endolysosomal dysfunction

Oxidative stress in keratoconus

PURPOSE. The purpose of this study was to establish the alterations of oxidative stress-related markers in keratoconus (KC) corneas. METHODS. A total of 6 healthy and 11 ectatic corneas (7 KC and 4 post-LASIK) were studied. Different oxidative stress-related markers were determined to assess their implication in the KC pathophysiology. Total antioxidant capacity and total nitrites present in the samples were assayed. Furthermore, lipid peroxidation products and the glutathione contents were determined, together with 4-hydroxynonenal (4-HNE) immunohistochemistry, to establish the relationship between KC and oxidative stress. RESULTS. The antioxidant capacity and glutathione content in KC corneas were decreased significantly when compared with healthy corneas. Moreover, the total nitrites and lipid peroxidation were significantly elevated in the corneas with KC when compared with the controls. There was a statistically significant difference in the amount of HNE-positive cells in KC corneas when compared with healthy corneas by immunohistochemistry. Post-LASIK ectatic corneas and KC corneas showed similar results. CONCLUSIONS. The increased levels of oxidative stress markers and the decreased antioxidant capacity and antioxidant defenses in KC corneas, as well as in the post-LASIK ectatic corneas, indicate that oxidative stress might be involved in the development of this disease and may provide new insights for its prevention and treatment in the future. (Invest Ophthalmol Vis Sci. 2011;52:8592-8597

Enlargement and the Historical Origins of the European Community's Democratic Identity, 1961–1978

This article examines how and when democracy entered the discursive politics of the European Community to become one of the fundamental tenets of European political identity – and in the process influenced how decision-makers approached the question of enlargement. Building on multiple archival sources, the article traces how all three Community institutions (Commission, Council and European Parliament) legitimised the expansion and continuation of the process of European integration through the discursive construction of democracy. It focuses on the debates elicited by the attempts of southern European countries to accede to the EEC in the 1960s and 1970s

<i>mito</i>-QC illuminates mitophagy and mitochondrial architecture <i>in vivo</i>

Autophagic turnover of mitochondria, termed mitophagy, is proposed to be an essential quality-control (QC) mechanism of pathophysiological relevance in mammals. However, if and how mitophagy proceeds within specific cellular subtypes in vivo remains unclear, largely because of a lack of tractable tools and models. To address this, we have developed “mito-QC,” a transgenic mouse with a pH-sensitive fluorescent mitochondrial signal. This allows the assessment of mitophagy and mitochondrial architecture in vivo. Using confocal microscopy, we demonstrate that mito-QC is compatible with classical and contemporary techniques in histochemistry and allows unambiguous in vivo detection of mitophagy and mitochondrial morphology at single-cell resolution within multiple organ systems. Strikingly, our model uncovers highly enriched and differential zones of mitophagy in the developing heart and within specific cells of the adult kidney. mito-QC is an experimentally advantageous tool of broad relevance to cell biology researchers within both discovery-based and translational research communities

Spinal Cord Injury Reveals Multilineage Differentiation of Ependymal Cells

Spinal cord injury often results in permanent functional impairment. Neural stem cells present in the adult spinal cord can be expanded in vitro and improve recovery when transplanted to the injured spinal cord, demonstrating the presence of cells that can promote regeneration but that normally fail to do so efficiently. Using genetic fate mapping, we show that close to all in vitro neural stem cell potential in the adult spinal cord resides within the population of ependymal cells lining the central canal. These cells are recruited by spinal cord injury and produce not only scar-forming glial cells, but also, to a lesser degree, oligodendrocytes. Modulating the fate of ependymal progeny after spinal cord injury may offer an alternative to cell transplantation for cell replacement therapies in spinal cord injury