I Would Prefer Not to Help You

Bartleby, the Scrivener recounts a story of a scrivener who would prefer not to do anything, whether that be parts of his job, changing his location, or eating his dinner. The narrator’s reaction to Bartleby’s lazy desires seem to be admirable, but his selfish motivation and false compassion are evident. The way the narrator views and treats Bartleby is consistent with the standards of philanthropy of the wealthy during the mid-nineteenth century. The narrator truly believes he has helped Bartleby to the best of his ability, yet fails to connect with Bartleby outside of offering him money and future assistance if required. This may be blamed on the narrator’s lack of relationship with God. People below the narrator’s socioeconomic status were viewed solely on how they could benefit him and his business and were expected to conform to the narrator’s standards. Bartleby the Scrivener, though a melancholy story leading to Bartleby’s death, can be used to see an accurate picture of philanthropy in the 1850s

Huntington\u27s Disease--A Review

Huntington’s disease is degenerative and effects both cognitive and motor functioning, beginning in the 20s and continuing a decline for about two decades until death. In this disease, the huntingtin gene on chromosome four codes for an abnormally elongated repeating CAG polypeptide sequence. This mutation causes an atrophy in the brain that translates into decreasing control of movements and other aspects of cognition. To date, there is no cure for Huntington’s disease, but there are treatments for many symptoms that accompany the disease. Even still, there are promising new methods that may be more beneficial to patients in the future

Sleep Duration, Sleep Quality, Excessive Daytime Sleepiness, and Chronotype in University Students in India: A Systematic Review

Introduction: Optimal sleep is an important aspect of academic performance and mental health. However, poor sleep health is often present among university students due to their lifestyle and academic requirements. University students in India have been shown to have poor sleep health. Though self-reported sleep issues have been evaluated among university students in India, these results have not been synthesized to date. We aimed to identify factors that may be associated with poor sleep health among university students in India from January 2010 to April 2021, inclusive. As a secondary aim, we sought to evaluate factors associated with sleep among university students in India during the COVID-19 pandemic. Methods: A systematic review was conducted using PubMed, CINAHL, and Google Scholar to identify studies conducted in India related to sleep among university students. The studies were synthesized by aspects of sleep (sleep quality, sleep duration, excessive daytime sleepiness (EDS)) and chronotype, types of university students in India (non-medical and medical) and if they examined sleep in university students during the COVID-19 pandemic. Results: 12 articles were identified that evaluated sleep duration, sleep quality, and excessive daytime sleepiness and included university students in India. Findings suggested that between 25- 72% of Indian university students reported poor sleep quality, and 17-44% experienced EDS. Similar associations were noted in both non-medical and medical undergraduate students. Students with evening chronotype vs. intermediate chronotype and morning chronotype were more likely to experience poor sleep quality. Studies conducted during the COVID-19 pandemic reported differing results of poor sleep quality and increased sleep duration. Discussion: Demographic, psychological, and socio-behavioral factors are statistically significantly related to poor sleep quality, EDS, and short sleep duration among university students in India. Take-home message: Poor sleep quality is prevalent among university students in India. To improve sleep issues among university students in India, researchers should design tailored sleep interventions that account for demographic, psychological, and socio-behavioral factors that may place students at risk for poor sleep quality, excessive daytime sleepiness, and short sleep duration

Dual Infection and Superinfection Inhibition of Epithelial Skin Cells by Two Alphaherpesviruses Co-Occur in the Natural Host

Hosts can be infected with multiple herpesviruses, known as superinfection; however, superinfection of cells is rare due to the phenomenon known as superinfection inhibition. It is believed that dual infection of cells occurs in nature, based on studies examining genetic exchange between homologous alphaherpesviruses in the host, but to date, this has not been directly shown in a natural model. In this report, gallid herpesvirus 2 (GaHV-2), better known as Marek’s disease virus (MDV), was used in its natural host, the chicken, to determine whether two homologous alphaherpesviruses can infect the same cells in vivo. MDV shares close similarities with the human alphaherpesvirus, varicella zoster virus (VZV), with respect to replication in the skin and exit from the host. Recombinant MDVs were generated that express either the enhanced GFP (eGFP) or monomeric RFP (mRFP) fused to the UL47 (VP13/14) herpesvirus tegument protein. These viruses exhibited no alteration in pathogenic potential and expressed abundant UL47-eGFP or -mRFP in feather follicle epithelial cells in vivo. Using laser scanning confocal microscopy, it was evident that these two similar, but distinguishable, viruses were able to replicate within the same cells of their natural host. Evidence of superinfection inhibition was also observed. These results have important implications for two reasons. First, these results show that during natural infection, both dual infection of cells and superinfection inhibition can co-occur at the cellular level. Secondly, vaccination against MDV with homologous alphaherpesvirus like attenuated GaHV-2, or non-oncogenic GaHV-3 or meleagrid herpesvirus (MeHV-1) has driven the virus to greater virulence and these results implicate the potential for genetic exchange between homologous avian alphaherpesviruses that could drive increased virulence. Because the live attenuated varicella vaccine is currently being administered to children, who in turn could be superinfected by wild-type VZV, this could potentiate recombination events of VZV as well

Challenges of Reducing Phosphorus Based Water Eutrophication in the Agricultural Landscapes of Northwest Europe

ISI Document Delivery No.: HJ7HC Times Cited: 1 Cited Reference Count: 180 Bol, Roland Gruau, Gerard Mellander, Per-Erik Dupas, Remi Bechmann, Marianne Skarbovik, Eva Bieroza, Magdalena Djodjic, Faruk Glendell, Miriam Jordan, Philip Van der Grift, Bas Rode, Michael Smolders, Erik Verbeeck, Mieke Gu, Sen Klumpp, Erwin Pohle, Ina Fresne, Maelle Gascuel-Odoux, Chantal van der Grift, Bas/0000-0003-4069-6703 INSU-CNRS Earth Sciences and Astronomy Observatory of Rennes (OSUR); Loire-Brittany Water Agency (AELB); French Catchment Network Observatory (SOERE Reseau des Bassins Versants) The INSU-CNRS Earth Sciences and Astronomy Observatory of Rennes (OSUR), the Loire-Brittany Water Agency (AELB), and the French Catchment Network Observatory (SOERE Reseau des Bassins Versants) are thanked for their financial support to the international workshop meeting which was held in Rennes (France) between 24th and 26th October 2017 and whose outputs and discussions have served as a basis for constructing this paper. 1 0 Frontiers media sa Lausanne 2296-7745In this paper, we outline several recent insights for the priorities and challenges for future research for reducing phosphorus (P) based water eutrophication in the agricultural landscapes of Northwest Europe. We highlight that new research efforts best be focused on headwater catchments as they are a key influence on the initial chemistry of the larger river catchments, and here many management interventions are most effectively made. We emphasize the lack of understanding on how climate change will impact on P losses from agricultural landscapes. Particularly, the capability to disentangle current and future trends in P fluxes, due to climate change itself, from climate driven changes in agricultural management practices and P inputs. Knowing that, future climatic change trajectories for Western Europe will accelerate the release of the most bioavailable soil P. We stress the ambiguities created by the large varieties of sources and storage/transfer processes involved in P emissions in landscapes and the need to develop specific data treatment methods or tracers able to circumvent them, thereby helping catchment managers to identify the ultimate P sources that most contribute to diffuse P emissions. We point out that soil and aqueous P exist not only in various chemical forms, but also in range of less considered physical forms e. g., dissolved, nanoparticulate, colloidal and other particulates, all affected differently by climate as well as other environmental factors, and require bespoke mitigation measures. We support increased high resolution monitoring of headwater catchments, to not only help verify the effectiveness of catchments mitigation strategies, but also add data to further develop new water quality models (e.g., those include Fe-P interactions) which can deal with climate and land use change effects within an uncertainty framework. We finally conclude that there is a crucial need for more integrative research efforts to deal with our incomplete understanding of the mechanisms and processes associated with the identification of critical source areas, P mobilization, delivery and biogeochemical processing, as otherwise even highintensity and high-resolution research efforts will only reveal an incomplete picture of the full global impact of the terrestrial derived P on downstream aquatic and marine ecosystems

Cigarette Smoke-Related Hydroquinone Dysregulates MCP-1, VEGF and PEDF Expression in Retinal Pigment Epithelium in Vitro and in Vivo

Age-related macular degeneration (AMD) is the leading cause of legal blindness in the elderly population. Debris (termed drusen) below the retinal pigment epithelium (RPE) have been recognized as a risk factor for dry AMD and its progression to wet AMD, which is characterized by choroidal neovascularization (CNV). The underlying mechanism of how drusen might elicit CNV remains undefined. Cigarette smoking, oxidative damage to the RPE and inflammation are postulated to be involved in the pathophysiology of the disease. To better understand the cellular mechanism(s) linking oxidative stress and inflammation to AMD, we examined the expression of pro-inflammatory monocyte chemoattractant protein-1 (MCP-1), pro-angiogenic vascular endothelial growth factor (VEGF) and anti-angiogenic pigment epithelial derived factor (PEDF) in RPE from smoker patients with AMD. We also evaluated the effects of hydroquinone (HQ), a major pro-oxidant in cigarette smoke on MCP-1, VEGF and PEDF expression in cultured ARPE-19 cells and RPE/choroids from C57BL/6 mice.MCP-1, VEGF and PEDF expression was examined by real-time PCR, Western blot, and ELISA. Low levels of MCP-1 protein were detected in RPE from AMD smoker patients relative to controls. Both MCP-1 mRNA and protein were downregulated in ARPE-19 cells and RPE/choroids from C57BL/6 mice after 5 days and 3 weeks of exposure to HQ-induced oxidative injury. VEGF protein expression was increased and PEDF protein expression was decreased in RPE from smoker patients with AMD versus controls resulting in increased VEGF/PEDF ratio. Treatment with HQ for 5 days and 3 weeks increased the VEGF/PEDF ratio in vitro and in vivo.We propose that impaired RPE-derived MCP-1-mediated scavenging macrophages recruitment and phagocytosis might lead to incomplete clearance of proinflammatory debris and infiltration of proangiogenic macrophages which along with increased VEGF/PEDF ratio favoring angiogenesis might promote drusen accumulation and progression to CNV in smoker patients with dry AMD

A systematic review of platinum and taxane resistance from bench to clinic: an inverse relationship

We undertook a systematic review of the pre-clinical and clinical literature for studies investigating the relationship between platinum and taxane resistance. Medline was searched for (1) cell models of acquired drug resistance reporting platinum and taxane sensitivities and (2) clinical trials of platinum or taxane salvage therapy in ovarian cancer. One hundred and thirty-seven models of acquired drug resistance were identified. 68.1% of cisplatin-resistant cells were sensitive to paclitaxel and 66.7% of paclitaxel-resistant cells were sensitive to cisplatin. A similar inverse pattern was observed for cisplatin vs. docetaxel, carboplatin vs. paclitaxel and carboplatin vs. docetaxel. These associations were independent of cancer type, agents used to develop resistance and reported mechanisms of resistance. Sixty-five eligible clinical trials of paclitaxel-based salvage after platinum therapy were identified. Studies of single agent paclitaxel in platinum-resistant ovarian cancer where patients had previously recieved paclitaxel had a pooled response rate of 35.3%, n=232, compared to 22% in paclitaxel naïve patients n=1918 (p<0.01, Chi-squared). Suggesting that pre-treatment with paclitaxel may improve the response of salvage paclitaxel therapy. The response rate to paclitaxel/platinum combination regimens in platinum-sensitive ovarian cancer was 79.5%, n=88 compared to 49.4%, n=85 for paclitaxel combined with other agents (p<0.001, Chi-squared), suggesting a positive interaction between taxanes and platinum. Therefore, the inverse relationship between platinum and taxanes resistance seen in cell models is mirrored in the clinical response to these agents in ovarian cancer. An understanding of the cellular and molecular mechanisms responsible would be valuable in predicting response to salvage chemotherapy and may identify new therapeutic targets

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Temporal shifts and temperature sensitivity of avian spring migratory phenology:A phylogenetic meta-analysis

There are wide reports of advances in the timing of spring migration of birds over time and in relation to rising temperatures, though phenological responses vary substantially within and among species. An understanding of the ecological, life-history and geographic variables that predict this intra- and interspecific variation can guide our projections of how populations and species are likely to respond to future climate change. Here, we conduct phylogenetic meta-analyses addressing slope estimates of the timing of avian spring migration regressed on (i) year and (ii) temperature, representing a total of 413 species across five continents. We take into account slope estimation error and examine phylogenetic, ecological and geographic predictors of intra- and interspecific variation. We confirm earlier findings that on average birds have significantly advanced their spring migration time by 2·1 days per decade and 1·2 days °C−1. We find that over time and in response to warmer spring conditions, short-distance migrants have advanced spring migratory phenology by more than long-distance migrants. We also find that larger bodied species show greater advance over time compared to smaller bodied species. Our results did not reveal any evidence that interspecific variation in migration response is predictable on the basis of species' habitat or diet. We detected a substantial phylogenetic signal in migration time in response to both year and temperature, suggesting that some of the shifts in migratory phenological response to climate are predictable on the basis of phylogeny. However, we estimate high levels of species and spatial variance relative to phylogenetic variance, which is consistent with plasticity in response to climate evolving fairly rapidly and being more influenced by adaptation to current local climate than by common descent. On average, avian spring migration times have advanced over time and as spring has become warmer. While we are able to identify predictors that explain some of the true among-species variation in response, substantial intra- and interspecific variation in migratory response remains to be explained