Amyloid Deposits: Protection Against Toxic Protein Species?

Neurodegenerative diseases ranging from Alzheimer’s disease and polyglutamine diseases to transmissible spongiform encephalopathies are associated with the aggregation and accumulation of misfolded proteins. In several cases the intracellular and extracellular protein deposits contain a fibrillar protein species called amyloid. However while amyloid deposits are hallmarks of numerous neurodegenerative diseases, their actual role in disease progression remains unclear. Especially perplexing is the often poor correlation between protein deposits and other markers of neurodegeneration. As a result the question remains whether amyloid deposits are the disease causing species, the consequence of cellular disease pathology or even the result of a protective cellular response to misfolded protein species. Here we highlight studies that suggest that accumulation and sequestration of misfolded protein in amyloid inclusion bodies and plaques can serve a protective function. Furthermore, we discuss how exceeding the cellular capacity for protective deposition of misfolded proteins may contribute to the formation of toxic protein species

Developing Linguistic Literacy: Perspectives from Corpus Linguistics and Multi-Dimensional Analysis

In their conceptual framework for linguistic literacy development, Ravid & Tolchinsky synthesize research studies from several perspectives. One of these is corpus-based research, which has been used for several large-scale research studies of spoken and written registers over the past 20 years. In this approach, a large, principled collection of natural texts (a \u27corpus\u27) is analysed using computational and interactive techniques, to identify the salient linguistic characteristics of each register or text variety. Three characteristics of corpus-based analysis are particularly important (see Biber, Conrad & Reppen 1998):(1) a special concern for the representativeness of the text sample being analysed, and for the generalizability of fndings; (2) overt recognition of the interactions among linguistic features: the ways in which features co-occur and alternate; (3) a focus on register as the most important parameter of linguistic variation: strong patterns of use in one register often represent only weak patterns in other registers. Corpus studies have documented the linguistic differences among spoken and written registers in English and other languages. Further, by analyzing systematic corpora produced by students at different stages, these same techniques have been used to track the patterns of extended language development associated with literacy. Two major patterns emerge from studies in this research tradition: (1) adult written language is dramatically different from natural conversation; and (2) written language is by no means homogeneous: rather, there are major linguistic differences among written registers. Thus, the developmental acquisition of linguistic literacy requires control over the patterns of register variation, in addition to a mastery of the mechanics of the written mode

Auditory-Motor Learning during Speech Production in 9-11-Year-Old Children

BACKGROUND: Hearing ability is essential for normal speech development, however the precise mechanisms linking auditory input and the improvement of speaking ability remain poorly understood. Auditory feedback during speech production is believed to play a critical role by providing the nervous system with information about speech outcomes that is used to learn and subsequently fine-tune speech motor output. Surprisingly, few studies have directly investigated such auditory-motor learning in the speech production of typically developing children. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we manipulated auditory feedback during speech production in a group of 9-11-year old children, as well as in adults. Following a period of speech practice under conditions of altered auditory feedback, compensatory changes in speech production and perception were examined. Consistent with prior studies, the adults exhibited compensatory changes in both their speech motor output and their perceptual representations of speech sound categories. The children exhibited compensatory changes in the motor domain, with a change in speech output that was similar in magnitude to that of the adults, however the children showed no reliable compensatory effect on their perceptual representations. CONCLUSIONS: The results indicate that 9-11-year-old children, whose speech motor and perceptual abilities are still not fully developed, are nonetheless capable of auditory-feedback-based sensorimotor adaptation, supporting a role for such learning processes in speech motor development. Auditory feedback may play a more limited role, however, in the fine-tuning of children's perceptual representations of speech sound categories

Intraperitoneal photodynamic therapy causes a capillary-leak syndrome.

BackgroundIn patients undergoing intraperitoneal (IP) photodynamic therapy (PDT), the combination of aggressive surgical debulking and light therapy causes an apparent systemic capillary-leak syndrome that necessitates significant intensive care unit (ICU) management after surgery.MethodsFrom May 1997 to May 2001, 65 patients underwent surgical debulking and PDT as part of an ongoing phase II trial for disseminated IP cancer. Perioperative data were reviewed retrospectively, and statistical analyses were performed to determine whether any identifiable factors were associated with the need for mechanical ventilation for longer than 1 day and with the occurrence of postoperative complications.ResultsForty-three women and 22 men (mean age, 49 years) were treated. Operative time averaged 9.8 hours, and mean estimated blood loss was 1450 mL. The mean crystalloid requirement for the first 48 hours after surgery was 29.3 L, and 49 patients required blood products. Twenty-four patients were intubated for longer than 24 hours, with a mean of 8.3 days for those intubated longer than 1 day. The median ICU stay was 4 days. Overall, 110 complications developed in 45 (69%) of the 65 patients. Significant complications included 6 patients with acute respiratory distress syndrome, 28 patients with infectious complications, and 4 patients with anastomotic complications. Statistical analyses revealed that surgery-related factors were significantly associated with these complication outcomes.ConclusionsPatients who undergo surgical debulking and IP PDT develop a significant capillary-leak syndrome after surgery that necessitates massive volume resuscitation, careful ICU monitoring, and, frequently, prolonged ventilatory support

Fluid Needs for Training, Competition, and Recovery in Track-and-Field Athletes

The 2019 International Amateur Athletics Federation Track-and-Field World Championships will take place in Qatar in the Middle East. The 2020 Summer Olympics will take place in Tokyo, Japan. It is quite likely that these events may set the record for hottest competitions in the recorded history of both the Track-and-Field World Championships and Olympic Games. Given the extreme heat in which track-and-field athletes will need to train and compete for these games, the importance of hydration is amplified more than in previous years. The diverse nature of track-and-field events, training programs, and individuality of athletes taking part inevitably means that fluid needs will be highly variable. Track-and-field events can be classified as low, moderate, or high risk for dehydration based on typical training and competition scenarios, fluid availability, and anticipated sweat losses. This paper reviews the risks of dehydration and potential consequences to performance in track-and-field events. The authors also discuss strategies for mitigating the risk of dehydration

The Legalization of Abortion and Subsequent Youth Homicide: A Time Series Analysis

In this article, we examine the association between the legalization of abortion with the 1973 Roe v. Wade decision and youth homicide in the 1980s and 1990s. An interrupted time series design was used to examine the deaths of all U.S. 15- to 24-year-olds that were classified as homicides according to the International Classification of Diseases (codes E960-969) from 1970 to 1998. The legalization of abortion is associated over a decade later with a gradual reduction in the homicides of White and non-White young men. The effect on the homicides of young women is minimal. We conclude that the 1990s decline in the homicide of young men is statistically associated with the legalization of abortion. Findings are not consistent with several alternative explanations, such as changes in the crack cocaine drug market. It is almost inconceivable that in the United States of today, policies affecting the choice to have children would be justified as a means to control crime. Yet, if the legalization of abortion had this unintended effect, the full range of policy implications needs to be discussed

Early Holocene Occupation at the West Lost River Site, Klamath County, Oregon

Excavations at the West Lost River Site (35KL972) provide new insights on early Holocene occupation of southwestern Oregon. The article focuses on the artifacts and specimens recovered from the site

The Mental Health Agency Research Network (MHARN): Developing a statewide network for knowledge sharing, technical assistance & collaborative research

The Mental Health Agency Research Network (MHARN) is a developing network for sharing knowledge and research collaboration between the UMMS Dept. of Psychiatry and other academics, DMH personnel, community providers, consumers and family members. Its mission is to close the gap between science and service in mental health services in Massachusetts by improving implementation of evidence based practices to benefit consumers. The MHARN provides a structure and mechanism for the Center for Mental Health Services Research (CMHSR) to better engage with DMH staff and community agencies around the state. As experience and research on science-to-service has demonstrated that dissemination of information about research findings is not sufficient to bring about changes in practice and benefits to consumers, the MHARN will incorporate principles and practices of the emerging science of implementation research

Two-years of stratospheric chemistry perturbations from the 2019/2020 Australian wildfire smoke

The very large pyrocumulonimbus events that occurred during the Australian summer of 2019/2020 caused extremely unusual partitioning of stratospheric chlorine in Southern Hemisphere midlatitudes and Antarctic regions. This was likely caused by enhanced HCl solubility in organic species that increased heterogeneous chemistry. Here, we show that observed HCl and ClONO2 values remain outside the pre-wildfire satellite range since 2005 in both the Southern Hemisphere midlatitude and Antarctic regions in 2021. Through model simulations, we replicate this multi-year prolonged chemical perturbation, in good agreement with observations. This was achieved by calculating HCl solubility in mixed wildfire and sulfate aerosols consistent with assumptions of 1) liquid-liquid phase separation and 2) linear dependence on organic and sulfate composition. The model simulations also suggest that the Australian pyrocumulonimbus organic aerosols contributed to low midlatitude ozone values in 2021. A marked photochemically controlled seasonality of the chemical perturbations and ozone depletion is also observed and simulated, and its underlying chemical drivers are identified. This work highlights that lower concentrations of smoke still had profound effects on stratospheric heterogeneous chemistry more than a year after the 2019/2020 wildfire event