Research priorities for liver glycogen storage disease:An international priority setting partnership with the James Lind Alliance

The international liver glycogen storage disease (GSD) priority setting partnership (IGSDPSP) was established to identify the top research priorities in this area. The multiphase methodology followed the principles of the James Lind Alliance (JLA) guidebook. An international scoping survey in seven languages was distributed to patients, carers, and healthcare professionals to gather uncertainties, which were consolidated into summary questions. The existing literature was reviewed to ensure that the summary questions had not yet been answered. A second survey asked responders to prioritize these summary questions. A final shortlist of 22 questions was discussed during an international multi-stakeholder workshop, and a consensus was reached on the top 11 priorities using an adapted nominal group technique.In the first survey, a total of 1388 questions were identified from 763 responders from 58 countries. These original uncertainties were refined into 72 summary questions for a second prioritization survey. In total 562 responders from 58 countries answered the second survey. From the second survey, the top 10 for patients, carers and healthcare professionals was identified and this shortlist of 22 questions was taken to the final workshop. During the final workshop, participants identified the worldwide top 11 research priorities for liver GSD. In addition, a top three research priorities per liver GSD subtype was identified.This unique priority setting partnership is the first international, multilingual priority setting partnership focusing on ultra-rare diseases. This process provides a valuable resource for researchers and funding agencies to foster interdisciplinary and transnational research projects with a clear benefit for patients

Macrophage Migration Inhibitory Factor as a Chaperone Inhibiting Accumulation of Misfolded SOD1

SummaryMutations in superoxide dismutase (SOD1) cause amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by loss of motor neurons and accompanied by accumulation of misfolded SOD1 onto the cytoplasmic faces of intracellular organelles, including mitochondria and the endoplasmic reticulum (ER). Using inhibition of misfolded SOD1 deposition onto mitochondria as an assay, a chaperone activity abundant in nonneuronal tissues is now purified and identified to be the multifunctional macrophage migration inhibitory factor (MIF), whose activities include an ATP-independent protein folding chaperone. Purified MIF is shown to directly inhibit mutant SOD1 misfolding. Elevating MIF in neuronal cells suppresses accumulation of misfolded SOD1 and its association with mitochondria and the ER and extends survival of mutant SOD1-expressing motor neurons. Accumulated MIF protein is identified to be low in motor neurons, implicating correspondingly low chaperone activity as a component of vulnerability to mutant SOD1 misfolding and supporting therapies to enhance intracellular MIF chaperone activity

Wintertime phytoplankton bloom in the subarctic Pacific supported by continental margin iron

Author Posting. © American Geophysical Union, 2006. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Global Biogeochemical Cycles 20 (2006): GB1006, doi:10.1029/2005GB002557.Heightened biological activity was observed in February 1996 in the high-nutrient low-chlorophyll (HNLC) subarctic North Pacific Ocean, a region that is thought to be iron-limited. Here we provide evidence supporting the hypothesis that Ocean Station Papa (OSP) in the subarctic Pacific received a lateral supply of particulate iron from the continental margin off the Aleutian Islands in the winter, coincident with the observed biological bloom. Synchrotron X-ray analysis was used to describe the physical form, chemistry, and depth distributions of iron in size fractionated particulate matter samples. The analysis reveals that discrete micron-sized iron-rich hot spots are ubiquitous in the upper 200 m at OSP, more than 900 km from the closest coast. The specifics of the chemistry and depth profiles of the Fe hot spots trace them to the continental margins. We thus hypothesize that iron hot spots are a marker for the delivery of iron from the continental margin. We confirm the delivery of continental margin iron to the open ocean using an ocean general circulation model with an iron-like tracer source at the continental margin. We suggest that iron from the continental margin stimulated a wintertime phytoplankton bloom, partially relieving the HNLC condition.This work was supported by the U.S. Department of Energy, Office of Science, Office of Biological and Environmental Research (KP1202030) to J. K. B and by NSFATM-9987457 to I. F. The Advanced Light Source is supported by the Director, Office of Science, Office of Basic Energy Sciences, Division of Materials Sciences and Division of Chemical Sciences, Geosciences, and Biosciences of the U.S. Department of Energy at Lawrence Berkeley National Laboratory under contract DE-AC03-76SF00098

De naguales y culebras. entidades sobrenaturales y “guardianes de los pueblos” en el sur de oaxaca

ResumenEl presente artículo tiene como finalidad analizar una serie de relatos sobre naguales de pueblos zapotecos de la sierra sur de Oaxaca, en la mayoría de los cuales se hace referencia a la culebra de agua como entidad sobrenatural que protege a las comunidades contra los ataques de naguales de otros pueblos, en particular del pueblo huave de San Mateo del Mar, en la región del istmo de Tehuantepec. Estos relatos están insertos en un contexto complejo de relaciones interétnicas de pueblos de diversos grupos etnoligüísticos que han habitado la franja sur del estado –entre ellos zapotecos, chontales, mixes, huaves y zoques–, conformada por las regiones de la sierra sur, la costa y el istmo de Tehuantepec. El análisis se hizo, básicamente, a partir de dos aspectos: el carácter de los naguales como entidades sobrenaturales guardianes de los pueblos; y las historias locales y las relaciones interétnicas entre los pueblos zapotecos del sur y los huaves de San Mateo del Mar.AbstractThis article aims to analyze a series of stories about naguales of the zapotecs from the south of Oaxaca, the most of which refer the water snake as a supernatural protective entity of communities against attacks by naguales of other villages, especially the huave people from San Mateo del Mar, in the region of the Isthmus of Tehuantepec. These stories are integrated in a complex context of interethnic relations among peoples of various groups that have lived in the south fringe of state –among them zapotecs, chontals, mixes, zoques and huaves–, comprising the regions of the Southern Highlands, Coast and the Istmo of Tehuantepec. The analysis was done from two aspects: the character of the naguales as supernaturals entities that protect the villages, and the local stories and ethnic relations among zapotecs villages from south and huaves from San Mateo del Mar

Workshop Report for the Air-Sea Observations for a Safe Ocean, a satellite event for the UN Decade of Ocean Science for Sustainable Development - Safe Ocean Laboratory

The “Air-Sea Observations for a Safe Ocean” satellite event to the UN Decade Safe Ocean Laboratory was held on April 7, 2022 at 0000 CEST with a total number of 39 participants. The 2-hour virtual workshop, also referred to on the Observing Air-Sea Interactions Strategy (OASIS) website as “OASIS for a Safe Ocean” (https://airseaobs.org/oasis-for-a-safe-ocean), included a 30-minute poster/social session in the interactive Gather.Town platform (Figure 1). Overall, the event was interactive and productive, fostering constructive discussions about the OASIS strategy. With a focus on Small Island Developing States (SIDS), three of the four speakers and one moderator were from island states. Overall, the group was diverse and demonstrated the strong interest of the global air-sea interactions community to promote a Safe Ocean, particularly for SIDS. Participants included many Early Career Ocean Professionals (ECOP), representing the stake they have in the future, and had active women participation

CT Scan Screening for Lung Cancer: Risk Factors for Nodules and Malignancy in a High-Risk Urban Cohort

Low-dose computed tomography (CT) for lung cancer screening can reduce lung cancer mortality. The National Lung Screening Trial reported a 20% reduction in lung cancer mortality in high-risk smokers. However, CT scanning is extremely sensitive and detects non-calcified nodules (NCNs) in 24-50% of subjects, suggesting an unacceptably high false-positive rate. We hypothesized that by reviewing demographic, clinical and nodule characteristics, we could identify risk factors associated with the presence of nodules on screening CT, and with the probability that a NCN was malignant.We performed a longitudinal lung cancer biomarker discovery trial (NYU LCBC) that included low-dose CT-screening of high-risk individuals over 50 years of age, with more than 20 pack-year smoking histories, living in an urban setting, and with a potential for asbestos exposure. We used case-control studies to identify risk factors associated with the presence of nodules (n=625) versus no nodules (n=557), and lung cancer patients (n=30) versus benign nodules (n=128).The NYU LCBC followed 1182 study subjects prospectively over a 10-year period. We found 52% to have NCNs >4 mm on their baseline screen. Most of the nodules were stable, and 9.7% of solid and 26.2% of sub-solid nodules resolved. We diagnosed 30 lung cancers, 26 stage I. Three patients had synchronous primary lung cancers or multifocal disease. Thus, there were 33 lung cancers: 10 incident, and 23 prevalent. A sub-group of the prevalent group were stable for a prolonged period prior to diagnosis. These were all stage I at diagnosis and 12/13 were adenocarcinomas.NCNs are common among CT-screened high-risk subjects and can often be managed conservatively. Risk factors for malignancy included increasing age, size and number of nodules, reduced FEV1 and FVC, and increased pack-years smoking. A sub-group of screen-detected cancers are slow-growing and may contribute to over-diagnosis and lead-time biases