Century-scale changes in phytoplankton phenology in the Gulf of Maine

The phenology of major seasonal events is an important indicator of climate. We analyzed multiple datasets of in situ chlorophyll measurements from the Gulf of Maine dating back to the early 20th century in order to detect climate-scale changes in phenology. The seasonal cycle was consistently characterized by a two-bloom pattern, with spring and autumn blooms. The timing of both spring and autumn blooms has shifted later in the year at rates ranging from ∼1 to 9 days per decade since 1960, depending on the phenology metric, and trends only emerged at time scales of >40 years. Bloom phenology had only weak correlations with major climate indices. There were stronger associations between bloom timing and physical and chemical variables. Autumn bloom initiation correlated strongly with surface temperature and salinity, and spring bloom with nutrients. A later spring bloom also correlated with an increased cohort of Calanus finmarchicus, suggesting broader ecosystem implications of phytoplankton phenology

Rapid Climate-Driven Circulation Changes Threaten Conservation of Endangered North Atlantic Right Whales

As climate trends accelerate, ecosystems will be pushed rapidly into new states, reducing the potential efficacy of conservation strategies based on historical patterns. In the Gulf of Maine, climate-driven changes have restructured the ecosystem rapidly over the past decade. Changes in the Atlantic meridional overturning circulation have altered deepwater dynamics, driving warming rates twice as high as the fastest surface rates. This has had implications for the copepod Calanus finmarchicus, a critical food supply for the endangered North Atlantic right whale (Eubalaena glacialis). The oceanographic changes have driven a deviation in the seasonal foraging patterns of E. glacialis upon which conservation strategies depend, making the whales more vulnerable to ship strikes and gear entanglements. The effects of rapid climate-driven changes on a species at risk undermine current management approaches

Chemical and Biological Folding Contribute to Temperature-Sensitive ΔF508 CFTR Trafficking

Proteostasis (Balch et al. (2008) Science 319: 916) refers to the biology that maintains the proteome in health and disease. Proteostasis is challenged by the most common mutation in cystic fibrosis, ΔF508, a chloride channel (the cystic fibrosis transmembrane conductance regulator (CFTR)) that exhibits a temperature-sensitive phenotype for coupling to the coatomer complex II (COPII) transport machine for exit from the endoplasmic reticulum (ER). Whether rescue of export of ΔF508-CFTR at reduced temperature simply reflects energetic stabilization of the chemical fold defined by its primary sequence, or requires a unique proteostasis environment is unknown. We now show that reduced temperature (30°C) export of ΔF508 does not occur in some cell types despite efficient export of wild-type CFTR. We find ΔF508 export requires a local biological folding environment that is sensitive to heat/stress inducible factors found in some cell types suggesting that the energetic stabilization by reduced temperature is necessary, but not sufficient for export of ΔF508. Thus, the cell may require a proteostasis environment that is in part distinct from the wild-type pathway to restore ΔF508 coupling to COPII. These results are discussed in the context of the energetics of the protein fold and the potential application of small molecules to achieve a proteostasis environment favoring export of a functional form of ΔF508

COPII-dependent export of cystic fibrosis transmembrane conductance regulator from the ER uses a di-acidic exit code

Cystic fibrosis (CF) is a childhood hereditary disease in which the most common mutant form of the CF transmembrane conductance regulator (CFTR) ΔF508 fails to exit the endoplasmic reticulum (ER). Export of wild-type CFTR from the ER requires the coat complex II (COPII) machinery, as it is sensitive to Sar1 mutants that disrupt normal coat assembly and disassembly. In contrast, COPII is not used to deliver CFTR to ER-associated degradation. We find that exit of wild-type CFTR from the ER is blocked by mutation of a consensus di-acidic ER exit motif present in the first nucleotide binding domain. Mutation of the code disrupts interaction with the COPII coat selection complex Sec23/Sec24. We propose that the di-acidic exit code plays a key role in linking CFTR to the COPII coat machinery and is the primary defect responsible for CF in ΔF508-expressing patients

From CFTR biology toward combinatorial pharmacotherapy:expanded classification of cystic fibrosis mutations

More than 2000 mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) have been described that confer a range of molecular cell biological and functional phenotypes. Most of these mutations lead to compromised anion conductance at the apical plasma membrane of secretory epithelia and cause cystic fibrosis (CF) with variable disease severity. Based on the molecular phenotypic complexity of CFTR mutants and their susceptibility to pharmacotherapy, it has been recognized that mutations may impose combinatorial defects in CFTR channel biology. This notion led to the conclusion that the combination of pharmacotherapies addressing single defects (e.g., transcription, translation, folding, and/or gating) may show improved clinical benefit over available low-efficacy monotherapies. Indeed, recent phase 3 clinical trials combining ivacaftor (a gating potentiator) and lumacaftor (a folding corrector) have proven efficacious in CF patients harboring the most common mutation (deletion of residue F508, ΔF508, or Phe508del). This drug combination was recently approved by the U.S. Food and Drug Administration for patients homozygous for ΔF508. Emerging studies of the structural, cell biological, and functional defects caused by rare mutations provide a new framework that reveals a mixture of deficiencies in different CFTR alleles. Establishment of a set of combinatorial categories of the previously defined basic defects in CF alleles will aid the design of even more efficacious therapeutic interventions for CF patients

The 25th Anniversary of the Baby Doe Rules: Perspectives from the Fields of Law, Health Care, Ethics, and Disability Policy

A highly publicized and controversial case involving the withholding of medical treatment from a “Baby Doe” with Down syndrome gave rise in 1984 to the federal law known as the Baby Doe Rules, which went into effect the following year. The law conditions the grant of federal funds for any state’s child protective services program on the state’s assurance that it can respond to reports of medical neglect, which may include the withholding of medical treatment from disabled infants with life-threatening conditions. Leading scholars and practitioners from the fields of health care, law, ethics, and disability policy who are experts in the field of neonatal medicine and decision-making involving very premature and other medically at-risk infants gathered to provide thoughtful commentary and debate on the occasion of the 25th Anniversary of the Baby Doe Rules. The Georgia State University Law Review will publish a symposium volume on the topic in Fall 2009

The 25th Anniversary of the Baby Doe Rules: Perspectives from the Fields of Law, Health Care, Ethics, and Disability Policy

A highly publicized and controversial case involving the withholding of medical treatment from a “Baby Doe” with Down syndrome gave rise in 1984 to the federal law known as the Baby Doe Rules, which went into effect the following year. The law conditions the grant of federal funds for any state’s child protective services program on the state’s assurance that it can respond to reports of medical neglect, which may include the withholding of medical treatment from disabled infants with life-threatening conditions. Leading scholars and practitioners from the fields of health care, law, ethics, and disability policy who are experts in the field of neonatal medicine and decision-making involving very premature and other medically at-risk infants gathered to provide thoughtful commentary and debate on the occasion of the 25th Anniversary of the Baby Doe Rules. The Georgia State University Law Review will publish a symposium volume on the topic in Fall 2009

SeaWiFS Technical Report Series

Two issues regarding primary productivity, as it pertains to the Sea-viewing Wide Field-of-view Sensor (SeaWiFS) Program and the National Aeronautics and Space Administration (NASA) Mission to Planet Earth (MTPE) are presented in this volume. Chapter 1 describes the development of a science plan for deriving primary production for the world ocean using satellite measurements, by the Ocean Primary Productivity Working Group (OPPWG). Chapter 2 presents discussions by the same group, of algorithm classification, algorithm parameterization and data availability, algorithm testing and validation, and the benefits of a consensus primary productivity algorithm

Rapid climate-driven circulation changes threaten conservation of endangered north atlantic right whales

As climate trends accelerate, ecosystems will be pushed rapidly into new states, reducing the potential efficacy of conservation strategies based on historical patterns. In the Gulf of Maine, climate-driven changes have restructured the ecosystem rapidly over the past decade. Changes in the Atlantic meridional overturning circulation have altered deepwater dynamics, driving warming rates twice as high as the fastest surface rates. This has had implications for the copepod Calanus finmarchicus, a critical food supply for the endangered North Atlantic right whale (Eubalaena glacialis). The oceanographic changes have driven a deviation in the seasonal foraging patterns of E. glacialis upon which conservation strategies depend, making the whales more vulnerable to ship strikes and gear entanglements. The effects of rapid climate-driven changes on a species at risk undermine current management approaches.publishedVersio