Climate change effects on biodiversity, ecosystems, ecosystem services, and natural resource management in the United States.

Climate change is a pervasive and growing global threat to biodiversity and ecosystems. Here, we present the most up-to-date assessment of climate change impacts on biodiversity, ecosystems, and ecosystem services in the U.S. and implications for natural resource management. We draw from the 4th National Climate Assessment to summarize observed and projected changes to ecosystems and biodiversity, explore linkages to important ecosystem services, and discuss associated challenges and opportunities for natural resource management. We find that species are responding to climate change through changes in morphology and behavior, phenology, and geographic range shifts, and these changes are mediated by plastic and evolutionary responses. Responses by species and populations, combined with direct effects of climate change on ecosystems (including more extreme events), are resulting in widespread changes in productivity, species interactions, vulnerability to biological invasions, and other emergent properties. Collectively, these impacts alter the benefits and services that natural ecosystems can provide to society. Although not all impacts are negative, even positive changes can require costly societal adjustments. Natural resource managers need proactive, flexible adaptation strategies that consider historical and future outlooks to minimize costs over the long term. Many organizations are beginning to explore these approaches, but implementation is not yet prevalent or systematic across the nation.

Biologics monitoring: incongruity between recommendations and clinician monitoring trends.

Background: Biologics are commonly used for moderate to severe psoriasis. Monitoring laboratory tests may provide little definitive benefit to patients.Objective: We queried a Humana database to gain insight regarding dermatologists' laboratory monitoring practices for psoriasis patients on biologics.Methods: Data were obtained from the Humana database. Our cohort included 333 patients with primary ICD-9 diagnosis of psoriasis (696.1) between the years 2008 and 2013 who are prescribed any biologic medication. Subjects on methotrexate, acitretin, or cyclosporine were excluded from the study. We separately queried laboratory tests by CPT codes and quantified based on frequency over a 2-year time period. Percentages of demographic group receiving a laboratory test at a given frequency category were calculated.Results: About 46% and 47% of patients received >4 comprehensive metabolic panel and complete blood count tests 2 years after starting a biologic. About 18% of individuals age >50 received greater than four Basic Metabolic Panel tests 2 years after starting a biologic.Limitations: Patient comorbidities might confound some of our findings, as these laboratory tests may have been ordered for a comorbidity rather than for biologics side effect monitoring.Conclusions: There are inconsistencies between current monitoring practices and guidelines. Clarifying biologics monitoring recommendations in psoriasis patients may reduce healthcare costs and provider workload.

Pustular psoriasis: pathophysiology and current treatment perspectives.

Psoriasis vulgaris is a chronic inflammatory disease that classically affects skin and joints and is associated with numerous comorbidities. There are several clinical subtypes of psoriasis including the uncommon pustular variants, which are subdivided into generalized and localized forms. Generalized forms of pustular psoriasis include acute generalized pustular psoriasis, pustular psoriasis of pregnancy, and infantile and juvenile pustular psoriasis. Localized forms include acrodermatitis continua of Hallopeau and palmoplantar pustular psoriasis. These subtypes vary in their presentations, but all have similar histopathologic characteristics. The immunopathogenesis of each entity remains to be fully elucidated and some debate exists as to whether these inflammatory pustular dermatoses should be classified as entities distinct from psoriasis vulgaris. Due to the rarity of these conditions and the questionable link to the common, plaque-type psoriasis, numerous therapies have shown variable results and most entities remain difficult to treat. With increasing knowledge of the pathogenesis of these variants of pustular psoriasis, the development and use of biologic and other immunomodulatory therapies holds promise for the future of successfully treating pustular variants of psoriasis.

Bimodal-hybrid heterocyclic amine targeting oxidative pathways and copper mis-regulation in Alzheimer's disease.

Oxidative stress resulting from metal-ion misregulation plays a role in the development of Alzheimer's disease (AD). This process includes the production of tissue-damaging reactive oxygen species and amyloid aggregates. Herein we describe the synthesis, characterization and protective capacity of the small molecule, lipoic cyclen, which has been designed to target molecular features of AD. This construct utilizes the biologically compatible and naturally occurring lipoic acid as a foundation for engendering low cellular toxicity in multiple cell lines, radical scavenging capacity, tuning the metal affinity of the parent cyclen, and results in an unexpected affinity for amyloid without inducing aggregation. The hybrid construct thereby shows protection against cell death induced by amyloid aggregates and copper ions. These results provide evidence for the rational design methods used to produce this fused molecule as a potential strategy for the development of lead compounds for the treatment of neurodegenerative disorders.

Modeling the dynamics of continental shelf carbon.

Continental margin systems are important contributors to global nutrient and carbon budgets. Effort is needed to quantify this contribution and how it will be modified under changing patterns of climate and land use. Coupled models will be used to provide projections of future states of continental margin systems. Thus, it is appropriate to consider the limitations that impede the development of realistic models. Here, we provide an overview of the current state of modeling carbon cycling on continental margins as well as the processes and issues that provide the next challenges to such models. Our overview is done within the context of a coupled circulation-biogeochemical model developed for the northeastern North American continental shelf region. Particular choices of forcing and initial fields and process parameterizations are used to illustrate the consequences for simulated distributions, as revealed by comparisons to observations using quantitative statistical metrics.

Accelerated warming and emergent trends in fisheries biomass yields of the world's large marine ecosystems.

Information on the effects of global climate change on trends in global fisheries biomass yields has been limited in spatial and temporal scale. Results are presented of a global study of the impact of sea surface temperature (SST) changes over the last 25 years on the fisheries yields of 63 large marine ecosystems (LMEs) that annually produce 80% of the world's marine fisheries catches. Warming trends were observed in 61 LMEs around the globe. In 18 of the LMEs, rates of SST warming were two to four times faster during the past 25 years than the globally averaged rates of SST warming reported by the Intergovernmental Panel on Climate Change in 2007. Effects of warming on fisheries biomass yields were greatest in the fast-warming northern Northeast Atlantic LMEs, where increasing trends in fisheries biomass yields were related to zooplankton biomass increases. In contrast, fisheries biomass yields of LMEs in the fast-warming, more southerly reaches of the Northeast Atlantic were declining in response to decreases in zooplankton abundance. The LMEs around the margins of the Indian Ocean, where SSTs were among the world's slowest warming, revealed a consistent pattern of fisheries biomass increases during the past 25 years, driven principally by human need for food security from fisheries resources. As a precautionary approach toward more sustainable fisheries utilization, management measures to limit the total allowable catch through a cap-and-sustain approach are suggested for the developing nations recently fishing heavily on resources of the Agulhas Current, Somali Current, Arabian Sea, and Bay of Bengal LMEs.

Toward parathyroid hormone minimization: conformational studies of cyclic PTH(1-14) analogues.

The N-terminal fragment of PTH(1-34) is critical for PTH1 receptor activation. Various modifications of PTH(1-14) have been shown to result in a considerable increase in signaling potency [Shimizu et al. (2000) J. Biol. Chem. 275, 21836-21843]. Our structural investigations revealed an unusually stable helical structure of the signaling domain (1-14), where residues 6 (Gln) and 10 (Gln or Asn) were located on the same face of the alpha-helix. To test whether a stable N-terminal alpha-helix is required for productive interaction with PTH1 receptor, we designed two conformationally restricted PTH(1-14) analogues, each containing a lactam bridge at positions 6 and 10. Specifically, substitutions Gln(6)-->Glu(6) and Asn(10)-->Lys(10) were introduced into the most potent [Ala(1,3,12),Gln(10),Har(11),Trp(14)]PTH(1-14)NH2 agonist. Both the Glu(6)-Lys(10) and Lys(6)-Glu(10) lactam-bridged analogues were characterized to examine the importance of orientation of the lactam. According to biological studies [Shimizu et al. (2003) Biochemistry 42, 2282-2290], none of the 6/10 substituted analogues (linear or cyclic) remained as active as the parent peptide. However, relative to their corresponding linear peptides, lactam-bridged analogues either maintained potency or showed 6-fold improvement. High-resolution structures as determined by 1H NMR and NOE-restrained molecular dynamics simulations clearly illustrate the structural differences between the linear and cyclic PTH(1-14) fragments, supporting the hypothesis that an alpha-helix is the preferred bioactive conformation of the N-terminal fragment of PTH. In addition, our results demonstrate that the structural order of the very first residues (1-4) of the signaling domain plays a significant role in PTH action.