David Lutz

Four Decades of Andean Timberline Migration and Implications for Biodiversity Loss with Climate Change

Rapid 21st-century climate change may lead to large population decreases and extinction in tropical montane cloud forest species in the Andes. While prior research has focused on species migrations per se, ecotones may respond to different environmental factors than species. Even if species can migrate in response to climate change, if ecotones do not they can function as hard barriers to species migrations, making ecotone migrations central to understanding species persistence under scenarios of climate change. We examined a 42-year span of aerial photographs and high resolution satellite imagery to calculate migration rates of timberline–the grassland-forest ecotone–inside and outside of protected areas in the high Peruvian Andes. We found that timberline in protected areas was more likely to migrate upward in elevation than in areas with frequent cattle grazing and fire. However, rates in both protected (0.24 m yr−1) and unprotected (0.05 m yr−1) areas are only 0.5–2.3% of the rates needed to stay in equilibrium with projected climate by 2100. These ecotone migration rates are 12.5 to 110 times slower than the observed species migration rates within the same forest, suggesting a barrier to migration for mid- and high-elevation species. We anticipate that the ecotone will be a hard barrier to migration under future climate change, leading to drastic population and biodiversity losses in the region unless intensive management steps are taken.

Myelin Basic Protein Cleaves Cell Adhesion Molecule L1 and Promotes Neuritogenesis and Cell Survival

Background: The cell adhesion molecule L1 plays important roles in the developing and adult nervous system. Results: L1 is cleaved by myelin basic protein (MBP) yielding a L1 fragment that promotes L1-dependent functions. Conclusion: L1 functions in the nervous system depend on MBP. Significance: Study of the L1 and MBP functions may contribute to understanding the pathogenesis of demyelinating and neurodegenerative diseases. The cell adhesion molecule L1 is a Lewisx-carrying glycoprotein that plays important roles in the developing and adult nervous system. Here we show that myelin basic protein (MBP) binds to L1 in a Lewisx-dependent manner. Furthermore, we demonstrate that MBP is released by murine cerebellar neurons as a sumoylated dynamin-containing protein upon L1 stimulation and that this MBP cleaves L1 as a serine protease in the L1 extracellular domain at Arg687 yielding a transmembrane fragment that promotes neurite outgrowth and neuronal survival in cell culture. L1-induced neurite outgrowth and neuronal survival are reduced in MBP-deficient cerebellar neurons and in wild-type cerebellar neurons in the presence of an MBP antibody or L1 peptide containing the MBP cleavage site. Genetic ablation of MBP in shiverer mice and mutagenesis of the proteolytically active site in MBP or of the MBP cleavage site within L1 as well as serine protease inhibitors and an L1 peptide containing the MBP cleavage site abolish generation of the L1 fragment. Our findings provide evidence for novel functions of MBP in the nervous system.

Remote sensing of boreal forest biophysical and inventory parameters: a review

The growing need to manage vegetation resources at regional and global spatial scales has led to the increased use of remote sensing technologies among forestry scientists and managers for use in their investigation and supervision of forested landscapes. With an array of extant and developing airborne and satellite sensors, as well as multiple analysis techniques, there is a need to discern the most acceptable methods with which to examine remotely sensed imagery for forest ecosystem parameters. We have reviewed the literature on the remote sensing of boreal forests in order to determine if common frameworks for monitoring and assessing change in forest biophysical and inventory parameters could be developed. Other important remote sensing techniques such as those for change detection and land cover identification were also examined. Our review examined studies documented within the scientific literature that involved the extraction of information on forest parameters with remote sensing instruments. Primarily, we focused on studies within the boreal forest, which plays an important part in the Earth-atmosphere system and contributes significantly to the global economy through forest-derived products and resources. Additionally, the boreal forest has served as the primary investigation site for many important forest remote sensing discoveries. In this review, we considered the forest parameter that was examined, the remote sensing platform used, and the calibration and validation accuracies for the study. The most effective methodology for examining each parameter, considering spatial scale, is described. In general, a fusion of multiple sensors provided the most accurate approach for parameter extraction; however, this may not be the most appropriate methodology for all studies, due to spatial and temporal considerations. In each case, we attempted to consider which methodology works the best in a variety of scenarios.

Nonyloxytryptamine mimics polysialic acid and modulates neuronal and glial functions in cell culture.

Polysialic acid (PSA) is a major regulator of cell–cell interactions in the developing nervous system and in neural plasticity in the adult. As a polyanionic molecule with high water‐binding capacity, PSA increases the intercellular space generating permissive conditions for cell motility. PSA enhances stem cell migration and axon path finding and promotes repair in the lesioned peripheral and central nervous systems, thus contributing to regeneration. As a next step in developing an improved PSA‐based approach to treat nervous system injuries, we searched for small organic compounds that mimic PSA and identified as a PSA mimetic 5‐nonyloxytryptamine oxalate, described as a selective 5‐hydroxytryptamine receptor 1B (5‐HT1B) agonist. Similar to PSA, 5‐nonyloxytryptamine binds to the PSA‐specific monoclonal antibody 735, enhances neurite outgrowth of cultured primary neurons and process formation of Schwann cells, protects neurons from oxidative stress, reduces migration of astrocytes and enhances myelination in vitro. Furthermore, nonyloxytryptamine treatment enhances expression of the neural cell adhesion molecule (NCAM) and its polysialylated form PSA‐NCAM and reduces expression of the microtubule‐associated protein MAP2 in cultured neuroblastoma cells. These results demonstrate that 5‐nonyloxytryptamine mimics PSA and triggers PSA‐mediated functions, thus contributing to the repertoire of molecules with the potential to improve recovery in acute and chronic injuries of the mammalian peripheral and central nervous systems.

Trade-offs between three forest ecosystem services across the state of New Hampshire, USA: timber, carbon, and albedo.

Forests are more frequently being managed to store and sequester carbon for the purposes of climate change mitigation. Generally, this practice involves long-term conservation of intact mature forests and/or reductions in the frequency and intensity of timber harvests. However, incorporating the influence of forest surface albedo often suggests that long rotation lengths may not always be optimal in mitigating climate change in forests characterized by frequent snowfall. To address this, we investigated trade-offs between three ecosystem services: carbon storage, albedo-related radiative forcing, and timber provisioning. We calculated optimal rotation length at 498 diverse Forest Inventory and Analysis forest sites in the state of New Hampshire, USA. We found that the mean optimal rotation lengths across all sites was 94 yr (standard deviation of sample means = 44 yr), with a large cluster of short optimal rotation lengths that were calculated at high elevations in the White Mountain National Forest. Using a regression tree approach, we found that timber growth, annual storage of carbon, and the difference between annual albedo in mature forest vs. a post-harvest landscape were the most important variables that influenced optimal rotation. Additionally, we found that the choice of a baseline albedo value for each site significantly altered the optimal rotation lengths across all sites, lowering the mean rotation to 59 yr with a high albedo baseline, and increasing the mean rotation to 112 yr given a low albedo baseline. Given these results, we suggest that utilizing temperate forests in New Hampshire for climate mitigation purposes through carbon storage and the cessation of harvest is appropriate at a site-dependent level that varies significantly across the state.

Polysialic acid enters the cell nucleus attached to a fragment of the neural cell adhesion molecule NCAM to regulate the circadian rhythm in mouse brain

In the mammalian nervous system, the neural cell adhesion molecule NCAM is the major carrier of the glycan polymer polysialic acid (PSA) which confers important functions to NCAMs protein backbone. PSA attached to NCAM contributes not only to cell migration, neuritogenesis, synaptic plasticity, and behavior, but also to regulation of the circadian rhythm by yet unknown molecular mechanisms. Here, we show that a PSA-carrying transmembrane NCAM fragment enters the nucleus after stimulation of cultured neurons with surrogate NCAM ligands, a phenomenon that depends on the circadian rhythm. Enhanced nuclear import of the PSA-carrying NCAM fragment is associated with altered expression of clock-related genes, as shown by analysis of cultured neuronal cells deprived of PSA by specific enzymatic removal. In vivo, levels of nuclear PSA in different mouse brain regions depend on the circadian rhythm and clock-related gene expression in suprachiasmatic nucleus and cerebellum is affected by the presence of PSA-carrying NCAM in the cell nucleus. Our conceptually novel observations reveal that PSA attached to a transmembrane proteolytic NCAM fragment containing part of the extracellular domain enters the cell nucleus, where PSA-carrying NCAM contributes to the regulation of clock-related gene expression and of the circadian rhythm.

Cathepsin E generates a sumoylated intracellular fragment of the cell adhesion molecule L1 to promote neuronal and Schwann cell migration as well as myelination

The cell adhesion molecule L1 regulates cellular responses in the developing and adult nervous system. Here, we show that stimulation of cultured mouse cerebellar neurons by a function‐triggering L1 antibody leads to cathepsin E‐mediated generation of a sumoylated 30 kDa L1 fragment (L1‐30) and to import of L1‐30 into the nucleus. Mutation of the sumoylation site at K1172 or the cathepsin E cleavage site at E1167 abolishes generation of L1‐30, while mutation of the nuclear localization signal at K1147 prevents nuclear import of L1‐30. Moreover, the aspartyl protease inhibitor pepstatin impairs the generation of L1‐30 and inhibits L1‐induced migration of cerebellar neurons and Schwann cells as well as L1‐dependent in vitro myelination on axons of dorsal root ganglion neurons by Schwann cells. L1‐stimulated migration of HEK293 cells expressing L1 with mutated cathepsin E cleavage site is diminished in comparison to migration of cells expressing non‐mutated L1. In addition, L1‐stimulated migration of HEK293 cells expressing non‐mutated L1 is also abolished upon knock‐down of cathepsin E expression and enhanced by over‐expression of cathepsin E. The findings of the present study indicate that generation and nuclear import of L1‐30 regulate neuronal and Schwann cell migration as well as myelination.

Dynamics of Resistance Development to Imatinib under Increasing Selection Pressure: A Combination of Mathematical Models and In Vitro Data

In the last decade, cancer research has been a highly active and rapidly evolving scientific area. The ultimate goal of all efforts is a better understanding of the mechanisms that discriminate malignant from normal cell biology in order to allow the design of molecular targeted treatment strategies. In individual cases of malignant model diseases addicted to a specific, ideally single oncogene, e.g. Chronic myeloid leukemia (CML), specific tyrosine kinase inhibitors (TKI) have indeed been able to convert the disease from a ultimately life-threatening into a chronic disease with individual patients staying in remission even without treatment suggestive of operational cure. These developments have been raising hopes to transfer this concept to other cancer types. Unfortunately, cancer cells tend to develop both primary and secondary resistance to targeted drugs in a substantially higher frequency often leading to a failure of treatment clinically. Therefore, a detailed understanding of how cells can bypass targeted inhibition of signaling cascades crucial for malignant growths is necessary. Here, we have performed an in vitro experiment that investigates kinetics and mechanisms underlying resistance development in former drug sensitive cancer cells over time in vitro. We show that the dynamics observed in these experiments can be described by a simple mathematical model. By comparing these experimental data with the mathematical model, important parameters such as mutation rates, cellular fitness and the impact of individual drugs on these processes can be assessed. Excitingly, the experiment and the model suggest two fundamentally different ways of resistance evolution, i.e. acquisition of mutations and phenotype switching, each subject to different parameters. Most importantly, this complementary approach allows to assess the risk of resistance development in the different phases of treatment and thus helps to identify the critical periods where resistance development is most likely to occur.

Small Molecule Agonists of Cell Adhesion Molecule L1 Mimic L1 Functions In Vivo.

Lack of permissive mechanisms and abundance of inhibitory molecules in the lesioned central nervous system of adult mammals contribute to the failure of functional recovery after injury, leading to severe disabilities in motor functions and pain. Peripheral nerve injury impairs motor, sensory, and autonomic functions, particularly in cases where nerve gaps are large and chronic nerve injury ensues. Previous studies have indicated that the neural cell adhesion molecule L1 constitutes a viable target to promote regeneration after acute injury. We screened libraries of known drugs for small molecule agonists of L1 and evaluated the effect of hit compounds in cell-based assays in vitro and in mice after femoral nerve and spinal cord injuries in vivo. We identified eight small molecule L1 agonists and showed in cell-based assays that they stimulate neuronal survival, neuronal migration, and neurite outgrowth and enhance Schwann cell proliferation and migration and myelination of neurons in an L1-dependent manner. In a femoral nerve injury mouse model, enhanced functional regeneration and remyelination after application of the L1 agonists were observed. In a spinal cord injury mouse model, L1 agonists improved recovery of motor functions, being paralleled by enhanced remyelination, neuronal survival, and monoaminergic innervation, reduced astrogliosis, and activation of microglia. Together, these findings suggest that application of small organic compounds that bind to L1 and stimulate the beneficial homophilic L1 functions may prove to be a valuable addition to treatments of nervous system injuries.

Biomass Energy and Climate Neutrality: The Case of the Northern Forest

We test the assumption that harvesting timber for energy production is assumed to have a carbon-neutral effect on climate. Our dynamic multiple-harvest Faustmann optimal rotation model of the Northern Forest and energy production in New Hampshire indicates that it is inappropriate to assume climate neutrality. We show that accounting for carbon means that timber bioenergy production causes negative externalities that lead to longer rotations. On average, carbon loss is 10.05 metric tons of stored carbon per hectare. To avoid this carbon release, logging rotations should be increased by up to 36%, or 12 years. (JEL Q23, Q42)