For most species, a precise understanding of how climatic parameters determine the timing of seasonal life cycle stages is constrained by limited long-term data. Further, most long-term studies of plant phenology that have examined relationships between phenological timing and climate have been local in scale or have focused on single climatic parameters. Herbarium specimens, however, can expand the temporal and spatial coverage of phenological datasets. Using Trillium ovatum specimens collected over > 100 yr across its native range, we analyzed how seasonal climatic conditions (mean minimum temperature (Tmin ), mean maximum temperature and total precipitation (PPT)) affect flowering phenology. We then examined long-term changes in climatic conditions and in the timing of flowering across T. ovatum's range. Warmer Tmin advanced flowering, whereas higher PPT delayed flowering. However, Tmin and PPT were shown to interact: the advancing effect of warmer Tmin was strongest where PPT was highest, and the delaying effect of higher PPT was strongest where Tmin was coldest. The direction of temporal change in climatic parameters and in the timing of flowering was dependent on geographic location. Tmin , for example, decreased across the observation period in coastal regions, but increased in inland areas. Our results highlight the complex effects of climate and geographic location on phenology.

© 2015 Mazer et al. Phenology is the study of seasonal biological events such as flowering, leaf-out, insect emergence, and animal migration. Long-term observational studies at numerous temperate zone sites have found that the timing of phenological events responds to temporal variation in climate. To assess the phenological effects of climatic variation on California's flora, The California Phenology Project (CPP) was established in 2010 to develop and to test monitoring protocols and to create tools to support long-term phenological monitoring and education in several California national parks. The CPP uses standardized protocols developed in collaboration with the USA National Phenology Network (USA-NPN) to track the phenological status of 30 plant species across key environmental gradients (e.g., latitude, elevation, and precipitation). To date, over 860K phenological records collected by trained citizen scientists, natural resource managers, and park interns participating in the CPP have been contributed to the National Phenology Database. Observations recorded up to twice per week during the first 40 months of monitoring by the CPP were of sufficiently high resolution to detect associations between local climatic conditions and the onset of targeted phenophases. Here, we present analyses of four of the most intensively-monitored species: Baccharis pilularis (Asteraceae), Quercus lobata (Fagaceae), Sambucus nigra (Caprifoliaceae), and Eriogonum fasciculatum (Polygonaceae). We examined the effects of monthly climate parameters during a four month window (December to March), including mean minimum temperatures (Tmin), total monthly precipitation, and their interactions, on the onset dates of four phenophases per species. Stepwise regressions explained a high proportion (30-99%) of the variation in the onset date of each phenophase. Species and phenophases differed, however, with respect to the strength and the direction of the relationship between each month's conditions (Tmin and/or precipitation) and the timing of vegetative and reproductive phenophases. Given the high climatic variation represented among the monitored sites and among years (2011-2013), it was possible to detect significant associations between local, recent winter conditions and the onset dates of subsequent phenophases, although interactions between monthly conditions were also common. These patterns permit preliminary predictions regarding how these species will respond to future winter warming and intensifying drought.

Nerve injury-induced expression of the spinal calcium channel alpha-2-delta-1 subunit (Ca(v)alpha(2)delta(1)) has been shown to mediate behavioral hypersensitivity through a yet identified mechanism. We examined if this neuroplasticity modulates behavioral hypersensitivity by regulating spinal glutamatergic neurotransmission in injury-free transgenic mice overexpressing the Ca(v)alpha(2)delta(1) proteins in neuronal tissues. The transgenic mice exhibited hypersensitivity to mechanical stimulation (allodynia) similar to the spinal nerve ligation injury model. Intrathecally delivered antagonists for N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxyl-5-methylisoxazole-4-propionic acid (AMPA)/kainate receptors, but not for the metabotropic glutamate receptors, caused a dose-dependent allodynia reversal in the transgenic mice without changing the behavioral sensitivity in wild-type mice. This suggests that elevated spinal Ca(v)alpha(2)delta(1) mediates allodynia through a pathway involving activation of selective glutamate receptors. To determine if this is mediated by enhanced spinal neuronal excitability or pre-synaptic glutamate release in deep-dorsal horn, we examined wide-dynamic-range (WDR) neuron excitability with extracellular recording and glutamate-mediated excitatory postsynaptic currents with whole-cell patch recording in deep-dorsal horn of the Ca(v)alpha(2)delta(1) transgenic mice. Our data indicated that overexpression of Ca(v)alpha(2)delta(1) in neuronal tissues led to increased frequency, but not amplitude, of miniature excitatory post synaptic currents mediated mainly by AMPA/kainate receptors at physiological membrane potentials, and also by NMDA receptors upon depolarization, without changing the excitability of WDR neurons to high intensity stimulation. Together, these findings support a mechanism of Ca(v)alpha(2)delta(1)-mediated spinal sensitization in which elevated Ca(v)alpha(2)delta(1) causes increased pre-synaptic glutamate release that leads to reduced excitation thresholds of post-synaptic dorsal horn neurons to innocuous stimuli. This spinal sensitization mechanism may mediate at least partially the neuropathic pain states derived from increased pre-synaptic Ca(v)alpha(2)delta(1) expression.

Nerve injury-induced expression of the spinal calcium channel alpha-2-delta-1 subunit (Cavalpha2delta1) has been shown to mediate behavioral hypersensitivity through a yet identified mechanism. We examined if this neuroplasticity modulates behavioral hypersensitivity by regulating spinal glutamatergic neurotransmission in injury-free transgenic mice overexpressing the Cavalpha2delta1 proteins in neuronal tissues. The transgenic mice exhibited hypersensitivity to mechanical stimulation (allodynia) similar to the spinal nerve ligation injury model. Intrathecally delivered antagonists for N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxyl-5-methylisoxazole-4-propionic acid (AMPA)/kainate receptors, but not for the metabotropic glutamate receptors, caused a dose-dependent allodynia reversal in the transgenic mice without changing the behavioral sensitivity in wild-type mice. This suggests that elevated spinal Cavalpha2delta1 mediates allodynia through a pathway involving activation of selective glutamate receptors. To determine if this is mediated by enhanced spinal neuronal excitability or pre-synaptic glutamate release in deep-dorsal horn, we examined wide-dynamic-range (WDR) neuron excitability with extracellular recording and glutamate-mediated excitatory postsynaptic currents with whole-cell patch recording in deep-dorsal horn of the Cavalpha2delta1 transgenic mice. Our data indicated that overexpression of Cavalpha2delta1 in neuronal tissues led to increased frequency, but not amplitude, of miniature excitatory post synaptic currents mediated mainly by AMPA/kainate receptors at physiological membrane potentials, and also by NMDA receptors upon depolarization, without changing the excitability of WDR neurons to high intensity stimulation. Together, these findings support a mechanism of Cavalpha2delta1-mediated spinal sensitization in which elevated Cavalpha2delta1 causes increased pre-synaptic glutamate release that leads to reduced excitation thresholds of post-synaptic dorsal horn neurons to innocuous stimuli. This spinal sensitization mechanism may mediate at least partially the neuropathic pain states derived from increased pre-synaptic Cavalpha2delta1 expression.

BACKGROUND AND OBJECTIVES: There have been numerous reports of neurologic manifestations identified in hospitalized patients infected with SARS-CoV-2, the virus that causes COVID-19. Here, we identify the spectrum of associated neurologic symptoms and diagnoses, define the time course of their development, and examine readmission rates and mortality risk posthospitalization in a multiethnic urban cohort. METHODS: We identify the occurrence of new neurologic diagnoses among patients with laboratory-confirmed SARS-CoV-2 infection in New York City. A retrospective cohort study was performed on 532 cases (hospitalized patients with new neurologic diagnoses within 6 weeks of positive SARS-CoV-2 laboratory results between March 1, 2020, and August 31, 2020). We compare demographic and clinical features of the 532 cases with 532 controls (hospitalized COVID-19 patients without neurologic diagnoses) in a case-control study with one-to-one matching and examine hospital-related data and outcomes of death and readmission up to 6 months after acute hospitalization in a secondary case-only analysis. RESULTS: Among the 532 cases, the most common new neurologic diagnoses included encephalopathy (478, 89.8%), stroke (66, 12.4%), and seizures (38, 7.1%). In the case-control study, cases were more likely than controls to be male (58.6% vs 52.8%, p = 0.05), had baseline neurologic comorbidities (36.3% vs 13.0%, p < 0.0001), and were to be treated in an intensive care unit (62.0% vs 9.6%, p < 0.0001). Of the 394 (74.1%) cases who survived acute hospitalization, more than half (220 of 394, 55.8%) were readmitted within 6 months, with a mortality rate of 23.2% during readmission. DISCUSSION: Hospitalized patients with SARS-CoV-2 and new neurologic diagnoses have significant morbidity and mortality postdischarge. Further research is needed to define the effect of neurologic diagnoses during acute hospitalization on longitudinal post-COVID-19-related symptoms including neurocognitive impairment.