The Discreet Structural Diversity of Briarellins: DU8+ Guided Multiple Structure Revisions Yielded Two Unknown Structural Types.

Briarellins, a subset of C2-C11 cyclized cembranoids, were proposed to contain a C3-C14 ether or lactone bridge, similar to asbestinins. However, the total synthesis of the proposed structure of briarellin J revealed a misassignment. We revisited briarellins, computationally, with the help of a recently developed hybrid DFT/parametric method, DU8+, and revised the structures of briarellin C14-C3 ε-lactones to new structural types containing either a C14-C11 or C14-C12 lactone bridge. The original structures of briarellin and asbestinin ethers were confirmed.

The value of universally available raw NMR data for transparency, reproducibility, and integrity in natural product research.

Covering: up to 2018With contributions from the global natural product (NP) research community, and continuing the Raw Data Initiative, this review collects a comprehensive demonstration of the immense scientific value of disseminating raw nuclear magnetic resonance (NMR) data, independently of, and in parallel with, classical publishing outlets. A comprehensive compilation of historic to present-day cases as well as contemporary and future applications show that addressing the urgent need for a repository of publicly accessible raw NMR data has the potential to transform natural products (NPs) and associated fields of chemical and biomedical research. The call for advancing open sharing mechanisms for raw data is intended to enhance the transparency of experimental protocols, augment the reproducibility of reported outcomes, including biological studies, become a regular component of responsible research, and thereby enrich the integrity of NP research and related fields.

Correction: The value of universally available raw NMR data for transparency, reproducibility, and integrity in natural product research.

Correction for 'The value of universally available raw NMR data for transparency, reproducibility, and integrity in natural product research' by James B. McAlpine et al., Nat. Prod. Rep., 2018, DOI: .

Heart rate variability for preclinical detection of secondary complications after subarachnoid hemorrhage.

BACKGROUND: We sought to determine if monitoring heart rate variability (HRV) would enable preclinical detection of secondary complications after subarachnoid hemorrhage (SAH). METHODS: We studied 236 SAH patients admitted within the first 48 h of bleed onset, discharged after SAH day 5, and had continuous electrocardiogram records available. The diagnosis and date of onset of infections and DCI events were prospectively adjudicated and documented by the clinical team. Continuous ECG was collected at 240 Hz using a high-resolution data acquisition system. The Tompkins-Hamilton algorithm was used to identify R-R intervals excluding ectopic and abnormal beats. Time, frequency, and regularity domain calculations of HRV were generated over the first 48 h of ICU admission and 24 h prior to the onset of each patient's first complication, or SAH day 6 for control patients. Clinical prediction rules to identify infection and DCI events were developed using bootstrap aggregation and cost-sensitive meta-classifiers. RESULTS: The combined infection and DCI model predicted events 24 h prior to clinical onset with high sensitivity (87 %) and moderate specificity (66 %), and was more sensitive than models that predicted either infection or DCI. Models including clinical and HRV variables together substantially improved diagnostic accuracy (AUC 0.83) compared to models with only HRV variables (AUC 0.61). CONCLUSIONS: Changes in HRV after SAH reflect both delayed ischemic and infectious complications. Incorporation of concurrent disease severity measures substantially improves prediction compared to using HRV alone. Further research is needed to refine and prospectively evaluate real-time bedside HRV monitoring after SAH.

Prolonged elevated heart rate is a risk factor for adverse cardiac events and poor outcome after subarachnoid hemorrhage.

INTRODUCTION: Sympathetic nervous system hyperactivity is common after subarachnoid hemorrhage (SAH). We sought to determine whether uncontrolled prolonged heart rate elevation is a risk factor for adverse cardiopulmonary events and poor outcome after SAH. METHODS: We prospectively studied 447 SAH patients between March 2006 and April 2012. Prior studies define prolonged elevated heart rate (PEHR) as heart rate >95 beats/min for >12 h. Major adverse cardiopulmonary events were documented according to the predefined criteria. Global outcome at 3 months was assessed with the modified Rankin Scale (mRS). RESULTS: 175 (39 %) patients experienced PEHR. Nonwhite race/ethnicity, admission Hunt-Hess grade ≥4, elevated APACHE-2 physiological subscore, and modified Fisher score were significant admission predictors of PEHR, whereas documented pre-hospital beta-blocker use was protective. After controlling for admission Hunt-Hess grade, Cox regression using time-lagged covariates revealed that PEHR onset in the previous 48 h was associated with an increased hazard for delayed cerebral ischemia, myocardial injury, and pulmonary edema. PEHR was associated with 3-month poor outcome (mRS 4-6) after controlling for known predictors. CONCLUSIONS: PEHR is associated with major adverse cardiopulmonary events and poor outcome after SAH. Further study is warranted to determine if early sympatholytic therapy targeted at sustained heart rate control can improve outcome after SAH.

Within-season flowering interruptions are common in the water-limited Sky Islands.

Within-season breaks in flowering have been reported in a wide range of highly variable ecosystems including deserts, tropical forests and high-elevation meadows. A tendency for interruptions in flowering has also been documented in southwestern US "Sky Island" plant communities, which encompass xeric to mesic conditions. Seasonal breaks in flowering have implications for plant reproductive success, population structure, and gene flow as well as resource availability for pollinators and dependent animals. Most reports of multiple within-season flowering events describe only two distinct flowering episodes. In this study, we set out to better quantify distinct within-season flowering events in highly variable Sky Islands plant communities. Across a >1,200 m elevation gradient, we documented a strong tendency for multiple within-season flowering events. In both distinct spring and summer seasons, we observed greater than two distinct within-season flowering in more than 10 % of instances. Patterns were clearly mediated by the different climate factors at work in the two seasons. The spring season, which is influenced by both temperature and precipitation, showed a mixed response, with the greatest tendency for multiple flowering events occurring at mid-elevations and functional types varying in their responses across the gradient. In the summer season, during which flowering across the gradient is limited by localized precipitation, annual plants exhibited the fewest within-season flowering events and herbaceous perennial plants showed the greatest. Additionally, more distinct events occurred at lower elevations. The patterns documented here provide a baseline for comparison of system responses to changing climate conditions.

Spring and summer patterns in flowering onset, duration, and constancy across a water-limited gradient.

PREMISE OF THE STUDY: Community-level flowering patterns can be characterized by onset, duration, and end as well as constancy, the degree to which species commence, cease, and reinitiate flowering within a season. In the mountainous Sky Islands region of the southwestern United States, flowering onset is clearly influenced by elevation in the spring, but much less so in the summer season. We evaluated whether these flowering metrics reflect these dissimilar patterns between distinct spring and summer seasons regarding the influence of the elevation and moisture gradient. • METHODS: We characterized flowering onset, end, duration, and constancy by plant functional type and their relationships to climate variables in spring and summer. We also evaluated the influence of climate on seasonal flowering patterns. • KEY RESULTS: Gaps in seasonal flowering occur frequently in this system in both seasons and among all plant functional types. In both seasons, annual plants exhibit the shortest flowering durations and highest constancies, and plants at low elevations, inhabiting environments with variable moisture conditions, show a greater tendency for longer flowering durations and lower constancy than high-elevation plants. Spring flowering characteristics are most influenced by the total amount of October-March precipitation as well as temperatures in these months, whereas summer flowering characteristics are influenced by the timing of summer-season precipitation, and next by the total amount of summer precipitation. • CONCLUSIONS: Flowering metrics, especially constancy and duration, show similar patterns in spring and summer and vary across elevation and moisture gradients. These patterns have substantial implications for plant and animal communities.

Forecasting phenology: from species variability to community patterns.

Shifts in species' phenology in response to climate change have wide-ranging consequences for ecological systems. However, significant variability in species' responses, together with limited data, frustrates efforts to forecast the consequences of ongoing phenological changes. Herein, we use a case study of three North American plant communities to explore the implications of variability across levels of organisation (within and among species, and among communities) for forecasting responses to climate change. We show how despite significant variation among species in sensitivities to climate, comparable patterns emerge at the community level once regional climate drivers are accounted for. However, communities differ with respect to projected patterns of divergence and overlap among their species' phenological distributions in response to climate change. These analyses and a review of hypotheses suggest how explicit consideration of spatial scale and levels of biological organisation may help to understand and forecast phenological responses to climate change.

Superior Ophthalmic Vein Flow Patterns as a Marker of Venous Sinus Stenosis and Hypertension in Idiopathic Intracranial Hypertension: A Case of Emergent Transverse Sinus Stenting as Treatment of Fulminant Idiopathic Intracranial Hypertension.

BACKGROUND: Fulminant idiopathic intracranial hypertension (IIH) can cause rapid vision loss. Transverse sinus stenosis is a finding commonly associated with IIH, and transverse sinus stenting has been used to rapidly reduce intracranial pressure and improve visual symptoms. Our objective was to describe a case of immediate alteration in reversed superior ophthalmic vein (SOV) flow in a fulminant IIH patient who underwent venous sinus stenting. METHODS: All charts, imaging, and notes spanning from the initial presentation to the post-intervention follow-up were reviewed and summarized for inclusion. RESULTS: A 24-year-old woman presented with several weeks of severe headaches and progressive vision loss. She was found to have severe papilledema and the opening pressure on lumbar puncture (LP) was 70 mm Hg. Computed tomography (CT) and magnetic resonance imaging demonstrated findings consistent with elevated intracranial pressure, and CT venography revealed stenosis of the right transverse sinus. She underwent an uncomplicated diagnostic cerebral angiogram, right venous sinus manometry, and right transverse to sigmoid sinus stenting procedure. Prior to deployment of the stent, a trans-stenotic pressure gradient of 12 mm Hg was observed within the right transverse-sigmoid junction, and flow through the bilateral SOVs was retrograde. Following stent placement, the pressure gradient normalized, and SOV flow was bidirectional. She subjectively reported improved vision, and there was improving papilledema. Repeat LP yielded an opening pressure of 21.6 mm Hg. CONCLUSIONS: This case demonstrates reversed SOV flow should be considered an indicator of severe venous sinus stenosis, and restoration to normal or near normal state following stenting for IIH is likely indicative of procedural success.

Onset of summer flowering in a 'Sky Island' is driven by monsoon moisture.

Temperatures for the southwestern USA are predicted to increase in coming decades, especially during the summer season; however, little is known about how summer precipitation patterns may change. We aimed to better understand how nonsucculent plants of a water-limited gradient encompassing xeric desert to mesic mountain-top may respond to changes in summer conditions. We used a species-rich 26-yr flowering record to determine species' relationships with precipitation and temperature in months coincident with and previous to flowering. The onset of summer flowering was strongly influenced by the amount and timing of July precipitation, regardless of elevation or life form, suggesting the critical importance of soil moisture in triggering summer flowering in this region. Future changes in the timing or consistency of the early monsoon will probably impact directly on the onset of flowering for many species in this region. In addition, a key implication of predicted increasing temperatures is a decrease in available soil moisture. At all elevations, many species may be expected to flower later in the summer under the decreased soil moisture conditions associated with warmer temperatures. However, impacts on summer flowering may be greater at higher elevations, because of the greater sensitivity of mesic plants to water stress.

Incidental Finding of a Duplicated Vertebral Artery Followed by a Spinal Dural Arteriovenous Fistula on Spinal Angiography.

Duplicated origin of the vertebral artery (VA) is an extremely rare normal anatomic variant. While most often considered non-pathological, duplicated origin carries an increased risk of dissection. An association with vascular pathologies such as aneurysms, arteriovenous malformations, and AV fistulas has been suggested. The objective is to describe this unusual anatomic variant with is concomitant vascular pathology and review current literature. The authors report a case of incidentally-discovered duplicated origin of the left VA in patients with a spinal dural arteriovenous fistula (dAVF). A 61-year-old man with a history significant for sarcoidosis presented with progressive lower extremity weakness and paresthesias. MRI of the thoracic spine demonstrated significant confluent edema and patchy contrast enhancement in the caudal spinal cord and conus medullaris which did not appear related to the patient's neurosarcoidosis. A diagnostic spinal angiogram incidentally demonstrated that the left V1 segment had a duplicated origin, one branch arising from the aortic arch and the other branch arising from the left subclavian artery, with union at the C5 transverse foramen. This finding represented an incidental anomaly discovery was noted to be incidental and was not believed to be related to the patients underlying pathology. Subsequently, a dAVF was discovered, originating from the right T7 spinal artery. Location of this vascular malformation directly correlated with the patient's symptoms. The patient then underwent embolization of the spinal dAVF and recovered uneventfully. Duplicated origin of the VA is an extremely rare but well-described variant, most commonly involving the left VA. To our knowledge, this is the only reported spinal dAVF associated with duplicated origin of the left VA. An association with other pathological entities has been suggested, and thus this case adds to a growing body of cases characterizing these relationships.

Enantioselective total synthesis of brevetoxin A: convergent coupling strategy and completion.

A highly convergent, enantioselective total synthesis of brevetoxin A is reported. The development of a [X+2+X] Horner-Wadsworth-Emmons/cyclodehydration/reductive etherification convergent coupling strategy allowed a unified approach to the synthesis of two advanced tetracyclic fragments from four cyclic ether subunits. The Horner-Wittig coupling of the two tetracyclic fragments provided substrates that were explored for reductive etherification, the success of which delivered a late-stage tetraol intermediate. The tetraol was converted to the natural product through an expeditious selective oxidative process followed by methylenation.

Enantioselective total synthesis of brevetoxin A: unified strategy for the B, E, G, and J subunits.

Brevetoxin A is a decacyclic ladder toxin that possesses 5-, 6-, 7-, 8-, and 9-membered oxacycles, as well as 22 tetrahedral stereocenters. Herein, we describe a unified approach to the B, E, G, and J rings based upon a ring-closing metathesis strategy from the corresponding dienes. The enolate technologies developed in our laboratory allowed access to the precursor acyclic dienes for the B, E, and G medium-ring ethers. The strategies developed for the syntheses of these four monocycles ultimately provided multigram quantities of each of the rings, supporting our efforts toward the completion of a convergent synthesis of brevetoxin A.

Ecohydrology of urban trees under passive and active irrigation in a semiarid city.

The infiltration of stormwater runoff for use by urban trees is a major co-benefit of green infrastructure for desert cities with limited water resources. However, the effects of this passive irrigation versus regular, controlled moisture inputs, or active irrigation, is largely unquantified. We monitored the ecohydrology of urban mesquite trees (Prosopis spp.) under these contrasting irrigation regimes in semiarid Tucson, AZ. Measurements included soil moisture, sap velocity, canopy greenness, and leaf-area index. We expected both irrigation types to provide additional deep (>20 cm) soil moisture compared to natural conditions, and that trees would depend on this deep moisture for transpiration and phenological activity. Results show that active irrigation supported higher soil moisture throughout the study than passive irrigation. Passive irrigation only provided additional deep moisture when green infrastructure features received impervious runoff from a city street. Sap velocity and greenness were similar under both irrigation types, outside of isolated periods of time. These differences occurred during the extremely wet summer 2017 when passively irrigated trees exhibited a greenness peak, and the dry conditions of spring when actively irrigated trees had higher sap flow and relative greenness. Finally, it was not determined that deep soil moisture had a stronger relationship with mesquite productivity than shallow moisture, but both relationships were stronger in the spring, before summer rains. This study aims to contribute empirical observations of green infrastructure performance for urban watershed management.

Severity of cerebral vasospasm associated with development of collaterals following aneurysmal subarachnoid hemorrhage.

INTRODUCTION: Cerebral collateral circulation has been studied extensively in ischemic stroke where it has been shown to be a predictor of reperfusion, final infarct size, and outcome. Little is known about the significance of the collaterals in the setting of aneurysmal subarachnoid hemorrhage (aSAH). We sought to evaluate the effect of cerebral vasospasm on the development of cerebral collaterals following aneurysmal subarachnoid hemorrhage and the effects of the latter on delayed cerebral ischemia (DCI). METHODS: We retrospectively evaluated 64 aSAH patients with evidence of DCI between day 5 and 7, enrolled in a prospectively maintained observational cohort study. Angiograms were evaluated by four blinded neurointerventionalists. We compared good collateral grades to poor collateral grades, additionally we compared enrolled individuals with any collaterals versus patients who had no collaterals. RESULTS: Inter-rater reliability for collateral grades was substantial (weighted kappa 0.632). Mild vasospasm was more frequent in patients with poor collateral grades compared with patients with good collateral grades (32% vs 4% P=0.012). There was no difference between the collateral groups with regards to DCI, functional, or cognitive outcome. Patients adjudicated to have any collaterals were more likely to have severe vasospasm (62% vs 33% P=0.023) and less likely to have mild vasospasm (37% vs 9% P=0.007). In a multivariable model, vasospasm severity remained associated with collateral status, while aneurysm location was not. CONCLUSIONS: The severity of vasospasm following aSAH was associated with the development of collaterals. There was no difference between collateral grades with regards to DCI or outcome.

Highly selective acetate aldol additions using mesityl-substituted chiral auxiliaries.

[reaction: see text] Highly diastereoselective acetate aldol additions using chlorotitanium enolates of mesityl-substituted N-acetyloxazolidinethione and N-acetylthiazolidinethione auxiliaries are reported. These additions proceed in high yields and diastereoselectivities (93:7 to 98:2) for aliphatic, aromatic, and ,-unsaturated aldehydes. Double diastereoselective acetate aldol additions are also reported and are found to proceed in high yields and diastereoselectivities (90:10 to 97:3).

Approach to the Synthesis of Briarane Diterpenes through a Dianionic Claisen Rearrangement and Ring-Closing Metathesis.

The synthesis of the briarane-brianthein A core has been accomplished utilizing an extension of the dianionic Ireland-Claisen rearrangement to establish the C1 quaternary carbon and the adjacent C10 ring juncture stereocenters. Two sequential ring-closing metathesis reactions were exploited to construct the 6-10 trans fused ring system.

USA National Phenology Network's volunteer-contributed observations yield predictive models of phenological transitions.

PURPOSE: In support of science and society, the USA National Phenology Network (USA-NPN) maintains a rapidly growing, continental-scale, species-rich dataset of plant and animal phenology observations that with over 10 million records is the largest such database in the United States. The aim of this study was to explore the potential that exists in the broad and rich volunteer-collected dataset maintained by the USA-NPN for constructing models predicting the timing of phenological transition across species' ranges within the continental United States. Contributed voluntarily by professional and citizen scientists, these opportunistically collected observations are characterized by spatial clustering, inconsistent spatial and temporal sampling, and short temporal depth (2009-present). Whether data exhibiting such limitations can be used to develop predictive models appropriate for use across large geographic regions has not yet been explored. METHODS: We constructed predictive models for phenophases that are the most abundant in the database and also relevant to management applications for all species with available data, regardless of plant growth habit, location, geographic extent, or temporal depth of the observations. We implemented a very basic model formulation-thermal time models with a fixed start date. RESULTS: Sufficient data were available to construct 107 individual species × phenophase models. Remarkably, given the limited temporal depth of this dataset and the simple modeling approach used, fifteen of these models (14%) met our criteria for model fit and error. The majority of these models represented the "breaking leaf buds" and "leaves" phenophases and represented shrub or tree growth forms. Accumulated growing degree day (GDD) thresholds that emerged ranged from 454 GDDs (Amelanchier canadensis-breaking leaf buds) to 1,300 GDDs (Prunus serotina-open flowers). Such candidate thermal time thresholds can be used to produce real-time and short-term forecast maps of the timing of these phenophase transition. In addition, many of the candidate models that emerged were suitable for use across the majority of the species' geographic ranges. Real-time and forecast maps of phenophase transitions could support a wide range of natural resource management applications, including invasive plant management, issuing asthma and allergy alerts, and anticipating frost damage for crops in vulnerable states. IMPLICATIONS: Our finding that several viable thermal time threshold models that work across the majority of the species ranges could be constructed from the USA-NPN database provides clear evidence that great potential exists this dataset to develop more enhanced predictive models for additional species and phenophases. Further, the candidate models that emerged have immediate utility for supporting a wide range of management applications.

Synthesis of the C29-C37 bicyclic ether core of (+)-sorangicin A.

Construction of the unique bicyclic bis-ether core of the macrolide (+)-sorangicin A has been achieved. This fragment was prepared by utilizing a one-pot cascade of three bond forming events. An epoxide opening of the epoxy tosylate 2 led to the formation of the tetrahydropyran and subsequently to a second epoxide. Finally, a second epoxide opening closed the tetrahydrofuran ring. The bicyclic fragment was synthesized in just nine steps from (E)-cinnamaldehyde.

Formal synthesis of 6-deoxyerythronolide B.

[reaction: see text] The enantioselective synthesis of the carbon skeleton of 6-deoxyerythronolide B has been achieved in 23 linear steps from propionaldehyde. The synthesis relies on an iterative approach employing an asymmetric acyl-thiazolidinethione propionate aldol reaction to establish eight of nine stereogenic centers. The remaining stereogenic center at C6 was set through a Myers alkylation employing a complex alkyl iodide.