Two Phase 3 Trials of Gantenerumab in Early Alzheimer's Disease.

BACKGROUND: Monoclonal antibodies that target amyloid-beta (Aß) have the potential to slow cognitive and functional decline in persons with early Alzheimer's disease. Gantenerumab is a subcutaneously administered, fully human, anti-Aß IgG1 monoclonal antibody with highest affinity for aggregated Aß that has been tested for the treatment of Alzheimer's disease. METHODS: We conducted two phase 3 trials (GRADUATE I and II) involving participants 50 to 90 years of age with mild cognitive impairment or mild dementia due to Alzheimer's disease and evidence of amyloid plaques on positron-emission tomography (PET) or cerebrospinal fluid (CSF) testing. Participants were randomly assigned to receive gantenerumab or placebo every 2 weeks. The primary outcome was the change from baseline in the score on the Clinical Dementia Rating scale-Sum of Boxes (CDR-SB; range, 0 to 18, with higher scores indicating greater cognitive impairment) at week 116. RESULTS: A total of 985 and 980 participants were enrolled in the GRADUATE I and II trials, respectively. The baseline CDR-SB score was 3.7 in the GRADUATE I trial and 3.6 in the GRADUATE II trial. The change from baseline in the CDR-SB score at week 116 was 3.35 with gantenerumab and 3.65 with placebo in the GRADUATE I trial (difference, -0.31; 95% confidence interval [CI], -0.66 to 0.05; P = 0.10) and was 2.82 with gantenerumab and 3.01 with placebo in the GRADUATE II trial (difference, -0.19; 95% CI, -0.55 to 0.17; P = 0.30). At week 116, the difference in the amyloid level on PET between the gantenerumab group and the placebo group was -66.44 and -56.46 centiloids in the GRADUATE I and II trials, respectively, and amyloid-negative status was attained in 28.0% and 26.8% of the participants receiving gantenerumab in the two trials. Across both trials, participants receiving gantenerumab had lower CSF levels of phosphorylated tau 181 and higher levels of Aß42 than those receiving placebo; the accumulation of aggregated tau on PET was similar in the two groups. Amyloid-related imaging abnormalities with edema (ARIA-E) occurred in 24.9% of the participants receiving gantenerumab, and symptomatic ARIA-E occurred in 5.0%. CONCLUSIONS: Among persons with early Alzheimer's disease, the use of gantenerumab led to a lower amyloid plaque burden than placebo at 116 weeks but was not associated with slower clinical decline. (Funded by F. Hoffmann-La Roche; GRADUATE I and II ClinicalTrials.gov numbers, NCT03444870 and NCT03443973, respectively.).

Asymmetric magnetic proximity interactions in MoSe2/CrBr3 van der Waals heterostructures.

Magnetic proximity interactions between atomically thin semiconductors and two-dimensional magnets provide a means to manipulate spin and valley degrees of freedom in non-magnetic monolayers, without using applied magnetic fields1-3. In such van der Waals heterostructures, magnetic proximity interactions originate in the nanometre-scale coupling between spin-dependent electronic wavefunctions in the two materials, and typically their overall effect is regarded as an effective magnetic field acting on the semiconductor monolayer4-8. Here we demonstrate that magnetic proximity interactions in van der Waals heterostructures can in fact be markedly asymmetric. Valley-resolved reflection spectroscopy of MoSe2/CrBr3 van der Waals structures reveals strikingly different energy shifts in the K and K' valleys of the MoSe2 due to ferromagnetism in the CrBr3 layer. Density functional calculations indicate that valley-asymmetric magnetic proximity interactions depend sensitively on the spin-dependent hybridization of overlapping bands and as such are likely a general feature of hybrid van der Waals structures. These studies suggest routes to control specific spin and valley states in monolayer semiconductors9,10.

Rates of cortical thinning in Alzheimer's disease signature regions associate with vascular burden but not with ß-amyloid status in cognitively normal adults at age 70.

BACKGROUND: Consistent patterns of reduced cortical thickness have been identified in early Alzheimer's disease (AD). However, the pathological factors that influence rates of cortical thinning within these AD signature regions remain unclear. METHODS: Participants were from the Insight 46 substudy of the MRC National Survey of Health and Development (NSHD; 1946 British birth cohort), a prospective longitudinal cohort study. Linear regression was used to examine associations of baseline cerebral ß-amyloid (Aß) deposition, measured using florbetapir positron emission tomography, and baseline white matter hyperintensity volume (WMHV) on MRI, a marker of cerebral small vessel disease, with subsequent longitudinal changes in AD signature cortical thickness quantified from baseline and repeat MRI (mean [SD] interval 2.4 [0.2] years). RESULTS: In a population-based sample of 337 cognitively normal older white adults (mean [SD] age at baseline 70.5 [0.6] years; 48.1% female), higher global WMHV at baseline related to faster subsequent rates of cortical thinning in both AD signature regions (~0.15%/year faster per 10 mL additional WMHV), whereas baseline Aß status did not. Among Aß positive participants (n=56), there was some evidence that greater global Aß standardised uptake value ratio at baseline related to faster cortical thinning in the AD signature Mayo region, but this did not reach statistical significance (p=0.08). CONCLUSIONS: Cortical thinning within AD signature regions may develop via cerebrovascular pathways. Perhaps reflecting the age of the cohort and relatively low prevalence of Aß-positivity, robust Aß-related differences were not detected. Longitudinal follow-up incorporating additional biomarkers will allow assessment of how these relationships evolve closer to expected dementia onset.

Surface currents shape protist community structure across the Indo-Pacific.

Biogeographic structure in marine protist communities is shaped by a combination of dispersal potential and environmental selection. High-throughput sequencing and global sampling efforts have helped better resolve the composition and functions of these communities in the world's oceans using both molecular and visual methods. However, molecular barcoding data are critically lacking across the Indo-Pacific, a region widely considered the epicenter of marine biodiversity. To fill this gap, we characterized protist communities in four sampling regions across Indonesia that represent the latitudinal, longitudinal, and human population gradients of the region: Lombok, Wakatobi, Misool, and Waigeo. We show high spatial structuring in marine protist communities across Indonesia, and biotic factors appear to play little role in driving this observed structure. Our results appear to be driven by abiotic factors linked to surface current patterns across the Indo-Pacific as a result of: (1) a choke point in circulation at the Indonesian Throughflow leading to low diatom diversity in Lombok, Wakatobi, and Misool; (2) an increase in nutrient availability at the edge of the Halmahera Eddy in Waigeo, leading to an increase in diatom diversity; and/or (3) seasonal variations in protist communities in line with shifts in velocity of the Indonesian Throughflow. Overall, our results highlight the importance of abiotic factors in shaping protist communities on broad geographic scales over biotic, top-down pressures, such as grazing from higher trophic levels.

A revision of the genus Wrangelia (Wrangeliaceae, Ceramiales) in Bermuda resolves six new species including W. ryancraigii from the mesophotic zone.

Four species of the genus Wrangelia are presently known from the western Atlantic Ocean: W. argus, W. bicuspidata, W. penicillata, and W. gordoniae, with the first three historically being reported from Bermuda. Morphological and molecular barcode (COI-5P) and phylogenetic analyses used in this study (SSU, LSU, rbcL) indicated eight species groupings of Wrangelia in Bermuda, excluding two of the historically recognized species, retaining only W. argus while adding seven new species, of which six are formally described. What had been historically reported as W. penicillata from Bermuda was shown to be distinct from Mediterranean Sea specimens (type locality) and was shown to be a mixture of W. hesperia sp. nov. and W. incrassata sp. nov. Along with these two, three other new species (W. laxa sp. nov., W. ryancraigii sp. nov., and W. secundiramea sp. nov.) have complete rhizoidal cortication tightly covering axial cells of indeterminate axes below the apices, distinguishing them from the two local incompletely corticated congeners W. argus and W. abscondita sp. nov., the latter a morphologically cryptic sister species with W. bicuspidata from the Caribbean Sea. Only one of the new species, W. ryancraigii, has thus far been observed in the mesophotic zone off the Bermuda platform, and it is morphologically cryptic with the euphotic zone's W. laxa.

Comparing first-principles density functionals plus corrections for the lattice dynamics of YBa2Cu3O6.

The enigmatic mechanism underlying unconventional high-temperature superconductivity, especially the role of lattice dynamics, has remained a subject of debate. Theoretical insights have long been hindered due to the lack of an accurate first-principles description of the lattice dynamics of cuprates. Recently, using the r2SCAN meta-generalized gradient approximation (meta-GGA) functional, we have been able to achieve accurate phonon spectra of an insulating cuprate YBa2Cu3O6 and discover significant magnetoelastic coupling in experimentally interesting Cu-O bond stretching optical modes [Ning et al., Phys. Rev. B 107, 045126 (2023)]. We extend this work by comparing Perdew-Burke-Ernzerhof and r2SCAN performances with corrections from the on-site Hubbard U and the D4 van der Waals (vdW) methods, aiming at further understanding on both the materials science side and the density functional side. We demonstrate the importance of vdW and self-interaction corrections for accurate first-principles YBa2Cu3O6 lattice dynamics. Since r2SCAN by itself partially accounts for these effects, the good performance of r2SCAN is now more fully explained. In addition, the performances of the Tao-Mo series of meta-GGAs, which are constructed in a different way from the strongly constrained and appropriately normed (SCAN) meta-GGA and its revised version r2SCAN, are also compared and discussed.

Rubble fields shape planktonic protist communities in Indonesia at a local scale.

The Coral Triangle encompasses nearly 30% of the world's coral reefs and is widely considered the epicenter of marine biodiversity. Destructive fishing practices and natural disturbances common to this region damage reefs leaving behind fields of coral rubble. While the impacts of disturbances in these ecosystems are well documented on metazoans, we have a poor understanding of their impact on microbial communities at the base of the food web. We use metabarcoding to characterize protist community composition in sites of varying fisheries management schemes and benthic profiles across the island of Lombok, Indonesia. Our study shows that rubble coverage and net primary productivity are the strongest explainers of variation in protist communities across Lombok. More specifically, rubble fields are characterized by increases in small heterotrophic protists, including ciliates and cercozoans. In addition to shifts in heterotrophic protist communities, we also observed increases in diatom relative abundance in rubble fields, which corresponded to sites with higher net primary productivity. These results are the first to characterize protist communities in tropical marine rubble fields and provide insight on environmental factors potentially driving these shifts on a local scale.

Competing stripe and magnetic phases in the cuprates from first principles.

Realistic description of competing phases in complex quantum materials has proven extremely challenging. For example, much of the existing density-functional-theory-based first-principles framework fails in the cuprate superconductors. Various many-body approaches involve generic model Hamiltonians and do not account for the interplay between the spin, charge, and lattice degrees of freedom. Here, by deploying the recently constructed strongly constrained and appropriately normed (SCAN) density functional, we show how the landscape of competing stripe and magnetic phases can be addressed on a first-principles basis both in the parent insulator YBa2Cu3O6 and the near-optimally doped YBa2Cu3O7 as archetype cuprate compounds. In YBa2Cu3O7, we find many stripe phases that are nearly degenerate with the ground state and may give rise to the pseudogap state from which the high-temperature superconducting state emerges. We invoke no free parameters such as the Hubbard U, which has been the basis of much of the existing cuprate literature. Lattice degrees of freedom are found to be crucially important in stabilizing the various phases.

Population-based blood screening for preclinical Alzheimer's disease in a British birth cohort at age 70.

Alzheimer's disease has a preclinical stage when cerebral amyloid-ß deposition occurs before symptoms emerge, and when amyloid-ß-targeted therapies may have maximum benefits. Existing amyloid-ß status measurement techniques, including amyloid PET and CSF testing, are difficult to deploy at scale, so blood biomarkers are increasingly considered for screening. We compared three different blood-based techniques-liquid chromatography-mass spectrometry measures of plasma amyloid-ß, and single molecule array (Simoa) measures of plasma amyloid-ß and phospho-tau181-to detect cortical 18F-florbetapir amyloid PET positivity (defined as a standardized uptake value ratio of >0.61 between a predefined cortical region of interest and eroded subcortical white matter) in dementia-free members of Insight 46, a substudy of the population-based British 1946 birth cohort. We used logistic regression models with blood biomarkers as predictors of amyloid PET status, with or without age, sex and APOE ε4 carrier status as covariates. We generated receiver operating characteristics curves and quantified areas under the curves to compare the concordance of the different blood tests with amyloid PET. We determined blood test cut-off points using Youden's index, then estimated numbers needed to screen to obtain 100 amyloid PET-positive individuals. Of the 502 individuals assessed, 441 dementia-free individuals with complete data were included; 82 (18.6%) were amyloid PET-positive. The area under the curve for amyloid PET status using a base model comprising age, sex and APOE ε4 carrier status was 0.695 (95% confidence interval: 0.628-0.762). The two best-performing Simoa plasma biomarkers were amyloid-ß42/40 (0.620; 0.548-0.691) and phospho-tau181 (0.707; 0.646-0.768), but neither outperformed the base model. Mass spectrometry plasma measures performed significantly better than any other measure (amyloid-ß1-42/1-40: 0.817; 0.770-0.864 and amyloid-ß composite: 0.820; 0.775-0.866). At a cut-off point of 0.095, mass spectrometry measures of amyloid-ß1-42/1-40 detected amyloid PET positivity with 86.6% sensitivity and 71.9% specificity. Without screening, to obtain 100 PET-positive individuals from a population with similar amyloid PET positivity prevalence to Insight 46, 543 PET scans would need to be performed. Screening using age, sex and APOE ε4 status would require 940 individuals, of whom 266 would proceed to scan. Using mass spectrometry amyloid-ß1-42/1-40 alone would reduce these numbers to 623 individuals and 243 individuals, respectively. Across a theoretical range of amyloid PET positivity prevalence of 10-50%, mass spectrometry measures of amyloid-ß1-42/1-40 would consistently reduce the numbers proceeding to scans, with greater cost savings demonstrated at lower prevalence.

Structure, functions, performance and gaps of event-based surveillance (EBS) in Sudan, 2021: a cross-sectional review.

BACKGROUND: Event-based surveillance (EBS) is an essential component of Early Warning Alert and Response (EWAR) as per the International Health Regulations (IHR), 2005. EBS was established in Sudan in 2016 as a complementary system for Indicator-based surveillance (IBS). This review will provide an overview of the current EBS structure, functions and performance in Sudan and identify the gaps and ways forward.  METHODS: The review followed the WHO/EMRO guidelines and tools. Structured discussions, observation and review of records and guidelines were done at national and state levels. Community volunteers were interviewed through phone calls. Directors of Health Emergency and Epidemic Control, surveillance officers and focal persons for EBS at the state level were also interviewed. SPSS software was used to perform descriptive statistical analysis for quantitative data, while qualitative data was analysed manually using thematic analysis, paying particular attention to the health system level allowing for an exploration of how and why experiences differ across levels. Written and verbal consents were obtained from all participants as appropriate. RESULTS: Sudan has a functioning EBS; however, there is an underestimation of its contribution and importance at the national and states levels. The link between the national level and states is ad hoc or is driven by the need for reports. While community event-based surveillance (CEBS) is functioning, EBS from health facilities and from non-health sectors is not currently active. The integration of EBS into overall surveillance was not addressed, and the pathway from detection to action is not clear. The use of electronic databases and platforms is generally limited. Factors that would improve performance include training, presence of a trained focal person at state level, and regular follow-up from the national level. Factors such as staff turnover, income in relation to expenses and not having a high academic qualification (Diploma or MSc) were noticed as inhibiting factors. CONCLUSION: The review recommended revisiting the surveillance structure at national and state levels to put EBS as an essential component and to update guidelines and standard operation procedures SOPs to foster the integration between EBS components and the overall surveillance system. The need for strengthening the link with states, capacity building and re-addressing the training modalities was highlighted.

Gregarine single-cell transcriptomics reveals differential mitochondrial remodeling and adaptation in apicomplexans.

BACKGROUND: Apicomplexa is a diverse phylum comprising unicellular endobiotic animal parasites and contains some of the most well-studied microbial eukaryotes including the devastating human pathogens Plasmodium falciparum and Cryptosporidium hominis. In contrast, data on the invertebrate-infecting gregarines remains sparse and their evolutionary relationship to other apicomplexans remains obscure. Most apicomplexans retain a highly modified plastid, while their mitochondria remain metabolically conserved. Cryptosporidium spp. inhabit an anaerobic host-gut environment and represent the known exception, having completely lost their plastid while retaining an extremely reduced mitochondrion that has lost its genome. Recent advances in single-cell sequencing have enabled the first broad genome-scale explorations of gregarines, providing evidence of differential plastid retention throughout the group. However, little is known about the retention and metabolic capacity of gregarine mitochondria. RESULTS: Here, we sequenced transcriptomes from five species of gregarines isolated from cockroaches. We combined these data with those from other apicomplexans, performed detailed phylogenomic analyses, and characterized their mitochondrial metabolism. Our results support the placement of Cryptosporidium as the earliest diverging lineage of apicomplexans, which impacts our interpretation of evolutionary events within the phylum. By mapping in silico predictions of core mitochondrial pathways onto our phylogeny, we identified convergently reduced mitochondria. These data show that the electron transport chain has been independently lost three times across the phylum, twice within gregarines. CONCLUSIONS: Apicomplexan lineages show variable functional restructuring of mitochondrial metabolism that appears to have been driven by adaptations to parasitism and anaerobiosis. Our findings indicate that apicomplexans are rife with convergent adaptations, with shared features including morphology, energy metabolism, and intracellularity.

Phylogenomics, divergence time estimation and trait evolution provide a new look into the Gracilariales (Rhodophyta).

The Gracilariales is a highly diverse, widely distributed order of red algae (Rhodophyta) that forms a well-supported clade. Aside from their ecological importance, species of Gracilariales provide important sources of agarans and possess bioactive compounds with medicinal and pharmaceutical use. Recent phylogenetic analyses from a small number of genes have greatly advanced our knowledge of evolutionary relationships in this clade, yet several key nodes were not especially well resolved. We assembled a phylogenomic data set containing 79 nuclear genes, 195 plastid genes, and 24 mitochondrial genes from species representing all three major Gracilariales lineages, including: Melanthalia, Gracilariopsis, and Gracilaria sensu lato. This data set leads to a fully-resolved phylogeny of Gracilariales, which is highly-consistent across genomic compartments. In agreement with previous findings, Melanthalia obtusata was sister to a clade including Gracilaria s.l. and Gracilariopsis, which were each resolved as well-supported clades. Our results also clarified the long-standing uncertainty about relationships in Gracilaria s.l., not resolved in single and multi-genes approaches. We further characterized the divergence time, organellar genome architecture, and morphological trait evolution in Gracilarales to better facilitate its taxonomic treatment. Gracilariopsis and Gracilaria s.l. are comparable taxonomic ranks, based on the overlapping time range of their divergence. The genomic structure of plastid and mitochondria is highly conserved within each clade but differs slightly among these clades in gene contents. For example, the plastid gene petP is lost in Gracilaria s.l. and the mitochondrial gene trnH is in different positions in the genome of Gracilariopsis and Gracilaria s.l. Our analyses of ancestral character evolution provide evidence that the main characters used to delimitate genera in Gracilariales, such as spermatangia type and features of the cystocarp's anatomy, overlap in subclades of Gracilaria s.l. We discuss the taxonomy of Gracilariales in light of these results and propose an objective and practical classification, which is in agreement with the criteria of monophyly, exclusive characters, predictability and nomenclatural stability.

Subjective cognitive complaints at age 70: associations with amyloid and mental health.

OBJECTIVE: To investigate subjective cognitive decline (SCD) in relation to ß-amyloid pathology and to test for associations with anxiety, depression, objective cognition and family history of dementia in the Insight 46 study. METHODS: Cognitively unimpaired ~70-year-old participants, all born in the same week in 1946 (n=460, 49% female, 18% amyloid-positive), underwent assessments including the SCD-Questionnaire (MyCog). MyCog scores were evaluated with respect to 18F-Florbetapir-PET amyloid status (positive/negative). Associations with anxiety, depression, objective cognition (measured by the Preclinical Alzheimer Cognitive Composite, PACC) and family history of dementia were also investigated. The informant's perspective on SCD was evaluated in relation to MyCog score. RESULTS: Anxiety (mean (SD) trait anxiety score: 4.4 (3.9)) was associated with higher MyCog scores, especially in women. MyCog scores were higher in amyloid-positive compared with amyloid-negative individuals (adjusted means (95% CIs): 5.3 (4.4 to 6.1) vs 4.3 (3.9 to 4.7), p=0.044), after accounting for differences in anxiety. PACC (mean (SD) -0.05 (0.68)) and family history of dementia (prevalence: 23.9%) were not independently associated with MyCog scores. The informant's perception of SCD was generally in accordance with that of the participant. CONCLUSIONS: This cross-sectional study demonstrates that symptoms of SCD are associated with both ß-amyloid pathology, and more consistently, trait anxiety in a population-based cohort of older adults, at an age when those who are destined to develop dementia are still likely to be some years away from symptoms. This highlights the necessity of considering anxiety symptoms when assessing Alzheimer's disease pathology and SCD.

Surgical Coaching for Advancement of Global Surgical Skills and Capacity: A Systematic Review.

BACKGROUND: Surgical coaching is an emerging concept of education and collaboration to improve surgical performance. Surgical education in low-resource settings remains a challenge because of confounding barriers of access, resources, and sustainability. No formal assessments of coaching as a means to improve surgical quality in low- or middle-income countries (LMICs) exist. The purpose of this review is to explore if surgical coaching could serve as an effective method of fostering continued education and advancement of surgical skills in low-resource settings. METHODS: We conducted a systematic literature search in July 2018. Included studies were peer-reviewed and met preestablished study criteria. Studies must have assessed surgical coaching, specifically defined as a means to establish continuous professional growth of trainees and practicing surgeons. RESULTS: Of 2189 articles, 175 were selected for full-text analysis, 23 met inclusion criteria for analysis, 13 of these 23 articles evaluated coaching of trainees, 10 articles assessed coaching surgeons in established careers. 18 of the 23 articles discussed skill acquisition, 4 of which assessed nontechnical skills alone, and 14 assessed technical skills or both technical and nontechnical skills. Remote or cross-institutional coaching was explored in 8 of the 23 studies. None of the studies discussed or evaluated coaching in LMICs. CONCLUSIONS: Coaching is a method of teaching surgeons at multiple stages of a career. The explored advantages of surgical coaching may be applied to continuous performance improvement and collaboration with surgeons in LMICs. Furthermore, coaching may aid in advancement of the well-established Lancet Global Surgery Indicators, improving surgical capacity and quality in LMICs.

Response to Preuss and Zuccarello (2020): biological definitions that can be unambiguously applied for red algal parasites.

In response to a comment in this issue on our proposal of new terminology to distinguish red algal parasites, we clarify a few key issues. The terms adelphoparasite and alloparasite were previously used to identify parasites that infected close or distant relatives. However, most red algal parasites have only been studied morphologically, and molecular tools have shown that these binary terms do a poor job at representing the range of parasite-host relationships. We recognize the need to clarify inferred misconceptions that appear to be drawing from historical terminology to contaminate our new definitions. We did not intend to replace the term adelphoparasite with neoplastic parasites and the term alloparasites with archaeplastic parasites. Rather, we seek to establish new terms for discussing red algal parasites, based on the retention of a native plastid, a binary biological trait that is relatively easy to identify using modern methods and has biological implications for the interactions between a parasite and its host. The new terminology can better account for the spectrum of relationships and developmental patterns found among the many independently evolved red algal parasites, and it is intended to inspire new research, particularly the role of plastids in the survival and evolution of red algal parasites.

Microbial Diversity in the Eukaryotic SAR Clade: Illuminating the Darkness Between Morphology and Molecular Data.

Despite their diversity and ecological importance, many areas of the SAR-Stramenopila, Alveolata, and Rhizaria-clade are poorly understood as the majority (90%) of SAR species lack molecular data and only 5% of species are from well-sampled families. Here, we review and summarize the state of knowledge about the three major clades of SAR, describing the diversity within each clade and identifying synapomorphies when possible. We also assess the "dark area" of SAR: the morphologically described species that are missing molecular data. The majority of molecular data for SAR lineages are characterized from marine samples and vertebrate hosts, highlighting the need for additional research effort in areas such as freshwater and terrestrial habitats and "non-vertebrate" hosts. We also describe the paucity of data on the biogeography of SAR species, and point to opportunities to illuminate diversity in this major eukaryotic clade. See also the video abstract here: https://youtu.be/_VUXqaX19Rw.

Recruitment tolerance to increased temperature present across multiple kelp clades.

Kelp systems dominate nearshore marine environments in upwelling zones characterized by cold temperatures and high nutrients. Worldwide, kelp population persistence and recruitment success generally decreases with rising water temperatures coupled with low nutrients, making kelp populations vulnerable to impending warming of the oceans. This response to climate change at a global scale, however, may vary due to regional differences in temperature variability, acclimation, and differential responses of kelp species to changing conditions. Culture experiments were conducted on 12 eastern Pacific kelp taxa across geographic regions (British Columbia, central California, and southern California) under three nitrate levels (1, 5, and 10 µmol/L) and two temperatures (12°C and 18°C) to determine sporophyte production (i.e., recruitment success). For all taxa from all locations, sporophytes were always present in the 12°C treatment and when recruitment failure was observed, it always occurred at 18°C, regardless of nitrate level, indicating that temperature is the driving factor limiting recruitment, not nitrate. Rising ocean temperatures will undoubtedly cause recruitment failure for many kelp species; however, the ability of species to acclimatize or adapt to increased temperatures at the warmer edge of their species range may promote a resiliency of kelp systems to climate change at a global scale.

Revisions to the Classification, Nomenclature, and Diversity of Eukaryotes.

This revision of the classification of eukaryotes follows that of Adl et al., 2012 [J. Euk. Microbiol. 59(5)] and retains an emphasis on protists. Changes since have improved the resolution of many nodes in phylogenetic analyses. For some clades even families are being clearly resolved. As we had predicted, environmental sampling in the intervening years has massively increased the genetic information at hand. Consequently, we have discovered novel clades, exciting new genera and uncovered a massive species level diversity beyond the morphological species descriptions. Several clades known from environmental samples only have now found their home. Sampling soils, deeper marine waters and the deep sea will continue to fill us with surprises. The main changes in this revision are the confirmation that eukaryotes form at least two domains, the loss of monophyly in the Excavata, robust support for the Haptista and Cryptista. We provide suggested primer sets for DNA sequences from environmental samples that are effective for each clade. We have provided a guide to trophic functional guilds in an appendix, to facilitate the interpretation of environmental samples, and a standardized taxonomic guide for East Asian users.