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The jaguar (Panthera onca) is the largest living cat species native to the Americas and one of few large American carnivorans to have survived into the Holocene. However, the extent to which jaguar diversity declined during the end-Pleistocene extinction event remains unclear. For example, Pleistocene jaguar fossils from North America are notably larger than the average extant jaguar, leading to hypotheses that jaguars from this continent represent a now-extinct subspecies (Panthera onca augusta) or species (Panthera augusta). Here, we used a hybridization capture approach to recover an ancient mitochondrial genome from a large, late Pleistocene jaguar from Kingston Saltpeter Cave, Georgia, United States, which we sequenced to 26-fold coverage. We then estimated the evolutionary relationship between the ancient jaguar mitogenome and those from other extinct and living large felids, including multiple jaguars sampled across the species' current range. The ancient mitogenome falls within the diversity of living jaguars. All sampled jaguar mitogenomes share a common mitochondrial ancestor ~400 thousand years ago, indicating that the lineage represented by the ancient specimen dispersed into North America from the south at least once during the late Pleistocene. While genomic data from additional and older specimens will continue to improve understanding of Pleistocene jaguar diversity in the Americas, our results suggest that this specimen falls within the variation of extant jaguars despite the relatively larger size and geographic location and does not represent a distinct taxon., (© The American Genetic Association. 2023.)

Background: Atogepant, an oral calcitonin gene-related peptide receptor antagonist, has been approved for the preventive treatment of migraine, but its efficacy and safety in people who have been failed by conventional oral preventive migraine treatments has not yet been evaluated in a dedicated clinical trial. The ELEVATE trial evaluated the safety, tolerability, and efficacy of atogepant for the preventive treatment of episodic migraine in participants for whom two to four classes of conventional oral preventive treatments have failed., Methods: ELEVATE was a randomised, double-blind, placebo-controlled, parallel-group, phase 3b trial done at 73 sites in Canada, the Czech Republic, Denmark, France, Germany, Hungary, Italy, the Netherlands, Poland, Russia, Spain, the UK, and the USA. Adults (18-80 years) with episodic migraine who had previously been failed by two to four classes of conventional oral treatments for migraine prevention were randomly assigned (1:1) using interactive web response technology to oral atogepant 60 mg once a day or placebo, stratified by baseline monthly migraine days, number of treatment classes participants have been failed by, and region. The primary endpoint was change from baseline in mean monthly migraine days across the 12-week treatment period in the off-treatment hypothetical estimand (OTHE) population, which included participants in the safety population (all participants who received ≥1 dose of study intervention) who had evaluable data available for the baseline period and for one or more of the 4-week post-baseline periods (whether on treatment or off treatment). The primary endpoint was analysed using a mixed model for repeated measures and a fixed-sequence procedure was used to control for multiple comparisons. The trial is registered with ClinicalTrials.gov (NCT04740827) and EudraCT (2019-003448-58), and is completed., Findings: Between March 5, 2021, and Aug 4, 2022, 540 participants were screened, 315 were randomly assigned, and 313 participants (280 [89%] female, 33 [11%] male, and 300 [96%] White) received at least one dose of study intervention. In the OTHE population, which comprised 309 participants (155 assigned to placebo and 154 to atogepant), least squares mean changes from baseline in monthly migraine days across 12 weeks were -1·9 (SE 0·4) with placebo and -4·2 (0·4) with atogepant (least squares mean difference -2·4, 95% CI -3·2 to -1·5; adjusted p<0·0001). The most common treatment-emergent adverse event with atogepant was constipation in 16 (10%) of 156 participants (vs four [3%] of 157 for placebo). Serious adverse events occurred in four [3%] of 156 participants in the atogepant group vs none in the placebo group, and treatment-emergent adverse events resulting in treatment discontinuation occurred in three [2%] in the atogepant group vs two [1%] in the placebo group., Interpretation: Atogepant 60 mg once a day was safe, well tolerated, and showed significant and clinically relevant reductions in mean monthly migraine days compared with placebo across 12 weeks in patients with episodic migraine who had previously been failed by two to four classes of conventional oral preventive treatments. Atogepant might be an effective preventive treatment option for patients in this difficult-to-treat population., Funding: Allergan (now AbbVie)., Competing Interests: Declaration of interests JMT, KN, HG, RDAF, and GF are employees of AbbVie and may hold AbbVie stock. CT reports support from Abbvie and Novartis for investigator-initiated trials; consulting fees from Abbvie, Eli Lilly, Dompé, Teva, Lundbeck, Pfizer, and Medscape for participating in advisory boards; support from Abbvie, Eli Lilly, Dompé, Teva, Lundbeck, and Pfizer for attending meetings; and personal fees from Abbvie, Eli Lilly, Teva, Lundbeck, and Pfizer for lecturing at symposia. She is principal investigator of clinical trials sponsored by Abbvie, Eli Lilly, Lundbeck, Pfizer, and Teva. She has received research grants from the European Commission, the Italian Ministry of Health, and the Migraine Research Foundation. PP-R reports support for the present study from AbbVie and personal fees for consulting from AbbVie, Biohaven, Chiesi, Eli Lilly, Lundbeck, Medscape, Novartis, Pfizer, and Teva. She has received personal fees for speaking from AbbVie, Chiesi, Eli Lilly, Lundbeck, Medscape, Novartis, and Teva, and has had grants paid to her research group from AbbVie, AGAUR, EraNet Neuron, FEDER RIS3CAT, Instituto Investigación Carlos III, International Headache Society, Novartis, and Teva. She has participated in an advisory board for Lilly Foundation Spain. ML-M reports support for the present study from AbbVie and reports personal fees for speaker panels from Amicus, Eli Lilly, Lundbeck, Teva, UPSA, and Zambon. He has received consulting fees from AbbVie, Eli Lilly, Grunenthal, Lundbeck, Medtronic, Novartis, Orion, Pfizer, Reckitt Benkiser, Sun Pharmaceutical, Teva, UPSA, and Zambon. He has received grants for institutional support from Eli Lilly, Lundbeck, Medtronic, Novartis, Pfizer, and Teva. SS has received consulting fees from Impel Neuropharma, and personal payment as a speaker for AbbVie, Amgen, BDSI, Biohaven, Eli Lilly, Impel Neuropharma, and Teva. She has participated in advisory boards for AbbVie, Amgen, BDSI, Biohaven, Eli Lilly, Impel Neuropharma, and Teva and serves as Board of Directors for the Southern Headache Society and Carolina Headache Foundation. TN reports support for the present study from AbbVie and has received personal payments for consulting fees and speaking fees from Eli Lilly, Glenmark, Lundbeck, Novartis, Pfizer, St Jude Medical, Teva Pharmaceuticals, and UCB. He has received grants for institutional support from Eli Lilly, Glenmark, Lundbeck, Novartis, Pfizer, St Jude Medical, Teva Pharmaceuticals, and UCB. He also has served on advisory boards or as a principal investigator in clinical trials for AbbVie, Amgen, Eli Lilly, Lundbeck, Neurocrine, Novartis, Teva Pharmaceuticals, and UCB., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Island oak (Quercus tomentella) is a rare relictual island tree species that exists only on six islands off the coast of California and Mexico, but was once widespread throughout mainland California. Currently, this species is endangered by threats such as non-native plants, grazing animals, and human removal. Efforts for conservation and restoration of island oak currently underway could benefit from information about its range-wide genetic structure and evolutionary history. Here we present a high-quality genome assembly for Q. tomentella, assembled using PacBio HiFi and Omni-C sequencing, developed as part of the California Conservation Genomics Project (CCGP). The resulting assembly has a length of 781 Mb, with a contig N50 of 22.0 Mb and a scaffold N50 of 63.4 Mb. This genome assembly will provide a resource for genomics-informed conservation of this rare oak species. Additionally, this reference genome will be the first one available for a species in Quercus section Protobalanus, a unique oak clade present only in western North America., (© The American Genetic Association. 2024.)

Townsend's big-eared bat, Corynorhinus townsendii, is a cave- and mine-roosting species found largely in western North America. Considered a species of conservation concern throughout much of its range, protection efforts would greatly benefit from understanding patterns of population structure, genetic diversity, and local adaptation. To facilitate such research, we present the first de novo genome assembly of C. townsendii as part of the California Conservation Genomics Project (CCGP). Pacific Biosciences HiFi long reads and Omni-C chromatin-proximity sequencing technologies were used to produce a de novo genome assembly, consistent with the standard CCGP reference genome protocol. This assembly comprises 391 scaffolds spanning 2.1 Gb, represented by a scaffold N50 of 174.6 Mb, a contig N50 of 23.4 Mb, and a benchmarking universal single-copy ortholog (BUSCO) completeness score of 96.6%. This high-quality genome will be a key tool for informed conservation and management of this vulnerable species in California and across its range., (© The American Genetic Association. 2023.)

The Yuma myotis bat (Myotis yumanensis) is a small vespertilionid bat and one of 52 species of new world Myotis bats in the subgenus Pizonyx. While M. yumanensis populations currently appear relatively stable, it is one of 12 bat species known or suspected to be susceptible to white-nose syndrome, the fungal disease causing declines in bat populations across North America. Only two of these 12 species have genome resources available, which limits the ability of resource managers to use genomic techniques to track the responses of bat populations to white-nose syndrome generally. Here we present the first de novo genome assembly for Yuma myotis, generated as a part of the California Conservation Genomics Project. The M. yumanensis genome was generated using a combination of PacBio HiFi long reads and Omni-C chromatin-proximity sequencing technology. This high-quality genome is one of the most complete bat assemblies available, with a contig N50 of 28.03 Mb, scaffold N50 of 99.14 Mb, and BUSCO completeness score of 93.7%. The Yuma myotis genome provides a high-quality resource that will aid in comparative genomic and evolutionary studies, as well as inform conservation management related to white-nose syndrome., (© The American Genetic Association. 2023.)

Genome assemblies are increasingly being used to identify adaptive genetic variation that can help prioritize the population management of protected species. This approach may be particularly relevant to species like Blainville's horned lizard, Phrynosoma blainvillii, due to its specialized diet on noxious harvester ants, numerous adaptative traits for avoiding predation (e.g. cranial horns, dorsoventrally compressed body, cryptic coloration, and blood squirting from the orbital sinuses), and status as Species of Special Concern in California. Rangewide decline since the early 20th century, the basis of its conservation status, has been driven mainly by habitat conversion, over-collecting, and invasion of a non-native ant that displaces its native ant prey base. Here, we report on a scaffold-level genome assembly for P. blainvillii as part of the California Conservation Genomics Project (CCGP), produced using Pacific Biosciences HiFi long reads and Hi-C chromatin-proximity sequencing technology. The de novo assembly has 78 scaffolds, a total length of ~2.21 Gb, a scaffold N50 length of ~352 Mb, and BUSCO score of 97.4%. This is the second species of Phrynosoma for which a reference genome has been assembled and represents a considerable improvement in terms of contiguity and completeness. Combined with the landscape genomics data being compiled by the CCGP, this assembly will help strategize efforts to maintain and/or restore local genetic diversity, where interventions like genetic rescue, translocation, and strategic land preservation may be the only means by which P. blainvillii and other low-vagility species can survive in the fragmented habitats of California., (Published by Oxford University Press on behalf of The American Genetic Association 2023.)