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Lung cancer patients treated with targeted therapies frequently respond well but invariably relapse due to the development of drug resistance. Drug resistance is in part mediated by a subset of cancer cells termed "drug-tolerant persisters" (DTPs), which enter a dormant, slow-cycling state that enables them to survive drug exposure. DTPs also exhibit stem cell-like characteristics, broad epigenetic reprogramming, altered metabolism, and a mutagenic phenotype mediated by adaptive mutability. While several studies have characterised the transcriptional changes that lead to the altered phenotypes exhibited in DTPs, these studies have focused predominantly on protein coding changes. As long non-coding RNAs (lncRNAs) are also implicated in the phenotypes altered in DTPs, it is likely that they play a role in the biology of drug tolerance. In this review, we outline how lncRNAs may contribute to the key characteristics of DTPs, their potential roles in tolerance to targeted therapies, and the emergence of genetic resistance in lung adenocarcinoma.

Plate tectonics is a fundamental factor in the sustained habitability of Earth, but its time of onset is unknown, with ages ranging from the Hadaean to Proterozoic eons 1-3 . Plate motion is a key diagnostic to distinguish between plate and stagnant-lid tectonics, but palaeomagnetic tests have been thwarted because the planet's oldest extant rocks have been metamorphosed and/or deformed 4 . Herein, we report palaeointensity data from Hadaean-age to Mesoarchaean-age single detrital zircons bearing primary magnetite inclusions from the Barberton Greenstone Belt of South Africa 5 . These reveal a pattern of palaeointensities from the Eoarchaean (about 3.9 billion years ago (Ga)) to Mesoarchaean (about 3.3 Ga) eras that is nearly identical to that defined by primary magnetizations from the Jack Hills (JH; Western Australia) 6,7 , further demonstrating the recording fidelity of select detrital zircons. Moreover, palaeofield values are nearly constant between about 3.9 Ga and about 3.4 Ga. This indicates unvarying latitudes, an observation distinct from plate tectonics of the past 600 million years (Myr) but predicted by stagnant-lid convection. If life originated by the Eoarchaean 8 , and persisted to the occurrence of stromatolites half a billion years later 9 , it did so when Earth was in a stagnant-lid regime, without plate-tectonics-driven geochemical cycling., (© 2023. The Author(s).)

Most of the described species in kingdom Fungi are contained in two phyla, the Ascomycota and the Basidiomycota (subkingdom Dikarya). As a result, our understanding of the biology of the kingdom is heavily influenced by traits observed in Dikarya, such as aerial spore dispersal and life cycles dominated by mitosis of haploid nuclei. We now appreciate that Fungi comprises numerous phylum-level lineages in addition to those of Dikarya, but the phylogeny and genetic characteristics of most of these lineages are poorly understood due to limited genome sampling. Here, we addressed major evolutionary trends in the non-Dikarya fungi by phylogenomic analysis of 69 newly generated draft genome sequences of the zoosporic (flagellated) lineages of true fungi. Our phylogeny indicated five lineages of zoosporic fungi and placed Blastocladiomycota, which has an alternation of haploid and diploid generations, as branching closer to the Dikarya than to the Chytridiomyceta. Our estimates of heterozygosity based on genome sequence data indicate that the zoosporic lineages plus the Zoopagomycota are frequently characterized by diploid-dominant life cycles. We mapped additional traits, such as ancestral cell-cycle regulators, cell-membrane- and cell-wall-associated genes, and the use of the amino acid selenocysteine on the phylogeny and found that these ancestral traits that are shared with Metazoa have been subject to extensive parallel loss across zoosporic lineages. Together, our results indicate a gradual transition in the genetics and cell biology of fungi from their ancestor and caution against assuming that traits measured in Dikarya are typical of other fungal lineages.

Plantago princeps var. princeps is an endangered native Hawaiian plant, and part of the recovery plan includes repopulation using plants grown in a nursery. However, disease pressure from downy mildew is hindering repopulation efforts. The organism associated with the downy mildew was determined to be a Peronospora species with brown, ellipsoid conidia measuring 21 by 16 µm on average, which was morphologically different from validly described species of Peronospora that infect Plantago species, but it was morphologically similar to the invalidly published species Peronospora lanceolatae (Art. 40.1). Comparison of mitochondrial cytochrome oxidase subunit I ( cox 1), mitochondrial cytochrome oxidase subunit II ( cox 2), nuclear internal transcribed spacer (ITS), and nuclear 28S rRNA D1-D2 (28S) loci revealed the unknown Peronospora to be molecularly divergent from Peronospora alta and Peronsopora plantaginis , but very similar to Peronospora from Plantago lanceolata , the type host of P. lanceolatae . Phylogenetic trees inferred with maximum likelihood and Bayesian inference from a concatenated alignmaent and individual gene trees confirmed the divergence of the unknown Peronospora from P. alta and P. plantaginis and its similarity to P. lanceolatae . However, attempts to inoculate Plantago lanceolata with the strain from Plantago princeps var. princeps were unsuccessful, which, in conjunction with divergence in ITS, suggests that the unknown Peronospora is specific to Plantago princeps var. princeps . Herein, the Peronospora strain on Plantago princeps var. princeps is described as the new species Peronospora kuewa based on morphology, molecular phylogenetics, and host specificity. In addition, Peronospora gaponenkoae is described here to honor Nina Ivanova Gaponenko on the basis of her description of P. lanceolatae .

Background: Devastating transient and permanent postoperative neurocognitive complications in previously healthy, low-risk patients have been observed after elective shoulder arthroscopy in the beach chair position (BCP). Continuous monitoring of cerebral oxygen saturation has been recommended to identify cerebral desaturation events (CDEs) and improve patient safety. However, the relatively high cost and limited availability of monitoring may not be cost-effective. More cost-effective and available measures, including the use of thigh-high compression stockings (CS), have been investigated. However, efficacy data of CS usage is limited, especially for obese patients, who have been shown to be at increased risk for CDEs. The purpose of this was study was to determine if the intraoperative addition of thigh-high compression stockings decreases the incidence, frequency, and magnitude of CDEs in obese patients undergoing shoulder arthroscopy in the BCP., Methods: Thirty-three patients in the treatment group wore both thigh-high compression stockings (CS) and sequential compression devices (SCDs), and the remaining 33 patients in the control group wore SCDs alone. Cerebral oximetry was monitored during surgery using near-infrared spectroscopy., Results: The incidence of CDEs was equal between groups, with 9 patients (27%) in each experiencing desaturation events. The median number of CDEs per patient was 3 for the control group and 1 for patients wearing CS (P = .29). There was no difference between groups in terms of median time from induction of anesthesia to onset of CDE (P = .79), median time from upright positioning to onset of CDE (P = .60), mean CDE duration per patient (P = .22), and median cumulative CDE duration (P = .19). The median maximal desaturation from baseline was also not different between groups: 27.6% in the control group and 24.3% in the treatment group (P = .35)., Conclusion: The combination of thigh-high CS and SCDs did not decrease the incidence, frequency, or magnitude of CDEs in patients undergoing shoulder arthroscopy in the BCP. Twenty-seven percent of patients undergoing shoulder arthroscopy in the BCP demonstrated CDEs with or without the use of CS. Therefore, further research is required to identify cost-effective, minimally invasive, and universally available methods of decreasing the incidence of CDEs during this common surgical procedure., (Copyright © 2020 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Motivation: Whole-genome sequencing of uncultured eukaryotic genomes is complicated by difficulties in acquiring sufficient amounts of tissue. Single-cell genomics (SCG) by multiple displacement amplification provides a technical workaround, yielding whole-genome libraries which can be assembled de novo. Downsides of multiple displacement amplification include coverage biases and exacerbation of contamination. These factors affect assembly continuity and fidelity, complicating discrimination of genomes from contamination and noise by available tools. Uncultured eukaryotes and their relatives are often underrepresented in large sequence data repositories, further impairing identification and separation., Results: We compare the ability of filtering approaches to remove contamination and resolve eukaryotic draft genomes from SCG metagenomes, finding significant variation in outcomes. To address these inconsistencies, we introduce a consensus approach that is codified in the SCGid software package. SCGid parallelly filters assemblies using different approaches, yielding three intermediate drafts from which consensus is drawn. Using genuine and mock SCG metagenomes, we show that our approach corrects for variation among draft genomes predicted by individual approaches and outperforms them in recapitulating published drafts in a fast and repeatable way, providing a useful alternative to available methods and manual curation., Availability and Implementation: The SCGid package is implemented in python and R. Source code is available at http://www.github.com/amsesk/SCGid under the GNU GPL 3.0 license., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Determining the age of the geomagnetic field is of paramount importance for understanding the evolution of the planet because the field shields the atmosphere from erosion by the solar wind. The absence or presence of the geomagnetic field also provides a unique gauge of early core conditions. Evidence for a geomagnetic field 4.2 billion-year (Gy) old, just a few hundred million years after the lunar-forming giant impact, has come from paleomagnetic analyses of zircons of the Jack Hills (Western Australia). Herein, we provide new paleomagnetic and electron microscope analyses that attest to the presence of a primary magnetic remanence carried by magnetite in these zircons and new geochemical data indicating that select Hadean zircons have escaped magnetic resetting since their formation. New paleointensity and Pb-Pb radiometric age data from additional zircons meeting robust selection criteria provide further evidence for the fidelity of the magnetic record and suggest a period of high geomagnetic field strength at 4.1 to 4.0 billion years ago (Ga) that may represent efficient convection related to chemical precipitation in Earth's Hadean liquid iron core., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

Entomopathogenic fungi routinely kill their hosts before releasing infectious spores, but a few species keep insects alive while sporulating, which enhances dispersal. Transcriptomics- and metabolomics-based studies of entomopathogens with post-mortem dissemination from their parasitized hosts have unraveled infection processes and host responses. However, the mechanisms underlying active spore transmission by Entomophthoralean fungi in living insects remain elusive. Here we report the discovery, through metabolomics, of the plant-associated amphetamine, cathinone, in four Massospora cicadina -infected periodical cicada populations, and the mushroom-associated tryptamine, psilocybin, in annual cicadas infected with Massospora platypediae or Massospora levispora , which likely represent a single fungal species. The absence of some fungal enzymes necessary for cathinone and psilocybin biosynthesis along with the inability to detect intermediate metabolites or gene orthologs are consistent with possibly novel biosynthesis pathways in Massospora . The neurogenic activities of these compounds suggest the extended phenotype of Massospora that modifies cicada behavior to maximize dissemination is chemically-induced., Competing Interests: Conflicts of interest Authors declare no competing interests.

The beach chair position (BCP) is commonly used position in upper extremity surgery. Although there are many advantages to surgery in this position, there are also potential drawbacks and described complications including devastating neurologic outcomes. The etiology of these complications is postulated to be due to the gravitational effects of the seated position leading to cerebral hypoperfusion. We review the current literature on intraoperative cerebral monitoring and neurocognitive complications with shoulder surgery performed in the BCP. A previous systematic review estimated the incidence of neurocognitive complications after surgery in the BCP to be 0.004%. However, the true incidence is unknown and is likely much more common. Reports of neurologic complications have revealed a need for heightened vigilance, alternative anesthesia techniques, and improved monitoring. Methods for monitoring have included near-infrared spectroscopy, a measurement of cerebral oximetry shown to reliably detect cerebral hypoperfusion. In this literature review, we sought to update the incidence of intraoperative cerebral desaturation events (CDEs) to investigate the relationship of CDEs to neurocognitive complications and to review recent reported cases of neurocognitive complications. Existing literature suggest that accurate intraoperative monitoring of cerebral perfusion may improve patient safety., (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)

Previous genome-scale phylogenetic analyses of Fungi have under sampled taxa from Zoopagales; this order contains many predacious or parasitic genera, and most have never been grown in pure culture. We sequenced the genomes of 4 zoopagalean taxa that are predators of amoebae, nematodes, or rotifers and the genome of one taxon that is a parasite of amoebae using single cell sequencing methods with whole genome amplification. Each genome was a metagenome, which was assembled and binned using multiple techniques to identify the target genomes. We inferred phylogenies with both super matrix and coalescent approaches using 192 conserved proteins mined from the target genomes and performed ancestral state reconstructions to determine the ancestral trophic lifestyle of the clade. Our results indicate that Zoopagales is monophyletic. Ancestral state reconstructions provide moderate support for mycoparasitism being the ancestral state of the clade., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Previous molecular phylogenetic studies have shown that families in Zoopagales are not monophyletic. To test the monophyly of genera and species in the order, we used a single-cell approach to generate nuclear 18S rRNA (18S) sequences for 10 isolates representing nine taxa. We provide the first sequences for the genus Zoopage and additional sequences for taxa in Cocholonema, Acaulopage, and Zoophagus. Our results reveal that Zoophagus, Zoopage, and Acaulopage tetraceros are not monophyletic. We conclude that morphology alone is not sufficient to delineate genera and species in the order and encourage studies that increase genetic sampling of taxa including type species.

The purpose of our research is to investigate morphology, zoospore ultrastructure, and molecular placement of six strains in the Asterophlyctis (Chytridiales) lineage. In previous molecular analyses strain JEL 186, putatively Asterophlyctis sarcoptoides, placed as basal in family Chytriomycetaceae. Recent sampling for chytrids resulted in isolation of five strains (WJD 209, MP 058, JEL 524, JEL 857, and JEL 885) molecularly related to strain JEL 186. Our morphological evaluations reveal that strains JEL 186 and WJD 209 are members of Asterophlyctis. Strain WJD 209 is considered representative of the type, A. sarcoptoides, and strain JEL 186 a new species, Asterophlyctis michiganensis. The four strains MP 058, JEL 524, JEL 857, and JEL 885 are distinct from Asterophlyctis, and we consider them as members of a new genus, Wheelerophlyctis, composed of two species, Wheelerophlyctis interior and Wheelerophlyctis interiexterior. Asterophlyctis and Wheelerophlyctis are sister taxa and we demarcate that lineage as Asterophlyctaceae. The two genera also have similar zoospore ultrastructure, which is unique among strains in Chytridiales. In consideration of their molecular position and zoospore ultrastructure, we hypothesize that Asterophlyctis and Wheelerophlyctis represent a bridge between Chytriomycetaceae and Chytridiaceae. This research expands our concepts of systematics and zoospore ultrastructural variation in Chytridiales., (Copyright © 2018 British Mycological Society. Published by Elsevier Ltd. All rights reserved.)

Food webs in temporary forest ponds are driven by decomposition of terrestrial inputs. Chytrid fungi are important components of the fungal community, degrading leaf litter in streams reliant on terrestrial inputs and in lake ecosystems where they may stabilize the food web. However, little is known about chytrid fungi in temporary forest ponds. We inventoried the chytrid diversity present in two temporary forest ponds via light microscopy of baited samples and ion semiconductor (Ion Torrent) sequencing of environmental DNA. We quantified trends of chytrid alpha and beta diversity as a function of spatial and temporal factors. A total of 59 chytrid taxa were detected throughout the study. Beta diversity exhibited variation across the sampled months for both the entire fungal community as well as for chytrids alone. Shifts in community composition were also apparent, although diversity metrics and composition patterns did not meet adjusted P values. The results of this study highlight the diversity of chytrid fungi in temporary forest ponds and the need for further studies on the spatial and temporal dynamics of chytrid species.

Zoospore ultrastructural characters combined with molecular phylogenetic hypotheses have been used to revise the taxonomy of zoosporic true fungi. An example is the reclassification of Rhizophlyctis rosea-like fungal strains into four new families and three new genera within the order Rhizophlyctidales. One genus was Borealophlyctis, which included a Canadian isolate, DAOMC 229843. A recent survey of chytrid diversity in Alabama (USA) yielded additional strains (WJD 170, WJD 171) in the Borealophlyctis lineage. With light and transmission-electron microscopy we examined strains DAOMC 229843, WJD 170 and WJD 171. We also analyzed partial nuc 28S rDNA D1-D3 domains (28S) and nuc rDNA region encompassing the internal transcribed spacers 1 and 2 and 5.8S (ITS) sequences to determine the phylogenetic placement of the strains within Rhizophlyctidales. Based on molecular divergence and morphological differences from the type Borealophlyctis paxensis, we recognize DAOMC 229843, WJD 170 and WJD 171 as representatives of the new species Borealophlyctis nickersoniae., (© 2016 by The Mycological Society of America.)

Knowing when the geodynamo started is important for understanding the evolution of the core, the atmosphere, and life on Earth. We report full-vector paleointensity measurements of Archean to Hadean zircons bearing magnetic inclusions from the Jack Hills conglomerate (Western Australia) to reconstruct the early geodynamo history. Data from zircons between 3.3 billion and 4.2 billion years old record magnetic fields varying between 1.0 and 0.12 times recent equatorial field strengths. A Hadean geomagnetic field requires a core-mantle heat flow exceeding the adiabatic value and is suggestive of plate tectonics and/or advective magmatic heat transport. The existence of a terrestrial magnetic field before the Late Heavy Bombardment is supported by terrestrial nitrogen isotopic evidence and implies that early atmospheric evolution on both Earth and Mars was regulated by dynamo behavior., (Copyright © 2015, American Association for the Advancement of Science.)

Many chytrid phylogenies contain lineages representing a lone taxon or a few organisms. One such lineage in recent molecular phylogenies of Rhizophydiales contained two marine chytrids, Rhizophydium littoreum and Rhizophydium aestuarii. To better understand the relationship between these organisms, we increased sampling such that the R. littoreum/R. aestuarii lineage included 10 strains of interest. To place this lineage in Rhizophydiales, we constructed a molecular phylogeny from partial nuc 28S rDNA D1-D3 domains (28S) of these and 80 additional strains in Rhizophydiales and examined thallus morphology and zoospore ultrastructure of our strains of interest. We also analyzed sequences of the nuc rDNA region encompassing the internal transcribed spacers 1 and 2, along with the 5.8S rDNA (ITS) of our 10 strains of interest to assess sequence similarity and phylogenetic placement of strains within the lineage. The 10 strains grouped together in three well supported clades: (i) Rhizophydium littoreum+Phlyctochytrium mangrovei, (ii) three strains of Rhizophydium aestuarii and (iii) five previously unidentified strains. Light microscopic observations revealed four distinct thallus morphologies, and zoospore ultrastructural analyses revealed four distinct constellations of ultrastructural features. On the bases of morphological, ultrastructural and molecular evidence we place these strains in the new family Halomycetaceae and four new genera (Halomyces, Paludomyces, Ulkenomyces, Paranamyces) in Rhizophydiales., (© 2015 by The Mycological Society of America.)

The PI3K/Akt signaling pathway is a major driving force in a variety of cellular functions. Dysregulation of this pathway has been implicated in many human diseases including cancer. While the activity of the cytoplasmic PI3K/Akt pathway has been extensively studied, the functions of these molecules and their effector proteins within the nucleus are poorly understood. Harboring key cellular processes such as DNA replication and repair as well as nascent messenger RNA transcription, the nucleus provides a unique compartmental environment for protein-protein and protein-DNA/RNA interactions required for cell survival, growth, and proliferation. Here we summarize recent advances made toward elucidating the nuclear PI3K/Akt signaling cascade and its key components within the nucleus as they pertain to cell growth and tumorigenesis. This review covers the spatial and temporal localization of the major nuclear kinases having PI3K activities and the counteracting phosphatases as well as the role of nuclear PI3K/Akt signaling in mRNA processing and exportation, DNA replication and repair, ribosome biogenesis, cell survival, and tumorigenesis.

Chytriomyces is a complex genus in Chytridiales. The morphological concept of the genus expanded as new taxa were added, and studies of zoospore ultrastructure and molecular phylogenies have revealed the genus to be polyphyletic. One problematic taxon is C. spinosus Fay, a distinctive species characterized by whorls of spines on the zoosporangium and a large accumulation of vesicle material beneath the operculum. With light-, scanning-electron and transmission-electron microscopy, we examined a culture (WJD186) isolated from a muck sample collected from a temporary forest pond. We also analyzed the D1-D2 variable domains of the nuc 28S rDNA (28S) sequences to confirm the phylogenetic placement of the species relative to the type of Chytriomyces, C. hyalinus Karling. The morphology of culture WJD186 is consistent with features Fay described for C. spinosus, and the zoospore ultrastructure is consistent with the Group I-type zoospore characters of Chytriomycetaceae (Chytridiales). In our molecular phylogeny C. spinosus does not group with the type of Chytriomyces. Consequently, we erect a new genus in Chytriomycetaceae and present the new combination Fayochytriomyces spinosus., (© 2015 by The Mycological Society of America.)

Background: This comparative case study investigates 2 successful community trail initiatives, using the Active Living By Design (ALBD) Community Action Model as an analytical framework. The model includes 5 strategies: preparation, promotion, programs, policy, and physical projects., Methods: Key stakeholders at 2 sites participated in in-depth interviews (N=14). Data were analyzed for content using Atlas Ti and grouped according to the 5 strategies., Results: PREPARATION: Securing trail resources was challenging, but shared responsibilities facilitated trail development. PROMOTIONS: The initiatives demonstrated minimal physical activity encouragement strategies., Programs: Community stakeholders did not coordinate programmatic opportunities for routine physical activity. POLICY: Trails' inclusion in regional greenway master plans contributed to trail funding and development. Policies that were formally institutionalized and enforced led to more consistent trail construction and safer conditions for users. PHYSICAL PROJECTS: Consistent standards for wayfinding signage and design safety features enhanced trail usability and safety., Conclusions: Communities with different levels of government support contributed unique lessons to inform best practices of trail initiatives. This study revealed a disparity between trail development and use-encouragement strategies, which may limit trails' impact on physical activity. The ALBD Community Action Model provided a viable framework to structure cross-disciplinary community trail initiatives.

The purpose of this study was to examine the effect of a thin pseudopalate on the speech of normal adults. It was hypothesized that speech would be initially altered, but speakers would adapt quickly to the device. Eleven speakers produced words without the pseudopalate and at six intervals with the appliance in place. Consonant acoustics were changed initially, but returned to baseline within approximately 30 minutes. Perceptually, consonant identification and distortion ratings were unchanged when wearing the pseudopalate. Results suggest an initial alteration to speech detectable acoustically, but rapid adaptation, for most speakers. Investigators using thin pseudopalates must recognize that speech is altered, at least initially, and account for this in their procedures and interpretation of results.

Background: Although maxillofacial injuries in the elderly population frequently result from falls and motor vehicle crashes, the association between osteoporosis and fractures of the maxillofacial region remains poorly defined., Objective: To evaluate the relationship between osteoporosis and maxillofacial trauma in the elderly. DESIGN, SETTING, AND MAIN OUTCOME MEASURES: A retrospective review of 59 patients 60 years or older treated for maxillofacial fractures at a trauma center between 1989 and 2000 was performed. The severity of osteoporosis was graded by evaluating the radiographic appearance of the vertebral bodies of each trauma patient using the Saville index. The number of maxillofacial fractures and the severity of osteoporosis in each patient was assessed to determine whether an association between osteoporosis and maxillofacial trauma exists., Results: Of the 59 patients evaluated, 51% were injured by falls and 46% were involved in motor vehicle crashes. Seventy-three percent of the patients had multiple facial fractures. As the severity of osteoporosis worsened, patients were more likely to sustain a greater number of maxillofacial fractures (P=.01). The mechanism of injury had no impact on the relationship between osteoporosis and the number of fractures., Conclusions: Osteoporosis is an independent risk factor for the development of maxillofacial fractures. Since more than half of these patients are injured by falls, safety measures must be instituted to prevent fall-related maxillofacial injuries in the home and the community.