Monocarboxylate transporters (MCTs) represent a diverse group of transmembrane proteins encoded by the SLC16 gene family found ubiquitously across mammalian species. Two members of this family, MCT1 ...and MCT4, have been linked to key roles in the metabolic activity of tissues through the proton-coupled transport of monocarboxylates, most notably L-lactate, ketone bodies, and pyruvate. This review aims to provide an overview of MCT1 and MCT4, followed by the implications of their expression in a multitude of cancers and in glioblastoma (GBM) specifically. Further, the possible mechanisms underlying these effects will be discussed. Given the relationships between MCT1 and MCT4 and cancer, they offer a unique opportunity for novel treatment strategies. We aim to explore current therapies focused on MCT1 and MCT4 and propose future studies to better understand their role in GBM to optimize future treatment regimens.
The proliferation of genomic sequencing approaches has significantly impacted the field of phylogenetics. Target capture approaches provide a cost‐effective, fast and easily applied strategy for ...phylogenetic inference of non‐model organisms. However, several existing target capture processing pipelines are incapable of incorporating whole genome sequencing (WGS). Here, we develop a new pipeline for capture and de novo assembly of the targeted regions using whole genome re‐sequencing reads. This new pipeline captured targeted loci accurately, and given its unbiased nature, can be used with any target capture probe set. Moreover, due to its low computational demand, this new pipeline may be ideal for users with limited resources and when high‐coverage sequencing outputs are required. We demonstrate the utility of our approach by incorporating WGS data into the first comprehensive phylogenomic reconstruction of the freshwater mussel family Margaritiferidae. We also provide a catalogue of well‐curated functional annotations of these previously uncharacterized freshwater mussel‐specific target regions, representing a complementary tool for scrutinizing phylogenetic inferences while expanding future applications of the probe set.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract
Characterizing the mechanisms influencing the distribution of genetic variation in aquatic species can be difficult due to the dynamic nature of hydrological landscapes. In North America’s ...Central Highlands, a complex history of glacial dynamics, long-term isolation, and secondary contact have shaped genetic variation in aquatic species. Although the effects of glacial history have been demonstrated in many taxa, responses are often lineage- or species-specific and driven by organismal ecology. In this study, we reconstruct the evolutionary history of a freshwater mussel species complex using a suite of mitochondrial and nuclear loci to resolve taxonomic and demographic uncertainties. Our findings do not support Pleurobema rubrum as a valid species, which is proposed for listing as threatened under the U.S. Endangered Species Act. We synonymize P. rubrum under Pleurobema sintoxia—a common and widespread species found throughout the Mississippi River Basin. Further investigation of patterns of genetic variation in P. sintoxia identified a complex demographic history, including ancestral vicariance and secondary contact, within the Eastern Highlands. We hypothesize these patterns were shaped by ancestral vicariance driven by the formation of Lake Green and subsequent secondary contact after the last glacial maximum. Our inference aligns with demographic histories observed in other aquatic taxa in the region and mirrors patterns of genetic variation of a freshwater fish species (Erimystax dissimilis) confirmed to serve as a parasitic larval host for P. sintoxia. Our findings directly link species ecology to observed patterns of genetic variation and may have significant implications for future conservation and recovery actions of freshwater mussels.
Potent, 1H-pyrazolo3,4-bpyridine-containing inhibitors of the human nicotinamide phosphoribosyltransferase (NAMPT) enzyme were identified using structure-based design techniques. Many of these ...compounds exhibited nanomolar antiproliferation activities against human tumor lines in in vitro cell culture experiments, and a representative example (compound 26) demonstrated encouraging in vivo efficacy in a mouse xenograft tumor model derived from the A2780 cell line. This molecule also exhibited reduced rat retinal exposures relative to a previously studied imidazo-pyridine-containing NAMPT inhibitor. Somewhat surprisingly, compound 26 was only weakly active in vitro against mouse and monkey tumor cell lines even though it was a potent inhibitor of NAMPT enzymes derived from these species. The compound also exhibited only minimal effects on in vivo NAD levels in mice, and these changes were considerably less profound than those produced by an imidazo-pyridine-containing NAMPT inhibitor. The crystal structures of compound 26 and the corresponding PRPP-derived ribose adduct in complex with NAMPT were also obtained.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
This article examines the use of the PageRank algorithm to rank the teams and predict team performance in the tournament. This method has the potential to be utilized as an alternative method to ...choose tournament participants, as opposed to the traditional ranking and seeding process currently employed by the NCAA. PageRank allows for the consideration of all games played during the regular season (average of 5832 games per season) and for customizable performance weights in the prediction. The PageRank algorithm is a viable tool in predicting tournament outcomes due to depth and extensiveness of the data. The PageRank analysis helped to predict over half of the tournament game outcomes correctly in 2014-2018 and produced an average bracket score of 81.8 points out of 192 possible over the same 5 years.
Abstract
This study seeks to examine and compare boxers throughout history creating a pound-for-pound list of the different fighters. A PageRank algorithm was utilized to rank the boxers from the ...network to determine a list of the top 10 fighters from 1897 to 2019. Two data sets were utilized, a truncated subset and a larger data set, to explore the impact of network size on the rank of boxers. Additionally, the researchers systematically varied the damping factor of the PageRank algorithm to determine the effects on the rankings. A discussion of the results includes a comparison of journalistic rankings and those from a points-based system from the respected boxing website BoxRec.
A co-crystal structure of amide-containing compound (4) in complex with the nicotinamide phosphoribosyltransferase (Nampt) protein and molecular modeling were utilized to design and discover a potent ...novel cyanoguanidine-containing inhibitor bearing a sulfone moiety (5, Nampt Biochemical IC50=2.5nM, A2780 cell proliferation IC50=9.7nM). Further SAR exploration identified several additional cyanoguanidine-containing compounds with high potency and good microsomal stability. Among these, compound 15 was selected for in vivo profiling and demonstrated good oral exposure in mice. It also exhibited excellent in vivo antitumor efficacy when dosed orally in an A2780 ovarian tumor xenograft model. The co-crystal structure of this compound in complex with the NAMPT protein was also determined.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Accurate taxonomic and distributional information are arguably the most critical components of conservation status assessments but can be greatly affected by misidentifications. The Louisiana pigtoe
...Pleurobema riddellii
is a freshwater mussel proposed as threatened under the US Endangered Species Act. The species belongs to the tribe Pleurobemini, which includes multiple taxa that are inherently challenging to identify without molecular data. We validated historical and recent survey records of
P. riddellii
using a combination of DNA sequence data and morphological characters to provide a more definitive assessment of range and spatiotemporal trends in distribution. Our comprehensive assessment identified specimens collected from the Pearl drainage as
P. riddellii
, extending the species’ known range into eastern Gulf of Mexico drainages. Contemporary records were unavailable from the Trinity drainage; however, we designed novel minibarcode PCR primers and used historical DNA from a specimen collected in the late 1800s to confirm the historical presence of
P. riddellii
at the species’ type locality in the Trinity River near Dallas, Texas, USA. Our range-wide genetic diversity assessment provides strong support for 2 main geographic groups, the Ouachita and all remaining populations, with individuals from the Pearl and Trinity drainages sharing haplotypes with conspecifics from other drainages. Available data suggest
P. riddellii
has been extirpated from a significant portion of the historical range, including the entire Trinity drainage. Additional surveys in Lake Pontchartrain, Trinity, and other drainages in the eastern periphery of the species’ range may provide additional clarity on the distribution and conservation status of
P. riddellii
.
The status of species in freshwater systems shift over time due to natural and anthropogenic causes. Determining the magnitude and cause of these shifts requires a long‐term perspective. This process ...is complicated when there are also questions about the taxonomic validity of a species. Addressing these issues is important because both can undermine conservation and management efforts if incorrect. Pleurobema riddellii, Louisiana Pigtoe, is under review for protection under the U.S. Endangered Species Act, but its status in the Trinity River basin, where the taxon was described, remains in doubt due to questions about its taxonomy and occurrence within this basin. To address these questions, we compared shell morphometrics of P. riddellii dating to the late Holocene with modern P. riddellii, late Holocene Fusconaia sp., and modern Fusconaia sp. using multivariate analyses to test associations between the putative morphotypes. Based on these analyses, we demonstrate that P. riddellii was likely present in the Trinity during the late Holocene, which indicates questions about its taxonomic validity or presence in this basin are unfounded. Our study further highlights the role zooarchaeological studies can play in status assessments and their utility in better understanding biogeographic patterns for rare species.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The Trinity Pigtoe,
Fusconaia chunii
(Lea, 1862), is a freshwater mussel endemic to the Trinity River drainage in Texas. Here, we report the first population of
F. chunii
in the San Jacinto River ...drainage in Texas. We identified three specimens of
F. chunii
using DNA barcoding, which were morphologically indistinguishable from syntopic
Fusconaia flava
(Rafinesque, 1820). A similar issue occurs in the Trinity River drainage.
Fusconaia chunii
is listed as state threatened, and future research is necessary to assess its status within the San Jacinto River drainage
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