Beef Fatty Acid Profiles from Steers Finished with De-oiled Dry Distillers Grains Plus Solubles vs. a Corn- Based Diet

A total of 128 steers were fed one of two finishing diets: 50% de-oiled dry distillers grains plus solubles (DDGS) or a corn- based control diet. Carcasses (n = 48) were selected to evaluate the effect of diet on the fatty acid profile of strip loin steaks. Th e C15:0, C16:1, C17:0, and C17:1 were greater for beef from steers finished on the corn- based control diet while the C18:1T, C18:2, C20:3ω6, total trans, ω6 and polyunsaturated fatty acids (PUFA) were greater in beef from cattle finished on 50% de-oiled DDGS. These findings confirm that feeding distillers grains plus solubles (be it wet or dry) increases the amount of PUFA’s in meat

Translation Control of Swarming Proficiency in \u3cem\u3eBacillus subtilis\u3c/em\u3e by 5-amino-pentanolylated Elongation Factor P

Elongation factor P (EF-P) accelerates diprolyl synthesis and requires a posttranslational modification to maintain proteostasis. Two phylogenetically distinct EF-P modification pathways have been described and are encoded in the majority of Gram-negative bacteria, but neither is present in Gram-positive bacteria. Prior work suggested that the EF-P-encoding gene (efp) primarily supports Bacillus subtilis swarming differentiation, whereas EF-P in Gram-negative bacteria has a more global housekeeping role, prompting our investigation to determine whether EF-P is modified and how it impacts gene expression in motile cells. We identified a 5-aminopentanol moiety attached to Lys32 of B. subtilis EF-P that is required for swarming motility. A fluorescent in vivo B. subtilis reporter system identified peptide motifs whose efficient synthesis was most dependent on 5-aminopentanol EF-P. Examination of the B. subtilis genome sequence showed that these EF-P-dependent peptide motifs were represented in flagellar genes. Taken together, these data show that, in B. subtilis, a previously uncharacterized posttranslational modification of EF-P can modulate the synthesis of specific diprolyl motifs present in proteins required for swarming motility

Multiomic profiling of breast cancer cells uncovers stress MAPK-associated sensitivity to AKT degradation

More than 50% of human tumors display hyperactivation of the serine/threonine kinase AKT. Despite evidence of clinical efficacy, the therapeutic window of the current generation of AKT inhibitors could be improved. Here, we report the development of a second-generation AKT degrader, INY-05-040, which outperformed catalytic AKT inhibition with respect to cellular suppression of AKT-dependent phenotypes in breast cancer cell lines. A growth inhibition screen with 288 cancer cell lines confirmed that INY-05-040 had a substantially higher potency than our first-generation AKT degrader (INY-03-041), with both compounds outperforming catalytic AKT inhibition by GDC-0068. Using multiomic profiling and causal network integration in breast cancer cells, we demonstrated that the enhanced efficacy of INY-05-040 was associated with sustained suppression of AKT signaling, which was followed by induction of the stress mitogen-activated protein kinase (MAPK) c-Jun N-terminal kinase (JNK). Further integration of growth inhibition assays with publicly available transcriptomic, proteomic, and reverse phase protein array (RPPA) measurements established low basal JNK signaling as a biomarker for breast cancer sensitivity to AKT degradation. Together, our study presents a framework for mapping the network-wide signaling effects of therapeutically relevant compounds and identifies INY-05-040 as a potent pharmacological suppressor of AKT signaling

Multiomic profiling of breast cancer cells uncovers stress MAPK-associated sensitivity to AKT degradation

More than 50% of human tumors display hyperactivation of the serine/threonine kinase AKT. Despite evidence of clinical efficacy, the therapeutic window of the current generation of AKT inhibitors could be improved. Here, we report the development of a second-generation AKT degrader, INY-05-040, which outperformed catalytic AKT inhibition with respect to cellular suppression of AKT-dependent phenotypes in breast cancer cell lines. A growth inhibition screen with 288 cancer cell lines confirmed that INY-05-040 had a substantially higher potency than our first-generation AKT degrader (INY-03-041), with both compounds outperforming catalytic AKT inhibition by GDC-0068. Using multiomic profiling and causal network integration in breast cancer cells, we demonstrated that the enhanced efficacy of INY-05-040 was associated with sustained suppression of AKT signaling, which was followed by induction of the stress mitogen-activated protein kinase (MAPK) c-Jun N-terminal kinase (JNK). Further integration of growth inhibition assays with publicly available transcriptomic, proteomic, and reverse phase protein array (RPPA) measurements established low basal JNK signaling as a biomarker for breast cancer sensitivity to AKT degradation. Together, our study presents a framework for mapping the network-wide signaling effects of therapeutically relevant compounds and identifies INY-05-040 as a potent pharmacological suppressor of AKT signaling

Early and Middle Holocene Hunter-Gatherer Occupations in Western Amazonia: The Hidden Shell Middens

We report on previously unknown early archaeological sites in the Bolivian lowlands, demonstrating for the first time early and middle Holocene human presence in western Amazonia. Multidisciplinary research in forest islands situated in seasonally-inundated savannahs has revealed stratified shell middens produced by human foragers as early as 10,000 years ago, making them the oldest archaeological sites in the region. The absence of stone resources and partial burial by recent alluvial sediments has meant that these kinds of deposits have, until now, remained unidentified. We conducted core sampling, archaeological excavations and an interdisciplinary study of the stratigraphy and recovered materials from three shell midden mounds. Based on multiple lines of evidence, including radiocarbon dating, sedimentary proxies (elements, steroids and black carbon), micromorphology and faunal analysis, we demonstrate the anthropogenic origin and antiquity of these sites. In a tropical and geomorphologically active landscape often considered challenging both for early human occupation and for the preservation of hunter-gatherer sites, the newly discovered shell middens provide evidence for early to middle Holocene occupation and illustrate the potential for identifying and interpreting early open-air archaeological sites in western Amazonia. The existence of early hunter-gatherer sites in the Bolivian lowlands sheds new light on the region's past and offers a new context within which the late Holocene "Earthmovers" of the Llanos de Moxos could have emerged. © 2013 Lombardo et al

Distinct disease mutations in DNMT3A result in a spectrum of behavioral, epigenetic, and transcriptional deficits

Phenotypic heterogeneity in monogenic neurodevelopmental disorders can arise from differential severity of variants underlying disease, but how distinct alleles drive variable disease presentation is not well understood. Here, we investigate missense mutations in DNA methyltransferase 3A (DNMT3A), a DNA methyltransferase associated with overgrowth, intellectual disability, and autism, to uncover molecular correlates of phenotypic heterogeneity. We generate a Dnmt3

Prospectus, September 23, 1974

ALL SET FOR STUGO ELECTION; Trustees Approve Budget For \u2774-\u2775, Partial Figures On Page 12; 16 Candidates On Ballot For 1st \u2774 Election; PC Counselors Offer More Than Counseling; Attention: Transfer Students; mercy for who?; The Short Circuit; The Kaleidoscope; Letters; Point-Counterpoint: How Do You View America\u27s Future?; Here Are Candidates\u27 Platforms; State House Candidates To Debate Here; Friends; Untitled; Lit. 1.: A Secret Something, Untitled, Rebirth, Everyone\u27s looking for...; \u27DIRT\u27 Comes Off Clean; Really Raunchy Record Review: Eric Clapton, 461 Ocean Boulevard; Meeting For Prospective Debators; Classified Ads; Books: All The President\u27s Men; Republicans To Have Coffee Wednesday; Phi Beta Lambda Meetings Scheduled; APO Chapter Formed Here; In The Dark: That\u27s Entertainment ; Jock Talk; Harriers Perform Well, Abbey Pleased; IM Football Starts Play On 25th; Howell First \u27Fast Freddy\u27; Bowling Bulletin Board; Watching A Counselor At Work; Registration Drive; Cross Country Schedule; Last Chance For Girls IM Football; Fast Freddy\u27s Football Forecast; Callboard; Parkland Events; Summary Of Approved Budget; Vets Elect Officers; A Column By And For Women; Fashion Forecasthttps://spark.parkland.edu/prospectus_1974/1009/thumbnail.jp

Effects of African dust deposition on phytoplankton in the western tropical Atlantic Ocean off Barbados

Bioassay incubation experiments conducted with nutrients and local atmospheric aerosol amendments indicate that phosphorus (P) availability limited phytoplankton growth in the low-nutrient low-chlorophyll (LNLC) ocean off Barbados. Atmospheric deposition provides a relatively large influx of new nutrients and trace metals to the surface ocean in this region in comparison to other nutrient sources. However, the impact on native phytoplankton is muted due to the high ratio of nitrogen (N) to P (NO3:SRP > 40) and the low P solubility of these aerosols. Atmospheric deposition induces P limitation in this LNLC region by adding more N and iron (Fe) relative to P. This favors the growth of Prochlorococcus, a genus characterized by low P requirements and highly efficient P acquisition mechanisms. A global three-dimensional marine ecosystem model that includes species-specific phytoplankton elemental quotas/stoichiometry and the atmospheric deposition of N, P, and Fe supports this conclusion. Future increases in aerosol N loading may therefore influence phytoplankton community structure in other LNLC areas, thereby affecting the biological pump and associated carbon sequestration

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead