The fatty acid composition of eggs is highly reflective of the diet of the laying hen; therefore, nutritionally important fatty acids can be increased in eggs in order to benefit human health. To ...explore the factors affecting the hen's metabolism and deposition of fatty acids of interest, the current research was divided into two studies. In Study 1, the fatty acid profile of eggs from Bovan White hens fed either 8%, 14%, 20%, or 28% of the omega‐6 fatty acid, linoleic acid (LA) (expressed as a percentage of total fatty acids), and an additional treatment of 14% LA containing double the amount of saturated fat (SFA) was determined. Omega‐6 fatty acids and docosapentaenoic acid (DPA) in the yolk were significantly (P < 0.05) increased, and oleic acid (OA) and eicosapentaenoic acid (EPA) were significantly decreased with an increasing dietary LA content. In Study 2, the fatty acid and sensory profiles were determined in eggs from Shaver White hens fed either (1) 15% or 30% of the omega‐3 fatty acid, alpha‐linolenic acid (ALA) (of total fatty acids), and (2) low (0.5), medium (1), or high (2) ratios of SFA: LA+OA. Increasing this ratio resulted in marked increases in lauric acid, ALA, EPA, DPA, and docosahexaenoic acid (DHA), with decreases in LA and arachidonic acid. Increasing the dietary ALA content from 15% to 30% (of total fatty acids) did not overcome the DHA plateau observed in the yolk. No significant differences (P ≥ 0.05) in aroma or flavor between cooked eggs from the different dietary treatments were observed among trained panelists (n = 8). The results showed that increasing the ratio of SFA: LA+OA in layer diets has a more favorable effect on the yolk fatty acid profile compared to altering the LA content at the expense of OA, all while maintaining sensory quality.
The fatty acid composition of eggs is influenced by dietary lipid composition. Altering the ratio of saturated to unsaturated fatty acids, and changing the nature of the dietary unsaturated fatty acids will influence the accumulation of long‐chain omega‐3 fatty acids into eggs without negatively impacting sensory properties.
Beyond the symptom: the biology of fatigue Raizen, David M; Mullington, Janet; Anaclet, Christelle ...
Sleep (New York, N.Y.),
09/2023, Letnik:
46, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Abstract
A workshop titled “Beyond the Symptom: The Biology of Fatigue” was held virtually September 27–28, 2021. It was jointly organized by the Sleep Research Society and the Neurobiology of ...Fatigue Working Group of the NIH Blueprint Neuroscience Research Program. For access to the presentations and video recordings, see: https://neuroscienceblueprint.nih.gov/about/event/beyond-symptom-biology-fatigue. The goals of this workshop were to bring together clinicians and scientists who use a variety of research approaches to understand fatigue in multiple conditions and to identify key gaps in our understanding of the biology of fatigue. This workshop summary distills key issues discussed in this workshop and provides a list of promising directions for future research on this topic. We do not attempt to provide a comprehensive review of the state of our understanding of fatigue, nor to provide a comprehensive reprise of the many excellent presentations. Rather, our goal is to highlight key advances and to focus on questions and future approaches to answering them.
Pharmacy faculty commonly report feeling stressed, overwhelmed, exhausted, and burnt out. Women may be disproportionally impacted by personal and professional demands. The purpose of this commentary ...is to describe one mechanism for creating a suborganization (Circle) that establishes a supportive community to combat burnout and promote professional fulfillment. This commentary is a description of one American Academy of Colleges of Pharmacy (AACP) Women Faculty Special Interest Group (SIG) Circle. The authors describe how one Circle sought to enhance the well-being of its members through the various domains of the Stanford Model of Professional Fulfillment, including personal resilience, workplace efficiency, and creating a culture of well-being. Circles and similar frameworks may be effective tools for combatting burnout, improving fulfillment, and promoting wellness and well-being among women and other groups of faculty.
Abstract
Background
Infant acute lymphoblastic leukemia (ALL) is a malignant disorder with poor clinical outcome. It is well-known that infant ALL cases with rearrangement of the KMT2A gene (KMT2A-r) ...have an even poorer prognosis than non-KMT2A-r cases. Interestingly, KMT2A-r infant ALL cases have remarkably few other genetic alterations. We hypothesized that non-coding events in cancer genomes (e.g. loss of expression or methylation) may play a role in this disease. Such events can be captured using genomic analyses in haploid genomes using analytical approaches for allelic imbalance quantification. Here, we examine whether allelic imbalance is a feature of infant ALL.
Methods
We performed whole genome sequencing (WGS) and RNA sequencing on peripheral blood or bone marrow specimens from 29 KMT2A-r cases and 14 non-KMT2A-r cases at diagnosis (DX), remission (MD), and relapse (RL) as applicable. WGS data from MD samples was phased using a 1000 Genomes reference panel. Biallelic expression was measured on the phased genome for transcripts with at least 2 SNPs and at least 15 aligned reads. Lesser allele fraction (LAF; allele fraction for the less prevalent allele) for DX/RL versus MD samples was compared for transcripts that had LAFs available in at least 3 cases using t-test. Transcript-level p-values were aggregated at the gene level using the Sidak method.
Results
Allelic imbalance in expression (LAF <= 0.2) was observed in an average of about 600 genes per sample in infant ALL regardless of timepoint. Disease-specific allelic imbalance (skewed in DX samples but not in paired MD samples) was detected in 431 genes for the KMT2A-r cohort and 77 genes for the non-KMT2A-r cohort. A total of 38 genes with allelic imbalance were shared between the two cohorts. Notably, KMT2A was observed to be imbalanced in KMT2A-r samples. Genes of known significance that were found to be skewed included HOXA9 and PARP8.
Discussion
Our study suggests that allelic imbalance quantification may help uncover novel molecular mechanisms in infant ALL, especially KMT2A-r cases. However, similar to gene expression, the patterns of allelic imbalance in KMT2A-r cases at DX do not allow efficient prediction of which patients go on to relapse.
Citation Format: Byunggil Yoo, Midhat S. Farooqi, Rumen Kostadinov, Warren Cheung, Emily Farrow, Shannon Kelley, Neil Miller, Bing Ge, Margaret Gibson, Patrick Brown, Erin M. Guest, Tomi Pastinen. Allelic imbalance in KMT2A-rearranged infant acute lymphoblastic leukemia abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3649.
Circadian rhythms impact a variety of behavioral and physiological functions contributing to longevity and successful reproduction. In their natural environments, individuals of a species are faced ...with a multitude of challenges and the coordination of internal processes and behavior with external pressures has been hypothesized to be an important target of natural selection. Several lines of evidence from cyanobacteria, Drosophila, and plants provide strong support for an important role of the circadian clock in survival and reproductive success. Similarly in mammals, disruptions in circadian function markedly impact reproduction and lifespan. The present review discusses research outlining the proximate and ultimate mechanisms responsible for the central and peripheral control of the reproductive axis. Because precise temporal coordination of the endocrine system is particularly crucial for reproduction by females, the present overview focuses on the role of circadian timing in this sex.
Introduction
Relapse of infant ALL with MLL-rearrangement (MLL-r) is an unsolved clinical problem. Of the 80% of infants with ALL that harbor MLL-r, 60% relapse and die with current treatment. The ...typical pattern of failure is remission induction, followed by early relapse and very low second remission rate (<30%), suggesting rapid emergence of chemoresistant subclones. Previously, whole genome sequencing (WGS) of 22 MLL-r infant ALL cases showed only 1.3 non-silent mutations in the predominant clone at diagnosis and no significant increase of mutations at relapse in 2 diagnosis-relapse pairs (Andersson et al. (2015) Nat. Gen. 47(4):330-337).
Here, we examined the extent to which relapse in infant MLL-r ALL is driven by acquisition of new somatic mutations and/or gene expression changes. We assembled a large cohort of 14 paired diagnosis-relapse (DX-RL) infant MLL-r ALL cases treated on Children's Oncology Group (COG) trial AALL0631. MLL partners were 8 AF4, 5 ENL, and 1 unspecified. Paired remission bone marrow samples (RM) served as germline controls.
Methods
We performed WGS and RNA sequencing (RNA-seq) on 14 DX-RM-RL trios (N=42) using Illumina Hiseq 4000 and 2500. WGS samples were sequenced to a minimum of 90Gb and RNA-seq samples to an average of 8.8Gb. Alignment and variant calling were performed using BWA, GATK. Variants present in DX and/or RL and absent in paired RM samples were considered somatic. Filters included allelic depth threshold of 7 reads, minor allele frequency ≤0.1%, and ACMG category 1-3. RNA-seq gene expression was evaluated using GSNAP, Cufflinks, and Cuffdiff. Genes were ranked by average magnitude of fold change in expression between DX and RL for each case. We combined the gene ranks across cases to identify the 300 most highly activated and inactivated genes in RL, and evaluated gene set enrichment with MSigDB and Ingenuity software.
Results
In total, we found 148 non-synonymous somatic variants; 20 small (<40 bp) insertions/deletions (indels) and 128 single nucleotide variants (SNVs), of which 108 were missense, 10 nonsense, 8 splicing, and 2 mitochondrial somatic mutations. The mean variant allele frequency was 0.40 ± 0.14 (range 0.15-0.93). The mean number of non-synonymous mutations per case at DX was 1.71 ± 1.21 (range 0-4). Mutations in PIK3CD and NRAS were observed, each only in a single case. No gene was recurrently mutated across diagnostic samples. At RL, the number of mutations retained was 0-3 and the number lost was 0-4 per case. A large number of mutations (mean 8 ± 11.25, range 0-41) were acquired at RL. Notably, 5 of the 14 cases acquired ≥10 mutations at RL. The total number of variants in the cohort increased by 5-fold (24 to 124) from DX to RL. Acquired mutations at RL were observed in NRAS, KRAS, FLT3, BRAF, HIF1A, NOTCH3, and APC, among others. No RL samples shared a similar pattern of SNVs, suggesting the drivers of relapse and chemoresistance are diverse for this disease.
MSigDB gene set enrichment analysis showed that the 300 most highly inactivated genes at RL were enriched in gene sets that were targets of H3K27me3, EED, SUZ12, and Polycomb Repression Complex 2 (PRC2) (FDR q<9.30E-14), as well as in gene sets integral to the plasma membrane (q<8.20E-13). Additionally, these highly activated genes were enriched in sets encoding extracellular matrix-associated and other membrane-associated proteins (q<2.24E-14). Ingenuity pathway analysis revealed that the 300 most highly inactivated genes at RL were components of AMPK (p<0.04), BMP (p<0.04), NOTCH, WNT/β-catenin signaling, and B-cell development pathways, and the 300 most highly activated genes were components of IL17- (p<0.05), IL8-, and HIF1α- signaling, and granulocyte cell adhesion (p<0.01) pathways. This suggests that inactivating epigenetic events and dysregulation of cell membrane proteins are significant factors in the development of chemoresistance.
Conclusion
Relapsed infant MLL-r ALL is characterized by major gains in somatic variants and gene expression changes within cell signaling, adhesion, and B-cell development pathways. No single pathway or specific genomic variant was unifying across cases, but the appearance of mutations in many known cancer-associated genes and pathways suggests emergence of complex subclonal disease at relapse. Further analyses are ongoing to determine the contribution of germline mutations, structural variants, and DNA methylation changes in this cohort.
No relevant conflicts of interest to declare.
To maximise reproductive success, organisms restrict breeding to optimal times of the day or year, when internal physiology and external environmental conditions are suitable for the survival of both ...parent and offspring. To appropriately coordinate reproductive activity, internal and external standing is communicated to the hypothalamic‐pituitary‐gonadal axis via a coordinated balance of stimulatory and inhibitory neurochemical systems. The cumulative balance of these mediators ultimately drives the pattern of gonadotrophin‐releasing hormone secretion, a neurohormone that stimulates pituitary gonadotrophin secretion. Until 2000, a complementary inhibitor of pituitary gonadotrophin secretion had not been identified. At this time, a novel, avian hypothalamic peptide capable of inhibiting gonadotrophin secretion in cultured quail pituitary cells was uncovered and named gonadotrophin‐inhibitory hormone (GnIH). Subsequently, the presence and functional role for the mammalian orthologue of GnIH, RFamide‐related peptide, (RFRP‐3), was examined, confirming a conserved role for this peptide across several rodent species. To date, a similar distribution and functional role for RFRP‐3 have been observed across all mammals investigated, including humans. This overview summarises the role that RFRP‐3 plays in mammals and considers the implications and opportunities for further study with respect to reproductive physiology and the neural control of sexual behaviour and motivation.
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