Defective textures in dry-cured ham are a common problem that causes important economic losses in the ham industry. An increase of proteolysis during the dry-cured ham processing may lead to high ...adhesiveness and consumer rejection of the product. Therefore, the influence of proteolysis index (PI) on instrumental adhesiveness, free amino acids and volatile profile of dry-cured ham was assessed. Two hundred Spanish dry-cured ham units were firstly classified according to their PI: low PI (<32%), medium PI (32–36%) and high PI (>36%). Instrumental adhesiveness was affected by PI, showing the lowest values in the batch with low PI. Significant differences (P < 0.05) among groups were found in six amino acids: serine, taurine, cysteine, methionine, isoleucine and leucine. The content of leucine, serine, methionine, and isoleucine significantly (P < 0.05) increased as the proteolysis index rose. However, taurine and cysteine content showed an opposite behaviour, reaching the highest values in the dry-cured hams with low PI.
Significant differences (P < 0.001) in the total content of volatile compounds among ham groups were observed, with the highest concentration in the batch with low PI, and decreasing the concentration as the PI increased. Regarding the different chemical families of volatiles, the hydrocarbons (the main family), alcohols, aldehydes, ketones and acids were more abundant in the hams showing the lowest PI. Esters did not show significant differences among the three batches of hams studied. The present study demonstrated that, apart from the effect on the adhesiveness, an excessive proteolysis seems to be associated with negative effects on the taste and aroma of the dry-cured ham.
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•An excessive proteolysis influenced negatively the aroma of dry-cured hams.•The total free amino acid content was not affected by the proteolysis index (PI).•The content of leucine, serine, methionine, and isoleucine significantly increased as the PI rose.•The highest concentration of volatile compounds were observed in hams with low PI.
The regular use of light cycle oil (LCO) for diesel fuel production by hydrotreatment (HDT) procedures has been facing difficulties of complying with the currently stricter environmental regulations ...due to the low quality of this middle distillate with high sulfur, nitrogen, and aromatic contents. An interesting alternative is to obtain valuable petrochemicals from this feedstock. LCO presents a high percentage of diaromatic hydrocarbons (naphthalene derivatives). To facilitate the study of the effect of the experimental conditions, a review regarding the hydrogenation-hydrocracking (HYD-HCK) procedures for obtaining enriched streams containing benzene, toluene, and xylene (BTX) from model mixtures (naphthalene, methylnaphthalenes, and tetralin) is presented. In addition to the economic advantages of using a middle distillate of reduced marketability, this research work opens the door to the development of technologies for obtaining valuable chemicals such as BTX from oil sources. The focus on model mixture studies facilitated the understanding of the involved kinetics and mechanisms and the effect of the experimental conditions on the chemical composition of the products as well.
Long interspersed element 1 (LINE-1 or L1) retrotransposons have markedly affected the human genome. L1s must retrotranspose in the germ line or during early development to ensure their evolutionary ...success, yet the extent to which this process affects somatic cells is poorly understood. We previously demonstrated that engineered human L1s can retrotranspose in adult rat hippocampus progenitor cells in vitro and in the mouse brain in vivo. Here we demonstrate that neural progenitor cells isolated from human fetal brain and derived from human embryonic stem cells support the retrotransposition of engineered human L1s in vitro. Furthermore, we developed a quantitative multiplex polymerase chain reaction that detected an increase in the copy number of endogenous L1s in the hippocampus, and in several regions of adult human brains, when compared to the copy number of endogenous L1s in heart or liver genomic DNAs from the same donor. These data suggest that de novo L1 retrotransposition events may occur in the human brain and, in principle, have the potential to contribute to individual somatic mosaicism.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Data on the efficacy of chemotherapy regimens in patients with advanced invasive lobular carcinoma (ILC) of the breast are limited. We investigated the efficacy of single‐agent eribulin ...for the treatment of advanced ILC when compared with invasive ductal carcinoma (IDC).
Patients and Methods
Results from the eribulin arms of two phase III studies (305 EMBRACE and 301) and a single‐arm, phase II study were pooled. The studies involved patients with metastatic breast cancer who had previously received treatment with an anthracycline and a taxane. In all three studies, the dose of eribulin mesylate was 1.4 mg/m2 given on days 1 and 8 of a 21‐day cycle. Overall survival (OS), progression‐free survival (PFS), and response rates in patients with ILC were assessed and compared with data from patients with IDC.
Results
In total, 1,152 patients were included in this analysis (118 patients with ILC and 1,034 patients with IDC). Median OS was similar in patients with ILC and IDC (13.4 vs. 13.5 months; hazard ratio HR, 1.10; 95% confidence interval CI, 0.87–1.38); as was median PFS (4.1 vs. 3.6 months; HR, 0.91; 95% CI, 0.72–1.14). There were no major differences in response rates between the two groups.
Conclusion
This retrospective analysis suggests that eribulin demonstrates similar efficacy in patients with ILC and IDC with metastatic disease who have previously received an anthracycline and a taxane.
Implications for Practice
Data on the efficacy of chemotherapy regimens in patients with advanced invasive lobular carcinoma (ILC) of the breast are limited. This pooled retrospective analysis of three clinical studies demonstrates that the magnitude of benefit of eribulin in the metastatic setting did not differ between patients with ILC versus invasive ductal carcinoma (IDC), even when restricting for patients with estrogen receptor‐positive/HER2‐negative IDC.
摘要
背景。关于化疗方案对晚期乳腺浸润性小叶癌 (ILC) 患者的有效性的数据十分有限。我们研究了单药艾日布林治疗晚期 ILC 对比浸润性导管癌 (IDC) 的有效性。
患者和方法。我们对来自两项 III 期研究 305 (EMBRACE)和 301 和一项单组 II 期研究的艾日布林组结果进行了汇总。这些研究涉及既往曾接受蒽环霉素和紫杉烷治疗的转移性乳腺癌患者。在所有三项研究中，在一个为期 21 天的周期中，甲磺酸艾日布林在第 1 天和第 8 天的剂量为 1.4 mg/m2。我们对 ILC 患者的总生存期 (OS)、无进展生存期 (PFS) 以及反应率进行评估，并将它们与 IDC 患者的数据进行对比。
结果。本分析中共包含 1 152 名患者(118 名 ILC 患者和 1 034 名 IDC 患者)。ILC 患者与 IDC 患者中的中位 OS 相似 13.4 个月vs. 13.5 个月；风险比 (HR)，1.10；95% 置信区间 (CI)，0.87–1.38；中位 PFS 也是如此(4.1 个月vs. 3.6 个月；HR，0.91；95% CI，0.72–1.14)。两组之间的反应率没有重大差异。
结论。本回顾性分析表明，艾日布林在既往曾接受蒽环霉素和紫杉烷治疗且患有转移性疾病的 ILC 患者和 IDC 患者中的有效性相似。
实践意义:关于化疗方案对晚期乳腺浸润性小叶癌 (ILC) 患者的有效性的数据十分有限。本次关于三项临床研究的汇总式回顾性分析证明，即使限制在雌激素受体‐阳性/HER2‐阴性 IDC 患者时，艾日布林在转移性疾病中的有益程度在 ILC 患者与浸润性导管癌 (IDC) 患者之间也没有任何差别。
This article reports on the efficacy of eribulin for the treatment of advanced invasive lobular carcinoma compared with invasive ductal carcinoma.
As the methodologies available for the detection of positive selection from genomic data vary in terms of assumptions and execution, weak correlations are expected among them. However, if there is ...any given signal that is consistently supported across different methodologies, it is strong evidence that the locus has been under past selection. In this paper, a straightforward frequentist approach based on the Stouffer Method to combine P -values across different tests for evidence of recent positive selection in common variations, as well as strategies for extracting biological information from the detected signals, were described and applied to high density single nucleotide polymorphism (SNP) data generated from dairy and beef cattle (taurine and indicine). The ancestral Bovinae allele state of over 440,000 SNP is also reported. Using this combination of methods, highly significant (P <3.17×10 −7) population-specific sweeps pointing out to candidate genes and pathways that may be involved in beef and dairy production were identified. The most significant signal was found in the Cornichon homolog 3 gene (CNIH3) in Brown Swiss (P = 3.82×10 −12), and may be involved in the regulation of pre-ovulatory luteinizing hormone surge. Other putative pathways under selection are the glucolysis/gluconeogenesis, transcription machinery and chemokine/cytokine activity in Angus; calpain-calpastatin system and ribosome biogenesis in Brown Swiss; and gangliosides deposition in milk fat globules in Gyr. The composite method, combined with the strategies applied to retrieve functional information, may be a useful tool for surveying genome-wide selective sweeps and providing insights in to the source of selection.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
More than half of the human genome is made of transposable elements whose ongoing mobilization is a driving force in genetic diversity; however, little is known about how the host regulates their ...activity. Here, we show that the Microprocessor (Drosha-DGCR8), which is required for microRNA biogenesis, also recognizes and binds RNAs derived from human long interspersed element 1 (LINE-1), Alu and SVA retrotransposons. Expression analyses demonstrate that cells lacking a functional Microprocessor accumulate LINE-1 mRNA and encoded proteins. Furthermore, we show that structured regions of the LINE-1 mRNA can be cleaved in vitro by Drosha. Additionally, we used a cell culture-based assay to show that the Microprocessor negatively regulates LINE-1 and Alu retrotransposition in vivo. Altogether, these data reveal a new role for the Microprocessor as a post-transcriptional repressor of mammalian retrotransposons and a defender of human genome integrity.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Basic psychological needs are an energizing state that, if satisfied, will produce an increase in confidence and a healthy motivational orientation that leads to wellness. Frustration of these needs ...is the opposite concept of satisfaction, which refers to the negative sensation experimented by an individual when he or she perceives that their psychological needs are being actively limited by the actions of the significant other. To date, we have not found instruments validated in Spanish that measure both the satisfaction and the frustration of basic psychological needs in the physical education (PE) context. Therefore, the aims of this study are adapting the Basic Psychological Need Satisfaction and Frustration Scale (BPNSFS) to the PE context in Mexico; and examine its psychometric properties, structure, and factorial invariance by gender in a sample of fifth- and sixth-grade elementary school students. This study included a total of 1,470 fifth- and sixth-grade students from elementary schools in the metropolitan area of Monterrey, Nuevo Leon, Mexico. The results support the reliability, validity, structure, and strict invariance of the sixth Mexican version of the BPNSFS in physical education (BPNSFS-PE). The BPNSFS-PE can be used to measure the satisfaction and/or frustration of the basic psychological needs of students in PE class and to perform comparisons between groups of boys and girls.
Lipid nanoparticles (LNPs) currently dominate the RNA delivery landscape; however their limited diffusivity hampers targeted tissue dissemination, and, hence, their capacity for intracellular drug ...delivery. This is especially relevant for tissues such as the central nervous system (CNS), where overcoming proactive brain barriers is crucial for the efficacy of genetic therapeutics. This research aimed to create ionizable nanoemulsions (iNEs), a new generation of RNA delivery systems with enhanced diffusivity. The developed iNEs (consisting of the combination of C12–200, DOPE, Vitamin E, and DMG-PEG) with a size below 100 nm, neutral surface charge, and high RNA loading capacity, showed excellent cell viability and transfection efficiency in various cellular models, including neurons, astrocytes, and microglia. Subsequently, iNEs containing mRNA GFP were tested for CNS transfection, highlighting their exceptional diffusivity and selective transfection of neurons following intra-parenchymal administration.
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•Ionizable nanoemulsions (iNEs) are new RNA delivery systems with brain diffusivity.•siRNA and mRNA-loaded iNEs were developed and extensively characterized.•mRNA-loaded iNEs efficiently transfected neurons and microglia cell models.•Brain administration of iNEs showed exceptional diffusivity and neuron transfection.
The impact of low temperature treatment and its combination with ultrasound has been evaluated in order to correct texture defects in dry-cured hams. A total of 26 dry-cured hams, classified as high ...proteolysis index (PI>36%), were used. From these hams, ten slices from each ham sample were cut, vacuum packed and submitted to three different treatments: control (without treatment), conventional thermal treatments (CV) and thermal treatment assisted by power ultrasound (US). The impact of these treatments on instrumental adhesiveness, free amino acid and volatile compounds profile were assessed. Statistical analysis showed that both US and CV treatments, significantly (P < .001) decreased the instrumental adhesiveness of dry-cured hams from 85.27 g for CO to 40.59 and 38.68 g for US and CV groups, respectively.
The total free amino acid content was significantly (P < .001) affected by both treatments, presenting higher values the samples from the US group (6691.5 vs. 6067.5 vs. 5278.2 mg/100 g dry matter for US, CV and CO groups, respectively). No significant differences were observed between US and CV treatments. All the individual free amino acids were influenced by ultrasound and temperature treatments, showing the highest content in sliced dry-cured ham submitted to ultrasounds at 50 °C, except for isoleucine which presented the highest level in samples from CV group. Similarly, significant differences (P < .05) were also detected in the total volatile compound content between CO and US groups, with a higher concentration in the CO batch (56,662.84 AU × 103/g of dry-cured ham) than in the US treatment (45,848.47 AU × 103/g of dry-cured ham), being the values in the CV treatment intermediate (48,497.25 AU × 103/g of dry-cured ham). Aldehydes, ethers and esters, carboxylic acids and sulphur compounds were more abundant in the CO group, while CV group showed higher concentrations of ketones, alcohols and nitrogen compounds.
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•Temperature and ultrasound were essayed for decrease adhesiveness in ham.•The effect of these treatments on free amino acid and volatile contents was studied.•Temperature and ultrasound significantly decreased the adhesiveness of hams.•Total free amino acid content significantly increased after both treatments.•Temperature and ultrasound significantly decreased the total volatile content.
The PI3K signaling pathway regulates diverse cellular processes, including proliferation, survival, and metabolism, and is aberrantly activated in human cancer. As such, numerous compounds targeting ...the PI3K pathway are currently being clinically evaluated for the treatment of cancer, and several have shown some early indications of efficacy in breast cancer. However, resistance against these agents, both de novo and acquired, may ultimately limit the efficacy of these compounds. Here, we have taken a systematic functional approach to uncovering potential mechanisms of resistance to PI3K inhibitors and have identified several genes whose expression promotes survival under conditions of PI3K/mammalian target of rapamycin (PI3K/mTOR) blockade, including the ribosomal S6 kinases RPS6KA2 (RSK3) and RPS6KA6 (RSK4). We demonstrate that overexpression of RSK3 or RSK4 supports proliferation upon PI3K inhibition both in vitro and in vivo, in part through the attenuation of the apoptotic response and upregulation of protein translation. Notably, the addition of MEK- or RSK-specific inhibitors can overcome these resistance phenotypes, both in breast cancer cell lines and patient-derived xenograft models with elevated levels of RSK activity. These observations provide a strong rationale for the combined use of RSK and PI3K pathway inhibitors to elicit favorable responses in breast cancer patients with activated RSK.
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