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| 2. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 3. |
- Langefeld, Carl D., et al.
(författare)
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Transancestral mapping and genetic load in systemic lupus erythematosus
- 2017
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (similar to 50% of these regions have multiple independent associations); these include 24 novel SLE regions (P < 5 x 10(-8)), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE.
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| 4. |
- Alonso, Lorena, et al.
(författare)
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TIGER : The gene expression regulatory variation landscape of human pancreatic islets
- 2021
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 37:2
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWASs) identified hundreds of signals associated with type 2 diabetes (T2D). To gain insight into their underlying molecular mechanisms, we have created the translational human pancreatic islet genotype tissue-expression resource (TIGER), aggregating >500 human islet genomic datasets from five cohorts in the Horizon 2020 consortium T2DSystems. We impute genotypes using four reference panels and meta-analyze cohorts to improve the coverage of expression quantitative trait loci (eQTL) and develop a method to combine allele-specific expression across samples (cASE). We identify >1 million islet eQTLs, 53 of which colocalize with T2D signals. Among them, a low-frequency allele that reduces T2D risk by half increases CCND2 expression. We identify eight cASE colocalizations, among which we found a T2D-associated SLC30A8 variant. We make all data available through the TIGER portal (http://tiger.bsc.es), which represents a comprehensive human islet genomic data resource to elucidate how genetic variation affects islet function and translates into therapeutic insight and precision medicine for T2D.
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| 5. |
- Lackey, Kimberly A., et al.
(författare)
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What's normal? Microbiomes in human milk and infant feces are related to each other but vary geographically : The inspire study
- 2019
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Ingår i: Frontiers in Nutrition. - : Frontiers Media SA. - 2296-861X. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Microbial communities in human milk and those in feces from breastfed infants vary within and across populations. However, few researchers have conducted cross-cultural comparisons between populations, and little is known about whether certain “core” taxa occur normally within or between populations and whether variation in milk microbiome is related to variation in infant fecal microbiome. The purpose of this study was to describe microbiomes of milk produced by relatively healthy women living at diverse international sites and compare these to the fecal microbiomes of their relatively healthy infants. Methods: We analyzed milk (n = 394) and infant feces (n = 377) collected from mother/infant dyads living in 11 international sites (2 each in Ethiopia, The Gambia, and the US; 1 each in Ghana, Kenya, Peru, Spain, and Sweden). The V1-V3 region of the bacterial 16S rRNA gene was sequenced to characterize and compare microbial communities within and among cohorts. Results: Core genera in feces were Streptococcus, Escherichia/Shigella, and Veillonella, and in milk were Streptococcus and Staphylococcus, although substantial variability existed within and across cohorts. For instance, relative abundance of Lactobacillus was highest in feces from rural Ethiopia and The Gambia, and lowest in feces from Peru, Spain, Sweden, and the US; Rhizobium was relatively more abundant in milk produced by women in rural Ethiopia than all other cohorts. Bacterial diversity also varied among cohorts. For example, Shannon diversity was higher in feces from Kenya than Ghana and US-California, and higher in rural Ethiopian than Ghana, Peru, Spain, Sweden, and US-California. There were limited associations between individual genera in milk and feces, but community-level analyses suggest strong, positive associations between the complex communities in these sample types. Conclusions: Our data provide additional evidence of within- and among-population differences in milk and infant fecal bacterial community membership and diversity and support for a relationship between the bacterial communities in milk and those of the recipient infant's feces. Additional research is needed to understand environmental, behavioral, and genetic factors driving this variation and association, as well as its significance for acute and chronic maternal and infant health.
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| 6. |
- Lundgren, Markus, et al.
(författare)
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Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
- 2017
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Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The use of analgesic antipyretics (ANAP) in children have long been a matter of controversy. Data on their practical use on an individual level has, however, been scarce. There are indications of possible effects on glucose homeostasis and immune function related to the use of ANAP. The aim of this study was to analyze patterns of analgesic antipyretic use across the clinical centers of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective cohort study and test if ANAP use was a risk factor for islet autoimmunity. Methods: Data were collected for 8542 children in the first 2.5 years of life. Incidence was analyzed using logistic regression with country and first child status as independent variables. Holm's procedure was used to adjust for multiplicity of intercountry comparisons. Time to autoantibody seroconversion was analyzed using a Cox proportional hazards model with cumulative analgesic use as primary time dependent covariate of interest. For each categorization, a generalized estimating equation (GEE) approach was used. Results: Higher prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared to Finland (78.1%) and Germany (80.2%). First-born children were more commonly given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non-Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p = 0.002). Acetaminophen and NSAID use in the absence of fever and infection was more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99-1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95% CI 1.01-1.09; p = 0.024). Conclusions: ANAP use in young children is not a risk factor for seroconversion by age 6 years. Use of ANAP is widespread in young children, and significantly higher in the U.S. compared to other study sites, where use is common also in absence of fever and infection.
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| 7. |
- Matabuena, Marcos, et al.
(författare)
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Identification of Asthma Phenotypes in the Spanish MEGA Cohort Study Using Cluster Analysis
- 2023
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Ingår i: Archivos de Bronconeumologia. - : Elsevier BV. - 0300-2896. ; 59:4, s. 223-231
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The definition of asthma phenotypes has not been fully established, neither there are cluster studies showing homogeneous results to solidly establish clear phenotypes. The purpose of this study was to develop a classification algorithm based on unsupervised cluster analysis, identifying clusters that represent clinically relevant asthma phenotypes that may share asthma-related outcomes. Methods: We performed a multicentre prospective cohort study, including adult patients with asthma (N = 512) from the MEGA study (Mechanisms underlying the Genesis and evolution of Asthma). A standardised clinical history was completed for each patient. Cluster analysis was performed using the kernel k-groups algorithm. Results: Four clusters were identified. Cluster 1 (31.5% of subjects) includes adult-onset atopic patients with better lung function, lower BMI, good asthma control, low ICS dose, and few exacerbations. Cluster 2 (23.6%) is made of adolescent-onset atopic asthma patients with normal lung function, but low adherence to treatment (59% well-controlled) and smokers (48%). Cluster 3 (17.1%) includes adult-onset patients, mostly severe non-atopic, with overweight, the worse lung function and asthma control, and receiving combination of treatments. Cluster 4 (26.7%) consists of the elderly-onset patients, mostly female, atopic (64%), with high BMI and normal lung function, prevalence of smokers and comorbidities. Conclusion: We defined four phenotypes of asthma using unsupervised cluster analysis. These clusters are clinically relevant and differ from each other as regards FEV1, age of onset, age, BMI, atopy, asthma severity, exacerbations, control, social class, smoking and nasal polyps.
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| 8. |
- Ruiz-Pavon, Lorena, et al.
(författare)
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What's normal? Immune profiling of human milk from healthy women living in different geographical and socioeconomic settings
- 2017
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 8:JUN
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Tidskriftsartikel (refereegranskat)abstract
- Human milk provides a very wide range of nutrients and bioactive components, including immune factors, human milk oligosaccharides, and a commensal microbiota. These factors are essential for interconnected processes including immunity programming and the development of a normal infant gastrointestinal microbiome. Newborn immune protection mostly relies on maternal immune factors provided through milk. However, studies dealing with an in-depth profiling of the different immune compounds present in human milk and with the assessment of their natural variation in healthy women from different populations are scarce. In this context, the objective of this work was the detection and quantification of a wide array of immune compounds, including innate immunity factors (IL1ß, IL6, IL12, INFγ, TNFα), acquired immunity factors (IL2, IL4, IL10, IL13, IL17), chemokines (IL8, Groα, MCP1, MIP1ß), growth factors [IL5, IL7, epidermal growth factor (EGF), granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, TGFß2], and immunoglobulins (IgA, IgG, IgM), in milk produced by healthy women of different ethnicities living in different geographic, dietary, socioeconomic, and environmental settings. Among the analyzed factors, IgA, IgG, IgM, EGF, TGFß2, IL7, IL8, Groa, and MIP1ß were detected in all or most of the samples collected in each population and, therefore, this specific set of compounds might be considered as the "core" soluble immune factors in milk produced by healthy women worldwide. This approach may help define which immune factors are (or are not) common in milk produced by women living in various conditions, and to identify host, lifestyle, and environmental factors that affect the immunological composition of this complex biological fluid.
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| 9. |
- Sosa-Yáñez, Lorena Carolina, et al.
(författare)
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Influencia de tres regímenes de riego sobre la calidad agronómica de centeno cultivado en la costa de Hermosillo, Sonora, México
- 2022
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Ingår i: Terra Latinoamericana. - 0187-5779. ; 40
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Tidskriftsartikel (refereegranskat)abstract
- Cereals are a fundamental part of the world diet; therefore, their adaptation in different environments due to climate change should be achieved. Studying the modifications that may occur during plant development is essential, as well as in the quality of the harvested product. Thus the objective of this research is to analyze the effect of water stress on development, growth, production, and agronomic quality of rye crop and harvested grain. For sowing, a completely randomized one-way experimental design was used, where the treatments consisted of three different soil moisture regimes. The variables evaluated at the time of harvest were plant height and number of spikes per linear meter. After harvest, the variables evaluated were spike size and the number of grains it contained, as well as size and color of the grain, weight of 1000 grains, test weight, yield, ash and protein content. An analysis of variance and Tukey’s comparison of means test (P < 0.05) were performed for ash and protein content, and Duncan (P < 0.05 and P ≤ 0.0001) for the rest of the determinations. The results showed that less irrigation did not negatively affect the crop with an appropriate agronomic development, highlighting an increase in the number and size of spikes, an increase in the number of grains per spike, as well as a high yield and protein content of the grain. These values were higher than those reported in previous research, which confirms that even though rye is considered a winter cereal, it managed to acclimate to soil conditions, decreased water, and high temperatures in the coastal area of Hermosillo, Sonora, México.
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