APOE4 is associated with elevated blood lipids and lower levels of innate immune biomarkers in a tropical Amerindian subsistence population

In post-industrial settings, apolipoprotein E4 (APOE4) is associated with increased cardiovascular and neurological disease risk. However, the majority of human evolutionary history occurred in environments with higher pathogenic diversity and low cardiovascular risk. We hypothesize that in high-pathogen and energy-limited contexts, the APOE4 allele confers benefits by reducing innate inflammation when uninfected, while maintaining higher lipid levels that buffer costs of immune activation during infection. Among Tsimane forager-farmers of Bolivia (N = 1266, 50% female), APOE4 is associated with 30% lower C-reactive protein, and higher total cholesterol and oxidized LDL. Blood lipids were either not associated, or negatively associated with inflammatory biomarkers, except for associations of oxidized LDL and inflammation which were limited to obese adults. Further, APOE4 carriers maintain higher levels of total and LDL cholesterol at low body mass indices (BMIs). These results suggest that the relationship between APOE4 and lipids may be beneficial for pathogen-driven immune responses and unlikely to increase cardiovascular risk in an active subsistence population.

Taxonomic and pathogenic diversity of the blast pathogen populations infecting wheat and grasses in Minas Gerais

The blast disease of Poaceae is caused by a large species complex, among which P. oryzae is composed of several host-specialized lineages. The Pyricularia oryzae Triticum pathotype (PoT) causes the blast disease in wheat, but is also capable of infecting other grasses, which may serve as an inoculum reservoir for epidemics in wheat. In Brazil, severe wheat blast epidemics are most common in the Cerrado region. The dominant hypothesis is that signal grass (Urochloa sp.) and other gramineous plants harbor the wheat blast pathogen, thus serving as a major reservoir of inoculum for epidemics in wheat. A two-year survey of the Pyricularia blast pathogens was conducted in both wheat and non-wheat areas as well as prior (February) and during (May) the wheat growing season in Minas Gerais. A total of 1,368 plant samples representative of 31 Poaceae species, including wheat, were collected and inspected for the presence of blast symptoms. During the isolations, 932 isolates were obtained, being one fourth obtained from gramineous plants. A subset of 572 isolates was selected for identification at the species level based on portions of the CH7-BAC9 gene sequences. Most of the isolates (n = 494) were P. oryzae, within which 68% were PoT and 32% non-PoT based on two PCR assays targeting (MoT3 and C17 PCR assays). The PoT lineage was found predominantly (97%) in wheat and rarely in the other hosts, even nearby wheat fields (2.1%), as well as at longer distances from wheat regions (0.1%). The blast pathogen population isolated from signal grass grouped in different clades from PoT, and therefore referred to Urochloa lineage (PoU). A series of cross-inoculation greenhouse experiments was conducted using wheat (cv. BRS Guamirim and BR 18-Terena) and signal grass (cv. Marandu) as host and 14 PoT and six PoU isolates as pathogen factor. In the first leaf-inoculation experiment, results showed a significant interaction between host and pathogen; PoT was strongly/weakly aggressive towards wheat/signal grass and PoU was strongly/weakly aggressive towards signal grass/wheat. In inoculated wheat heads, PoT was more aggressive (>91% infected spikelets) than PoU (52% infected spikelets). In a third experiment, four signal grass cultivars (Marandu, Basilisk, Piatã, and Xaraés) were inoculated with the same set of 20 isolates. Similarly, signal grass cultivars were generally more susceptible to PoU than PoT. Severity induced by PoU was twice (7.7% severity) as high as PoT (3.8%) and so was the number of conidia/leaf produced by PoU (47,500) and PoT (23,200). Two groups of signal grass cultivars were formed, the most susceptible composed of Marandu and Basilisk and the least susceptible composed of Piatã and Xaraés. Results of our study confirm the host-specialization and the shaping of the blast populations according to the host. We further suggest that grasses in general, especially signal grass, may not play a major role as an inoculum reservoir for PoT, as it harbors mainly the PoU population. However, due to the large extent of pasture-growing regions and cross-infection ability in wheat, signal grass may harbor amounts of PoT inoculum that are sufficient for initiating leaf and head blast epidemics in wheat blast in Minas Gerais state.

Analysis of Cultural and Pathogenic Diversity in Bipolaris sorokiniana Causing Spot Blotch of Bread Wheat in North India

Present study was conducted to analyse the cultural and pathogenic diversity in different isolates of Bipolaris sorokiniana the causal organism of spot blotch in bread wheat. Six isolates of Biplorais sorokiniana (BS-F-5, BS-D-2, BS-K,4, BS-DWR-K-1, BS-V-6, and BS-P-3) were evaluated simultaneously for cultural and pathogenic variability on the basis of diverse characteristics against seven different genotypes of wheat grown in the region viz: BOW’S’, HS 375, HUW 234, PBW 343, PBW 443, K9107 and A9-30-1. The results indicated that isolates varied significantly among themselves for all the characters analysed. The isolate BS-F-5 exhibited the maximum colony diameter, maximum average dimension (length and width) of conidiophore, maximum number of septa in conidiophore and conidia. Variations were also observed in texture of the colony. Among the seven genotypes tested against six isolates, BOW’S’ showed resistance against three isolates (BS-D-2, BS-K,4, BS-DWR-K-1) and genotype A-9-30-1 showed high susceptibility against all isolates except BS-D-2. The isolates BS-F-5 and BS-P-3 exhibited maximum pathogenic virulence among the isolates analysed in the present investigation.

APOE4 is associated with elevated blood lipids and lower levels of innate immune biomarkers in a tropical Amerindian subsistence population

In post-industrial settings, APOE4 is associated with increased cardiovascular and neurological disease risk. However, the majority of human evolutionary history occurred in environments with higher pathogenic diversity and low cardiovascular risk. We hypothesize that in high-pathogen and energy-limited contexts, the APOE4 allele confers benefits by reducing baseline innate inflammation when uninfected, while maintaining higher lipid levels that buffer costs of immune activation during infection. Among Tsimane forager-farmers of Bolivia (N=1266), APOE4 is associated with 30% lower C-reactive protein, and higher total cholesterol and oxidized-LDL. Blood lipids were either not associated, or negatively associated with inflammatory biomarkers, except for associations of oxidized-LDL and inflammation which were limited to obese adults. Further, APOE4 carriers maintain higher levels of total and LDL cholesterol at low BMIs. These results suggest the relationship between APOE4 and lipids is likely beneficial for pathogen-driven immune responses, and unlikely to increase cardiovascular risk in an active subsistence population.

Genetic variability of Colletotrichum lindemuthianum isolates from Turkey and resistance of Turkish bean cultivars

Aim of study: To evaluate genetic variability and population structure of C. lindemuthianum isolates in Turkey and to record the reactions of some common bean cultivars to the pathogen isolates representing different genetic groups.Area of study: The study was performed in seven provinces of Turkey.Material and methods: Genetic diversity of 91 C. lindemuthianum isolates obtained from different provinces of Turkey was characterized by 27 iPBS and 30 ISSR primers. Also, the resistance of 40 common bean cultivars was scored against three isolates representing different genetic groups.Main results: The dendrogram based on the combined dataset of iPBS and ISSR markers classified the isolates into two main groups with a genetic similarity of 72%, which closely associated with the geographic distribution of the isolates. The dendrogram of Nei’s genetic distances and Structure analysis supported the clustering of C. lindemuthianum isolates according to the geographical provinces. The results indicated that high level of genetic diversity (GST= 0.4) and low level of gene flow (NM=0.748) exist among the populations. AMOVA analysis showed that 58.7% of total genetic variability resulted from genetic differences between the isolates within populations, while 41.29% was among populations. Four cultivars showed resistant reaction to three isolates, while the other cultivars were susceptible to at least one isolate.Research highlights: The results indicated that iPBS and ISSR markers were reliable and effective tools for analyzing population structure of C. lindemuthianum and revealed high level of genetic and pathogenic diversity among pathogen populations in Turkey.

Pathogenic diversity of RNA variants and RNA variation-associated factors in cancer development

Recently, with the development of RNA sequencing technologies such as next-generation sequencing (NGS) for RNA, numerous variations of alternatively processed RNAs made by alternative splicing, RNA editing, alternative maturation of microRNA (miRNA), RNA methylation, and alternative polyadenylation have been uncovered. Furthermore, abnormally processed RNAs can cause a variety of diseases, including obesity, diabetes, Alzheimer’s disease, and cancer. Especially in cancer development, aberrant RNAs caused by deregulated RNA modifiers or regulators are related to progression. Accumulating evidence has reported that aberrant RNAs promote carcinogenesis in many cancers, including liver cancer, leukemia, melanoma, lung cancer, breast cancer, and other cancers, in which abnormal RNA processing occurs in normal cells. Therefore, it is necessary to understand the precise roles and mechanisms of disease-related RNA processing in various cancers for the development of therapeutic interventions. In this review, the underlying mechanisms of variations in the RNA life cycle and the biological impacts of RNA variations on carcinogenesis will be discussed, and therapeutic strategies for the treatment of tumor malignancies will be provided. We also discuss emerging roles of RNA regulators in hepatocellular carcinogenesis.

Localized Genetic and Phenotypic Diversity of Xanthomonas translucens Associated With Bacterial Leaf Streak on Wheat and Barley in Minnesota

Bacterial leaf streak (BLS) of wheat and barley has been a disease of increasing concern in the Upper Midwest over the past decade. In this study, intra- and interfield genetic and pathogenic diversity of bacteria causing BLS in Minnesota was evaluated. In 2015, 89 strains were isolated from 100 leaf samples collected from two wheat and two barley fields naturally infected with BLS. Virulence assays and multilocus sequence alignments of four housekeeping genes supported pathovar identifications. All wheat strains were pathogenic on wheat and barley and belonged to the same lineage as the Xanthomonas translucens pv. undulosa-type strain. All barley strains were pathogenic on barley but not on wheat. Three lineages of barley strains were detected. The frequency and number of sequence types of each pathovar varied within and between fields. A significant population variance was detected between populations of X. translucens pv. undulosa collected from different wheat fields. Population stratification of X. translucens pv. translucens was not detected. Significant differences in virulence were detected among three dominant sequence types of X. translucens pv. undulosa but not those of X. translucens pv. translucens. Field trials with wheat and barley plants inoculated with strains of known sequence type and virulence did not detect significant race structures within either pathovar. Knowledge of virulence, sequence types, and population structures of X. translucens on wheat and barley can support studies on plant–bacterial interactions and breeding for BLS disease resistance.