Postnatal exposure to di-(2-ethylhexyl)phthalate alters cardiac insulin signaling molecules and GLUT4Ser488 phosphorylation in male rat offspring

Di-(2-ethylhexyl)phthalate (DEHP), a distinctive endocrine-disrupting chemical, is widely used as a plasticizer in a variety of consumer products. It can easily cross the placenta and enter breast milk and then it is rapidly absorbed by offspring. Since it is generally accepted that individuals are more sensitive to chemical exposure during vital developmental periods, we investigated whether DEHP exposure during lactation affects cardiac insulin signaling and glucose homeostasis in the F₁ male rat offspring at postnatal day 22 (PND22). Lactating Wistar rats were administered with DEHP (1, 10, and 100 mg/kg/d) or olive oil from lactation day 1 to 21 by oral gavage. All the male pups were perfused and killed on PND22. On the day before the killing, they were kept for fasting overnight and blood was collected. The cardiac muscle was dissected out, washed in ice-cold physiological saline repeatedly and used for the assay of various parameters. DEHP-exposed offspring had significantly lower body weight than the control. DEHP-exposed offspring showed elevated blood glucose, decreased ¹⁴C-2-deoxyglucose uptake and ¹⁴C-glucose oxidation in cardiac muscle at PND22. The concentration of upstream insulin signaling molecules such as insulin receptor subunit β (InsRβ) and insulin receptor substrate 1 (IRS1) were downregulated in DEHP-exposed offspring. However, no significant alterations were observed in protein kinase B (Akt) and Akt substrate of 160 kDa (AS160). Surprisingly, phosphorylation of IRS1 ^Tyr632 and Akt ^Ser473 were diminished. Low levels of glucose transporter type 4 (GLUT4) protein and increased GLUT4 ^Ser488 phosphorylation which decreases its intrinsic activity and translocation towards plasma membrane were also recorded. Lactational DEHP exposure predisposes F ₁ male offspring to cardiac glucometabolic disorders at PND22, which may impair cardiac function.     

AMPA receptor expression in mouse testis and spermatogonial GC-1 cells: A study on its regulation by excitatory amino acids

Excitatory amino acids (EAAs) are found present in the nervous and reproductive systems of animals. Numerous studies have demonstrated a regulatory role for Glutamate (Glu), d -aspartate ( d -Asp) and N-methyl- d -aspartate (NMDA) in the control of spermatogenesis. EAAs are able to stimulate the Glutamate receptors, including the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR). Here in, we assess expression of the main AMPAR subunits, GluA1 and GluA2/3, in the mouse testis and in spermatogonial GC-1 cells. The results showed that both GluA1 and GluA2/3 were localized in mouse testis prevalently in spermatogonia. The subunit GluA2/3 was more highly expressed compared with GluA1 in both the testis and the GC-1 cells. Subsequently, GC-1 cells were incubated with medium containing l -Glu, d -Glu, d -Asp or NMDA to determine GluA1 and GluA2/3 expressions. At 30 minutes and 2 hours of incubation, EAA-treated GC-1 cells showed significantly higher expression levels of both GluA1 and GluA2/3. Furthermore, p-extracellular signal-regulated kinase (ERK), p-Akt, proliferating cell nuclear antigen (PCNA), and Aurora B expressions were assayed in l -Glu-, d -Glu-, and NMDA-treated GC-1 cells. At 30 minutes and 2 hours of incubation, treated GC-1 cells showed significantly higher expression levels of p-ERK and p-Akt. A consequent increase of PCNA and Aurora B expressions was induced by l -Glu and NMDA, but not by d -Glu. Our study demonstrates a direct effect of the EAAs on spermatogonial activity. In addition, the increased protein expression levels of GluA1 and GluA2/3 in EAA-treated GC-1 cells suggest that EAAs could activate ERK and Akt pathways through the AMPAR. Finally, the increased PCNA and Aurora B levels may imply an enhanced proliferative activity.     

Mutation in a flexible linker modulates binding affinity for modular complexes

Tandem beta zippers are modular complexes formed between repeated linear motifs and tandemly arrayed domains of partner proteins in which β-strands form upon binding. Studies of such complexes, formed by LIM domain proteins and linear motifs in their intrinsically disordered partners, revealed spacer regions between the linear motifs that are relatively flexible but may affect the overall orientation of the binding modules. We demonstrate that mutation of a solvent exposed side chain in the spacer region of an LHX4–ISL2 complex has no significant effect on the structure of the complex, but decreases binding affinity, apparently by increasing flexibility of the linker.     

A comprehensive examination of the network position hypothesis across multiple river metacommunities

The hierarchical branching nature of river networks can have a strong influence on the assembly of freshwater communities. This unique structure has spurred the development of the network position hypothesis (NPH), which states that the strength of different assembly processes depends on the community position in the river network. Specifically, it predicts that 1) headwater communities should be exclusively controlled by the local environment given that they are more isolated and environmentally heterogeneous relative to downstream reaches. In contrast, 2) downstream communities should be regulated by both environmental and dispersal processes due to increased connectivity given their central position in the riverscape. Although intuitive, the NPH has only been evaluated on a few catchments and it is not yet clear whether its predictions are generalizable. To fill this gap, we tested the NPH on river dwelling fishes using an extensive dataset from 28 French catchments. Stream and climatic variables were assembled to characterize environmental conditions and graph theory was applied on river networks to create spatial variables. We tested both predictions using variation partitioning analyses separately for headwater and downstream sites in each catchment. Only 10 catchments supported both predictions, 11 failed to support at least one of them, while in 7 the NPH was partially supported given that spatial variables were also significant for headwater communities. We then assembled a dataset at the catchment scale (e.g. topography, environmental heterogeneity, network connectivity) and applied a classification tree analysis (CTA) to determine which regional property could explain these results. The CTA showed that the NPH was not supported in catchments with high heterogeneity in connectivity among sites. In more homogeneously connected catchments, the NPH was only supported when headwaters were more environmentally heterogeneous than downstream sites. We conclude that the NPH is context dependent even for taxa dispersing exclusively within streams.     

Phosphorylation of NHERF1 S279 and S301 differentially regulates breast cancer cell phenotype and metastatic organotropism

Metastatic cancer cells are highly plastic for the expression of different tumor phenotype hallmarks and organotropism. This plasticity is highly regulated but the dynamics of the signaling processes orchestrating the shift from one cell phenotype and metastatic organ pattern to another are still largely unknown. The scaffolding protein NHERF1 has been shown to regulate the expression of different neoplastic phenotypes through its PDZ domains, which forms the mechanistic basis for metastatic organotropism. This reprogramming activity was postulated to be dependent on its differential phosphorylation patterns. Here, we show that NHERF1 phosphorylation on S279/S301 dictates several tumor phenotypes such as in vivo invasion, NHE1-mediated matrix digestion, growth and vasculogenic mimicry. Remarkably, injecting mice with cells having differential NHERF1 expression and phosphorylation drove a shift from the predominantly lung colonization (WT NHERF1) to predominately bone colonization (double S279A/S301A mutant), indicating that NHERF1 phosphorylation also acts as a signaling switch in metastatic organotropism.     

Biochemical insights into basal and induced resistance in cabbage to black rot

Black rot, caused by Xanthomonas campestris pv. campestris (Xcc), is the most devastating disease of brassica, but the mechanisms of basal or induced resistance in cabbage remain largely unknown. Here, we performed three experiments to investigate biochemical features associated with cabbage resistance to black rot. In the first experiment, biochemical changes were assessed in plants that were inoculated with a highly (UFPR 5) or a moderately (Xcc 10) aggressive Xcc isolate. In the second experiment, we examined the biochemical responses in two cultivars (Chato de Quintal [CQ] and Louco de Verão [LV], susceptible and moderately resistant to Xcc, respectively). Finally, we examined whether acibenzolar‐S‐methyl (ASM) could induce cabbage resistance to Xcc. Plants inoculated with the Xcc 10 isolate displayed higher activities of superoxide dismutase (SOD), peroxidase (POX) and ascorbate peroxidase (APX), whereas activities of chitinase (CHI), β‐1,3‐glucanase (GLU) and polyphenol oxidase (PPO) as well as the concentrations of hydrogen peroxide (H₂O₂) and malondialdehyde (MDA) were lower compared to plants inoculated with the UFPR 5 isolate. The resistance of the cultivar LV to Xcc was linked to increases in the activities of CHI, GLU, and PPO and decreases in the activities of SOD, POX and APX as well as in the concentrations of H₂O₂ and MDA relative to the cultivar CQ. In general, ASM‐sprayed plants displayed higher activities for the enzymes studied, which was associated with decreased disease symptoms and oxidative stress. Taken together, our results demonstrated that high activities of both defence and antioxidant enzymes played a major role in both basal and induced resistance of cabbage to black rot.     

Acaricidal properties of essential oils from agro‐industrial waste products from citric fruit against Tetranychus urticae

Tetranychus urticae is a major agricultural pest with worldwide distribution that has caused considerable damage to vegetable crops in north‐eastern Brazil. The aim of the present study was to investigate the chemical and lethal/sublethal effects of essential oils from the peels of the lime (Citrus aurantiifolia), lemon (C. limon), mandarin orange (C. reticulata) and (C. reticulata × C. sinensis) as well as selected constituents (linalool, α‐terpineol, α‐pinene, β‐pinene, terpinolene and limonene) against T. urticae. The greatest yield was achieved with the mandarin and tangerine peel oils. The chemical analysis (gas chromatography‐mass spectrometry) of the essential oils from the Citrus fruit peels enabled the identification of 127 compounds, revealing a predominance of monoterpenes. Limonene was the major constituent, and α‐pinene, β‐pinene, linalool and α‐terpineol were found in substantial quantities. Regarding the susceptibility of T. urticae, the Citrus oils and selected constituents were more effective by fumigation than residual contact. The C. reticulata oil was the most toxic by fumigation, and the C. limon oil was the most toxic by residual contact. The constituent α‐terpineol exhibited the highest toxicity with both methods. At a sublethal concentration, the oils and selected constituents had significant effects on the fecundity, feeding preference and oviposition of the mite. Citrus oils and their constituents are potentially useful for the future integrated management of T. urticae due to their lethal and sublethal properties. However, further studies are needed to evaluate the action of these essential oils against non‐target organisms and determine the cost–benefit ratio for the formulation of an acaricide harvested from agro‐industrial waste from citric fruit processing activities for use in the integrated control of T. urticae.     

Seasonal variation in natural mortality factors of Tuta absoluta (Lepidoptera: Gelechiidae) in open‐field tomato cultivation

The seasonal variation in natural mortality of phytophagous insects is determined by the relative importance of biotic and abiotic factors in agroecosystems. Knowledge regarding these factors throughout the year represents a key concern for IPM programmes. Seasonal population fluctuations of tomato pinworm, Tuta absoluta, led to an investigation of its natural mortality factors during the rainy season when the population level is low and during the dry season when population peaks occur. The aim of this study was to verify the seasonal variation in T. absoluta mortality factors in tomato crops. Immature stages of T. absoluta were obtained from laboratory‐rearing in the laboratory. These were taken to the field and monitored over two years. The mortality causes for each stage of insect development from egg to adult were assessed daily. Multiple biotic and abiotic mortality factors affected the immature T. absoluta stages such as rainfall, physiological disturbances, diseases, parasitoids and predators. The key T. absoluta mortality factor during summer–spring was predation. In addition, larvae predation correlated positively with temperature, wind velocity, photoperiod and rainfall. Nevertheless, during winter–fall, the key mortality factor was parasitism. Therefore, the critical stage for mortality was 3rd‐ and 4th‐instar larvae, being more vulnerable to natural control factors. Finally, the results showed the importance of vertical and horizontal action on natural mortality factors.     

Low genetic diversity in the vulnerable Goitred Gazelle,Gazella subgutturosa (Cetartiodactyla: Bovidae), in Iran: potential genetic consequence of recent population declines

The Goitered Gazelle, Gazella subgutturosa, is the most widespread gazelle species in the Middle East and central Asia inhabiting desert and semi-desert habitats. Today it is threatened and its geographic range and population size have experienced significant decline in the last decades. In Iran, the remnant populations are confined to fragmented habitats. We aimed to characterise genetic diversity and phylogenetic status of the populations of Goitered Gazelle in Central Iran and to evaluate the potential effect of a historic population bottleneck on the genetic variation of today’s population. We used noninvasive sampling to uncover structure and level of genetic variation in a fragment of the cytochrome-b gene from 170 samples. Genealogical analyses were performed using HKY+I model and phylogenetic trees reconstructed using Bayesian inference and maximum likelihood. We found extremely low levels of genetic variation, with altogether only five haplotypes in samples from different populations. Overall haplotype diversity was 0.081 and nucleotide diversity 0.0003. The mean observed mismatch between any two sequences was 0.093 with the largest peak for small numbers. The mismatch distribution fit the model of population expansion and suggested that gazelles had experienced a sudden expansion. An unrooted median-joining network analysis of mtDNA haplotypes showed a star-like structure which few mutations steps separating the haplotypes from other regions. Our findings strengthen the urgency of preserving the species’ genetic diversity to prevent local extinction.