Multidisciplinary studies supporting conservation programmes of two rare,endangered Limonium species from Spain

Plant and Soil - To build a more holistic understanding of soil pH change we assessed the synchronised effects of a contrived soil pH change on soil chemistry, vegetation growth and nutrition, and...     

ISG15 Regulates Peritoneal Macrophages Functionality against Viral Infection

Upon viral infection, the production of type I interferon (IFN) and the subsequent upregulation of IFN stimulated genes (ISGs) generate an antiviral state with an important role in the activation of innate and adaptive host immune responses. The ubiquitin-like protein (UBL) ISG15 is a critical IFN-induced antiviral molecule that protects against several viral infections, but the mechanism by which ISG15 exerts its antiviral function is not completely understood. Here, we report that ISG15 plays an important role in the regulation of macrophage responses. ISG15−/− macrophages display reduced activation, phagocytic capacity and programmed cell death activation in response to vaccinia virus (VACV) infection. Moreover, peritoneal macrophages from mice lacking ISG15 are neither able to phagocyte infected cells nor to block viral infection in co-culture experiments with VACV-infected murine embryonic fibroblast (MEFs). This phenotype is independent of cytokine production and secretion, but clearly correlates with impaired activation of the protein kinase AKT in ISG15 knock-out (KO) macrophages. Altogether, these results indicate an essential role of ISG15 in the cellular immune antiviral response and point out that a better understanding of the antiviral responses triggered by ISG15 may lead to the development of therapies against important human pathogens.     

PI3-Kinase γ Promotes Rap1a-Mediated Activation of Myeloid Cell Integrin α4β1, Leading to Tumor Inflammation and Growth

Tumor inflammation, the recruitment of myeloid lineage cells into the tumor microenvironment, promotes angiogenesis, immunosuppression and metastasis. CD11b+Gr1lo monocytic lineage cells and CD11b+Gr1hi granulocytic lineage cells are recruited from the circulation by tumor-derived chemoattractants, which stimulate PI3-kinase γ (PI3Kγ)-mediated integrin α4 activation and extravasation. We show here that PI3Kγ activates PLCγ, leading to RasGrp/CalDAG-GEF-I&II mediated, Rap1a-dependent activation of integrin α4β1, extravasation of monocytes and granulocytes, and inflammation-associated tumor progression. Genetic depletion of PLCγ, CalDAG-GEFI or II, Rap1a, or the Rap1 effector RIAM was sufficient to prevent integrin α4 activation by chemoattractants or activated PI3Kγ (p110γCAAX), while activated Rap (RapV12) promoted constitutive integrin activation and cell adhesion that could only be blocked by inhibition of RIAM or integrin α4β1. Similar to blockade of PI3Kγ or integrin α4β1, blockade of Rap1a suppressed both the recruitment of monocytes and granulocytes to tumors and tumor progression. These results demonstrate critical roles for a PI3Kγ-Rap1a-dependent pathway in integrin activation during tumor inflammation and suggest novel avenues for cancer therapy.     

Lack of Relationship between Cord Serum Angiopoietin-Like Protein 4 (ANGPTL4) and Lipolytic Activity in Human Neonates Born by Spontaneous Delivery

Background

Ligands of peroxisome-proliferator activated receptors (PPARs), such as non-esterified fatty acids (NEFAs), induce expression of angiopoietin-like protein 4 (ANGPTL4). Recently ANGPTL4 has been reported to be a mediator of intracellular adipose lipolysis induced by glucocorticoids.

Objective

To determine the concentrations of ANGPTL4 in cord serum of neonates born by spontaneous vaginal delivery (SVD) and by pre-labor cesarean section (CS) from healthy women, and to relate them to parameters of neonatal lipolytic activity at birth.

Measurements

In 54 neonates born by SVD and in 56 neonates born by CS, arterial cord blood was drawn to determine insulin, cortisol, triacylglycerols (TAGs), glycerol, non-esterified fatty acids (NEFAs), individual fatty acids, ANGPTL4, adiponectin, retinol binding protein 4 (RBP4) and leptin.

Results

Birth weight and neonatal fat mass in SVD and CS showed no difference, but the concentrations of glycerol, adiponectin, RBP4, NEFAs and most individual fatty acids were higher in cord serum of neonates born by SVD compared to CS, indicating a higher adipose tissue breakdown in the SVD group. The concentrations of TAG and cortisol were also higher and that of insulin was lower in cord serum of SVD compared to the CS group. However, the concentration in cord serum of ANGPTL4 did not differ between the two groups and no positive correlation with either NEFA or glycerol concentrations were detected.

Conclusion

ANGPTL4 is known to stimulate lipolysis in adults, but does not appear to mediate the increased activity in SVD, indicating the presence of different regulatory inputs.     

Race to the Future: Integrating 21st Century Skills into Science Instruction

Race to the Future is an exciting and dynamic activity modeled after the reality television show The Amazing Race. It exemplifies how 21st century skills can be incorporated into core subject instruction and at the same time positively enhance student engagement. In this activity, students work quickly and cooperatively with their teammates and use 21st century skills to successfully decipher five clues related to science content. We have used this activity with excellent results with different groups of students (middle school, high school, and university students), for different purposes (ice-breaker, team-building, course assessment, and evaluation), and in broad curriculum areas (science and math). However, the activity is especially powerful when introduced during the first day or week of class. The meaningful and enjoyable student collaboration, the upbeat class environment, and the enhanced student engagement achieved at the conclusion of this challenging activity set an optimal teaching and learning environment for the entire quarter/semester.     

Host Association of Cryptosporidium parvum Populations Infecting Domestic Ruminants in Spain

A stock of 148 Cryptosporidium parvum DNA extracts from lambs and goat kids selected from a previous study examining the occurrence of Cryptosporidium species and GP60 subtypes in diarrheic lambs and goat kids in northeastern Spain was further characterized by a multilocus fragment typing approach with six mini- and microsatellite loci. Various degrees of polymorphism were seen at all but the MS5 locus, although all markers exhibited two major alleles accounting for more than 75% of isolates. A total of 56 multilocus subtypes (MLTs) from lambs (48 MLTs) and goat kids (11 MLTs) were identified. Individual isolates with mixed MLTs were detected on more than 25% of the farms, but most MLTs (33) were distinctive for individual farms, revealing the endemicity of cryptosporidial infections on sheep and goat farms. Comparison with a previous study in calves in northern Spain using the same six-locus subtyping scheme showed the presence of host-associated alleles, differences in the identity of major alleles, and very little overlap in MLTs between C. parvum isolates from lambs and those from calves (1 MLT) or isolates from lambs and those from goat kids (3 MLTs). The Hunter-Gaston index of the multilocus technique was 0.976 (95% confidence interval [CI], 0.970 to 0.982), which supports its high discriminatory power for strain typing and epidemiological tracking. Population analyses revealed the presence of two host-associated subpopulations showing epidemic clonality among the C. parvum isolates infecting calves and lambs/goat kids, respectively, although evidence of genetic flow between the two subpopulations was also detected.     

Iron and Proinflammatory Cytokines in Chronic Hepatitis C Virus Infection

Steatohepatitis is a common finding in chronic hepatitis C virus (HCV) infection. As in other forms of steatohepatitis, oxidative damage may play an outstanding role. However, there are conflicting results relative to the role of iron on hepatic lipogenesis. Proinflammatory cytokines up-regulate ferritin expression, probably reflecting a defensive mechanism against increased oxidative stress, capable to open haem ring and release reactive iron. On the contrary, some adipokines, such as adiponectin, are associated with low ferritin levels. The aim of this study is to analyse the relationships of the amount of liver steatosis with serum iron, transferrin and ferritin as well as with proinflammatory cytokines, such as tumour necrosis factor (TNF)-α and interleukin (IL)-6, and adiponectin levels. We included 82 HCV infected patients and assessed the amount of liver fat by histomorphometry and its relationships with serum iron, ferritin and transferrin, adiponectin and TNF-α and IL-6. Liver steatosis was observed in 67 patients out of 82; in the remaining 15 patients, no steatosis at all was found. Patients with steatosis showed significantly higher serum ferritin levels than patients without steatosis (Z?=?2.14; p?=?0.032). When patients were classified in quartiles according to the intensity of steatosis, we observed that both TNF-α (KW?=?10.6; p?=?0.014) and IL-6 (KW?=?15.2; p?=?0.002) were significantly different among the four groups. Patients with more intense steatosis (highest quartile) showed the highest TNF-α and IL-6 values. Patients with severe hepatitis had higher levels of serum iron than patients with mild to moderate hepatitis. Serum iron also showed a correlation with the proportion of fibrosis (ρ?=?0.30; p?=?0.007). Serum iron levels are related with biochemical and histological parameters derived from liver inflammation in HCV-associated liver disease. Serum ferritin is higher among those with intense steatosis and also shows a (non-significant) trend to be associated with the more severe forms of hepatitis.     

TMEM59 defines a novel ATG16L1‐binding motif that promotes local activation of LC3

Selective autophagy underlies many of the important physiological roles that autophagy plays in multicellular organisms, but the mechanisms involved in cargo selection are poorly understood. Here we describe a molecular mechanism that can target conventional endosomes for autophagic degradation. We show that the human transmembrane protein TMEM59 contains a minimal 19‐amino‐acid peptide in its intracellular domain that promotes LC3 labelling and lysosomal targeting of its own endosomal compartment. Interestingly, this peptide defines a novel protein motif that mediates interaction with the WD‐repeat domain of ATG16L1, thus providing a mechanistic basis for the activity. The motif is represented with the same ATG16L1‐binding ability in other molecules, suggesting a more general relevance. We propose that this motif may play an important role in targeting specific membranous compartments for autophagic degradation, and therefore it may facilitate the search for adaptor proteins that promote selective autophagy by engaging ATG16L1. Endogenous TMEM59 interacts with ATG16L1 and mediates autophagy in response to Staphylococcus aureus infection.